Term
| Identify the methods used to detect Rubella infection |
|
Definition
| ELISA or EIA with synthetic Rubella peptides are the target test antigen |
|
|
Term
| How is a significant titer interpreted in regards to post-vaccination or as an indication of current infection of Rubella? |
|
Definition
Post vaccination has to have a titer greater than 1:8
There is a 4-fold rise in IgM titer in samples that are drawn 5 days apart to indicate current infection |
|
|
Term
| What is the disease caused by Rubella? |
|
Definition
| German Measles. Acquired rubella infection is very contagious but mostly in school-aged children and symptoms are usually benign |
|
|
Term
| What is the most serious infection caused by Rubella? |
|
Definition
| Congenital rubella infection. Very rare and has a lot of side effects. |
|
|
Term
| Identify the methods used to detect VZV infection versus immunity to VZV. |
|
Definition
| To identify the virus, Shell viral cultures coupled with immunofluorescent staining are used as well as PCR for the VZV DNA. To detect immunity, ELISA tests are used. |
|
|
Term
| Identify the two diseases caused by Varicella-Zoster Virus (VZV) and the site in the body where the virus remains latent. |
|
Definition
Varicella (Chiken Pox)
Herpes Zoster (Shingles) |
|
|
Term
| Identify the problems associated with seriological testing for antibody to CMV |
|
Definition
| In order for CMV to be detected, a 4 fold rise in titer must be documented in 2 samples. Unfortunately, it takes 4 weeks for the rise (if there is one) to occur so the samples must be taken 4 weeks apart. Additionally, because of newborns lack of antibody response, assays for IgM anti-CMV have false negatives. False positives can also occur if the mother has rheumatoid arthritis and the IgM anti CMV is cross reactive to the rheumatoid factor present. |
|
|
Term
| Identify the patient population at greatest risk from cytomegalovirus (CMV) infection and the possible consequences of infection. |
|
Definition
Newborns and Immunocompromised, are at a greater risk.
Consequences of infection: Death, Hearing loss, mental retardation, vision loss |
|
|
Term
| Identify confirmatory testing for EBV infection and the significance of these tests in disease staging. |
|
Definition
-IgM antibody to viral capsid antigen (IgM anti-VCA) which indicates acute disease.
-IgG anti-VCA also present during acute IM but persists and indicates previous infection
-Antibody to EBV nuclear antigen (anti-EBNA) which appears during convalescence. |
|
|
Term
| Associate detection/screening for heterophile antibodies with diagnosis of infectious mononucleosis. |
|
Definition
| Heterophile antibodies are IgM antibodies capable of reacting with similar antigens from two or more unrelated species, such as cows. These antibodies are found in cases other than IM, but they are now usually reserved to designate IM. For IM screening, heterophile antibodies are detected with extract of bovine (cow) RBC antigens. |
|
|
Term
| What is the disease caused by Epstein-Barr Virus (EBV)? |
|
Definition
| infectious mononucleosis (Mono) |
|
|
Term
| What is the immune cell target of EBV and the receptor that it uses to target the cell? What is the effect of EBV on the infected cell? |
|
Definition
| EBV targets epithelial cells of the oropharynx as well as B-Cells, via the CD21 receptor. This causes proliferation of B-cells throughout the body and leads to lymph node swelling. |
|
|
Term
| What is the testing for detection of HSV-1 and HSV-2 infection? Is Ag or Ab to the virus detected by serology? |
|
Definition
| EIA or latex agglutination are the test available to detect HSV-1 and HSV-2. Viral antigen to the virus is detected by serology. |
|
|
Term
| Which test is currently available to distinguish between HSV-1 and HSV-2? |
|
Definition
|
|
Term
| What is the target tissue of HSV-1? |
|
Definition
| dorsal root ganglia and arises as cold sores or fever blisters. |
|
|
Term
| What is the target tissue of HSV-2? |
|
Definition
|
|
Term
| Which is of greater concern: HSV-1 or HSV-2? |
|
Definition
|
|
Term
| What are the other viruses that belong to the Herpes Virus Fammily? |
|
Definition
Herpes Simplex viruses (HSV-1 and HSV-2)
Epstein-Barr Virus (EBV or HHV-4)
Cytomegalovirus (CMV or HHV-5)
Varicella-Zoster Virus (VZV or HHV-3)
Human Herpes Viruses (HHV-6, HHV-7, HHV-8) |
|
|
Term
|
Definition
| IgM antibodies that are capable of reacting with similar antigens from two or more unrelated species |
|
|
Term
|
Definition
| form of immunity that occurs when the vaccination of a significant portion of a population (or herd) provides a measure of protection for individuals who have not developed immunity and prevent disastrous congenital infection. |
|
|
Term
| Explain how a RIBA test (such as that used to confirm HCV infection) differs from a western blot test. |
|
Definition
| A RIBA test, or Recombinant Immunoblot Assay, is similar to a western blot except for the fact that recombinant HCV proteins are blotted directly onto nitrocellulose membranes. In a western blot, the proteins would first be separated/denatured before being transferred to the membrane. |
|
|
Term
| Recognize the significance of IgM isotype antibody, IgG isotype antibody, and viral Ag or nucleic acid (RNA or DNA) in general staging of viral infections by laboratory testing. |
|
Definition
| When IgM is present but IgG is not, it is indicative of current or recent acute infection. When IgG is present but IgM is not, it indicates a past infection and immunity. |
|
|
Term
| What is the main health concern associated with viral hepatitis (acute, chronic)? |
|
Definition
Acute: gastrointestinal problems and sometime jaundice
MAJOR CONCERN IN CHRONIC: scarring of the liver or liver cancer |
|
|
Term
|
Definition
| Inflammation of the liver |
|
|
Term
|
Definition
| mode of transmission of disease by food or water. |
|
|
Term
| Which Hepatitis Viruses can enter via fecal-oral route? |
|
Definition
|
|
Term
|
Definition
| mode of transmission via blood/ body fluids (anything other than intestine) |
|
|
Term
| Which Hepatitis Virus can enter via parenteral? |
|
Definition
|
|
Term
|
Definition
| Hepatitis B core antigen, a protein surrounding viral DNA in virus core |
|
|
Term
|
Definition
| Hepatitis Be antigen. Antigen associated with the capsid of hepatitis B virus |
|
|
Term
|
Definition
| surface antigen of hepatitis B virus, the first marker to appear in hepatitis B infection |
|
|
Term
|
Definition
| antibody to hepatitis B core antigen. It appears later and persists for life and indicates past infection |
|
|
Term
|
Definition
| Antibody to hepatitis B surface antigen, appears during recovery. persists for years and provides protective immunity, failure of infected patient to develop anti-HBs indicates chronic infection. |
|
|
Term
| What is the number one criteria used for diagnosing progression from HIV+ to AIDS? |
|
Definition
|
|
Term
| Correlate an increase or decrease in HIV viral load to the success of drug therapy in the patient. |
|
Definition
| Successful drug therapy results in a drop of the viral load level, indicating an inverse correlation. |
|
|
Term
| What is the preferred methodology for detecting HIV infections in newborn infants? |
|
Definition
| Qualitative Real- Time Polymerase Chain Reaction (PT-PCR) that detect cDNA provirus in the baby's mononuclear cells |
|
|
Term
| Why can't the usual screening test for HIV be used to diagnose infection in infants? |
|
Definition
| You have to wait until the baby is about a month old and then test it again when the baby is two months |
|
|
Term
| How does a western blot test adds specificity to the diagnosis of HIV infection? |
|
Definition
| allows the clinician to look for the presence of each individual HIV protein and it is a minimum of 2 necessary to give a positive reading. |
|
|
Term
| Why do we prefer a screening test to be more sensitive and less specific in diagnosis of HIV infection? |
|
Definition
| allows clinicians to rule out anyone that is not infected more easily. If you can pass a sensitive test without a positive reading than you are not infected. Conversely, the lack a specificity in the initial screening leads to many false positives, requiring the use of the confirmatory Western Blot. |
|
|
Term
| What is the confirmatory test for HIV diagnosis? |
|
Definition
|
|
Term
| What are the drawbacks of the early generations ELISA tests for HIV diagnosis? |
|
Definition
| ELISA had a large window period of ~45 days, in which someone could be infected but test negative. There were also false positives due to human cell contaminants and it couldn't detect HIV-2 infections. |
|
|
Term
| How does the "fourth generation" ELISA test limited the drawbacks for HIV diagnosis? |
|
Definition
| by decreasing the window period of false negatives to 14-21 days instead of 45. The test could now detect both HIV-1 and HIV-2. But there are still many false positives in “low risk” populations. |
|
|
Term
| Explain the basics of ELISA testing for detection of either patient antibody, or antigen in patient serum. |
|
Definition
| It uses a solid support to detect antigen-antibody reactions, usually by addition of an enzyme/substrate pair that produces a colored product. The antigen is mixed with the antibody and then washed. then the enzyme antiglobulin conjugate is added, then it’s washed again. When the enzyme binds it will change the color of the liquid and if there’s no color then it’s negative, but if it changes color it’s positive. |
|
|
Term
| Correctly identify the next step to be taken in HIV diagnosis if the initial screening test is positive, or if the repeat duplicate samples are positive. |
|
Definition
| If the initial screening is positive, 2 more tests are done. If both of those tests are negative, the diagnosis can be reported as negative. If at least 1 of the 2 tests are positive, the sample will be sent for confirmatory testing (Western Blot). |
|
|
Term
| Interpret HIV screening test results using the CDC testing algorithm for HIV diagnosis. |
|
Definition
| If the initial screening test is negative, report it as negative. If the initial screening test is positive, repeat a duplicate screening test using the same serum sample. If it is negative on both repeats, report it as negative. If two out of the three tests are positive, send for confirmatory testing. |
|
|
Term
| Interpret HIV confirmatory test results using the CDC testing algorithm for HIV diagnosis. |
|
Definition
| n the confirmatory test, if there are no bands on the patient’s test strip then the sample is negative. If two out of the tree of the following is present, then it is a positive sample: p24, gp41, and gp 120/160. If one or more bands do not meet the criteria for a positive result, the sample is indeterminate and the patient should be retested |
|
|
Term
| Identify the two main analytes that can be measured in serological tests for infectious disease. |
|
Definition
Testing to detect pathogen antigen.
Testing to detect host antibody to the pathogen (thus indicating presence of pathogen) |
|
|
Term
|
Definition
| The Study of non-cellular components of the blood; Serum, and antibodies |
|
|
Term
|
Definition
| Enzyme immunoassay, a test using solid support to determine antigen antibody reactions |
|
|
Term
|
Definition
| a period of time where a false negative could occur, this is because antibodies population is still low, and the test is not sensitive enough to pick up on the small amount |
|
|
Term
|
Definition
| a negative result occurs even though it should be positive |
|
|
Term
|
Definition
| a positive results occurs even though it should be negative |
|
|
Term
|
Definition
| test's ability to identify positive results, the false negative rate is low |
|
|
Term
|
Definition
| test's ability to identify negative results, the false positive rate is low |
|
|
Term
|
Definition
| when a result is given that does not fit into the positive or negative criteria |
|
|
Term
| List of the characteristics of HIV that make it difficult to create an effective vaccine against HIV |
|
Definition
| Very high mutation rate of HIV genome , RT lacks proofreading capability and antigens are always changing within an individual. The vaccine must target both CD8+ T cell response and mucosal antibody response to be effective. THe HIV must remain latent as the provirus integrated into host genome and can reactivate at a later date. |
|
|
Term
| Define the acronym HAART and explain why HAART drug treatment is used in fighting HIV infection instead of single drug therapy. |
|
Definition
| HAART stands for highly active antiretroviral therapy. This drug treatment is used because the combination of the different classes of drugs allows multiple mechanisms of action so that there is an even smaller chance of infection. |
|
|
Term
| Explain why CD4+ T cell numbers temporarily plummet during the end of the acute infection stage of HIV, and then rebound at least partially. |
|
Definition
| The number of CD4+ T cells drops by about 75% initially due to them being attacked by CD8+ Cytotoxic T cells. There is then a slight rebound of CD4+ levels due to stimulation of the bone marrow/thymus realizing that CD4+ levels have dropped significantly. |
|
|
Term
| Explain how long the incubation period of primary HIV infection when acute symptoms can arise, and whether the infected individual is infectious to others at this time |
|
Definition
| Incubation period is about 4-8 weeks. Yes, they are infectious to others at this time. |
|
|
Term
| Identify the function of gp120 and gp41 in the interaction with host cell membranes and eventual infection of host cells. |
|
Definition
HIV gp 120 -protein forms knobs that protrude from the viral envelope and bind CD4 and a chemokine receptor
gp 41- allows fusion with plasma membrane |
|
|
Term
| State whether the number of people infected with HIV worldwide has leveled off, declined, or is still increasing. |
|
Definition
| The total number of infected is still rising, but the prevalence has decreased due to increase global population. |
|
|
Term
| Identify whether HIV-1 or HIV-2 is more common in the U.S. |
|
Definition
|
|
Term
| Is AIDS due to HIV infection a primary or secondary immunodeficiency? |
|
Definition
| secondary immunodeficieny |
|
|
Term
| What are the 2 routine lab tests that can performed using patient blood samples that are useful in evaluating possible immune defects in humoral immunity |
|
Definition
| Serum protein electrophoresis & B cell counts by flow-cytometry |
|
|
Term
| Serum Protein Electrophoresis |
|
Definition
| looks for the decrease or absence of gamma globulins |
|
|
Term
| Identify whether deficiencies of early components of the classical complement pathway, the alternative complement pathway, or the lectin complement pathway can cause a risk for systemic lupus autoimmunity, and why this risk develops. |
|
Definition
| Early components of the classical complement pathway can’t be activated very easily and can cause a risk for systemic lupus autoimmunity. Risk develops due to the high concentration of immune complexes in the bloodstream. |
|
|
Term
| X-Linked agammaglobulineamia |
|
Definition
| result of a complete absence of B cells and antibodies in the bloodstream, and is the result of a Bruton’s Tyrosine kinase deficiency. ALL pre-B cells die in the Bone Marrow |
|
|
Term
| X-linked Hyper-IgM Syndrome |
|
Definition
| result of B cells only making IgM and the complete lack of isotype switching to any other antibody. IgM levels are very high while all other Ig’s are nonexistent. |
|
|
Term
| What are the two primary immune deficiencies that lead to selective susceptibility to viral infections? |
|
Definition
MHC Class I
NK cell absence |
|
|
Term
| What does MHC Class 1 deficiency lead to? |
|
Definition
| lack of CD8 T lymphocytes and has the susceptibility to all viral infections |
|
|
Term
| What does NK cell absence lead to? |
|
Definition
| susceptibility to all of herpes virus infections |
|
|
Term
|
Definition
| decrease of T lymphocytes due to thymic aplasia (lack of thymus) that affects the adaptive immune system |
|
|
Term
| Why can DiGeorge Syndrome have variable levels of severity associated with it? |
|
Definition
| because lack of T cell development is thymus means CD8 and CD4 T cells are both missing, but to varying degrees. You can still have some which would make it less severe, or none which would make it the worst. |
|
|
Term
| What are the known mutations that can lead to SCID? |
|
Definition
| deficiencies in ADA/PNP, lack of a γ chain cytokine receptor or Jak3 kinase, and DNA repair defects (RAG-1/RAG-2) |
|
|
Term
| What are the consequences of SCID in regards to infectious disease susceptibility? |
|
Definition
| all types of infections (bacterial,fungal,viral) and presents symptoms soon after passive immunity from the mother wears off; months after birth |
|
|
Term
| What is the class-1 like molecule that presents antigen to NKT cells? |
|
Definition
|
|
Term
| Where are NKT cells located in the body? |
|
Definition
| liver, intestine, pancreas, uterus, thymus, and tonsils |
|
|
Term
| What do NKT cells do in response to antigen presentation that can influence a subsequent adaptive immune response? |
|
Definition
| NKT cells do not generate memory, therefore cannot influence an adaptive immune response |
|
|
Term
| Identify what kind of antigen is presented by CD1a, CD1b, and CD1c molecules and what cell they present this unique antigen to. |
|
Definition
CD1a through CD1c all bind foreign lipids that are synthesized by some pathogens but are not synthesized in humans.
They are presented to TCRαβ CD4+ and CD8+ T cells |
|
|
Term
| Describe how HLA-E is involved in controlling NK cell killing of healthy self-cells |
|
Definition
| The leader peptide that is cleaved when producing MHC Class 1 is presented by HLA-E to NK cells, if there is a lot of MHC Class 1, then there is a lot of HLA-E with leader peptides, this in turn inhibits NK Cells from destroying the cell. |
|
|
Term
| Identify the specific ligand for the NKG2D receptor, whether it is an activating or inhibitory receptor, and what the NK cell will do if it encounters this ligand. |
|
Definition
| Specific Ligand for NKG2D is MIC-A and MIC- B , NKG2D is activating receptor and when an NK cell encounters this ligand the activating receptor (NKG2D) kills all cells expressing MIC- A/ MIC-B. |
|
|
Term
| Describe the “ligand” for NK cell receptors (in general) and how the signals through these receptors are interpreted by the NK cell. |
|
Definition
| NK cells target and kill virus-infected cells by detecting a loss of MHC class 1 on the infected cell. The receptors fall into two categories: “lectin-like receptors” and “Ig-like receptors”. Both of these families contain inhibitory and activating receptors. The ligands for these receptors are variable, but often involve MHC class 1 proteins of “class I-like” proteins in some way. |
|
|
Term
| Identify the CD protein expressed on the surface of all human NK cells. |
|
Definition
| CD56 AND CD16. There is CD56 high NK cells that secrete large amounts of cytokines when activated and CD56 low NK cells that circulate in the bloodstream looking for something to kill. |
|
|
Term
Vγ9:Vδ2 Tcells
where do they bind? |
|
Definition
| bind phosphoantigens - small phosphorylated intermediates of isoprenoid biosynthesis |
|
|
Term
Vγ9:Vδ2 Tcells
where are the T cell populations located in the body? |
|
Definition
| 80% in inflames / infected sites |
|
|
Term
|
Definition
| act as a cytotoxic T cells by secreting INF-γ and TNF-α as well as granulysin. |
|
|
Term
Vγ:Vδ1 Tcells
where do they bind? |
|
Definition
| to MIC-A and MIC-B - stress proteins expressed by epithelial cells that resemble MHC Class I heavy chains |
|
|
Term
Vγ:Vδ1 Tcells
where are they found in the body? |
|
Definition
| in blood of fetus and neonate but become contained in mucosa and spleen in adults |
|
|
Term
|
Definition
| cytotoxic and kill damaged or infected gut epithelial cells |
|
|
Term
|
Definition
| (Gamma-Delta) use certain V gene segments that are used abundantly used by a high proportion of the cells to perform certain tasks |
|
|
Term
|
Definition
| instead of using peptide presented by Class 1, they use a collection of inhibitory, and activating receptors to determine whether the cell is under stress and should be killed or turns the NK cell “off” so it can move on to another cell |
|
|
Term
|
Definition
| recognize lipid antigens presented by CD1 (like MHC Class 1) |
|
|
Term
| Describe how the immune system seems to compensate for a lack of IgA in “Selective IgA Deficiency”. |
|
Definition
| The immune systems to compensate for a lack of IgA will over-produce IgM and exporting IgM across mucosa. The J-chain and the poly-Ig receptor is used for transport like in IgA. |
|
|
Term
| Two main function of dimeric IgA in the mucosa |
|
Definition
-IgA can act as a way to transport toxins out of the lamina propria, simply by binding the toxins and then being transported through the epithelial cell.
-IgA can also bind and neutralize toxins that are outside of the lamina propria. |
|
|
Term
| 3 known cytokines that cause plasma cells located in the gut to istoype switch to IgA production |
|
Definition
|
|
Term
| Identify chemokine and integrin receptors expressed differentially on IEL, lamina propria lymphocytes, and skin lymphocytes that are responsible for these cells homing to the correct body site. |
|
Definition
IEL- expresses receptor CCR9 and integrin receptor αEβ7 which bind to E-cadherin.
Lamina Propria lymphos (B/T)- express CCR9 and α4β7 which bind MAdCAM-1 (mucosal addressin cell adhesion molecule)
Skin- CCR4 and α4β1 |
|
|
Term
| Associate intraepithelial lymphocytes (IEL) with the gut, and describe what their characteristics are and how abundant they are. |
|
Definition
| IELs are dispersed in the epithelial layer, there is 1 IEL for every 7-10 epithelial cells. They are CD8+ cytotoxic cells and contain a mix of alpha/beta and delta/gamma TCRs. |
|
|
Term
| Describe the organization of Peyer’s patches, being sure to identify abundant cell types within them and the function of the M cells. |
|
Definition
organized like lymph nodes and have lymph node drainage.
Peyer's patches contain a Tcell area, Bcell follicle, germinal center and an M-cell. M-cells are the most abundant and their function is to endocytose and phagocytose particles and transport them from one side to the other. |
|
|
Term
| Describe the role of RBC in removing immune complexes from the plasma. |
|
Definition
| A small antibody-antigen complex forms in the circulation and activates complement. This immune complex is coated with covalently bound C3b. CR1 on RBC surface binds C3b-tagged immune complex. The RBC carries this immune complex to the liver or spleen, where it is detached and taken up by a macrophage. |
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
| Identify the two forms of passive antibody immunity that a fetus/newborn receives from its mother. |
|
Definition
1. Dimeric IgA- protection against gut bacteria, concentrated in the breast milk
2. IgG- protects against infectious agents and is transferred across the placenta. |
|
|
Term
| Important function of FcRn (Brambell receptor) in pre-natal human |
|
Definition
| used to transport the mother’s IgG to the child and provide the passive immunity for the child |
|
|
Term
|
Definition
| used to actively transport IgG across endothelial cells of blood vessels |
|
|
Term
| Important function of FcRn in post-natal human |
|
Definition
| used to transport IgG from the bloodstream to the extracellular spaces and tissues, this done all the time, not just during inflammatory responses. |
|
|
Term
| Describe how IgA produced in mucosal lamina propria can get across the mucosal epithelial layer to be released in high concentration into mucus. |
|
Definition
| First the IgA binds to the receptor on the basolateral face of the epithelial cell, then the IgA gets endocytosed, then the IgA gets transported to the apical face of the epithelium cell. Finally the receptor is cleaved, IgA is bound to the mucus through the secretory phase. |
|
|
Term
| Identify the protein that is necessary to produce IgA as a dimer. |
|
Definition
| The protein necessary is J-chain. The J-chain is bound by poly-Ig receptor on the basolateral surface of mucosal epithelial cells. |
|
|
Term
| Identify the 3 major antibody isotype(s) in body fluids and specifically indicate whether each isotype is confined to the bloodstream or can enter tissue fluids. |
|
Definition
IgA - Circulate in blood and can diffuse into tissue fluids to encounter antigen.
IgM and IgG - Can circulate in the blood but has very little access to tissues. |
|
|
Term
|
Definition
| mechanism by which antibodies to sites on pathogens that prevent growth of the pathogen. Example: anti-venom for spiders, snakes and scorpions; it has high affinity of IgG and dimeric IgA that can block exotoxin and venom binding to receptors. |
|
|
Term
|
Definition
| coats surface of pathogen so a phagocytic cell can recognize it. |
|
|
Term
|
Definition
| covalently binds C3b or C4b to a pathogen surface. |
|
|
Term
|
Definition
| (antibody-dependent cell-mediated cytotoxicity) mechanism that eliminates B- cells and B-cell tumors. It requires isotype-switched IgG antibodies. Example: Influenza-infected cells. They express viral glycoproteins at the surface that can bind influenza-specific IgG (which makes them a target for ADCC). |
|
|
Term
|
Definition
| Stands for Fc receptor. These receptors act as transport molecules. They bind the constant region of specific antibody and carry it across the endothelium. |
|
|
Term
|
Definition
| Stands for fragment crystalizable. It is essentially the constant domain of the heavy chain locus (determines isotype). |
|
|
Term
|
Definition
| the poly-Ig receptor becomes the secretory component once it and bound dimeric IgA have been transported across the epithelial cell. It is the portion of the poly-Ig receptor that is secreted into the lumen with the dimeric IgA. |
|
|
Term
|
Definition
| multipurpose protein that holds the tails together of the dimeric IgA as well as the pentameric IgM. J stands for joining chain. |
|
|
Term
|
Definition
| receptor on the basolateral surface of mucosal epithelial cell. Binds to the J-chain of dimeric IgA and initiates the transfer of IgA into the lumen |
|
|
Term
|
Definition
| IgM binds to surface of pathogen and assumes the staple form. This allows C1 to bind to IgM and initiate the enzymes to cleave C4 into C4b2a (the classical C3 convertase). |
|
|
Term
| Explain the 2 signals a B cell requires in a germinal center to maintain activation, and the consequence if it does not receive these signals. |
|
Definition
1: bind antigen held on FDC
2: antigen is processed and presented by the B cell to CD4+ T cell that provides second signal through CD40 =linked recognition=cognate interaction.
cells that do not receive these two signals will die of apoptosis. |
|
|
Term
| Identify the cytokine that is required for differentiation of FDC. |
|
Definition
FDC requires lymphotoxin (LTalpha and LTbeta) for differentiation and follicles don’t form in absences of lymphotoxins.
Without one there’s no phenotype and without both there’s no germinal center in lab animals. |
|
|
Term
| Identify as many important functions of FDC as you can, and predict the ultimate effect on the immune system if FDC were absent from secondary lymphoid tissues. |
|
Definition
FDCs :-provide the antigen source to allow B-cells to undergo affinity maturation.
-bind immune complexes
If FDCs were absent, B-cells would not be able to stay alive and die via apoptosis. |
|
|
Term
| List the cell(s) that are normally located in the dark zone, light zone and mantle zone of a germinal center (include centroblasts, centrocytes, FDC and T helper cells in your list). |
|
Definition
Dark Zone: Centroblasts
Light Zone: FDC, B cells, CD4+ T Cells, Centrocytes, Th Cells
Mantle Zone: Unactivated B Cells |
|
|
Term
| List the 4 cell types that are minimally required to allow a T-dependent antibody response to occur in a secondary lymphoid tissue and the relative physical location of each cell within the secondary lymphoid tissue. |
|
Definition
1. Dendritic cell exhibiting antigen in MHC II located in the Tcell zone surrounding HEV.
2. T cell (CD4+) leave HEV and interacts with DC in Tcell zone
3. B cell phagocytizes the pathogen and displays the SAME antigen in MHCII as the DC. This also takes place in the Tcell zone
4. Follicular Dendritic Cells and B-T cell cognate interact in the germinal center of the secondary follicle. |
|
|
Term
| Explain how TI-1 and TI-2 antigens differ. |
|
Definition
| The TI-2 antigen is highly repetitive on the surface of the pathogen, and they do not require a TLR. |
|
|
Term
| Compare and contrast T-dependent and T-independent B lymphocyte antibody responses. |
|
Definition
-T dependent is a IgG and that requires T cell help for proper response. T dependent antibody responses are high affinity isotype switched and they do provide memory. Is also antigen specific
- T independent antigen cause B cell responses in the absence of T cell help. They produce IgM antibody isotype. polyspecific, no protective memory response, minimal isotype switching ,low affinity. |
|
|
Term
| List the 3 CD proteins that form the B cell co-receptor complex, and the functions of each of the proteins (if known). |
|
Definition
CD21 (CR2) - binds iC3b and signals through CD19
CD19 - gets signal from CD21 to increase BCR signal 1000-10000 fold
CD81 - function not yet known |
|
|
Term
|
Definition
| Cells of bone marrow origin, They present antigen to T-cells in secondary lymphoid tissues. |
|
|
Term
| FDC - Follicular Dendritic Cells |
|
Definition
| - Embryo-derived stromal cells. They require lymphotoxin for differentiation and bind immune complexes and hold them on the surface for a long time. They also provide the antigen source for affinity maturation of B-Cells. |
|
|
Term
|
Definition
| They are formed from binding of antibody to antigen. |
|
|
Term
| List the 3 main cells that accomplish cell-mediated immunity |
|
Definition
| Cytotoxic T cells, Th1 cells, macrophages |
|
|
Term
| Describe how interferons (IFN’s; IFN-G, IFN-A, IFN-B) are especially important to fight viral infections. |
|
Definition
- They inhibit replication of viruses in infected cells
- Increase processing and presentation of viral antigens in Class 1 (by increasing LMP2/LMP7 in proteasome to cleave smaller peptides)
- Activate bystander macrophages to phagocytize apoptotic cells |
|
|
Term
| Identify the three major proteins found in Tc lytic granules and the functions of each protein. |
|
Definition
1. perforin - forms pore in target cell membrane to contribute to cell killing
2. granzymes - induces apoptosis of target cell
3. granulysin - works with perforin to make pore in target cell membrane |
|
|
Term
| Identify the functions of Fas ligand (FasL) and CD40 ligand (CD40L) in regards to effector T cell functions. |
|
Definition
They are proteins on the cell surface.
FasL is on Cytotoxic T-cells and induces apoptosis of any target cell expressing Fas.
CD40L is used by T-helper 1 and T-helper 2 cells to activate macrophages/B-cells. It allows for maximum activation of both macrophages and B-cells. |
|
|
Term
| For the following cellular adhesion molecules, identify the cell that expresses it, the ligand(s) that it binds to, and the specific purpose the adhesion molecule performs: VLA-4, CD2. |
|
Definition
VLA-4: Expressed on Effector T cells and binds to the adhesion molecule VCAM-1 on the endothelial cells of blood vessels in inflamed tissues.
CD2: Expressed on Effector T cells and binds to LFA-3. |
|
|
Term
| Identify where Th1, Th2, and Tc reside following activation in the secondary lymphoid tissue. |
|
Definition
Th1 cells and Tc cells leave the lymphnodes and travel through circulatory system to the site of infection where they can act on macrophages and infected cells respectively.
Th2 cells stay in the secondary lymphoid tissues and assist B cells by sending signals to induce isotype switching and affinity maturation. |
|
|
Term
| Describe the 3 ways in which naïve CD8+ T cells can be fully activated to differentiate into Tc effector cells. |
|
Definition
1. Dendritic Cell with high co-stimulatory molecule expression triggers an optimal IL-2 response
2. APC activates CD4+ T Cell, which in turn activates APC to express necessary co-stimulator molecules to activate CD8+ T Cells
3. APC activates CD4+ T cell to secrete IL-2, which in turn binds to unregulated IL-2 receptor on CD8+ T cell |
|
|
Term
| What cytokines do Th1, Th2, and Treg secrete and what transcription factors are responsible for activating this secretion in each cell type? |
|
Definition
| -Treg secretes TGF-beta and IL-10 and the trans factor is Fox P3. TH1 secrets IL-2 and IFN-gamma and the transfactor is T-bet. TH2 secretes IL-4 and IL-5 and the trans factor is GATA-3 |
|
|
Term
| Discuss what factors (minimally, the 4 mentioned in class) can influence the choice of a naïve CD4 T cell to a functional subset choice (Th1, Th2…), and which of these factors appears dominant. |
|
Definition
T cell subset choice is influenced by:
1. Cytokines in vicinity (most dominant!)
2. APC co-stimulatory molecules
3. Concentration of Ag
4. TCR affinity |
|
|
Term
| Describe the importance of IL-2 in T cell responses. |
|
Definition
| IL-2 is needed for T-cells to grow/proliferate and to become effector T-cells. Naïve T-cells express IL-2 receptor and two-signal activation causes the cells to secrete IL-2. A lack of co-stimulatory signal at the time of TCR activation stops production of IL-2 and leaves the cell anergic. |
|
|
Term
|
Definition
| inhibit IL-2 production by the naïve T-cells after they are activated |
|
|
Term
|
Definition
| inhibits the signaling through IL-2 receptor so the T-cell can no longer respond to that signal |
|
|
Term
| Define the “two-signal hypothesis” and identify the ligand/receptor proteins that provide the second signal, including specifically what cells these ligands and receptors are expressed on. |
|
Definition
| The “two-signal hypothesis” is the primary signal that provides MHC with antigen peptide groove that triggers the TCR and has to provide a co-stimulatory signal which maintains and amplifies autocrine IL-2 production that is necessary for T cell activation. The co-stimulatory molecule B7 on the APC binds to CD28 on naïve T cell. |
|
|
Term
| Identify the primary antigen type (bacteria, yeast, virus, soluble protein) that DC, macrophages, and B cells specialize in presenting. |
|
Definition
DC- virus
Macrophages- bacteria, yeast?
B-cells- soluble protein, toxins, viruses |
|
|
Term
|
Definition
Cell that expresses it: Naive T Cell
Ligands that bind to: CD34 & GlyCAM-1 in HEV and MAdCAM-1 in mucosal endothelium
Purpose:Rolling through secondary Lymphoid tissue |
|
|
Term
|
Definition
Cell that expresses it: Naive T Cells, T Cells, and APC’s
Ligands that binds to: ICAM-1, ICAM-2 of Vascular endothelium and APC’s, ICAM-3 of T Cells
Purpose: Tight Binding and Extravasation by diapedesis, T Cell and DC interaction in secondary lymphoid tissues |
|
|
Term
|
Definition
Cell that expresses it: High endothelial venules
Ligand that it binds to: L-selectin
Purpose: Rolling through secondary Lymphoid tissue |
|
|
Term
|
Definition
Cell that it expresses it: High endothelial venules
Ligand that it binds to: L-selectin
Purpose: Rolling through secondary Lymphoid tissue |
|
|
Term
|
Definition
Cell that expresses it: mucosal endothelium
Ligand that it binds to: L-selectin
Purpose: Rolling through secondary Lymphoid tissue |
|
|
Term
|
Definition
Cell that expresses it: vascular endothelium and APC's
Ligand that it binds to: LFA-1
Purpose: Tight Binding and extravasation by diapedesis. T Cell and DC interaction in secondary Lymphoid Tissues |
|
|
Term
|
Definition
Cell that expresses it: Vascular Endothelium and APC’s
Ligand that expresses it: LFA-1
Purpose: Tight Binding and extravasation by diapedesis. T Cell and DC interaction in secondary Lymphoid Tissues |
|
|
Term
|
Definition
Cells that expresses it: T cells
Ligand that expresses it: LFA-3
Purpose: T Cell and DC interaction in secondary Lymphoid Tissues |
|
|
Term
|
Definition
Cell that expresses it: APC's
Ligand that expresses it: ICAM-3
Purpose: T Cell and DC interaction in secondary Lymphoid Tissues |
|
|
Term
|
Definition
Cell that expresses it: APCs
Ligand that expresses it: CD2
Purpose: T Cell and DC interaction in secondary Lymphoid Tissues |
|
|
Term
| Role of selectins in lymphocyte trafficking |
|
Definition
| provide low affinity adhesion that causes cells to roll along blood vessel walls within HEV or activated endothelium of inflamed tissues they bind to such as vascular addressins, which are glycoproteins on endothelium that bind selectins. |
|
|
Term
| Role of integrins in lymphocyte trafficking |
|
Definition
| provide high strength binding that allows firm attachment and squeezing b/t endothelial cells and extended contact b/t lymphocytes and APC. They bind to some Ig superfamily proteins. |
|
|
Term
| Describe the two ways that foreign antigen can reach the secondary lymphoid tissues to activate an adaptive immune response. |
|
Definition
| Antigens reach secondary lymphoid tissues to activate adaptive immune response by either attaching to a dendritic cell or just entering in the lymph fluid itself to lymph node through the afferent lymph |
|
|
Term
| Identify the 3 main effector T cells |
|
Definition
CD8+ cytotoxic T cell
CD4+ Th1
CD4+ Th2 |
|
|
Term
| Important role of CD8+ cytotoxic T cell |
|
Definition
| Kill infected cells by releasing cytotoxins |
|
|
Term
| Important role of CD4+ Th1 |
|
Definition
| Cell-mediated immunity, helps macrophages, and facilitates cytotoxic T-cell proliferation |
|
|
Term
| Important role of CD4+ Th2 |
|
Definition
| Humoral immunity - Stimulates B-cells to proliferate and induces antibody class switching |
|
|
Term
|
Definition
| immunity that is mediated by antibodies and can be transferred to a non-immune recipient by serum. |
|
|
Term
|
Definition
| adaptive immune response in which antigen-specific effector T cell dominated. It cannot be transferred to a naïve recipient with serum antibody. |
|
|
Term
|
Definition
| molecule on antigen presenting cell (APC) that delivers signals to a naïve lymphocyte that is required in addition to the antigen-binding signal for the lymphocyte to respond. |
|
|
Term
|
Definition
| B71 and B72 proteins, which are co-stimulatory molecules present on the surface of professional antigen-presenting cells. |
|
|
Term
|
Definition
| low-affinity receptor on T cells that interacts with B7 co-stimulatory molecules to activate T-cell activation. |
|
|
Term
|
Definition
| T cell must receive a minimum of two signals to respond to antigen. This includes a primary signal through the TCR binding cognate expressed in self-MHC and co-stimulatory signal through a co-stimulator molecule on APC surface. |
|
|
Term
|
Definition
| high affinity inhibitory receptor on T cells that interacts with B7 co-stimulatory molecules. |
|
|
Term
| Define Treg and describe their cellular characteristics and the role they play in tolerance. |
|
Definition
| Treg cells are CD4+ Tcells that suppress the T activation of other CD4+ cells. They suppress CD4+ cells that become activated in the periphery by self antigen. They allow for peripheral tolerance. |
|
|
Term
| Describe the difference between central tolerance and peripheral tolerance in regards to T cells, and whether each is achieved by either anergy or apoptosis. |
|
Definition
Central Tolerance is induced by negative selection in the Thymus, which leads to deletion of self-reactive T lymphocytes preventing autoimmune diseases. This is done through apoptosis.
Peripheral tolerance is done by regulatory T Cells that go around and suppress CD4+ T cells through the release of suppressive cytokines (IL-10 and TGF-Beta) |
|
|
Term
| Describe how “strength of TCR binding” is important for positive and negative selection. |
|
Definition
| If TCR binding is too tight, the self MHC will fail negative selection and undergo apoptosis. |
|
|
Term
| Describe the function of dendritic cells and macrophages in the thymus (note: they are different). |
|
Definition
Dendritic cells contribute to negative selection by presenting antigen to T-cells in the thymus. A T-cell with either too much or no binding will then subsequently die by apoptosis.
Macrophages remove the cells that die via apoptosis. Macrophages can also express antigen, just at a much lower level than Dendritic cells. |
|
|
Term
| Identify what cell(s) mediate positive selection and negative selection of T cells. |
|
Definition
Positive Selection: cortical epithelial cells
Negative Selection: dendritic cells, macrophages, thymocytes |
|
|
Term
| Describe the purpose of “positive selection” |
|
Definition
| checkpoint where Tcells are checked to make sure they can bind to MHC I or MHC II containing self antigen and not become activated. This occurs in the inner cortex. |
|
|
Term
| Describe the purpose of “negative selection” |
|
Definition
| check point in Tcell development where Tcells that are reactive to self antigen are removed. γδ Tcells do not undergo negative selection |
|
|
Term
| Identify whether B cells, alphabeta T cells, and gammadelta T cells each undergo positive and/or negative selection. |
|
Definition
B Cell- Negative Selection, B Cells that react to self antigen are sent through apoptosis
T Cell- first undergo positive selection in the Thymus to bind to self antigen and then negative selection to make sure there is a useful amount and not dangerous. |
|
|
Term
| Identify the normal proportion of to T cells produced after birth. |
|
Definition
90%-alpha- beta
10% gamma-delta |
|
|
Term
| Identify whether a pre-T cell would be a double-negative thymocyte, a double-positive thymocyte, or a single positive T cell. |
|
Definition
| A double-negative thymocyte has yet to turn on CD4 or CD8. Double-positive thymocytes express CD4 and CD8 but have not decided on which it will ultimately express. Single-positive thymocytes have either CD4 or CD8 |
|
|
Term
| List the proteins that compose the pre-TCR. |
|
Definition
| Two zeta chains, CD3 complex ( consisting of ε and δ chains), γ and ε chains, along with a pTα. |
|
|
Term
| Define “thymic involution” and when it occurs. |
|
Definition
| Thymic involution is when the thymus atrophies. Typically occurs around age 30. This means the Tcell pool is completed by age 30. Though it occurs “early” in life, thymic involution does not affect Tcell immunity which means naive T lymphocytes live much longer than naive B lymphocytes. |
|
|
Term
| Identify the cortex of the thymus and what cell lineages can be found |
|
Definition
- Cortical epithelial cells
- Thymocytes
- Macrophages (Small scattered presence) |
|
|
Term
| Identify the medulla of the thymus and what cell lineages can be found |
|
Definition
- Medullary epithelial cells
- Dendritic cells
- Macrophages
- Thymocytes |
|
|
Term
| Identify what receptor/ligand interaction triggers commitment of an uncommitted lymphoid progenitor to the T lymphocyte lineage and where this interaction occurs. |
|
Definition
| Notch one receptor on progenitor binding to delta one ligand in thymus, commits the progenitor to T cell lineage. |
|
|
Term
|
Definition
| the surrogate alpha chain that combines with the T cell receptor beta chain to form the pre-t cell receptor |
|
|
Term
|
Definition
| a late stage of T cell development in the thymus and characterized by the expression of either CD4 or CD8 co-receptor on the cell surface. |
|
|
Term
| Double-positive thymocyte |
|
Definition
| T cell in an intermediate stage of development in the thymus. It expresses both CD4 and CD8 |
|
|
Term
| Double-negative thymocyte |
|
Definition
| immature T cell in the thymus that expresses neither CD4 nor CD8 |
|
|
Term
| List the 3 main options for what a B lymphocyte can do functionally (what it can become) after it is activated by antigen. |
|
Definition
-Become a memory cell for future infection.
-Become IgM-secreting plasma cell.
-Become an IgG-secreting plasma cell. |
|
|
Term
| Identify the main function of a plasma cell and the 4 locations where it may reside in the body. |
|
Definition
| The main function of a plasma cell is to secrete as much antibody as fast as it can. The four locations where it may reside in the body are in the lymph node medulla, spleen red pulp, bone marrow, and GALT (under epithelium in the lamina propria). |
|
|
Term
| Identify the cell that provides necessary periodic survival signals to a naïve B lymphocyte, where this cell is located, and what molecule it produces that provides the survival signal. |
|
Definition
| Follicular dendritic cells provide survival signals for the B cells, located in primary lymphoid follicles. BAFF from FDC provides life saving maturation to B cell lymphotoxin provide life signal for FDC. |
|
|
Term
| State the average life-span of a B lymphocyte after it exits the bone marrow and enters circulation. |
|
Definition
| B-cells have a half-life of ~100 days, assuming they don’t encounter antigen or become activated. |
|
|
Term
|
Definition
| matured centroblasts; small non-proliferating cells that are isotype switched and have undergone somatic hypermutation. |
|
|
Term
|
Definition
| large activated B cells that proliferate |
|
|
Term
|
Definition
| fully differentiated Bcells that produce massive amounts of antibody. Life span of 4 weeks. Can migrate to lymph nodes (secrete Ig into lymph), red pulp in spleen or bone marrow(secrete Ig into blood), GALT and sit directly under epithelium (secrete dimeric IgA which migrates across mucosal membrane). |
|
|
Term
|
Definition
| in the lymphoid follicle; concentration of proliferating B cells |
|
|
Term
| Secondary Lymphoid Follicle |
|
Definition
| this is a primary follicle where Bcells (that have been activated) for a germinal center. |
|
|
Term
| Primary Lymphoid Follicle |
|
Definition
| Where immature Bcells interact with follicular dendritic cells to receive maturation signals. Bcells enter the PLF after the Tcell area of the cortex. |
|
|
Term
|
Definition
| produced by follicular dendritic cells that provide life-saving maturation signal to immature B cells. |
|
|
Term
|
Definition
| lympho toxin which is produced by immature B cells and provides life signal to follicular dendritic cells when these cells are interacting in follicles of LNs. |
|
|
Term
|
Definition
| when immature Bcells can bind soluble self antigen (self Ig) but do not react. They treat self Ig as “normal” and are not activiated. |
|
|
Term
|
Definition
| occurs in mature Bcells when the BCR (IgM) is crosslinked by self antigen and still exhibits self reactivity even after receptor editing. The self reactive Bcell undergoes apoptosis. |
|
|
Term
| Identify the two CD markers that when used in combination, can identify B-1 B lymphocytes (note: need to differentiate B cell from T cell). |
|
Definition
|
|
Term
| What percent of developing B lymphocytes successfully make it through the heavy chain rearrangement? |
|
Definition
| About ⅔ of B lymphocytes make it through heavy chain rearrangement (2 chances). |
|
|
Term
| What percent of developing B lymphocytes successfully make it through the light chain rearrangement? |
|
Definition
|
|
Term
| What is the overall percent of B cells that make it through development? |
|
Definition
|
|
Term
| List the 2 growth factors that support B cell development in the bone marrow. |
|
Definition
| SCF (Stem Cell Factor) and soluble cytokine growth factor interleukin-7 (IL-7) |
|
|
Term
| What is the role of stromal cells in B cell development? |
|
Definition
| Stromal cells provide two important signals for developing B Cells: cell contact through adhesion molecules (CAM’s) and membrane-bound growth factor |
|
|
Term
| Where are the stromal cells located in the body? |
|
Definition
|
|
Term
| List when RAG-1 and RAG-2 are expressed during B cell development (i.e. what stages?). |
|
Definition
| RAG-1 and RAG-2 are only expressed during heavy and light chain rearrangement, they are immediately turned off after the rearrangement is complete. The presence of pre-BCR or BCR turns off the RAG-1 and RAG-2 gene expression, because that is when heavy and light chain rearrangement is completed respectively. |
|
|
Term
| Explain why it is advantageous for a pre-B cell to undergo a burst of proliferation following signaling through the pre-BCR. |
|
Definition
| Pre B cells transiently express rearranged mu heavy chain with surrogate light chain. Efficiency of effort you’re getting the numbers out there and you’re not losing anything. Each one of them paired up with a different light chain rearrangement so antigen specificity of that pool is still diverse. |
|
|
Term
| What are the cell stages that occur during B cell development? |
|
Definition
| Stem Cell, Pro-B cell, Pre-B cell, Immature B cell, mature B cell |
|
|
Term
|
Definition
| have surface expression of productively rearranged μ heavy chain plus rearranged light chain. It has IgM expressed on the surface |
|
|
Term
|
Definition
| cells with productive heavy chain rearrangement. Transiently express rearranged μ heavy chain with surrogate light chain. Surrogate light chain consists of VpreB + λ5. PreB = μ, VpreB, λ5, Igα, Igβ |
|
|
Term
|
Definition
| earliest identifiable B lineage cell. Heavy chain D-J → V-D-J rearrangement occurs. Still no Ig status and no light chain change. |
|
|
Term
|
Definition
| in bone marrow. Both heavy and light chain are germline and there is no Ig status |
|
|
Term
|
Definition
| Signals and causes burst of proliferation of pre-B cells. Its composed of μ heavy chain, VpreB, λ5, Igα, Igβ |
|
|
Term
|
Definition
| Mimics Ab light chain. A combination of VPreB and λ5. |
|
|
Term
|
Definition
| Recombination-activating genes. Recognize RSS’s and make dsDNA cuts to initiate recombination. |
|
|
Term
|
Definition
| Cell-adhesion molecules. Proteins on the cell surface involved in binding to other cells. |
|
|
Term
|
Definition
| Antibody that can bind to multiple structurally related species but at a low affinity to each. |
|
|
Term
| Describe the relationship between interferon (IFN-)/IFN- and changes in Class I expression. |
|
Definition
| Interferon cytokines help cells to resist viral infections. (IFN-α, IFN-β , IFN-γ.). One of the functions of interferons is to upregulate (increase of cellular component) MHC I and MHC II. Higher MHC I expression increases the amount of viral peptides to cytotoxic T cells and NK cells and increases the recognition and killing of infected cells. |
|
|
Term
|
Definition
| binds peptides of Class I leader fragments and presents them to inhibitory receptors on NK cells. MHC molecules will not move to surface of cell without binding peptide. So, it binds self peptide and move to surface to show NK cells that it is a normal non infected cell and thus avoids being killed. |
|
|
Term
| Degenerate Peptide Binding |
|
Definition
| allows MHC class 1 and 2 to bind to multiple types of Antigens, by only requiring the “Anchor Residues” to bind through a NON-covalent bond. This allows a high level of variability in what can bind to the MHC class 1 or 2 molecule. |
|
|
Term
|
Definition
| The 2 or 3 amino acid peptides that MUST be bonded to within the MHC binding groove in order for the antigen to bind. |
|
|
Term
| Describe why transplantation of solid tissue or bone marrow cells from one human to another requires HLA typing and “matching”. |
|
Definition
| organ/tissue transplant compatibility and disease susceptibility prediction |
|
|
Term
| What are the two possible adverse consequences of mismatches of HLA typing and "matching"? |
|
Definition
| lead to graft rejection (e.g. kill the kidney) or graft versus host disease which is a bone marrow transplant that creates a whole immune system for host and if host is not compatible, it will attack the host very painfully. |
|
|
Term
| Describe the inheritance of HLA haplotypes |
|
Definition
Every person inherits a complete haplotype from each parent. A person
expresses all alleles from each parent, so a heterozygous person expresses two
haplotypes. |
|
|
Term
| What is the number of Class I and Class II isoforms that can compose an individual's haplotype? |
|
Definition
| Most individuals express 6 Class I and 6 Class II |
|
|
Term
| What is the minimum and maximum amount of alleles in Class I and II? |
|
Definition
The minimum is 3 class 1 and 3 class 2 alleles
The maximum is 6 class 1 and 8 class 2 alleles. |
|
|
Term
| Appreciate the relative numbers of alleles that exist for each HLA gene within the human population. |
|
Definition
| Most individuals express 12 HLA alleles, 6 Class I and 6 Class 2. |
|
|
Term
|
Definition
| rejection of donated tissue. Body fights off the graft. Found when wrong bone marrow is transferred. Bone Marrow is a primary lymphoid tissue and so it creates an immune system against the host. |
|
|
Term
|
Definition
| Antibodies produced following the introduction of allotissue from a donor. Used before microbio techniques were developed to assess compatibility. Tested serum to see if there were antibodies that could bind and initiate the killing of donor tissue |
|
|
Term
|
Definition
| the response to a foreign allele that is viewed as antigenic. |
|
|
Term
|
Definition
| literally means other gene. Refers to HLA typing and Tissue typing. Other alleles are viewed as antigen and the body fights thinking it’s an infection. |
|
|
Term
|
Definition
| hundredes of different alleles of the MHC genes (HLA’s) exist in human population. The genes vary from person to person but not randomly like BCR and TCR. |
|
|
Term
|
Definition
| means more than one gene encodes MHCI and MHC II molecules |
|
|
Term
|
Definition
| Human Leukocyte Antigen Complex they are the genes that code for MHC I and MHC II |
|
|
Term
|
Definition
| the loading of exogenous peptides into a MHC class I molecule to stimulate CD8 cytotoxic T cells in response to a virus |
|
|
Term
| What are the 3 professional antigen-presenting cells? |
|
Definition
| dendritic cells, B lymphocytes, macrophages |
|
|
Term
| How do dendritic cells obtain the antigen they present? |
|
Definition
| is highly pinocytotic and phagocytic when immature and the ONLY APC that can activate naive T lymph. |
|
|
Term
| How do B lymphocytes obtain the antigen they present? |
|
Definition
| present soluble antigens endocytosed bound to BCR. They are antigen specific to b lymphocytes. they are looking for help from the CD4 positive T lymphocytes when they present antigen in class II. |
|
|
Term
| How do the macrophages obtain the antigen they present? |
|
Definition
| present phagocytized bacteria,yeast etc to activate CD4 positive T cells. All APC’s have a lot of MHC class 1 and high expression of MHC class 2. |
|
|
Term
| What are the body cells that do not express MHC Class I and why? |
|
Definition
| Erythrocytes because red blood cells do not have a nucleus |
|
|
Term
| Describe the general structure of the peptide-binding groove of MHC Class I. |
|
Definition
| composed of 2 α-helices of the Class I heavy chain and a floor made by an antiparallel β-sheet. This binding groove is described as a pita pocket, where the ends of the α-helices are pinched towards one another. |
|
|
Term
| What is the size of the peptide that MHC Class I can hold? |
|
Definition
|
|
Term
| Describe the general structure of the peptide-binding groove of MHC Class II. |
|
Definition
| composed of 2 α-helices and an antiparallel β-sheet floor, however the α-helices are from the α chain and β chain, thus working cooperatively. The MHC class II peptide binding groove resembles a hot dog bun, with open ends allowing for peptide fragments to overhang |
|
|
Term
| What is the size of the peptide that MHC Class II can hold? |
|
Definition
|
|
Term
| What is the usual source of peptide that is presented in MHC Class I and MHC Class II? |
|
Definition
Class I: endogenous proteins
Class II: exogenous proteins |
|
|
Term
| endogenous proteins vs exogenous proteins |
|
Definition
endo: intracellular proteins produced from the cell cytosol
exo: extracellular proteins picked up by pinocytosis, endocytosis, and phagoccytosis |
|
|
Term
| For MHC Class I and MHC class II, identify which T cell co-receptor molecule they associate with. |
|
Definition
Class I: CD8 T cells
Class II: CD4 T cells |
|
|
Term
|
Definition
| releases CLIP and pops in a peptide from the endosome digest |
|
|
Term
|
Definition
| In endosomes, invariant chain is digested by cathepsin S, so only a small peptides of it remains in peptide groove. |
|
|
Term
|
Definition
| polypeptide that associates with major histocompatibility complexes (MHC) class 2 proteins in the endoplasmic reticulum and prevents them from binding peptides there. It guides the MHC class 2 molecules to endosomes, where the invariant chain is degraded, enabling MHC class 2 molecules to bind peptides present in the endosomes. |
|
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Term
|
Definition
| large multisubunit protease present in the cytosol of all cells that degrades cytoplasmic proteins. It generates the peptides presented by MHC class 1 molecules. |
|
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Term
|
Definition
| TAP associated protein. associate the MHC class 1 heavy chain with TAP |
|
|
Term
|
Definition
| TAP associated protein. associate the MHC class 1 heavy chain with TAP |
|
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Term
|
Definition
| a heterodimeric protein that takes peptides from the proteasome and brings them into the ER. |
|
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Term
|
Definition
| cytosolic serine/threonine phosphatase that contributes to T-cell activation. The immunosuppressive drugs cyclosporin A and tacrolimus act by inhibiting calcineurin |
|
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Term
|
Definition
| membrane protein of the endoplasmic reticulum that facilitates the folding of MHC molecules and other glycoproteins |
|
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Term
|
Definition
| second protein in MHC 1 dimer |
|
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Term
|
Definition
| Persist long-term after an infection has subsided. Upon later infection, they quickly expand to large numbers. These cells may express either CD4 or CD8. |
|
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Term
|
Definition
| Destroy infected cells and recognize targets by binding to antigen presented by MHC I. Express CD8 protein. |
|
|
Term
|
Definition
| Release cytokines, assist in maturation of B cells into plasma cells/memory B cells, and allow for activation of cytotoxic T cells and macrophages. Become activated when presented with peptide antigen by MHC II and express CD4 protein. |
|
|
Term
| List the proteins that compose a complete functional TCR (including the signaling molecules). |
|
Definition
| TCR α and TCR β are the proteins that are associated with 2 ζ(zeta) signaling molecules along with either a CD4 or CD8. A CD3 is located on both sides of the TCR, one comprising of CD3ε and CD3δ and the other one comprising of CD3ε and CD3γ. |
|
|
Term
| Correctly identify Vα, Vβ, VH, VL, Cα, Cβ, CH, and CL as belonging to the BCR or TCR. |
|
Definition
TCR- Vα, Vβ, Cα, Cβ
BCR- CH, CL VH, VL |
|
|
Term
| Identify which of the V, D, and J gene segments are used to create the V, V, VH, and VL protein domains (e.g. V is composed of only V and J gene segments). |
|
Definition
Vα= Vα+Jα
Vβ= Vβ1+ Dβ1+Jβ1 or Vβ2+Dβ2+Jβ2 (can’t mix β1’s and β2’s)
VH= V+D+J
VL= V+J |
|
|
Term
| Does somatic recombination happen in T lymphocytes, B lymphocytes or both? |
|
Definition
|
|
Term
| Does junctional diversity happen in T lymphocytes, B lymphocytes or both? |
|
Definition
|
|
Term
| Does somatic hypermutation happen in T lymphocytes, B lymphocytes or both? |
|
Definition
|
|
Term
| Does isotype switching happen in T lymphocytes, B lymphocytes or both? |
|
Definition
|
|
Term
| Does affinity maturation happen in T lymphocytes, B lymphocytes or both? |
|
Definition
|
|
Term
| Identify which antibody isotype can be produced as either a monomer or dimer, and which tissue fluids each would be found in. |
|
Definition
| IgA can be produced as a dimer and is found in the epithelial tissue. IgA can also be produced as a monomer and that can be found in extravascular sites. |
|
|
Term
| Which antobody isotypes are best at performing neutralization? |
|
Definition
|
|
Term
| Which antobody isotypes are best at performing opsonization? |
|
Definition
|
|
Term
| Which antobody isotypes are best at sensitizing for NK killing? |
|
Definition
|
|
Term
| Which antobody isotypes are best at activating complement? |
|
Definition
|
|
Term
| What are the 5 main isotypes of antibody? |
|
Definition
| IgA, IgD, IgE, IgG, and IgM |
|
|
Term
| Which isotype antibody is the biggest (molecular weight)? |
|
Definition
|
|
Term
| Which isotype antibody is the most abundant in serum and body fluids? |
|
Definition
|
|
Term
| Which isotype antibody exists as a pentamer? |
|
Definition
|
|
Term
| Which isotype antibody can cross the placenta? |
|
Definition
|
|
Term
| Which 3 isotypes antibodies that combine to comprise 99% of all antibody in blood/ body fluids? |
|
Definition
|
|
Term
| Which isotype antibody is in the highest concentration in mucus? |
|
Definition
|
|
Term
| What are the two isotype antibodies that can bind (fix) complement? |
|
Definition
|
|
Term
| Explain why IgM must be a pentamer to be effective. |
|
Definition
| IgM has a very low antigen binding affinity. To compensate for this low affinity IgM increases the number of antigen binding sites by forming a pentamer. 2 poor antigen binding sites are bad but as a pentamer, the 10 poor binding sites are additive to make decent binding affinity. |
|
|
Term
| Describe the process of isotype switching |
|
Definition
1. enzyme AID induces cytosine to uracil in switch sequence
2. DNA repair enzyme UNG removes base from uracil nucleotide
3. Endonuclease APE1 excises the abasic nucleotide, leaving a nick
4. Nicked switch sequences associate to promote DNA strand recombination. |
|
|
Term
| Is diversity of antigen binding added by isotype switching? |
|
Definition
| The Antigen binding of the antibody does not change. There is no Junctional Diversity, because the functional domain has not been mutated, you are simply changing the function of the antibody molecule. |
|
|
Term
| List what factor(s) primarily control which isotype of antibody will be produced by a B lymphocyte |
|
Definition
| Helper T Cell secretion of certain cytokines |
|
|
Term
|
Definition
| Increased point mutations initiated by A.I.D enzyme in Variable regions of the heavy and light chains |
|
|
Term
|
Definition
| B-cells with Ig that randomly have higher affinity for antigen are “selected” to proliferate further |
|
|
Term
|
Definition
| When the antibody pool progressively gains affinity for antigen through somatic hyperstimulation + clonal selection |
|
|
Term
|
Definition
| Willingness/ability for antibody to bind to antigen |
|
|
Term
| List the proteins that compose a complete BCR (including the signaling molecules). |
|
Definition
| IgM and IgD are the proteins that compose a complete BCR. The signaling molecules associated with these are Igβ and Igα |
|
|
Term
| Identify which Ig molecule(s) are expressed on the surface of naïve B lymphocytes. |
|
Definition
| IgM and IgD are both expressed on the cell surface simultaneously due to alternative splicing of mRNA |
|
|
Term
| Identify which 2 C gene segments are closest to the variable gene segments in the Ig heavy chain locus and the significance of this location. |
|
Definition
| C(mu) and C(Delta) are the two gene segments that are closest to the Variable gene segments. This is important because it ensures every naive B cell codes for IgM and IgD which in turn allows all antigenic specificity on one cell. |
|
|
Term
| List the two types of light chains that may be used in the formation of an antibody molecule |
|
Definition
| The two types that can be used in antibody formation are Lambda (λ, Chromosome 22) and Kappa (κ, Chromosome 2). |
|
|
Term
| List the main gene segments that must be spliced together to form either an antibody light chain |
|
Definition
|
|
Term
| List the main gene segments that must be spliced together to form either an antibody heavy chain |
|
Definition
|
|
Term
| Describe the basic protein folding structure that defines a “Ig-like domain” and why it is commonly found in immune system proteins. |
|
Definition
| The basic folding structure, Ig-like domain, is composed of 100-110 amino acids each. It is a “clam like” structure that is very hard to degrade and pull apart. Many of the proteins secreted by immune cells make use of this structure so that they are stable in extreme environments (pH, salinity, protease degradation). |
|
|
Term
| How many heavy and light chains compose an antibody molecule? How are these chains held together? |
|
Definition
There are two identical Heavy Chains and Two Light chains, Heavy Chains consist of 4-5 Ig like domains while Light chains consist of only 2
connected by Disulfide bonds (Covalent Bonds). |
|
|
Term
| Where is the "Hinge Region" and what is it's function? |
|
Definition
| The Hinge connects the chains and allows for movement, and flexibility in relation to each other the variable gene segments. |
|
|
Term
| What is the only effector function of B lymphocytes? |
|
Definition
|
|
Term
|
Definition
| fluid component of clotted blood from an immune individual that contains antibodies against a given antigen. Antiserum contains a heterogeneous collection of antibodies that bind in organ transplantation. |
|
|
Term
|
Definition
| antibodies produced by a single clone of B lymphocytes and which are therefore all identical in structure and antigen specificity. |
|
|
Term
|
Definition
| nucleotides added at random by TdT onto the P nucleotides. The N nucleotides are added until equal bond attraction is created between the two DNA strands so they are able to bond again. |
|
|
Term
|
Definition
| short palindromic sequences formed by cleavage of hairpins done by RAG enzyme that form at the blunt-end cut sites of the DNA also done by RAG enzymes. |
|
|
Term
|
Definition
| occurs at the cut site joining the V-(D)-J segments. Random addition of the P and N nucleotides between these segments greatly increases this diversity. |
|
|
Term
|
Definition
| the diversity of antigens created by somatic recombination of randomly-selected gene segments. Included in the gene segments are all the lambda light chain loci V, J, and C, kappa light chain loci V, J, and C, and heavy chain loci V, D, J, and C. |
|
|
Term
|
Definition
| Recombination activating genes. Binds and cuts DNA between gene segments at RSS’s to allow for recombination. |
|
|
Term
|
Definition
| terminal deoxynucleotidyl transferase. Randomly adds N nucleotides after RAG opens hairpins and until equal bond attraction is achieved in DNA sequence during the generation of junctional diversity. |
|
|
Term
|
Definition
| recombination signal sequences. Direct the RAG enzymes that cut the DNA between the gene segments. They are identical heptamers (7 nucleotides) and nonamers (9 nucleotides) with either 12 or 23 nucleotide spacers. |
|
|
Term
| Hypervariable Region / CDR |
|
Definition
| Complementary variable region, also known as hyper-variable region. 3 exposed loops at the end of the V Ig-like domain that form the Ag-binding site. |
|
|
Term
| What is the main function of Th1 cells and do they possess CD4 or CD8 on their surface? |
|
Definition
| activates macrophages upon recognition of MHC II. Possess CD4 |
|
|
Term
| What is the main function of Th2 cells and do they possess CD4 or CD8 on their surface? |
|
Definition
| Activates B-cells upon recognition of MHC II Cytotoxic T-Cells. Possess CD4 |
|
|
Term
| What is the main function of Tc cells and do they possess CD4 or CD8 on their surface? |
|
Definition
| kills infected or "transformed" self cells upon recognition of MHC Class I. Possess CD8 |
|
|
Term
| List the two T cell co-receptor molecules and whether they bind to MHC Class I or MHC Class II molecules. |
|
Definition
1. CD4- binds to MHC Class II
2. CD8- binds to MHC Class I |
|
|
Term
| What are the two main functions of antibodies? |
|
Definition
| neutralization and opsonization |
|
|
Term
| Identify whether the variable regions or constant regions of T cell and B cell receptors function in antigen binding or are responsible for the effector function. |
|
Definition
| The constant region of the heavy chain is inserted into immunoglobulin molecule.The constant region determines the antibody(immunoglobulin) class. The class simply means the “isotype” and the five classes include IgG,IgM,IgD,IgE,IgA. |
|
|
Term
| Describe the type of antigen(s) that T lymphocytes and B lymphocytes are able to bind. |
|
Definition
T Lymphocytes are able to recognize and bind peptide fragments (broken proteins 9-25 amino acids long)
B Lymphocytes are able to bind primary,secondary, tertiary, or quaternary structures of proteins, glycoproteins, lipoproteins, or proteoglycans |
|
|
Term
|
Definition
| (Major Histocompatibility Complex): protein that holds the peptide fragments and carries them to surface of antigen presenting cell and displays fragments on surface for the T cell receptors to come and test it. Applies to T cells |
|
|
Term
|
Definition
| able to recognize peptide antigens derived from the breakdown of proteins. Applies to t cells |
|
|
Term
|
Definition
| able to intact to pathogens and toxins. Applies to B cells |
|
|
Term
| Cellular (cell-mediated) Immunity |
|
Definition
| immunity due to cells and cannot be transferred to a naive recipient with serum antibody. Applies to T cells |
|
|
Term
|
Definition
| immunity due to antibodies and can be transferred to a non-immune recipient. Applies to B cells |
|
|
Term
|
Definition
| constant region of the heavy chains of antibody |
|
|
Term
|
Definition
| an antigen-binding molecules that is attached to the membrane. Applies to B cells |
|
|
Term
|
Definition
| secreted version of the immunoglobulin. Applies to B cells |
|
|
Term
|
Definition
| expands the population of lymphocytes to create an “army” of cells that are useful and then are selected for clonal selection. Applies to T and B cells. |
|
|
Term
|
Definition
| process that removes B and T lymphocytes that have the potential to respond to self antigen. Applies to T and B cells |
|
|
Term
|
Definition
| process where lymphocytes receptors on the surface are tested to see if they are functional or not. Applies to T cells |
|
|
Term
|
Definition
| molecule consisting of 2+ amino acids |
|
|
Term
| antigenic determinant (epitope) |
|
Definition
| portion of an antigen that is bound to an antibody |
|
|
Term
| Which interferons are "Type 1 interferons"? |
|
Definition
|
|
Term
| What type of microbial infection do the type 1 interferons combat? |
|
Definition
1) They increase the synthesis of proteases and diseases which degrade viral RNA
2) Increase antigen presentation, which activate Cytotoxic T-lymphocytes, which kill virally infected cells
3) Also act on NK cells, which are innate immune cells that can also kill virally infected cells but recognize them differently to Cytotoxic T-lymphocytes. |
|
|
Term
| Identify the major macrophage cytokine that triggers the “acute phase” response and the proteins that are produced as a part of the acute phase response. |
|
Definition
The acute phase response is triggered by IL-6. The proteins produced are MBL
and CRP. MBL activates the lectin complement pathway and CRP activates the classical complement pathway. |
|
|
Term
| Identify the immune system defect that causes Chronic Granulomatous Disease. |
|
Definition
| CGD results from defective NADPH oxidase subunits. This makes “respiratory burst” defective and allows bacteria/fungi to survive inside phagosomes even after they've been phagocytized. These infected cells form a granuloma to “wall off” the harmful pathogen that can't be killed in the current state. |
|
|
Term
| Explain what is meant by “respiratory burst” in regards to phagocytes. |
|
Definition
| “Respiratory Burst” occurs in the macrophages and in neutrophils. It’s a metabolic change that happens when there is a rapid increase of oxygen consumption. Oxygen is used for energy by NADPH oxidase enzymes, they power an electron transport chain to pump out hydrogen ions out of the phagosome and raises the pH which activates the protease. |
|
|
Term
| Describe (in general) what a cell that expresses a chemokine receptor does in response to binding it’s chemokine ligand. |
|
Definition
| In general a cell will move toward the source of the chemokine. The cell will crawl up the chemokine concentration gradient (from low concentration to high). Refer to figure 2.31 on page 21 |
|
|
Term
|
Definition
| family of small proteins secreted by immune cells and many non immune cells that are under stress and act as a chemoattractant. |
|
|
Term
| What are the two signature amino acid sequence motifs that characterize the chemokine family? |
|
Definition
CXC: Cysteine-(any amino acid)-Cysteine
These attract neutrophils and naive T cells and can control angiogenesis
CC: Cysteine-Cysteine
attract neutrophils as well as monocytes, effector t cells and memory T cells |
|
|
Term
| What are the cytokines released by macrophages that cause beneficial LOCAL immune system effects? |
|
Definition
| IL-6, TNF-alpha, IL_1beta, CXCL8, IL-12 |
|
|
Term
| Describe how neutrophils and macrophages differ in their lifespan and function as phagocytes. |
|
Definition
| Neutrophils enter inflammatory sites, phagocytize and digest bacteria/fungi, and then die resulting in pus formation. Macrophages usually respond first to pathogen entry. They release cytokines which allow for regrowth of vascular tissue. They are also phagocytic and clean up dying cells/debris. |
|
|
Term
| Identify the role of TLR in innate immune responses. |
|
Definition
| Toll-like receptors (TLR) sends out an alarm to the immune system, letting it know that there is an infection. The vast majority of the receptors are in innate immune cells and it is their responsibility to recognize the invasion and release cytokines to activate the adaptive immune cells. Some TLRs are located in the plasma membrane while the others are located in the endosomes. |
|
|
Term
| List the various receptors phagocytes possess that allow them to recognize and phagocytize pathogens. |
|
Definition
| Lectins, Scavenger Receptors, and Complement Receptors |
|
|
Term
| Describe how 2-macroglobulins and defensins function in innate immune system protection of the body. |
|
Definition
Defensins:
Small amphipathic proteins that insert themselves into cell membranes, this causes the bacteria to hemorrhage its insides and results in the death of the bacteria, these are present in Phagocytes and it is how they “digest” foreign elements.
2-macroglobulins:
Glycoproteins that clean up degraded proteases and deliver them to the receptors present on hepatocytes, fibroblasts, and macrophages which are in blood filtering organs like the liver. |
|
|
Term
| List the two points at which complement activation can be inhibited, and identify the product of C3b cleavage produced by Factor I. |
|
Definition
-1:inactivate C3 convertase 2: prevent MAC formation
-Factor H binds to C3b,targeting it for cleavage by factor I (to iC3b) |
|
|
Term
| What is the single protein that can amplify complement activation and what pathway of complement does it amplify? |
|
Definition
Protein is properdin (Factor P)
Amplifies the alternative pathway |
|
|
Term
| What is the mechanism Factor P uses to accomplish amplification? |
|
Definition
| protects activated C3 convertase from protease degradation which keeps the alternative pathway activated longer. |
|
|
Term
| Identify which complement component actually polymerizes to form a pore in the pathogen membrane. |
|
Definition
| The complement protein C9 polymerizes. A total of 12 are required to form a pore in the membrane. |
|
|
Term
| Identify the complement components that compose the membrane attack complex |
|
Definition
| Membrane Attack Complex (MAC)- what forms the pore. The complement components that compose this include C5-C9. |
|
|
Term
| Explain what the similarities and differences are between iC3 versus iC3b, as well as iC3Bb versus C3bBb, being certain to identify which are enzymatically active and which are inactivated. |
|
Definition
iC3 results from the spontaneous hydrolysis, and iC3b results from a cleaving of the iC3 molecule by iC3Bb convertase. Both iC3 and iC3b are enzymatically inactive.
C3bBb is membrane bound while iC3Bb is non-membrane bound. |
|
|
Term
| Identify the actual complement proteins that are complexed together to form the C3 convertase and C5 convertase for both the classical and alternative complement pathways. |
|
Definition
C3 convertase: Alternative pathway=C3bBb Classical pathway=C4b2a
C5 convertase:Alternative pathway=C3bBb3b
Classical pathway=C4b2a3b |
|
|
Term
| What are the 3 separate pathways that can trigger complement activation in order? |
|
Definition
| alternative pathway, lectin pathway, and classical pathway |
|
|
Term
| What is the first complement component that initiates the 3 separate pathways? |
|
Definition
| The alternative pathway is activated by water, which hydrolyzes C3. Mannose Binding Lectin (MBL) triggers the lectin pathway by binding to the pathogen surface. And the classical pathway is triggered by C-reactive protein (CRP) which binds to a specific antigen or the pathogen surface. |
|
|
Term
| What are the four main functions that the complement proteins can perform for the immune system? |
|
Definition
| opsonization, anaphylatoxin, chemoattraction, lysis |
|
|
Term
|
Definition
| Complement cascade can create a pore (perforation in lipid bilayer) in the membrane leading to cell lysis |
|
|
Term
|
Definition
| Complement fragments can help recruit immune cells to inflammatory sites by creating a gradient that can be followed by the cells |
|
|
Term
|
Definition
| These fragments can increase local inflammation (ex. C5a, C3a, C4a) |
|
|
Term
| List the major advantage that complement has compared to antibody in tagging pathogens for disposal. |
|
Definition
| complements can covalently bond to the pathogen surface or soluble immune complexes which means that it’s permanent. Antibody forms non-covalent bonds, which implies that it is reversible. |
|
|
Term
|
Definition
| Complement Receptors and the number following “CR” indicates which complement fragment it is a receptor for. |
|
|
Term
|
Definition
| binding of C3b to pathogen be a covalent chemical bond |
|
|
Term
|
Definition
| Stands for complement protein, the type of complement protein is denoted by the number following “C” |
|
|
Term
|
Definition
| Immune cell that engulfs and consumes foreign material, microorganisms, and debris |
|
|
Term
| What are the main advantages of the adaptive immune response? |
|
Definition
| adaptive immunity improves during a response. It has numerous highly selective specificities for activation. Receptors on B and T cells form due to gene rearrangement versus being mapped in the genome where they never change. |
|
|
Term
| List where T lymphocytes and B lymphocytes are primarily located in the lymph nodes |
|
Definition
B cells are located mostly in the outer lymphoid follicle
T cells are located more towards the center between the germinal center and the medullary sinus (inner cortex) |
|
|
Term
| List where T lymphocytes and B lymphocytes are primarily located in the spleen |
|
Definition
T cells are located in the PALS (periarteriolar lymphoid sheath) surrounding a central arteriole
B cells organized in germinal center and B cell corona peripheral to PALS |
|
|
Term
| Describe how antigen enters a lymph node. |
|
Definition
| It is taken up by a dendritic cell which then migrates to the lymph node due to the increase in fluid flow from inflammation or antigens can also enter lymphatics by washing in there |
|
|
Term
| Describe how a naïve lymphocyte enters a lymph node, and how it would exit if it did not get stimulated by antigen. |
|
Definition
| enters the lymph node via arterioles (blood vessels). Naïve lymphocytes that are not activated leave via the efferent lymphatics |
|
|
Term
| List the 2 tissues/organs that represent the primary lymphoid tissues. |
|
Definition
|
|
Term
|
Definition
| microfolded envagenated cells located in GALT. Embeded in mucosal epithelium; Deliver pathos across epithelium. |
|
|
Term
|
Definition
| mucosal associated lymphoid tissue; vag, urogenital tract |
|
|
Term
|
Definition
| bronchial associated lymphoid tissue; RSN tract |
|
|
Term
|
Definition
| gut, tonsils adenoids, appendix & Peyer’s patches- accumulation of lymphos in small intestine. |
|
|
Term
|
Definition
| periarteriolar lymphoid sheath; where Tcells are located in white pulp of spleen. |
|
|
Term
|
Definition
| inactivated lymphocyte enter lymph node via arterial circulation where they mix with pathogens |
|
|
Term
|
Definition
| fluid of the lymphatic system; contains lymphocytes, pathogens etc. |
|
|
Term
| Secondary Lymphoid Tissue |
|
Definition
| Spleen and Lymph Nodes; where lymphocytes are activated |
|
|
Term
|
Definition
| Bone Marrow and Thymus; lymphocytes are made and mature here. |
|
|
Term
| List the 3 polymorphonuclear leukocytes (granulocytes) found in peripheral blood, and the color of cytoplasmic granules each possesses. |
|
Definition
Eosinophils- like eosin dye; cytoplasmic granules stain orange pink
Basophils- like basic dye; cytoplasmic granules stain dark purple/black
Neutrophils- like neutral dye; cytoplasmic granules stain pink/blue |
|
|
Term
| Explain the relationship between monocytes and macrophages |
|
Definition
| Monocytes are located in the blood whereas macrophages are located in tissues |
|
|
Term
| List the common CD markers that can be used to identify T lymphocytes |
|
Definition
T lymphocytes all have CD3+
Th (T helper cells) also have CD4+ (Th1 and Th2)
Tc (cytotoxic Tcells) also have CD8+
Treg (regulatory Tcells) also have CD4+ |
|
|
Term
| List the common CD markers that can be used to identify B lymphocytes |
|
Definition
B lymphocytes all have CD19+ and CD20+
B-1
B-2 |
|
|
Term
Speed of Response:
innate vs. adaptive immunity |
|
Definition
Innate: rapid (hours)
Adaptive: slow (days to weeks) |
|
|
Term
Variability of Antigen Recognition:
innate vs. adaptive immunity |
|
Definition
Innate: limited number of specificities. Fixed #, do not change
Adaptive: variable. Numerous highly selective specificities |
|
|
Term
Ability to improve during response / with repeated exposure:
Innate vs. adaptive immunity |
|
Definition
Innate: constant during response
Adaptive: improve during response. BCR and TCR form by gene rearrangement |
|
|
Term
|
Definition
| refers to Eosinos, Basos and neutros they have many nuclear clusters in their cells. |
|
|
Term
|
Definition
| enzymes that lyse cells. Found in tears |
|
|
Term
|
Definition
| amphipathic peptides; partly hydrophobic, partly hydrophilic can then embed in cells and lyse them. |
|
|
Term
|
Definition
| oily/waxy matter that lubes and waterproofs skin. Contains enzymes and can change pH |
|
|
Term
|
Definition
| cluster of differentiation used to distinguish B lymphos and T lymphos |
|
|
Term
|
Definition
| adaptive improves during response, immunity memory is a big advantage. Involves Bcells and Tcells |
|
|
Term
|
Definition
| most all living orgs have innate immunity, response is rapid but the same every time, never changes. |
|
|
Term
|
Definition
| substance that evokes the production of one or more antibodies. This is the part of the pathogen that actives the lymphocytes. |
|
|
Term
| Explain the role of HLA alleles in development of autoimmunity (i.e. what are the HLA molecules doing exactly to trigger autoimmunity?). |
|
Definition
The MHC class 2 alleles are particularly important to autoimmunity because they present antigen to CD4+ T helper cells, which are the cells that are greatly connected to autoimmunity.
They present self antigen as foreign and cause the body to react |
|
|
Term
| Identify 2 autoimmune diseases that have a much higher incidence rate (> 5 times) in women than in men. |
|
Definition
| Sjogren's syndrome and SLE (lupus) have the highest rate in women compared to men. |
|
|
Term
| What is the causative agent of Lyme Disease and the characteristic symptom of primary infection? |
|
Definition
Borrelia burgdorferi transmitted by ticks. Primary
symptoms include a “bullseye”
rash surrounding the bite area which is seen in 80% of patients |
|
|
Term
| What are the chronic infection symptoms of Lyme Disease? |
|
Definition
include:migratory joint pain, pain in tendons
and muscles, facial palsy with ~15% of patients exhibiting neurological or cardiac problems |
|
|
Term
Identify the screening test for Lyme disease, whether a positive is
diagnostic, and whether a confirmatory test is necessary (if so, ID the
confirmatory test). |
|
Definition
Enzyme Immunoassays or Immunofluorescent assays are used for the screening
tests. Positive screening test are tested using the western blot as a confirmatory test. |
|
|
Term
Identify the causative agent of syphilis, the 2 primary modes of
transmission, and the usual treatment of the disease if diagnosed early. |
|
Definition
The causative organism is Treponema pallidum ssp. pallidum (spirtochete). It is
primarily an STD but can cause congential infections too. It can be easily treated
with antibiotics early but if left untreated can cause severe consequences. |
|
|
Term
| What are the 4 stages of syphilis? |
|
Definition
1. primary syphilis
2. secondary syphilis
3. Latent syphilis
4. tertiary syphilis |
|
|
Term
|
Definition
well
defined painless lesion with an ulcerated center and red
raised border forms. Usually on genitals, lesion will resolve on its own if untreated. |
|
|
Term
|
Definition
occurs
in 25% of untreated infections. Organism spreads
through body and causes generalized lymphadenopathy and flu like symptoms |
|
|
Term
|
Definition
| no symptoms for many years despite organism presence |
|
|
Term
|
Definition
| develops 10-30 years later in about 30% of those who have latent syphilis |
|
|
Term
List the components of the test antigen (reagent) used for nontreponemal
tests for syphilis. |
|
Definition
| Cholesterol, lecithin and cardiolipin to detect nonspecific antibodies or reagin antibodies. |
|
|
Term
Identify the only test that is currently approved to diagnose tertiary
neurosyphilis and the patient sample used for this testing. |
|
Definition
| VDRL is the only approved syphilis test to diagnose neurosyphilis |
|
|
Term
| Identify the case in which the ASO test would be expected to be negative following true Group A Streptococcus infection and alternative tests that could be used instead to document secondary sequelae of infection |
|
Definition
The ASO test is positive in 80% of strep throat cases but does not become positive in strep pyoderma. An alternative test that could be used instead of document
secondary sequeale of infection is antiDNase B assay. |
|
|
Term
| General usefulness of IVIg used in the therapeutic treatment of humans |
|
Definition
concentrated
human IgG pooled from donors that is to people to treat primary
antibody immunodeficiency disorders. |
|
|
Term
| General usefulness of RhoGAM used in the therapeutic treatment of humans |
|
Definition
used
in prevention of hemolytic disease of the newborn (polyclonal antibody
purified from pooled Rhnegative
Mom’s who have antiRh antibody) |
|
|
Term
| General usefulness of monoclonal antibody therapies used in treatment of humans |
|
Definition
| used to target and kill tumor cells or as immunosuppressants. |
|
|
Term
| Describe the general process of hybridoma creation for the production of monoclonal antibodies. |
|
Definition
1. Inject a mouse with antigen to create an immune response and cause production of antibody to antigen.
2. Harvest the plasma cells from the spleen and fuse it to an immortalized myeloma (tumor cell).
3. Grow these fused hybrid cells in a media where only the fused cells can survive(individual B cells and myeloma cells die).
4. clone the surviving “hybridoma” cell and select for cells which produce the high affinity antibody against the desired antigen. |
|
|
Term
| Monoclonal vs. polyclonal antibodies |
|
Definition
Monoclonal antibodies are antibody preparations in which the antibody is all identical. Derived from a single cell line and are made from several different immune cells
Polyclonal antibodies react against the same different antigenic determinants of one antigen molecule. Produced by inoculation of a mammal (mouse, rabbit,
or goat). Antigen is injected into the mammal and IgG is purified from
mammal’s serum. |
|
|
Term
What are HAMA? Would they cause false positive or false negatives in
clinical laboratory EIA testing? |
|
Definition
HAMA stands for human antimouse
antibody. When they interfere with
immunoassays they usually cause a false positive result that doesn’t correlate with patient history. |
|
|
Term
|
Definition
| IgE detects some soluble antigen, and causes Mast Cells to degranulate |
|
|
Term
|
Definition
IgG binds to something that is fixed on a surface, which leads to either the
activation of a receptor, or it can neutralize the receptor and can keep it from doing its job. (Over vs. Under activation) |
|
|
Term
|
Definition
| IgG binds to soluble antigen which leads to complement activation. |
|
|
Term
|
Definition
T Cells (Th1, Th2, CTL) which bind to soluble or cellassociated
antigen and cause a misactivation
of multiple types of cells. |
|
|
Term
| "Wheal and Flare Reaction" and what type of hypersensitivity is being tested |
|
Definition
almost instantaneous. An allergic reaction will occur within
minutes of injection of antigen. Type 1 hypersensitivity |
|
|
Term
| "Delayed-Type Hypersensitivity" (DTH) and what type of hypersensitivity is being tested |
|
Definition
response tests for type IV hypersensativity. Symptoms
occur 13 days following contact with allergen. A TB test is an example of DTH
testing. |
|
|
Term
| Associate histamine with a Type I hypersensitivity. |
|
Definition
Histamine is a mediator stored in granules that are released in seconds. It is associated with Type 1 hypersensitivity because the effector mechanism is
mast cell activation and histamine is 10% of the total mast cell granule contents. |
|
|
Term
| What are the 3 granulocytes that play a role in allergic and parasitic diseases? What is the antibody isotype that triggers degranulation of them? |
|
Definition
| Basophils, Eosinophils, and Mast Cells. IgE triggers degranulation |
|
|
Term
Identify what cell type produces IL4
and is currently thought to be the
trigger of Th2 responses by naïve CD4+ T cells. |
|
Definition
|
|
Term
| Advantages and Disadvantages of total serum IgE |
|
Definition
screening tool that tests for type I hypersensitivity ( elevated
levels of total serum IgE. Some Disadvantages are it’s not sensitive and it does not identify the offending allergen. Advantages: cheap, and suggests further testing. |
|
|
Term
| Advantages and Disadvantages of skin testing |
|
Definition
is a cutaneous or intradermal procedure performed by a allergist or nurse and graded for wheal reaction ex greater than 3mm swelling in 15 minutes
disadvantages: danger of systemic reaction, traumatic, and only tests limited individual allergens. Advantages: a positive test is clinically significant |
|
|
Term
| Advantages and Disadvantages of lab specific testing for IgE |
|
Definition
performed on large automated
analyzers, which can test on total IgE or a huge array of individual common
allergens. There is a solid phase carbbased assay used to provide high test antigen dose for increased sensitivity. Lower specificity than skin testing. Can be used when patient is taking antihistamine and performed in large panels which can be pricy. |
|
|
Term
| Advantages and Disadvantages of microarray testing |
|
Definition
| testing advantage is that it greatly increases the number of allergens that can be tested on a tiny individual patient sample |
|
|
Term
| Identify two common causes of type II hypersensitivities. |
|
Definition
| Hemolytic anemia and thrombocytopenia |
|
|
Term
| What type of hypersensitivity is serum sickness? |
|
Definition
|
|
Term
| What type of hypersensitivity is celiac disease? |
|
Definition
|
|
Term
| What type of hypersensitivity is poison ivy? |
|
Definition
|
|
Term
| What type of hypersensitivity is allergic asthma? |
|
Definition
| Type 1 and if chronic, Type 4 |
|
|
Term
| What type of hypersensitivity is food allergy? |
|
Definition
|
|
Term
| Identify which types of hypersensitivity responses can cause autoimmune disorders, and which of these is most commonly encountered. |
|
Definition
Type II, III, and IV hypersensitivity can cause autoimmune disorders. Type II
hypersensitivity is the most common |
|
|
Term
Grave's Disease:
auto-antibodies observed, testing done, immune mechanism responsible for tissue destruction |
|
Definition
The autoantibody found is antibody to TSHR, The tests that can be performed are assays for T3,T4, or TSH as well as testing for thyroid antibodies.
In this disease, the Ab acts as a ligand that stimulates excessive T3/T4 secretion. |
|
|
Term
Hasimoto's Thyroiditis:
auto-antibodies observed, testing done, immune mechanism responsible for tissue destruction |
|
Definition
| Both AntiThyroglobulin and AntiThyroid Peroxidase are found. Testing is done through either EIA, particle agglutination, or indirect immunofluorescence; and these tests look for AntiThyroglobulin or AntiThyroid Peroxidase. Even with autoantibody present, Tc cells cause destruction of the thyroid tissue. |
|
|
Term
Addison's Disease:
auto-antibodies observed, testing done, immune mechanism responsible for tissue destruction |
|
Definition
This disease is a primary adrenal insufficiency. It is diagnosed
by tests for decreased cortisol response to ACTH injections. Autoantibody destroys the adrenal cortex (Type 2 Hypersensitivity) |
|
|
Term
Type 1 Diabetes:
auto-antibodies observed, testing done, immune mechanism responsible for tissue destruction |
|
Definition
| Autoantibodies present are antiGAD, antiIA2, and IAA. It is diagnosed through testing for autoantibodies and a test for blood sugar after fasting. In type 1 diabetes, autoimmune Tc cells destroy pancreatic β cells that normally secrete insulin. |
|
|
Term
Identify the autoantigens
that are targeted in Multiple sclerosis, the disease
pathophysiology, and the immune mechanism(s) responsible for the
disease. |
|
Definition
| The autoantigens are MBP (myelin basic protein) and MOG (myelin oligodendrocyte gylcoprotein). MS is an inflammatory autoimmune disease of the central nervous system. The autoantigens are targeted by both antibody and T cells, specifically Th1 and Tc cells. It seems that both Tc cells and antibody play a role in myelin destruction. The myelin sheath around the axons is what’s being destroyed. |
|
|
Term
| What is the auto-antigen that is targeted in Myasthenia gravis? |
|
Definition
|
|
Term
|
Definition
is a neuromuscular disorder with fatigue and skeletal muscle
weakness.Normally
what happens in body is ACH is released from motor neuron ending and
binds to ACHR on muscle fiber to initiate action potential but in MG, Disease is
due to antibody that blocks binding to ACHR and also increases receptor uptake
by the muscle cell, decreasing the available receptor. |
|
|
Term
| What is the lab test used in diagnosis in Myasthenia Gravis? |
|
Definition
Lab diagnosis by detection of anti ACHR
antibody by precipitation
radioimmunoassay. |
|
|
Term
| Identify the autoantibody that is responsible for Goodpasture’s syndrome, the 2 primary tissues that are targeted, and the laboratory testing used for detection of the autoantibody. |
|
Definition
| The Autoantibody to Type IV collagen, which is in the tissues of the kidney glomeruli and lung alveoli. The tests for this autoantibody are RIA, EIA, or IFA while the western blot test should be the confirmatory test. |
|
|
Term
Be able to comment on the current rate of incidence of autoimmune diseases in
developed nations (i.e. are autoimmune diseases rare, or relatively common?) |
|
Definition
| 5% of individuals in developed nations have autoimmune diseases. |
|
|
Term
| Identify the two most common rheumatologic diseases that are considered autoimmune diseases. |
|
Definition
| Rheumatoid arthritis and lupus |
|
|
Term
| Explain why autoimmune rheumatologic diseases are difficult to diagnose. |
|
Definition
These diseases are difficult to diagnose because many of the symptoms and
laboratory tests results overlap and are not specific for individual diseases. |
|
|
Term
|
Definition
is IgM, IgG, or IgA antibody to the Fc portion of IgG, so it’s an
antiimmunoglobulin antibody |
|
|
Term
| What diseases can the RF be found in? |
|
Definition
| rheumatoid arthritis, Sjogren’s, and MCTD. It can have a high positive in Sjogren’s and MCTD |
|
|
Term
| What disease is RF to be considered most significant? |
|
Definition
| In RA it can be found using IgM but it is not specific enough, it’s best to use IgG or IgA which have a 100% positivity for RA. |
|
|
Term
Define the antigen used for antiCCP
testing, the disease this antibody is
associated with, and its usefulness in relation to RF testing. |
|
Definition
Lupus is the disease that the antibody is associated with antiCCP testing. It
is useful in combination with the RF testing because it has a 98% specificity to Rheumatoid arthritis. |
|
|
Term
Recognize the laboratory tests that may be used to follow the course of RA
and monitor disease severity, and whether the result will be abnormally high or abnormally low. |
|
Definition
RA progress can be monitored by testing for 3 inflammatory factors.
1. Erythrocyte sedimentation rate, INCREASED in severe disease
2. C-reactive protein, INCREASED in severe disease
3. Complement components, C3 and C4. DECREASED during acute attacks |
|
|
Term
Identify the novel therapy that is now being used to treat RA and prevent
disease progression. |
|
Definition
Treatment with antiTNFalpha
monoclonal antibody can be used to alleviate severe disease flares. It’s injected usually once a month intramuscularly. Blocks in
inflammatory function of TNFalpha.
It does make people susceptible to anything that needs cell mediated immunity. |
|
|
Term
|
Definition
Testing
to identify the presence of antibody to nuclear antigens, using animal
cells and a fluorescent labeled antihuman immunoglobulin. |
|
|
Term
|
Definition
Antibody produced to different components of the nucleus during the course several autoimmune diseases. Examples include antiDNA,
antideoxyribonucleoproteins and antiribonuclear protein antibodies, all of which occur in systemic lupus erythematosus. |
|
|
Term
|
Definition
| soluble cytoplasmic and nuclear components that are antibody targets with over 100 different antigens described. |
|
|
Term
| What are the 2 specific ENAs that are diagnostic for Lupus? |
|
Definition
| Anti-daDNA and Anti-sm are specific for SLE diagnosis but are not very sensitive. anti-daDNA only positive 50-70% of the time and Anti-Sm only positive 15-30% of the time. |
|
|
Term
| Describe how titer is important in interpretation of FANA and what the titer for normal usually is. |
|
Definition
| Titer typically tests for sensitivity as you are diluting patient serum to see if you still yield a positive result. Anything less than or equal to a 1:80 dilution yielding a positive result is considered normal. Anything that is greater than or equal to a 1:160 dilution of patient serum still yielding a positive result is considered positive. |
|
|
Term
Identify other diseases that may show a low positive titer in an FANA test, as
well as other “nondisease” states. |
|
Definition
| Rheumatoid Arthritis (~50%), scleroderma (60-90%) and Sjogren syndrome (80%) |
|
|
Term
| Identify the specific ENA that is associated with drug-induced lupus. |
|
Definition
| Anti-histone antibody is ENA+ in drug-induced lupus. However 70% of patients with lupus have a low titer of this antibody anyway. |
|
|
Term
Explain why lupus patients can have a false positive syphilis test. Choose
whether this false positive would be in either the nontreponemal or treponemal test for syphilis, or both. |
|
Definition
They can have a false positive due to having the antiphospholipid antibody
anticardiolipin.
This antibody is part of antigen preperation in the nontreponemal
test for syphilis. |
|
|
Term
Identify two proteins involved in T cell tolerance that when defective in
humans lead to generalized autoimmune disease. |
|
Definition
|
|
Term
Explain how an allele of CTLA4
normally found in the human population
can lead to increased susceptibility to autoimmune disease. |
|
Definition
| This one allele of CTLA4 is normally found in about 50% of the population but is found in 60% of patients with autoimmune diseases, indicating a slight risk factor. This may be the case because this allele limits production of soluble CTLA4 which is important in Treg function and could lead to problems. |
|
|
Term
Identify 2 autoimmune diseases that have a much higher incidence rate (> 5
times) in women than in men. |
|
Definition
Sjogren's syndrome and SLE (lupus) have the highest rate in women compared to
men. |
|
|
Term
| Explain the role of HLA alleles in development of autoimmunity (i.e. what are the HLA molecules doing exactly to trigger autoimmunity?). |
|
Definition
The MHC class 2 alleles are particularly important to autoimmunity because they present antigen to CD4+ T helper cells, which are the cells that are greatly
connected to autoimmunity. They present self antigen as foreign and cause the body to react |
|
|
