Term
| What characterizes the humoral immune response? |
|
Definition
| Production of antibodis directed against the immunizing antigen |
|
|
Term
| What secretes antibodies? |
|
Definition
| Terminally differentiated B cells, after contact with exogenous antigen. |
|
|
Term
|
Definition
| Immediately follows antigen exposureB cells undergo clonal selection and differentiate into plasma cells. |
|
|
Term
| What happens upon re-exposure to the same antigen? |
|
Definition
| A second response develops albeit with different kinetics |
|
|
Term
| When does primary response occur? |
|
Definition
| After first contact with the antigen |
|
|
Term
| What happens in primary response? |
|
Definition
Kinetics vary, depending on antigen and route of admin and genotype of host.
IgM initially, followed by IgG |
|
|
Term
| Duration of primary response? |
|
Definition
| Can last one week to several. Depending on nature of the antigen |
|
|
Term
| What happens in secondary response? |
|
Definition
| Memory B cells (made in primary) are activated |
|
|
Term
| Distinguish secondary from primary response? |
|
Definition
Shorter Lag Phase
Greater magnitude
Longer Duration
Antibodies have higher afffinity of r the antigen
Variety of isotypes+IgM |
|
|
Term
| More effective: Primary or Secondary? |
|
Definition
|
|
Term
| Light chain recombination: |
|
Definition
|
|
Term
| Heavy chain recombination: |
|
Definition
|
|
Term
| Where does development of aB occur? |
|
Definition
| During development in the bone marrow |
|
|
Term
| Where do additional point mutations occur? |
|
Definition
|
|
Term
| Total diversity of antibodies: |
|
Definition
|
|
Term
What is critical for diversity during recombination?
D=?
J=?
V=? |
|
Definition
Number of gene segments.
D-Diversity
J-joining
V-Variable |
|
|
Term
| First step of recombination? |
|
Definition
Somatic recombination of germline DNA:
D-J segments (heavy chain) |
|
|
Term
| Second step of recombination? |
|
Definition
DJ-V joining
J-V joining=light chain |
|
|
Term
| What results in the primary transcript RNA? |
|
Definition
| Transcription of the rearranged DNA |
|
|
Term
| What happens when you splice the introns |
|
Definition
| mRNA where VDJ-C genes are combined and ready for translation into a functional polypeptide |
|
|
Term
| When an antigen enters the body, where does it go? |
|
Definition
| Carried and concentrated in the drainging lymph nodes and to the spleen by antigen transporting cells. |
|
|
Term
| Where are the B cells that the antigens are delivered to located? |
|
Definition
|
|
Term
| What happens once antigen + B cell interact? |
|
Definition
Bound
Endocytosed/processed |
|
|
Term
| What does the B cell do after antigen endocytosed? |
|
Definition
B cell increases in size
Increase expression of surface Ig
Increase expression of MHC 2 and B7 molecules |
|
|
Term
| What happens to endocytosed molecule? |
|
Definition
| Expressed on the surface of B cell w/ class 2 mhc |
|
|
Term
| Where do B cells present antigens to T cells? |
|
Definition
| At the border of T/B cell areas in the lymph node |
|
|
Term
| What happens to B cells in response to cytokines? |
|
Definition
Proliferation, then differentiate into Plasma cells.
Plasma cells secrete ab that constitue the immune response |
|
|
Term
| What stimulates IL-2 production? |
|
Definition
| CD4 helper T in the paracortex activation |
|
|
Term
|
Definition
| Autocrine factor; induces proliferation of CD4; which produce more IL2 |
|
|
Term
| What ccan the activated/prolif T cells develop into? |
|
Definition
|
|
Term
|
Definition
TH2= IL4,IL5, IL6
IL4: B cell growth factor, initial prolif and diff
IL5:B cell diff
4+5: stim diff of B-->plasmablasts
IL6:By macrophages to boost Ab secretion by term diff plasma cells |
|
|
Term
| What does immuglobulin switching require? |
|
Definition
|
|
Term
|
Definition
| Switch between IgG1 and IgE |
|
|
Term
| What does interferon gamma (IFN-gamma) produce? |
|
Definition
| Switch between IgG3 and IgG2a |
|
|
Term
| What interaction is CRUCIAL for isotype switching? |
|
Definition
|
|
Term
| What happens about a week after primary antigen exposure? |
|
Definition
| Proliferations and diff centers give rise to secondary follicle/germinal center |
|
|
Term
| What do B cells do after leaving germinal center? |
|
Definition
migrate to medulla
Become plasma cells/secrete Ab
or Diff into memory B |
|
|
Term
|
Definition
| Remain in the follicular mantle, or leave via efferent lymphatics (circulate to other parts of the body ie. bone marrow |
|
|
Term
| Phenomena associated w/ Bcells in the germinal center: |
|
Definition
*Actively proliferating cells. Resulting daughter can diff into plasma cells that secrete high Ab
*High rates of mutation (somatic hypermutation) in the hypervariable sites w/ in the Ig variable regions leading to changes in the aa composition of the antigen binding site. (loss or gain in affinity of the antigen)
*Actively prolif B cells can also swith Ig isotype; depends on nature of antigen/cytokines |
|
|
Term
| B cells affinity after pro/diff mutation |
|
Definition
*B cells that have mutations that result in higher affinity for the antigen pr/diff into plasma/memory cells
*B cells that have mutation sthat lower the affinity for antigen result in apapotosis. |
|
|
Term
| Which antibodies inhibit attachment of toxins or microbes? |
|
Definition
|
|
Term
| Which antibodies enhance phagocytosis? |
|
Definition
|
|
Term
| Which antibodies enhance phagocytosis? |
|
Definition
|
|
Term
| Which antibodies mediate antibody-dependent cellular cytotoxixity? |
|
Definition
|
|
Term
| Which antibodies activate compliment? |
|
Definition
|
|
Term
| Which antibodies de-granulate Mast cells? |
|
Definition
|
|
Term
| What usually accompanies immune response against exogenous antigens and pathogens? |
|
Definition
| Cell death and local/systemic injury to body tissues |
|
|
Term
|
Definition
| Pathologic consequence of an altered reaction to an antigen. |
|
|
Term
| How does hypersensitivity develop? |
|
Definition
| As humoral or cell mediated immune responses following 2nd exposure of certain antigens. |
|
|
Term
| Antigen responsible for hypersensitivity? |
|
Definition
|
|
Term
| When do allergic reactions occur? |
|
Definition
| Following re-exposure to the sensitizing antigen (a by-product of immunologic memory) |
|
|
Term
| Initial exposure to an individual to an allergen?? |
|
Definition
|
|
Term
|
Definition
| Genetic predisposition to develop hypersensitive reactions when exposed to allergens |
|
|
Term
| Effectors of hypersensitivity |
|
Definition
Pharmacological agents released by various inflammatory cells
Immunoglobulins
Components of the compliment system |
|
|
Term
Type 1 Hypersensitivity:
Kinetics
Mediator
Nature
Mechanism |
|
Definition
Immediate Acting
IgE antibody
Small protein; low concentration
Degranulation of mast cells/basophils |
|
|
Term
Type 2 hypersensitivity
Kinetics
Mediator
Nature
Mechanism |
|
Definition
Immediate acting
IgG/IgM antibody
Cell or matrix bound allergen
Compliment and Fc receptor mediated cytotoxicity; ADCC (NIK cells); phagocytosis |
|
|
Term
Type 3 hypersensitivity
Kinetics
Mediator
Nature
Mechanism |
|
Definition
Immediate acting
IgG/IgM Ab
Soluble allergen
Immunoe complex deposition, inflammation localized tissue and vascular damage |
|
|
Term
Type 4 hypersensitivity
Kinetics
Mediator
Nature
Mechanism |
|
Definition
Delayed action
T-cell=mediator
Small molecules; can complex skin w/ proteins
Specialized cytokines and lytic enxymes; edema |
|
|
Term
|
Definition
| Mucosal surfaces, Subcutaneous, IV |
|
|
Term
| Re-exposure to the antigen: Type 1 |
|
Definition
| Cross links the IgE- bound Fc receptors |
|
|
Term
| What do the release of pharmacologically active substances from degranulated mast cells and basophils mediate the effects of? |
|
Definition
| Smooth muscle contraction, increased vasular permeability and vasodilation. |
|
|
Term
| Type 1 hypersensitivity can induce: |
|
Definition
| Hay Fever/eczema and seriousuus life threatening conditions such as systemic anaphylaxis |
|
|
Term
|
Definition
mediator of hypersensitivity
Induces smooth musc. contraction; increase vascular permeability |
|
|
Term
|
Definition
mediator of hypersensitivity
Incuces vasodilation and bronchoconstriction, act as chemoatractant for inflammatory cells |
|
|
Term
|
Definition
mediator of hypersensitivity
Induce vasodilation and bronchoconstirction |
|
|
Term
| Platelet activating factor |
|
Definition
| Induces platelet agg. and hypotension |
|
|
Term
|
Definition
mediator of hypersensitivity
Incudes smooth muscle contraction, increased vascular permeability and induces pain |
|
|
Term
| What compliment proteins play what role in hypersensitivy? |
|
Definition
C3A, C4A, C5A
Induce mast cell degranulization by themselves through IgE- independent mechanisms.
They are sometimes referred to as anaphylatoxins |
|
|
Term
|
Definition
| Immunotherapy or drug therapy |
|
|
Term
|
Definition
Anti-body dependent cell mediated cytotoxicity.
Effector cells are NK cells that express Fc receptors for IgG |
|
|
Term
| Example of Type 2 hypersensitity |
|
Definition
| Penicillin/other drug allergy |
|
|
Term
| What type of reaction occurs in individuals given blood transfusions from blodd group incompatable donors? |
|
Definition
|
|
Term
| Hemolytic disease of the newborn? |
|
Definition
Type 2
Incompatibility of Rh antigen |
|
|
Term
| In type 3 hypersensitivity, what does deposition of the immune complexes induce? |
|
Definition
| Chemoattraction of inflammatory cells at the site of deposition |
|
|
Term
|
Definition
| 2-8 hours after antigen is injected into tissue. |
|
|
Term
| Compliment comonents in type 3 hypersensititivy? |
|
Definition
C3a, C4a, C5a released at the site of reaction.
They function as anaphylatoxins and cause degranulation of mast cells in the area leading to edema and erythema. |
|
|
Term
| In type 3, when lots of immune complexes are present in the blood stream, what can it lead to? |
|
Definition
| Vasculitis, lymphadenopathy, arthritis, and sometimes glomerulonephritis. |
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
| What mediates type 4 hypersensitivity? |
|
Definition
| TH1 type helper T cells (TDTH) |
|
|
Term
| Type 4 hypersensitivity site of entry/process? |
|
Definition
Enter skin/mucosa
Bind to cell-surface proteins on epidermal keratinocytes or langerhans' cells |
|
|
Term
| To what cell is the antigen presented to in type 4? |
|
Definition
|
|
Term
|
Definition
| Sensitization phase where small molecule or chemical penetrates the skin and reacts with self protein to forma a hapten |
|
|
Term
|
Definition
| protein complex that induces a t cell response |
|
|
Term
|
Definition
| Occurs on secondary exposure to the hapeten which activates the antigen-specific T cells. |
|
|
Term
|
Definition
Example of type 4
Reaction casused by urushipol resin binding to self MHC antigens to make them look like 'non self' |
|
|
Term
| What gives the mammalian germline the capacity to mount an immune response to an infinite number of antigens? |
|
Definition
| the numerous immunoglobulin and TCR variable region gene segments that can recombine and diversify to give a large number of specificities |
|
|
Term
|
Definition
The lack of immune response, or the state of unresponsiveness (against self)
can therefore be defined as antigen-induced block in the development, growth or differentiation of specific lymphocytes |
|
|
Term
| Two major categories of tolerance: |
|
Definition
Central tolerance-primary lymphoid
Peripheral-2 lymphoid |
|
|
Term
| Two mechanisms for induction of tolerance |
|
Definition
| Colnal deletion and clonal anergy |
|
|
Term
|
Definition
| Physical elimination of antigen-reactive lymphocytes |
|
|
Term
|
Definition
| Functional silencing of antigen specific lymphocytes |
|
|
Term
| What is the major means of eliminating potentially self-reactive lymphocytes within the primary lympoid organs such as the thymus and bone marrow during deveolopment? |
|
Definition
|
|
Term
| What happens to lymphocytes recognizing antigens that are not presented @ the primary sites? |
|
Definition
| May be eliminated or silenced in the periphery. |
|
|
Term
| How can clonal deletion occur? |
|
Definition
Interactions of FasL (CD8 T cell)-Fas (target cell) which induces apoptosis of the target cell.
Killing by the T suppressor / regulatory cells by
*Perforins (produce holes in target cell membrane)
*Granzymes (proteolytic enzymes that induce apoptosis) |
|
|
Term
What do T regulatory cells also express?
What does that bind to? |
|
Definition
|
|
Term
| Ways to suppress T cell function |
|
Definition
Signalling throgh CTLA-4
T-reg produce cytokines that suppress prolif.
(transforming growth factor B, TGFb, and IL10)
Particularly important for tolerence in the intestine |
|
|
Term
| Induction of clonal anergy |
|
Definition
| Absence of co-stimulatory signal (B7-CD28) upon interaction with antigen for Tcells,or through as yet unknown mechanism for B cells (prob CD40/Cd40L) |
|
|
Term
|
Definition
|
|
Term
|
Definition
| A transcription factor expressed in the thymus that activates transription of several hundred tissue-specific genes. |
|
|
Term
|
Definition
| Not completely understood, since it is known that mothers make antibodies to the fathers MHC and RBC |
|
|
Term
| Potential mechanisms for fetus tolerance: |
|
Definition
Placenta
Outler layer does note express classical MHC proteins
Expresses a molecule that inhibits NK cell killing
Depletion of tryptophan-necessary T cell nutrient |
|
|
Term
|
Definition
Breakdown of tolerance, which is multi-layered, consisting of both central and peripheral mechanisms.
Self response against self antigens, which results in destruction of host tissue or damage to the function of an organ or tissue |
|
|
Term
| What contributes to autoimmunity? |
|
Definition
| Genetic and environmental factors |
|
|
Term
| What are genetic autoimmunities linked to? |
|
Definition
|
|
Term
| Environmental factors contributing to autoimmune disease: |
|
Definition
1. Environmental exposure to chemicals (pesticides/dyes)
2. Infections by bacteria or viruses. There may be some corss-reactivity between the microbe and a self-antigen that results in an autoimmune response to that antigen. |
|
|
Term
Female vs. Male Autoimmune
Left vs. Right |
|
Definition
Females have a much higher rate for developing autoimmune
Left>Right |
|
|
Term
| How can autoimmune diseases be classified? |
|
Definition
Organ or Systemic
Based on the "effector" mechanism
(Antibody mediated) or (Cell mediated) |
|
|
Term
| Contributing factors to autoimmune disease? |
|
Definition
Defect in AIRE
Non-Infectious Environmental Triggers
Antibody Mediated
Cell Mediated |
|
|
Term
| How does defect in AIRE contribute to autoimmune? |
|
Definition
Defect in the expression of some self antigens during negative selection in the thymus, T cells specific for self antigens are released into the periphery, found with some requency in people from Finalnd Sardinia,k and certain Persian Populations (iranian Jews).
These patients develop APD |
|
|
Term
| Non-Infectious Envirnmental Triggers of autoimmune |
|
Definition
| These can include smoking, a breakdown in oral tolerance, or physical trauma that results in the release of sequestered self-antigens so that they can then be processed, presented, and induce an autoimmune response. |
|
|
Term
| Infectious Environmental Triggers of autoimmune |
|
Definition
| Tissue damage and inflammation after an infection, the production of cetrain cytokines (IFNgamma) and moleculear mimircry of self antigens by some microbes can contribute to autoimmune responses |
|
|
Term
| Antibody mediated factors contributing to autoimmune disease |
|
Definition
| autoimmune disease occurs when antibodies are made to a self protein. The antibody may block a receptor and inhibit a normal response (Myasthenia Gravis). Antibody – antigen complexes (immune complexes) can lead to pathology by initiating the complement cascade or immune complexes can become lodged in joints, organs, or vasculature and lead to initiation of the complement cascade and inflammation leading to damage (Systemic Lupus Erythematosus, Type III hypersensitivity). |
|
|
Term
| Cell mediated factors influencing autoimmune |
|
Definition
autoimmune diseases occur when a T cell response is made to a self antigen. CD4 T helper cells can produce cytokines (IFN-gamma) that lead to inflammation and activation of macrophages (Rheumatoid Arthritis). The activated macrophages in turn produce very inflammatory cytokines (TNF-alpha, IL-1) that lead to tissue damage. CD8 T cytotoxic cells to self antigens can directly destroy host cells (Type 1 Insulin-Dependent Diabetes Mellitus)
Some immunotherapeutic drugs can block the action of cytokines and reduce inflammation. |
|
|
Term
| What do some immunotherapic drugs do? |
|
Definition
| Block the action of cytokines and resuce inflammation |
|
|
Term
| When does immunodeficiency occur? |
|
Definition
| When one or more component of the immune system is defected |
|
|
Term
| Inherited immunodeficiency |
|
Definition
|
|
Term
| Most common inherited immunodeficiency |
|
Definition
IgA=most common of these
1/800 vs. 1/10,000 |
|
|
Term
| Acquired Immunodeficiency |
|
Definition
| Can be caused by many things that impari the immune system. |
|
|
Term
| Things that lead to acquired immunodeficiency |
|
Definition
Malnutrition (infants/child)
Drugs and Irradiation (cancer patient)
Viral infections (HIV)
Alcoholism and diabetes
Age plays a role (very young and very old) |
|
|
Term
| Why are the young and the old immunodeficient? |
|
Definition
Young, not fully developed
Old, many factors |
|
|
Term
| What does immunodeficiency effect? |
|
Definition
| Innate, Adaptive or both(rare_ |
|
|
Term
| Defects in the innate immune system in relation to immunodeficiency? |
|
Definition
Defects cell populations such as phagocytes or granulocytes, or in complement components.
Suseptability of bacterial infections |
|
|
Term
| Adaptive arm defects of immunodeficiency? |
|
Definition
B cells (Bruton's tyrosine kinase)
Defects in B cells result in the inability to produce antibodies and lead to susceptability to extracellular bacteria. |
|
|
Term
| Defects in CD4 adaptive arm? |
|
Definition
Can result in the inability to make good antibody responses or to undergo isotype switching since there is a lack of T help and cytokine production necessary for isotype switching
Suseptability for extracellular bacteria. |
|
|
Term
| Defects in MHC1 in ad. arm |
|
Definition
| Nucleated cells, prevents the efficient presentation of antigen to CD8 cytotoxic cells leading to a suseptibility to viral infections. |
|
|
Term
| Defects in MHC2 (ad. arm) |
|
Definition
| On APC prevents the efficient presentation of antigen to CD4 T cells and results in the severe combined immunodefient phenotype (SCID) and a general susceptability to all infections. |
|
|
Term
| Defects in B and T cell development (ad. arm) |
|
Definition
| Severe combined immunodeficient pheoptype (SCID) and a general susceptability to all infections. |
|
|
Term
| How are immunodeficiencies usually recognized? |
|
Definition
| Having recurrent infections. The type of infection can be indicative of the immunodeficiency. |
|
|
Term
|
Definition
| Administration of recmbiant cytokines to augment immune responses. |
|
|
Term
|
Definition
|
|
Term
|
Definition
Enhance TH1 response
(cell mediated immunity toward tumor) |
|
|
Term
|
Definition
| Enhance MHC-1 expression, stop cancer cell growth, used in melanoma, chromic mylogenous leukemia |
|
|
Term
|
Definition
| Machrophage, Neurtophil, Dentritic cell growth factor |
|
|
Term
| Problem with cytokine therapy? |
|
Definition
| Often significant toxicity with systemic effcts. |
|
|
Term
| Non-specific immune stimulation |
|
Definition
William Coley (1890s)
Coley's toxins, bacterial extracts used to stimulate immune responses that would non-specifically attack tumors |
|
|
Term
| What can be used as a treatment for bladder cancer? |
|
Definition
|
|
Term
|
Definition
A cahteter is used to place the BCG solution into the bladder.
Stimulates massive inflammatory responce with the influx of neutrophils, macrophages, and the production of cytokines and chemokines that can induce apoptosis of cancer cells. |
|
|
Term
| For what kinds of tumors are anti-tumor vaccines possible? |
|
Definition
Tumor associated antigens
Tumor specific antigens |
|
|
Term
| How do anti-tumor vaccines work? |
|
Definition
| Incude both CTL and antibodies that could kill tumor cells |
|
|
Term
| Antigen requirements for anti-tumor vaccines: |
|
Definition
| Distant from self to avoid autimmunity and must still be immunogenic. Can be difficult since the tumor cell is "altered self" and tumor cells can undergo mutations and lose that antigen. |
|
|
Term
|
Definition
HPV-cervical cancer
Hepatitis B to reduce hepatic carcinomas |
|
|
Term
| Strategies for tumor cell modification: |
|
Definition
Transfect tumors with co-stil molecule, B7
Transfect tumor with cytokine to activate APC, GM-CSF |
|
|
Term
| Problems with genetic modification of tumor cells |
|
Definition
| Tumor cells have to be removed from patient, transfected, and then infused back into the patient. Risk of increasing tumor burden and metastases. |
|
|
Term
|
Definition
| Antibody specific for a tumor cell antigen can be fused to bacteria toxin or radioisotope that can then kill the tumor cells. |
|
|
Term
| Problem with immunotoxins? |
|
Definition
| Same issue with identifying ggood tumor associated antigen |
|
|
Term
| To what can an monoclonal aB be coupled to in tumor therapy? |
|
Definition
|
|
Term
| FDA approved monoclonal ab for use in cancer therapy? |
|
Definition
Antibody=Rituximab
Target=CD20
Developer=IDEC Pharmacetutical
Approved cancer treatments= Non-hodgkin lymphoma |
|
|
Term
|
Definition
|
|
Term
| What does Rituximab bind to? |
|
Definition
|
|
Term
| What is Rituximab used for? |
|
Definition
| Indolent B cell non hodgkin lymphoma |
|
|
Term
|
Definition
Non-Hodgkin Lymphoma
Malignamcies of lymphocytes.
About 80-90% express B cell markers and CD 20 is expressed on nearly every cell |
|
|
Term
| Treatment with rituximab? |
|
Definition
| Standard weekly dosing. Effective in 50% of patients w/ relapsed or refractory CD20-positive follicular non-hodgkin lymphoma, however it does NOT cure cancer. |
|
|
Term
| What often happens with Rituximab? |
|
Definition
|
|
Term
| Mechanism of cell death with rituximab therapy? |
|
Definition
1.Activation of cell signaling pathways leading to apoptosis
2. Activation of the compliment pathway
3. Antibody dependent cellylar cytoxicity |
|
|
Term
|
Definition
Humanized, monoclonal ab that binds membrane bound and soluble IL-6.
Blocks interaction of IL-6 w/ IL-^ receptor (IL6 activates chemokine production, reqruitment of leukocytes to sites of inflammation, there are high levels of IL6 in RA pettients serum and joint fluid.
Induces proliferation of osteoclasts and could contribute to bond degredation in RA |
|
|
Term
|
Definition
Human IgG1 antibody that binds to the p40 subunit of IL-12 recoptor
IL-12 promotes TH1 responses leading to IFNgamma production and other inflammatory responses
IL-23 promotes TH17 responses leading to increased macrophage activation and inflammation |
|
|
Term
What is the T cell that binds to:
MHC2+ag
B7
CD40 |
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
| On the TH2 cytokine: What is induced; inhibitied? |
|
Definition
IL4 induces IgG1
Inhibitis IgG3 |
|
|
Term
| On the TH1 cytokine: What is induced; inhibitied? |
|
Definition
| IFN-gamma induces IgG3; inhibitis IgG1 |
|
|
Term
|
Definition
| Increase in affinity of the overall antibody response |
|
|
