Term
| How many days after the initial infection will the adaptive immune response begin? What is the trigger for this? |
|
Definition
| Typically 4-7 days after the infection begins. Induction of the adaptive immune response triggered by the level of infection crossing a 'threshold'. |
|
|
Term
| What are the four stages of response to a pathogen invasion? |
|
Definition
1. local infection and penetration of epithelium
2. local infection of tissues
3. lymphatic spread
4. adaptive immunity |
|
|
Term
| If you had to choose between not having RAG (for recombination) or not having macrophages and neutrophils, which would be better? |
|
Definition
Better not to have RAG than not to have neutrophils/macrophages.
If you don't have an adaptive immune system, the innate immune system can still compensate for it. Without an innate immune system, the adaptive immune system never can even get activated, so you have neither. |
|
|
Term
| How is the balance between Treg and Th17 regulated? |
|
Definition
| In the absence of an infection, DCs predominately secrete TGF-beta and little IL-6. In the presence of an infection, predominately IL-6 is secreted. IL-6 promotes differentiation of CD4 cells to Th17 cells. |
|
|
Term
| Which interleukin promotes differentiation of CD4 T cells to Th17 cells? |
|
Definition
|
|
Term
| What type of T cell predominates early in an infection? |
|
Definition
|
|
Term
| What "signal 3" causes differentiation of CD4 T cells into Treg cells? |
|
Definition
|
|
Term
| What "signal 3" causes differentiation of CD4 T cells into Th1 cells? |
|
Definition
|
|
Term
| What "signal 3" causes differentiation of CD4 T cells into Th2 cells? |
|
Definition
|
|
Term
What sort of pathogens cause DCs to produce IL-12.
What does IL-12 cause differentiation of CD4 T cells into? |
|
Definition
Viruses and intracellular bacteria
IL-12 helps to stimulate differentiation of CD4 T-cells into Th1 cells. |
|
|
Term
| How does the immune system know which pathogen is present? |
|
Definition
| TLR signaling on DC (or other APCs) |
|
|
Term
| Why do you usually see either a predominately Th1 or a Th2 response? |
|
Definition
Th1 and Th2 are mutually exclusive.
Both T21 and Th2 inhibit Th17 expression. |
|
|
Term
| How do Th2 cells inhibit development of Th1 cells? |
|
Definition
| Th2 cells secrete Il-10 and TGF-beta which inhibit Th1 activation and growth. |
|
|
Term
| How do Th1 cells inhibit development of Th2 cells? |
|
Definition
| Activated Th1 cells secrete IFN-gamma which inhibits Th2 proliferation. |
|
|
Term
| Which signals inhibit development of Th17? |
|
Definition
|
|
Term
| How does T cell adhesion change between naive and activated T cells? |
|
Definition
Naive cells adhere to the HEVs of lymph nodes (L-selectin)
Effector cells adhere to inflamed tissue |
|
|
Term
IL-12 and IL-23 (and receptors). What do they have in common?
What does each do? |
|
Definition
IL-12 and IL-23 share a p40 subunit.
IL-12 keeps Th1 activated
IL-23 promotes Th17 expansion |
|
|
Term
| In the absence of P40, what happens to the Th1 response? |
|
Definition
| As the IL-12 receptor cannot fully recognize IL-12, Th1 cannot be activated. |
|
|
Term
| Which are more easy to activate? CD4 or CD8? Why? |
|
Definition
CD4
Activation of a CD4 cell by an APC causes upregulation of B7 secretion by APC and causes the CD4 cell to secrete IL-2 which encourage CD8 activation |
|
|
Term
| Can CD8 cells be activated without CD4? |
|
Definition
Yes
DC upregulates B7 in response to infection by some pathogens instead of relying on activated CD4 to cause upregulation. |
|
|
Term
| How long do plasma cells live? |
|
Definition
Early plasma cells (IgM producing) can live for about 3 days
Plasma cells formed after isotype switching and somatic hypermutation can live for months |
|
|
Term
| How do NK cells know which cells to kill? |
|
Definition
By recognizing epitopes displayed on MHC 1 of infected cells.
(Remember--MHC1 displays cytosolic proteins (those which are made in cytosol, not swallowed)) |
|
|
Term
| Which lymphocyte responds better to extracellular infections? |
|
Definition
| B cells (however they still require T cells for activation) |
|
|
Term
| How are Treg and Th17 regulated between? |
|
Definition
DCs turn on one and turn off the other
They do not directly inhibit one another |
|
|
Term
|
Definition
| A B cell that has undergone isotype switching (to a recognized antigen) but is not a plasma cell, producing [high numbers of] antibodies |
|
|
Term
| Primary difference between a primary and a secondary B cell response? |
|
Definition
Primary response: primarily low-afffinity IgM
Secondary response: primarily high-affinity IgA and IgG that contains about 100x the number of B cells responding to that antigen as seen in the primary response |
|
|
Term
| How do repeated exposures to an antigen effect the antibody expression? |
|
Definition
| Overall antibody level increases, particularly of IgG. Affinity of IgG increases |
|
|
Term
| Why are B cells with the highest affinity to their antigen selected to live? |
|
Definition
| B cell Ig binds to antigen, the Igs with the highest affinity binding the most tightly. As more B-cells/antibody binds to antigen, and unbound antigen becomes increasingly scarce, it becomes increasingly important for the Ig to have a high affinity to the antigen so it can bind. In the absence of a signal, the cell will die. |
|
|
Term
| IL-7 expression on T cells |
|
Definition
IL-7 needed for T cell expansion and growth
Il-7 favors CD8 development
IL-7R is present on memory CD8 cells, Tc cells, but not on effector T cells. |
|
|
Term
| Which type of (T) cells have the IL-7R? |
|
Definition
Naive and Memory T cells
Keeps cell alive and dividing |
|
|
Term
| 3 types of memory T cells |
|
Definition
1. central memory T cells
2. effector memory T cells
3. quiescent memory T cells |
|
|
Term
| What is the difference between central memory T cells and effector memory T cells? |
|
Definition
central memory T cells live in lymphoid tissue; express CCR7; activated more slowly than effector memory T cells and seem to go through a stage of similarity to effector memory T cells before becoming an effector T cell
effector memory T cells live in tissues; do not express CCR7; may be activated quickly |
|
|
Term
| Are CD4 T cells necessary for CD8 memory T cell activation? |
|
Definition
They appear to be necessary in most cases
Need MHCII to activate CD8 memory T cells |
|
|
Term
| What is immunological sin? |
|
Definition
Immunological memory is good only against the original antigen. Presence of any immunological memory against an antigen will prevent another adaptive response against that antigen.
If the pathogen mutates its gene and reinfects the host, the host can still only make antibodies to those epitopes shared with the original, limiting the effectiveness of the immune response. |
|
|
Term
| Benefits of immunological sin |
|
Definition
Prevents immunological diseases
Prevents hemolytic disease of newborn (mother is Rh negative, fetus is Rh positive) |
|
|
Term
| Memory B cells vs plasma cells |
|
Definition
Memory cells live longer than plasma
Memory cells can undergo somatic hypermutation; plasma cells cannot
Plasma cell makes and secretes antibodies |
|
|
Term
| Histology of mucous membrane |
|
Definition
1. Mucous Coat
2. Epithelium (one layer of living cells)
3. Basement Membrane
4. Lamina Propria (contains WBCs)
5. Muscle (2-3 layers) |
|
|
Term
| How does the immune tissue in the tonsils receive antigens? |
|
Definition
Antigens in saliva enter through crypts in the tonsil surface.
Stimulates IgA response. |
|
|
Term
| How is GALT different from lymph nodes/spleen? |
|
Definition
Less overall organization
More Treg than in other areas (more tolerance)
In the gut, the target of the lymph cells goes right past the lymph tissue but everywhere else the immune cells have to go to the site of the infection |
|
|
Term
|
Definition
| Afferent lymphatic vessels drain to this (from gut) |
|
|
Term
|
Definition
Organized T-cells and follicles
Found in ilium and appendix |
|
|
Term
| What are M cells? What is their function? |
|
Definition
Thin membranous area in intestinal wall
Trancytose antigens from intestine to Peyer's patches(active transport)
No mucous layer |
|
|
Term
| How do DCs get antigen from the intestine (without any go-between cell) |
|
Definition
| cell processes can reach through the epithelium across tight junctions. DC forms tight junctions with surrounding epithelial cells |
|
|
Term
| Non-organized immune cells in intestinal wall |
|
Definition
Many effector T cells (activated T cells and plasma cells)
CD8 T cells
Dendritic cells (in lamina propria, reach through epithelium)
Macrophages, T cells, B cells, Mast cells |
|
|
Term
| Immune cells of lamina propria (in gut) |
|
Definition
Plasma cells (IgA producing)
Memory T cells
Activated Th and Tc cells
NOT neutrophils
Dendritic cells
Macrophages
Mast cells |
|
|
Term
| T cell circulation (mucosal immune system) |
|
Definition
| Bloodstream-->Peyer's Cell-->DC for activation-->efferent lymphatic-->bloodstream-->intestines |
|
|
Term
| T cells that are activated in the gut make their way back to the gut after draining to mesenteric lymph nodes. How is this accomplished? |
|
Definition
| T cells activated in the gut have a particular adhesion molecule on their surface that targets them back to the gut. |
|
|
Term
| Do activated T cells remain in the area where they were activated? |
|
Definition
| No, they travel to all mucosal membranes |
|
|
Term
| How does IgA move across the epithlium? |
|
Definition
| After secretion in the lamina propria by the plasma cell, IgA is moved across the epithelium by trancytosis |
|
|
Term
| Once IgA is on the apical side of the epithelium, what does it do? |
|
Definition
| IgA binds to the mucous which traps pathogens |
|
|
Term
| Does IgA only bind pathogens on the apical side of the epithelium? |
|
Definition
No, it also can:
1. Bind to and transport out toxins in the lamina propria
2. Bind to and transport out endosomal antigens |
|
|
Term
| If IgA is missing, is there anything that can be used in its place? |
|
Definition
|
|
Term
| What is the significance of hepatobiliary route? |
|
Definition
Alternative means for transportation of IgA into gut (chickens, rabbits, mice, not humans)
IgA transported via hepatic portal vein to liver and into the bile where it is carried to the gall bladder and squirted into the intestine with the bile
Gets the IgA into the earlier part of the intestine (Peyer's patches are in the ilium) |
|
|
Term
| Type a intraepithelial lymphocytes |
|
Definition
| Tc cells induce apoptosis in cells exposed to commonly ingested pathogens |
|
|
Term
| Type b intraepithelial lymphocytes |
|
Definition
Stressed epithelial cells produce an MHC-like molecule that does not bind to TCR but to another receptor on the cell surface; this tells the Tc cell that the target cell is stressedso it induces apoptosis
No match needed between antigen and TCR |
|
|
Term
| What is unique about CD8 cells in the gut? |
|
Definition
|
|
Term
|
Definition
Both recognize PAMPs (Pathogen Associated Molecular Patterns)
TLR are in the membrane
NOD free floating in the cytosol |
|
|
Term
| Which receptor, TLR or NOD, recognize a pathogen that is in an endosome? |
|
Definition
| TLR because it is on the plasma membrane, which is what forms the endosome |
|
|
Term
| What happens when TLR or NOD binds a pathogen? |
|
Definition
| Signal for the production of a transcription factor that turns on NF-KB (which is a pro-inflammatory TF) |
|
|
Term
| What do intracellular bacteria use to move around in epithelial cells or between cells? |
|
Definition
| They use the host cell's actin to move around and can use it to propel them to a neighboring cell |
|
|
Term
| Three ways Salmonella typhimurium can infect |
|
Definition
1. Kills M cells and lives inside macrophages
2. Infects epithelial cells
3. Infects sampling DCs |
|
|
Term
| How does Shigella flexneri infect? |
|
Definition
1. It infects the lamina propria through M cells and then enters epithelial cells from the basal side
3. Uses actin polymerization to spread from cell to cell
2. Epithelial cells recognize LPS (by NOD) and send out inflammatory molecules |
|
|
Term
|
Definition
?
Appears to say that if a protein is fed to (mouse) and the mucosal immune system encounters it, that an adjuvant shot later will not cause any immune reaction |
|
|
Term
| What sort of relationship do commensal bacteria have with their host? |
|
Definition
| Symbiotic (good for each other) |
|
|
Term
| Is there an immune response to commensal bacteria? |
|
Definition
Yes: IgA holds the commensal bacteria in the mucous
There is an immune response, therefore, but not an inflammatory one |
|
|
Term
| What are some of the benefits of commensal bacteria? |
|
Definition
| 1. Compete with pathogens for nutrition/resources |
|
|
Term
| Differentiation between 'good' and 'bad' bacteria |
|
Definition
Commensal bacteria does not break forcefully across the epithelium like pathogens do. Received either by DCs or M-cells. DCs give weak co-stimulatory signals to T cells so they differneiate into Treg cells
Pathogens invades by breaking across epithelium forcefully. Activated DC gives strong co-stimulatory signals to CD4 T cells so they differentiate into effector Th1 or Th2 cells. |
|
|
Term
| How do commensal bacteria avoid causing inflammation? |
|
Definition
Two methods:
1. Block inflammatory molecule transcription by activating a protein that removes NF-KB from the nucleus
2. Block degradation of phosphorylated IkB (which, when bound to NF-KB keeps it deactivated) |
|
|
Term
| Mechanism of activation of NF-KB |
|
Definition
Pathogen recognition by TLR signals for IKK activation.
IKK phosphorylates IkB, which when bound to NF-KB keeps it deactivated
Activated IkB leaves NF-KB, activating it |
|
|
Term
| Helminth infections in gut: what reacts? |
|
Definition
| Th2 activated which activates IgE which binds to and activates Mast Cells |
|
|
Term
| What makes Th2 the better helminth response than Th1? |
|
Definition
Th1 causes more inflammation
Th2 secretes IL-13 which induces epithelial repair; attracts eosinophils; causes B cells to make IgE; mast cells recruited by IL-3, IL-9
Th1 recruits macrophages, complement-fixing antibodies |
|
|
Term
| How does S pneumoniae evade the immune system? |
|
Definition
| Can make many different polysaccharide coats. With each new infection is the potential for a new coat, so that the host has to undergo the whole process to get to adaptive immunity instead of relying on immunological memory |
|
|
Term
| Antigenic drift vs antigenic shift |
|
Definition
Drift: antigen mutates so that it is not recognized by hosts
Shift: virus recombines in host cell so that the host has two versions of its antigen |
|
|
Term
| What are trypanosomes and why are they a problem? |
|
Definition
Cause African Sleeping Sickness
Has many different possible (variable) glycoprotein coats, but only one is expressed at a time.
Causes 'cycles' of illness as the trypanosome changes its genome and coat so that the immune system has to mount an entirely new response to it |
|
|
Term
| What do latent viruses do? Example? |
|
Definition
| Hide out in host neurons. Herpes |
|
|
Term
| Why is herpes able to hide in neurons? |
|
Definition
| Neurons display little MHC I, so Tc cells don't recognize the pathogen presence |
|
|
Term
| Herpes simplex causes what and hides where? |
|
Definition
| Causes cold sores and hides in the trigeminal ganglion |
|
|
Term
| Herpes zoster causes what and hides where? |
|
Definition
| Causes chickenpox and hides in the dorsal root ganglia |
|
|
Term
| What is shingles and what causes it? |
|
Definition
Shingles is caused by the reappearance of herpes zoster in the dermatome of an infected nerve
Often caused by stress |
|
|
Term
| How does M. tuberculosis subvert the immune response? |
|
Definition
| M tuberculosis prevents formation of the phagolysosome |
|
|
Term
| How does L monocytogenes subvert the immune response? |
|
Definition
| L monocytogenes can break out of the phagolysosome |
|
|
Term
| How does T pallidum subvert the immune response? |
|
Definition
| T pallidum coats itself with host proteins |
|
|
Term
| 3 common ways viruses subvert the immune response |
|
Definition
1. turn off MHCI/TAP
2. make proteins that inhibit complement
3. alter cytokine production |
|
|
Term
| What are bacterial superagents and what do they cause? |
|
Definition
exotoxins
Cause CD4+ T cells to bind to MHC II they normally wouldn't bind
This leads to massive non-specific T-cell activation
Overactivation of T cells |
|
|
Term
| Micobacterium leprae is a single bacterial species that can cause two diseases. What causes the difference in presentation? |
|
Definition
If Th1 responds to M. leprae, and macrophages and Tc are activated, M leprae presents as the milder tuberculosis.
If Th2 responds, M leprae can multiply uninhibited in the macrophages, leading to the more serious leprosy |
|
|
Term
| Are most immunodeficiency diseases genetic or contracted? |
|
Definition
| Most are genetic (mutations in genes such as those that encode for: MHC, TAP, RAG, AID, CD40, etc.,) |
|
|
Term
| What sort of infections are often seen in people with a T cell deficiency? |
|
Definition
|
|
Term
| What sort of infections are often seen in people who have a B-cell, phagocytosis, or complement deficiency? |
|
Definition
Pyogenic infection
(Pyogenic means pus-forming and refers to the gylcoprotein "slime coat" of some bacteria |
|
|
Term
| What is a good type of immune response against a pyogenic infection? |
|
Definition
| Compelement is probably the best way to defend against a pyogenic infection. Antibodies cannot bind slime coats. |
|
|
Term
| What ix X-linked agammaglobulinemia and whom does it affect? |
|
Definition
A protein required for intracellular BCR signalling is missing
The cell dies in the pre-B cell phase
No antibodies in blood
Affects men more than women as it is on the sex gene. Women who are heterogenic for this trait can compensate with their normal allele. |
|
|
Term
| X-linked Hyper-IgM syndrome |
|
Definition
No germinal centers in lymph nodes
Both Th1 andTh2 are missing and B cells cannot switch types |
|
|
Term
| What causes transient antibody deficiency? |
|
Definition
In normal infants, this is simply caused by the mother's IgG wearing off.
Between 3 months and a year, the mother's IgG, IgE, and IgA (unless breastfead), levels decrease in the infant and it must begin to make its own |
|
|
Term
| Complement deficieny in the classical pathway. What is missing and what does this cause? |
|
Definition
| C1, C2, or C4 may be missing. Immune complexes cannot be cleared and may get stuck in capillaries, particularly those in the kidney glomeruli. |
|
|
Term
| Complement deficiency in the lectin pathway. What is missing and what does this cause? |
|
Definition
MBL, C2, or C4 may be missing. This allows bacterial infections.
More of a problem for children, as immunological memory develops with age to compensate for the absence of the lectin pathway |
|
|
Term
| About how much of the population is missing MBL (Mannose binding lectin)? |
|
Definition
| about 5% This leads to a deficiency in the lectin-binding pathway of complement |
|
|
Term
| Complement deficiency in the alternative pathway. What is missing and what does this cause? |
|
Definition
Factor D or P
leads to infection with pyogenic (slime coat) bacteria |
|
|
Term
| C3 deficiency. This causes problems with which pathways of complement? |
|
Definition
In all pathways (C3 convertase)
pyogenic bacteria infection |
|
|
Term
| Problems with the membrane attack complex? Which are the proteins that may be affected? |
|
Definition
C5b, C6, C7, C8, or C9
The membrane attack complex cannot therefore be formed, so lysis of pathogen by complement is not possible. (Complement is the best for killing pyogenic (coated with saccharides) bacteria, so this encourages infection by pyogenic baceria) |
|
|
Term
| Severe congenital neutropenia |
|
Definition
| low levels of neutrophils |
|
|
Term
| Leukocyte adhesion deficiency |
|
Definition
cell adhesion molecule is missing
phagocytes cannot migrate to infected tissue |
|
|
Term
| Chronic granulomatous disease |
|
Definition
| phagocytes cannot kill ingested pathogens and so make granulomas |
|
|
Term
| What is the mutation in X-linked SCID and what receptors are missing? |
|
Definition
Mutation in shared gamma chain
Missing receptors for IL2,4,7 |
|
|
Term
| What is the mutation in Omenn syndrome and what does this result in? |
|
Definition
Mutations in RAG genes
Some overactive T cells form--no B cells |
|
|
Term
| What is mutated in Bare lymphocyte syndrome and what does this result in? |
|
Definition
Missing MHC II
No CD4 cells and since CD4 cells are needed for B cell activation, there are little/no antibodies produced |
|
|
Term
| Bone marrow transplants can help to alleviate immunodeficiency. What are qualifications for a successful transplant? |
|
Definition
| Donor and recipient must have at least a partial MHC match |
|
|
Term
| Graft vs host disease and graft failure. What are they? Differences? |
|
Definition
graft vs host: Naive T cells from graft become activated against host cells
graft failure: Host T cells become activated against donor stem cells |
|
|
Term
| AIDS patients are very susceptible to diseases and infections. Two cancers in particular were mentioned in lecture: what are they? |
|
Definition
| Kaposi's Sarcoma and B-cell cancer |
|
|
Term
|
Definition
| RNA is protected by a nucleocapsid--which is a protein coat. Proteases, reverse transcriptase, other proteins, and then the phospholipid bilayer membrane. GP120 is a fusion molecule on the membrane surface. |
|
|
Term
| What is the fusion molecule on the surface of HIV? |
|
Definition
|
|
Term
| What were the first anti-HIV drugs and how did they work? |
|
Definition
anti-proteases
prevented the HIV from making the protein capsulare around its RNA |
|
|
Term
|
Definition
1. Virus binds CD4 and a coreceptor
a. CD4 is present on DCs, macs, and T-cells. Co-receptor different between phagocytes and lymphocytes.
2. Reverse transcriptase makes DNA from the RNA
3. DNA provirus inserts into host cell's genome
4. T-cell activation induces transcription of HIV: begins with Tat and Rev, which prepare the host cell for the full-scale viral synthesis
5. Early proteins amplify transcription and activate all proteins.
6. New virus emerges from cell |
|
|
Term
| HIV binds to its target cell by binding CD4 and a coreceptor. Coreceptor details? |
|
Definition
In phagocytic cells (Dendritic cells and macrophages) coreceptor is CCR5
In CD4+ T cells, coreceptor is CXCR4 |
|
|
Term
| HIV coreceptor specificity |
|
Definition
| HIV is specific for either CCR5 or CXCR4 or both. If it is specific for CCR5, it is M-tropic (M for macrophage) and if it is specific for CXCR4, it is T-tropic (T for T cell) |
|
|
Term
| Is the initial HIV infection typically M-tropic or T-tropic? |
|
Definition
| Often, M-tropic. HIV usually enters in areas rich with mucous membrane, and so it encounter the mucosal immune system first. There it infects DCs and macrophages that carry it to lymph nodes and CD4+ T cells. |
|
|
Term
| How does HIV get from M-tropic to T-tropic? |
|
Definition
| HIV is capable of rapid mutation, so it mutates several times on its way to the lymph nodes while inside its CD4 phagocyte. |
|
|
Term
| 4 phases of HIV infection |
|
Definition
1. Initial infection: flu-like symptoms; 2-6 weeks
2. Asymptomatic phase: mean of 10 years
3. Symptomatic phase
4. Aids |
|
|
Term
| In which age group does HIV progress more quickly? |
|
Definition
| In the old (and v. young) |
|
|
Term
|
Definition
Highly active antiretroviral therapy
Combination therapy against HIV (typically 3-4 different drugs/inhibitors)
Idea is that if enough places on HIV are being targeted, it cannot easily mutate all 3/4 places in one division in order to make it to the next step |
|
|
Term
| How quickly does HAART work? |
|
Definition
| Within the first two days of HAART treatment, the viral load halves |
|
|
Term
| 4 common types of antiretroviral drugs (HIV)(against 4 things) |
|
Definition
1. Fusion: inhibition of GP120
2. Replication: inhibition of reverse transcriptase
3. Integration
4. Protease inhibitors |
|
|
