Term
| three ways super antigens differ from conventional peptide antigens |
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Definition
1) super antigens can react with MHC Class II in unprocessed form (do not need to be taken up)
2) react on the "side" of the class II/TCR complex, not in the normal
3) elicit an immediate polyclonal response in T cells |
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Term
| how does super antigen binding to the side of TCR/MHCII complex activate T-cells? |
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Definition
| - tricks the T-cell into thinking its bound to its appropriate antigen |
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Term
What causes "cytokine storm"
What two organs are affected the most?
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Definition
- massive release of vasoactive and proinflammatory cytokines
- liver and kideny |
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Term
| What dictates the intensity of the response of cytokine storm? |
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Definition
| polymorphisms in the host's MHC II and probably TNF gene |
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Term
| What type of pathogen is more likely to cause cytokine storm? |
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Definition
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Term
| Why is it adventageous for a pathogen to activate T-cells? |
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Definition
| - the activated immune effector cells undergo widespread apoptosis and lose their abilty to react in a regulated fashion |
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Term
| What type of response is associated with cytokine storm? |
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Definition
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Term
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Definition
1) INF-γ activates macrophages
2) macrophages release TNF α
3) loss of endothelial integrity, decreased vascular resistance
= shock |
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Term
Which cytokine is responsible for the shock of toxic shock?
What does it do? |
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Definition
TNF-α
- loss of endothelial integrity, decreased vascular resistance |
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Term
| Ways viruses can use MHC to their advantage |
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Definition
1) interfering iwth the methods by which Class I transports antigen to the sruface for CD8 cell presentation
2) Preventing cytokine regulation of MHC Classs I and II antigens. |
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Term
Structure of cytokine receptors?
What happens after binding (4 steps) |
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Definition
- each one has two chains, the cytoplasmic one binds Janus Kinases, and the extracellular domains bind cytokines
- cytokines bind and their receptors dimerize and the Janus kinases can then phosphorylate eachother.
- transcription factors binds to the phosphorylated cytoplasmic domains and can be activated by the Janus Kinases.
- these then go into the nucleus to initiate gene transcription |
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Term
| How can bacteria and virus's prevent activation of innate immunity? |
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Definition
| - both can downregulate TLR receptors. |
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Term
| How can virus and bacteria deal with Tregs? |
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Definition
| induce production of CD4,25 Tregs that will block the immune system from reacting to them |
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Term
Types of cells that virus and bacteria can use to prevent appropriate immune response to them?
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Definition
- CD4,25 - recruit them to block immune response
- Suppress DC function
- NK cells - use genes to inhibit them
- CD4 - can switch on Th1 system and prevent IgE production |
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Term
| monozygotic twins vs. dizygotic with respect to autoimmune diseases |
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Definition
| - monozygotic twins are more likely to share an auto immune disease than dizygotic twins |
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Term
what type of hormones modulate susceptibility to auto immune diseases?
What is this evidence for? |
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Definition
- sex hormones modulate susceptibility
- gender plays a role - and it does, a disproportionate amount of females have autoimmune diseases. |
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Term
| Three more indicators for the gender inbalance of autoimmune diseases |
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Definition
1) females have more vigorous Th 1 respsonses
2) Females have more vigorous antibody responses
3) Estrogen and progesterone have concentration dependent effectson Th1, Th2, Treg and inflammatory responses. |
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Term
| Two mechanisms for establishing central tolerance |
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Definition
1) negative selection - destruction to T-cells that bind too strongly to self antigens
2) AIRE - T-cells in corticomedullary junctions are presented with peripheral antigen by thymic endothelial cells |
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Term
| What happens in AIRE process to T-cells that react with AIRE self antigens? |
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Definition
- conversion to CD4, 25 regulatroy cells.
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Term
What cytokine modulates Tregs?
What does it do? |
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Definition
- Il2
- survival and proliferation of Tregs |
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Term
| Where else is AIRE expressed? what does this imply? |
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Definition
- AIRE is expressed in peripheral lymphoid tissue like the gut
- suggests taht AIRE may have a regional role in tolerance enforcement during an immune reaction |
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Term
What is a major site for peripheral tolerance?
What dictates it? |
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Definition
- gut
- TLR and DC function |
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Term
| How are we able to coexist with comensal bacteria? |
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Definition
| - bacteria in the gut mucosa activate TLR systems on T cells and DC's that promote tolerance rather than innate immunity to their PAMPs |
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Term
| Deficiencies that will cause autoimmune disease |
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Definition
1) no AIRE
2) loss of FoxP3
3) defect in IL2
4) over or underexpression of TLR |
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Term
What Th reaction has been implicated in autoimmune disease?
What does blocking INF-gamma end up being unsuccessful in treating autoimmune diseases? |
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Definition
- Th17
- cannot block INF-gamma and TIMMI all together because INF-gamma inhibits IL17. |
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Term
| Steps in Th17 autoimmunity |
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Definition
1) DC has Il17-stimulating TLR activated
2) DC presents this to a Th0 while simultaneously secreting IL17, IL23 and TGF-β
3) Th0->Th17
4) Th17 cell then secretes IL17 |
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Term
| What does Th17 secretion of IL 17 activate? |
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Definition
1) macrophages
2) endothelial changes
3) Netorphils
4) osteoblasts
5) chondrocytes |
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Term
| Three things that will inhibit Th17 response |
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Definition
1) Th1/INF-γ
2) Th2/IL-4
3) Tregs |
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Term
| What conditions will favor Th17 and production of IL17, Il23 and TGF-β |
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Definition
- viral or hormonal suppression of Tregs that would allow brekaout of Th17 clones
- abnormal TLR signaling that trigers DC to produce IL6 and 23 instead of IL 12 or 4. |
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Term
| Five ways viruses have been implicated in Diabetes Type I autoimmunity |
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Definition
1) directly infect beta cells and initiate a CD8 attack against them
2) Exhibit antigens that mimic beta cell antigens so CD8's mistakenly also attack beta cells
3) Infect non-Beta sites of pancreas and incite enough collateral dammage during the immune response to destroy beta cells
4) Unmask partial AIRE defects that are linked to loss of tolerance for beta cells
5) Activate CD8 cells with dual antigen specificities - when CD8 cell is activated by a virus, it can develop cytotoxicity for both antigens |
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Term
| When can self reactive B cells develop? |
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Definition
| - can develop during antigen driven somatic hypermutaiton in the periphery; may synthesize antibodies that block functions of cells or accelerate cell functions by mimicking agonists or promote cytotoxic responses. |
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