Term
| Go through the endogenous pathway of antigen presentation; what uses it, what size antigens, what are the antigens from, and all the components involved? |
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Definition
-Viral proteins (endogenous) are chopped up by proteosomes to about 8-10AA's in length (LMP-2&7 encode proteosome)
-They are transported through TAP (transporter for antigen processing) into the ER to MHC I molecules (associated w tap1&2 proteins)
-The loaded up MHC I molecules are then exocytosed out of the RER, through the golgi, and to the membrane
-Remember, all cells can use this type signaling |
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Term
| Go through the exogenous pathway of antigen presentation; what uses it, what size antigens, what are the antigens from, and all the components involved? |
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Definition
-Antigen from outside the cell (bacteria, etc.) is phagocytosed into endosomes and degraded by lysosomal enzymes (in phagolysosomes) to 10 to 20 AAs in length
-Meanwhile, an MHC II molecules is produced in the rough ER with its α and β chains, and in addition, an INVARIANT CHAIN is also produced, which blocks the binding groove (later by CLIP)
-The blocked MHC II molecule then buds off the RER, goes through the golgi, and eventually fuses with the phagolysosome
-The invariant chain is selectively degraded, thus allowing the exogenous antigen to fuse with the MHC II (requires action of HLA-DM)
-The loaded MHC II is then exocytosed to the membrane |
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Term
| What are the adherence molecules on the T cell vs macrophage during T cell activation? |
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Definition
-T cell; TCR, CD2 (an IgCAM), & LFA-1 (an integrin)
-Mac; MHC II, LFA-3 (an integrin), & ICAM-1 (an IgCAM)
-In addition CD4/CD8 functions in binding to MHC II/I and in signal transduction (along with CD3) |
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Term
| What are the costimulatory molecules for T cell activation on T cell vs macrophage? What encourages this interaction? What is the result of the different interactions? |
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Definition
-T cell; CD4/8, CD28
-Macrophage; MHC II/I, B7
-The B7 molecule is upregulated by TLR (toll-like receptor) interactions with pathogens
-The B7 molecule stimulates the macrophage to release IL-1*, IL-6, & TNF-α (proinflammatory molecules)
-These in turn cause upregulation of IL-2 secretion and receptor expression which finally leads to T-cell proliferation
-The CD4/8, along with CD3 + TCR, leads to T cell activation and secretion of IFN-γ (*activates macrophage*) |
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Term
| Run through the cytokines produced by the T cells vs macrophages, what chain of events stimulates their production, and what do they do? |
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Definition
Macrophage; IL-1*, IL-6, TNF-α
-These are stimulated by pathogen--->TLR--->B7 (binds CD28--->secretion
-Their function (other than inflammation) is to stimulate IL-2 and IL-2 receptor production, leading to T cell proliferation
T cell; IFN-γ, IL-2
-The IFN-γ has release stimulated by T cell activation (from TCR and CD4/8 binding to the MHC). This is the activator of macrophages that turns them into "killing machines"
-The IL-2 is stimulated mostly by IL-1 and leads to T cell proliferation |
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Term
| Where do we find CD2, what class of molecule is it, and what does it bind to? |
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Definition
-On the T cell
-It is an IgCAM
-CD2 binds to LFA-3 (an integrin) |
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Term
| Where do we find CD28, and what does it bind to? |
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Definition
-It is on the T cell (probably others too)
-It binds to B7 (leads to macrophage cytokines) |
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Term
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Definition
| -It is an autocrine cytokine causing proliferation of T cells |
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Term
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Definition
-Produced by activated TH1 cells to activate macrophages
-Also produced by NK cells |
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Term
| What is a superantigen? What does this cause? Molecules responsible? What bacteria produce these? |
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Definition
-They cross link TCR with MHC II molecules without using the antigen specific binding sites (bind to β-TCR chain)
-This will lead to polyclonal activation of TH cells, over-production of IFN-γ, over-activation of macrophages, over-expression of proinflammitory molecules (IL-1, IL-6, & TNF-α), and ultimately, toxic shock
-Common bacteria producing these are staph & strep (staph makes toxic shock syndrome toxin-1) |
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Term
| What are the overall functions of TH1 and TH2 cells? |
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Definition
-TH1 cells handle cell mediated response (i.e. they activate macrophages and CTLs)
-TH2 cells do humoral (i.e. activate B cells) |
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Term
| What molecules are responsible for TH0 cell differentiation to TH1 and TH2 cells? |
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Definition
-TH1 cells are created when there is IL-12 or IFN-γ around
-IL-12 is from macrophages
-IFN-γ is from NK or already active TH2 cells
-In other words, TH1 cells are activated when the innate system has been activated
-TH2 cells are made from high levels of IL-4
-IL-4 is initially made by TH0 cells in higher and higher amounts as they do not receive signals from innate cells
-After activation, TH2 cells produce IL-4 in high amounts |
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Term
| After differentiation, what do TH1 and TH2 cells produce. Which are inhibitory to the alternate pathway. What do those cytokines do? |
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Definition
TH1 cells produce;
-IFN-γ: activate macrophages and more TH1 cells, inhibits TH2 cells
-IL-2: T cell proliferation (esp. CTL)
-TNF-β: proinflammatory (cell mediated cell stimulation)
TH2 cells produce;
-IL-4,5,6,10, & 13: 4-6 activate B cells, 4 & 10 inhibit TH1 differentiation, 4 calls for more TH2 cells
-TGF-β: Call for TH0---->THreg&17
-notice that both produce cytokines to up-regulate themselves and down regulate the other pathway |
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Term
| What are THreg cells? What identifies them? What is their overall function? What calls for them? |
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Definition
-They are one of two minor classes of TH cells
-They have CD25 as a marker and produce FoxP3
-They secrete anti-inflammatory cytokines such as IL-10 and are critical in PREVENTING AUTOIMMUNITY
-Remember, IL-10 inhibits TH1 cells
-TGF-β (transforming growth factor) dictates their production (comes from TH2 cells) |
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Term
| What are TH17 cells? What identifies them and what do they produce? What have they been associated with? What calls for them? |
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Definition
-They are one of two minor classes of TH cells
-They are identified by transcription factor RORgammat and by their production of proinflammatory cytokine IL-17
-They have been associated with tissue damage in autoimmune diseases
-TGF-β + IL-6 dictates their production (come from TH2 cells) |
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Term
| What makes IL-12 and what does it do? |
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Definition
-Produced by macrophages
-Takes TH0----> TH1 |
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Term
| What is the difference between tuberculoid and lepromatous leprosy? How are each stimulated? What clinical finding other than appearance differentiates the two? |
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Definition
-Tuberculoid is much less severe that lepromatous, although it still leads to some skin damage from rashes
-Tuberculoid results from the cell mediated approach where granuloma formation is used to eradicate the bac.
-Lepromatous ensues when humoral immunity is stimulated. Ineffective antibodies are produced and the bac. is left to reproduce unchecked in macrophages leading to disfiguring infections
-With lepromatous, you often get hypergammaglobulinemia (from lots of Igs)
-Remember that humoral and cell mediated both inhibit the other and encourage themselves, so once the body goes down the humoral path, you're screwed |
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Term
| What specifically do IL-4 and IL-5 do in terms of B cell activation? |
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Definition
-Both promote class switching
-IL-4-----> IgG & IgE
-IL-5-----> IgA |
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Term
| What kind of TH cell would people with allergies be more likely to have increased levels of? |
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Definition
-Of TH2, because they are the ones that increase humoral response
-Specifically, they make IL-4 which calls for IgE from B cells (as well as IgG) |
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Term
| CD8 interacts with what on presenting cells? What does CD4 interact with? |
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Definition
-CD8 interacts with α-3 subunit of MHC-1 receptors
-CD4 interacts with β-2 subunit of MHC-2 receptors |
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Term
| Where does the antigen bind to on MHC I vs. MHC II and about what size? |
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Definition
-MHC I; α1 and α2 make the groove for an 8-10AA peptide
-MHCII; α1 and β1 make the groove for a 10-20AA peptide |
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