Term
| What are 5 different effector functions of Macrophages and how are they activated? |
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Definition
Activation
1) NK cells and T cells activate macrophages through IFN-y release
2) Microbes activate macrophages through binding to TLRs
EFFECTOR Functions
1) Make ROIs
2) Make NO
3) Make TNF and IL-12 (stimulate NK and T-cells and vascular endothelium)
4) MMP-mediated tissue remodeling
5) Enhanced MHC-II presentation. |
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Term
| What is the second signal required by B-cells to differentiate into plasma cells in response to blood-borne pathogens? |
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Definition
| C3d from the alternate pathway binds CD21 (CR2) on B-cells, acting as a second signal. |
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Term
| What is the difference between TCRs and BCRs in terms of antigen recognition |
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Definition
1) TCRs bind 1-3 AA residues of peptides and polymorphic residues on an MHC
2) BCRs bind linear and conformational determinants of macromolecules and small chemicals. |
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Term
| What are the 2 types of sequence changes responsible for junctional diversity in V(D)J recombination in both T and B cells. |
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Definition
1) RAG-1/RAG-2 remove nucleotides from V, D and J regions at time of recombination
2) TdT takes nucleotides that are not parts of germ-line genes and adds them in randomly in "N-regions")
**Overhanging DNA sequences are filled in by "P-nucleotides."** |
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Term
| Where are the different "check-points" of B-cell maturation |
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Definition
1) Selected expansion of pre-B cells that express functional u heavy chain (mostly cytoplasmic). Completion of checkpoint 1 stops recombination of Vh (allelic exclusion) and starts VL.
2) Selected expansion of immature B cells which express functional IgM in membrane.
Negative selection occurs if mature B-cells recognize self molecules too strongly, and it can be avoided by receptor editing. |
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Term
| What are the 2 primary functions of CD40L:CD40 interactions on T-cells and APCs? |
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Definition
1) Make APCs better APCs by up-regulating B7 expression and IL-12 release
2) Required by B-cell class switching (remember HIGM1 and HIGM2 are associated with deficits in CD40L and CD40) |
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Term
| Where does T-cell mediated B-cell activation occur, and where does affinity maturation of activated B cells occur? |
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Definition
1) Mature, naive B cells meet T cells at the edge of lymphoid follicles, where CD40:CD40L interactions drive B cell proliferation
2) Activated B cells undergo AID-mediated class switching and somatic hypermutation/affinity maturation (with selection from fDCs) in the germinal centers. |
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Term
How does each of the following compounds inhibit Complement acivation?
1) DAF
2) MCP
3) Factor I
4) Factor H |
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Definition
1) Inhibits C3b:Factor B binding and C4b2a:C3b binding (both alternative and classical)
2) Factor I cofactor for C3b innactivation
3) Proteolytic cleavage of C3b
4) Dissociation of alternate pathway C3 convertase (C3Bb)
Cofactor for factor I-cleavage of C3b |
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Term
| What are the different mechanisms of peripheral T-cell tolerance? |
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Definition
1) Anergy
2) Deletion (FasL and Fas on T cells)
3) T reg suppresion |
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Term
| Which transplants do you use HLA matching for and which do you use ABO matching? |
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Definition
Blood transfusions require ABO but not HLA
Bone marrow requires HLA but not ABO
Solid organ uses both. |
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Term
| What is the triad of "GAP"? |
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Definition
1) Glomerulonephritis
2) Granulomatous infection
3) Upper/Lower respiratory tract infection |
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Term
| What disease is associated with autoantigen complementarity? |
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Definition
GAP
ANCA antibodies are produced against PR3 (Staph aureus "molecular mimicry"), and antibodies bind to these antibodies. |
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Term
| Why are Penicillin reactions considered type II hypersensitivity reactions? |
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Definition
| Penicillin can be to RBCs (hapten-like) and become immunogenic, leading to hemolytic anemia. |
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Term
| What are the different timelines of hypersensitivity reactions? |
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Definition
1) Seconds to minutes (hay fever)
2) Minutes to hours (Penicillin, hemolytic anemia
3) 8-10 days (Arthus, SLE, glomerulonephritis)
4) days (PPD, poison ivy) |
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Term
| What are the "immediate" and "late" phases of an asthmatic reaction? |
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Definition
1) immediate- 30 seconds to 30 minutes (wheal and flare rash with IgE-mediated histamine and prostaglandin release)
2) late phase- 8h (widespread edematous) |
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Term
| What are the 4 mechanisms by which tumors evade immune surveillance? |
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Definition
1) Not expressing immunogenic neo-antigens
2) Poor MHC expression
3) Antigen shedding and conformational shifting.
4) Binding of "enhancing" antibodies
5) Release of IL-10 and TGF-b
6) MDSC and Tregs, which suppress immune system |
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Term
| What is Lymphokine activated Killer (LAK) therapy? |
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Definition
| Treat patient's cells with IL-15 and IL-2 and then return them |
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Term
| What is Trastuzmamb and how is it used? |
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Definition
| anti-HER2 naked monoclonal antibody for breat cancer |
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Term
| Where is IBD most commonly found in the GI tract and why? |
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Definition
| Distal Ileum and Colon- these are sites of greatest floral diversity. |
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Term
| Why is TNF-a a target in IBD? |
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Definition
| TNF mediates inflammation by Th1 cells- Inflixumab is often given to inhibit |
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Term
| What cell types are implicated in IBD pathogenesis? |
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Definition
Th1 (TNF-a)
Th17/ IL-23 axis (PMN recruitment)
Tregs
Paneth Cells (NOD and ATG16 issues) |
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Term
| Which T-helper cell lines use IL-10? |
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Definition
1) Th2 uses it to suppress INF-y-mediated macrophages activation (Th1 suppression)
2) Tregs use it to suppress immune function. |
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Term
| Which NSAID has no inflammatory effects |
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Definition
Acetaminophen- reversible, non-competitive.
NO GI effects, but can have hepatic issues. |
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Term
| How can too much aspirin cause Tinnitus? |
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Definition
| Salycylism uncouples OxPhos in skeletal muscle, which leads to respiratory alkalosis, which compensated for by bicarbonate excretion. If CO2 is retained, uncompensated respiratory acidosis can occur. |
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Term
| What are 3 mechanisms of peripheral B cell tolerance? |
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Definition
1) Impaired migration to Germinal center because of competition
2) FasL mediated deletion
3) Germinal center deletion (somatic hypermutation might generate self-reactive B cells) |
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Term
| What are 4 ways by which neo/cryptic antigens are generated? |
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Definition
1) Apoptosis (SLE)
2) PTM (deimination of arginine to citrulline); may cause epitope spreading
3) Paraneoplastic (cross-reaction of anti-tumora antibodies)
4) Cleavage by viral proteases |
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Term
| What does IFN-y have to do with the development of autoimmunity? |
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Definition
| In addition to activating macrophages, IFN-y leads to up-regulation of MHC-II expression, which can cause over-presentation. |
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Term
| How can molecular mimicry cause autoimmune responses (provide 2 examples). |
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Definition
| Guellian Barre and Rheumatic Fever |
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Term
Which systemic autoimmune disorder is resistant to corticosteroids?
Which is resistant to TNF-a? |
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Definition
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Term
| Why should people with HLA-DR4 SE not smoke? |
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Definition
This HLA type is especially good at binding citrullinated peptides (smoking causes PADI to deiiminate arginine to citruline).
You might get RA |
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