Immunology Week 3 Flashcards by Allie Lockwood

Isograft vs. allograft vs. xenograft

Iso is between identical twins/inbred mice. Allo is between individuals of the same species. Xeno is between species

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What is the main target of donor reactive immune response after transplantation

Polymorphic HLA/MHC molecules are major antigen

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What destroys a transplanted organ?

alloantibodies and effector T cells after both donor and recipient APCs go to LNs

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When can alloreactive antibodies develop?

Upon exposure to alloantigens in pregnancy, blood transfusion, transplant, or cross reactivity

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Direct allorecognition

Donor APC presents donor self peptide, but is activated because of DAMPs so they go to nearest lymph node – recipient anti-donor T cells are activated, proliferate, attack graft. This is more potent than indirect (which is closer to nl immune rxn).

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Indirect allorecognition

is exact same thing as direct, but with recipient APC

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What is a DAMP

Danger-Associated-Molecular-Patterns. Can initiate and perpetuate immune response in the noninfectious inflammatory response. Released from ischemic tissues

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What does calcineurian do?

Helps activate IL-2 gene, which stimulates T cell differentiation and proliferation

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What does CD28 bind to?

B7, costimulation

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DTH

delayed type hypersensitivity, type IV. Macrophage activation, chemoattraction, TNF released. May account for acute cellular rejection.

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What is the FAS ligand?

Part of the tumor necrosis factor TNF family. Induces apoptosis when bound to receptor. both TMs

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How do you diagnose acute cellular rejection?

Decreased kidney fxn (rise in serum creatinine) - do renal biopsy. Mononuclear cells, T-cells, and macrophages predominate, but antibodies also contribute. Thought to be due to the direct pathway.

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Immunosuppression

Primarily targets T, not B cells. Nonspecific. Chronic rejection can lead to kidney fibrosis.

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How do corticosteroids help with transplant immunity?

Block IL2 transcription

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Graft vs. Host disease

Bone marrow transplant - donor bone marrow lymphocytes can react to host/recipient cells. Causes tissue damage.

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What are some ideas for acquired immune tolerance?

“reset” immune system by depleting through chemo, let it reconstitute, may be tolerant to both donor and recipient. Also could isolate Tregs from transplant candidate, stimulate in vitro with donor antigen and expand using IL2.

What are some minor histocompatibility antigens?

H-Y (male antigens), mitochondrial proteins (MTFbeta), myosin related protein. Even if siblings have same HLA, they might mismatch in minor antigens.

Inductive vs. Effector Sites in Mucosal Immunity

Peyer’s patches, mesenteric lymph nodes, and isolated lymphoid follicles are considered inductive sites, where antigen presentation to naïve T and B cells generates an immune response on first exposure. Lamina propria are part of the effector sites of the mucosal immune system because they are comprised of memory T cells that are primed to respond to re-exposure to the antigen recognized by their T cell receptor.

What are some mechanisms of tolerance induction in the gut?

Systemic suppression of IgG and IgM,
High levels of TGF-β in the environment, and
Suppressive CD8+ T cells.

To prevent against unwanted inflammation the gut is populated by T cells that are regulatory or suppressive in nature secreting cytokines such as TGF-β or IL-10. CD4+ T cells that respond to enteric bacteria are not tolerance inducing, and are in fact a problem in excessive gut inflammation in disease.

What is a hybridoma?

B cell HYBRIDOMA is an immortalized B cell that will endlessly make a single antibody
of single specificity. Fuse with tumor cell line.

ELISA

enzyme linked immune sorbent assay. Use 2 antibodies that bind to different epitopes, 1 Ab is enzyme-linked so you can visualize. Can be like a sandwich or used to determine whether someone has antibodies to, say HIV, in their blood.

How do you diagnose HIV exposure?

p24 antigen detectable after day 19ish but then disappears, HIV antibody detectable after day 22ish and sticks around

Why do you get false positives from HIV tests?

Antibodies may react to non-HIV cellular proteins because you’re using HIV-infected human cells that produce normal and HIV proteins - someone with an autoimmune disease would have this problem. Must confirm with Immunoblot (western blot)

Axes of flow cytometry graph

Horizontal is size, vertical is granularity

How can flow cytometry be used to diagnose types of leukemia?

Stain peripheral blood or bone marrow cells for T or B cell antigen

What is multiple myeloma? How do you dx it?

malignant clonal expansion of plasma cells that produce a monoclonal IgG light chain (kappa OR lambda chain, not both). Do flow cytometry to see whether a TON of kappa or lambda chain is produced to see what type of cell is affected (the one producing the most is the one affected).

Immunohistochemistry

similar to immunofluorescence, but uses enzyme-linked Ab. Enzyme causes color change and precipitation of colored reagent at site of rxn so you can see cell types without destroying nl tissue architecture.

What is ELISPOT

Detects cytokine production by individual antigen-reactive T cells, Uses anti-cytokine Abs, one enzyme linked so you can see SPOTs if cytokines are secreted. Quantifies frequency of antigen specific T cells.

What is the largest lymphoid organ?

Technically the intestine because of large amount of lymphocytes in loose connective tissue stroma

What are some unique aspects of mucosal immunity?

Oral tolerance, controlled inflammation, suppression of IgG and IgM while sIgA is produced, and unique cell populations like IELs and LPLs that have distinct activation requirements.

What does sIgA do?

Inhibits adhesion of viruses and bacteria to epithelium

Inflammatory Bowel Disease

dysregulated mucosal immune response (CD4 T cells) to enteric bacterial antigens in a genetically susceptible host. IL23 produced by macros and dentritic cells in gut – triggers expression of IL17 and IL22 which recruit neutrophils and antibacterial peptides from paneth cells. If ANY of these molecules is produced in large amounts, it’s bad – damage from neutrophils.

What is a Peyer's Patch?

biggest lymphoid structures in GI tracts, B cells, T cells, and dendritic cells. Have M cells. Picks up antigen and presents to macrophages. Can initiate immune response there in Peyer’s patch.

What do paneth cells produce?

antimicrobials

Crohn's

can happen anywhere in gut, but is localized. dense inflammatory infiltrates – can be whole width of wall of gut. Can form large granulomas. Requires intervention by blocking TNF, which is downstream of IFNgamma producing cells.

What are innate lymphoid cells?

Innate lymphoid cells also a source of cytokines, cousins of T cells with no TCRs, don’t go to thymus. Mostly live in mucosal tissues. Relevant ones are ILC3

Celiac disease

- IL15 and INFgamma produced - Flattened villi in upper small intestine, poor ADEK and fat absorption - Genetic - Abdmnl bloating - Tx remove gluten, crypts reform

Food allergy

- not always associated with eosinophilia - freq associated with urticarial (skin) - elevated tryptase and IgE