Autoimmunity 2 Flashcards
Name the 5 main functional classes of cytokines.
- mediate innate immunity 2. regulate lymphocytes 3. activate inflammatory cells 4. affect leukocyte movement 5. Stimulate hematopoiesis
What is the action of IL-12?
initiates the TH1 pathway
What is the action of IL-4?
initiates the TH2 pathway recruits eosinophils and promotes IgE
What is th action of IL-17?
initates TH17 pathway and recuriting neutrophils
What is the action of TGF-B?
down-regulates the immune response
What is the action of IL-5?
activates eosinophils
What important proteins are encoded on chromosome 6?
chromosome 6 encode MHC/HLA proteins (class I and II invovled in antigen presentation)
Describe the location and structure of class I MHC.
present on all nucleated cells and platelets, consist of a polymorphic a-chain linked to B2-microglobulin (loci HLA-A,B and C) and function to display all proteins made in the cell
How do class MHC I cells interact with other cells?
CD8+ cells are class MHC I restricted and NK cells kill cells with abnormal or low class I MHC
Describe the location and structure of class II MHC.
present on APCs, coded by HLA D (DP, DQ and DR) polymorphic a and B chains bind antigens
What type of cells do MHC II class interact with?
CD4+ helper T-cells ar class II MHC restricted
Name 4 diseases that show a strong association with specifc HLA molecules
ankylosing spondylitis (HLA B27), rheumatoid arthritis (DR4), hereditary hemochromatosis (HLA-A), 21-hydroxylase deficiency (HLSBw47)
List the 4 broad headings of autoimmune disorders.
hypersensitivity reactions, autoimmune diseases, immune deficiency, amyloidosis
What 3 general catagories of substances can trigger a hypersensitivity repsonse?
exogenous antigens, homologous substances and autologous substances
What is the cause and result of a type I hypersentivity?
cause: antigen binds and cross links bound IgE on mast cells; results in variable rxn between hives and anaphylaxis
Describe the 2 phases of type I hypersensitivity.
phase 1 is the immediate release of histamine that cuases vasodilation, edema and SM contraction; phase 2 cytokine release occurs 2-24hrs with infiltrate of eos, polys, basos and CD4+ which often cause tissue damage
Explain the steps in the activation and degranulation of mast cells.
mast cells express Fc receptors that can bind IgE, antigen binds two adjacent surface IgE antibodies, cross linking activates the cell and causes degranulation
Contrast primary and secondary mediators released in a type I hypersensitivity rxn.
primary: histamine, proteases, chemotactic factors ; secondary: cytokines and products of membrane phopholipids
Besides cross linked IgE, name 5 stimui hat can act as mast cell activators.
complement anaphylatoxins (C5a/C3a), macrophage derived cytokines (IL-8), drugs (codeine/morphine), bee venom, physical stimuli (heat, cold, sunlight)
Describe the sensitization process that mast cells undergo during first antigen exposure.
APC present the antigen to CD4+ cell which causes cytokine release and TH differentiation of that T cell to TH2, these cells produce more cyotkines driving the type 1 rxn (IL-4 IgE, TH2 devo; IL-5 eos; IL-13 IgE)
What are the most fatal parts of anaphylactic shock?
laryngeal edema, bronchoconstriction, drop in BP
What mediates a type II hypersensitivity rxn?
antibodies
Summarize the classes of antibodies using MADGE.
IgM (Macro), IgA (malt-mucousal), IgD (surface of na•ve B-cells), IgG (gestation) IgE (eosinophil- AAA)
Name the 4 major mechanisms of type II hypersensitivity.
opsonization/phagocytosis, ADCC, complement/Fc mediated inflammation and antibody mediated cellular dysfunction
What are the mediator and effector cell types in a type II hypersensitivty reaction?
mediator: plasma cell produces antibody, effector: complement proteins and phagocytic cells
Describe the process of antibody-dependent cellular cytotoxicity.
effector cells (with Fc receptor) kill target cells with IgG on the surface (does not invovle phagocytosis ro complement)
Give several examples of type II hypersensitivity reactions.
transfusion rxns. Erythroblastosis fetalis, autoimmune hemolytic anemia
What is the basis of complement and Fc mediated inflammation (type II hypersensitivity)?
antibodies are deposited in the extracellular tissues/matrix and IgG of IgM activate the complement causing inflammation (ie. Good pasture Syndrome where basement membrane is the target)
