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80 Cards in this Set
- Front
- Back
APCs
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Macrophage
Dendritic cell B cell |
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B-cell class switching
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IL-4
IL-5 IL-6 (from Th2 cell - signal 1) And CD40 receptor on B-cell binds CD40 ligand on T-cell |
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Cytotoxic T-cell activation
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MHC I protein presented (1)
IL-2 from Th cell (2) |
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Th1 cell
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Regulates cell-mediated response
Secretes Th1 cytokines: IL-2, IFN-gamma Activates macrophage & CD8 T-cell Inhibited by IL-10 |
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Th2 cell
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Regulate HUMORAL response
Secretes Th2 cytokines: IL-4, IL-5, IL-10 Helps B cells make anti-body (IgE>IgG) Inhibited by IFN-gamma (from Th1 cell) |
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What do activated lymphocytes release?
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IFN-gamma
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What do activated macrophages release?
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IL-1, TNF-alpha
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What do cytotoxic cells contain?
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Preformed proteins
-perforin - helps deliver the contents of granules into target cell -granzyme- a serine protease, activates apoptosis inside target cell -granulysin- antimicrobial, induces apoptosis |
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What's the Fab fragment?
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Antigen-binding fragment
Determines idiotype: unique antigen-binding pocket; only 1 antigenic specificity expressed per B cell |
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What's the Fc section?
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Constant
Carboxy terminal Complement binding at CH2 (IgG + IgM only) Carbohydrate side chains Determines isotype (IgM, IgD) |
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Antibody diversity is generated by:
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Four mechanisms:
1. Random "recombination" of VJ (light chain) or V(D)J (heavy chain) genes 2. Randomcombination of heavy chain with light chains. 3. Somatic hypermutation (following antigen stimulation) 4. Addition of nucleotides to DNA during "recombination" by terminal deoxynucleotidyl transferase. |
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Major B-cell functions
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Make antibody - opsonize bacteria, neutralize viruses (IgG); activate complement (IgM, IgG); sensitize mast cells (IgE)
Allergy (type I hypersensitivity): IgE Cytotoxic (type II) and immune complex (type III) hypersensitivity: IgG Hyperacute organ rejection (antibody mediated). |
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What are the T-cell functions?
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CD4 T cells help B cells make antibody and produce gamma-interferon, which activates macrophages.
CD8 T cells kill virus-infected cells directly. Delayed cell-mediated hypersensitivity (type IV) Acute & chronic organ rejection |
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Where in the thymus does positive selection occur?
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Cortex
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Where in the thymus does negative selection occur?
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Medulla
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Which cytokine stimulates Th1 and Th2 (respectively)?
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IL-12 (--> Th1)
IL-4 (--> Th2) |
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HLA-A3
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Hemachromatosis
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HLA-B27
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Psoriasis, Ankylosing Spondylitis, IBD, Reiter's Syndrome
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HLA-B8
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Grave's Disease
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HLA-DR2
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MS, Hay Fever, SLE, Goodpastures
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HLA-DR3
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DM1
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HLA-DR4
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R.A.; DM1
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HLA-DR5
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Pernicious anemia --> B12 deficiency, Hashimoto's thyroiditis
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HLA-DR7
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SeveN=
Steroid-responsive Nephrotic syndrome |
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IL-1
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Endogenous pyrogen
Secreted by Macrophages Activates Endothelium to express Adhesion molecules Vascular permeability --> Chemokines --> Leukocyte recruitment |
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IL-2
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Released by T cells (Th1)
Stimulates cytotoxic and helper T-cell production |
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IL-3
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Made by T-cells
Stimulates the growth and differentiation of Bone Marrow stem cells Like GM-CSF |
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IL-4
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Released by Th2 cells
Induces differentiation into Th2 cells Stimulates B cell growth Class switching to IgE and IgG |
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IL-5
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Released by Th2 cells
Stimulates isotype switching --> IgA Stimulates B-cell differentiation Stimulates Eosinophil growth & differentiation |
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IL-6
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Released by Macrophages
Endogenous pyrogen Causes fever & stimulates production of acute phase proteins. |
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IL-8
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Recruits neutrophils
Clean up on "aisle 8" Released by macrophages |
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IL-10
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Released by Th2 and T-reg cells
Inhibits actions of T-cells and Th1 Activates Th2 |
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TNF-alpha
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Secreted by macrophages
Mediates septic shock Activates endothelium Causes leukocyte recruitement Vascular leak |
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Interferon-gamma
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Secreted by Th1 cells
Activates macrophages & Th1 Supresses Th2 cells Antiviral & antitumor properties |
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Interferon (alpha, beta, gamma)
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Proteins that place uninfected cells in an ANTIVIRAL state
Induce the production of a ribonuclease that inhibits viral protein synthesis by degrading viral mRNA (but NOT host mRNA) |
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Alpha and Beta-interferons
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Inhibit viral protein synthesis
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Gamma interferons
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Increase MHC I and II expresssion and antigen presentation in ALL cells
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Interferons
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Activate NK cells to kill virus-infected cells
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Cell surface proteins: T-Cells
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TCR
CD-3 CD28 |
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Cell surface proteins: Th-cells
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CD4
CD40L (binds CD40 on B-cells) |
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Cell surface proteins: Tc-cells
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CD-8
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Cell-surface proteins: B-cells
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Ig (binds antigen)
CD19, CD20, CD21 CD40 MHC II B7 |
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Cell-surface proteins: Macrophages
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MHC II, B7, CD40, CD14
Receptors for Fc and C3b |
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Cell-surface proteins: NK cells
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Receptors for MHC I
CD-16 (finds Fc of IgG) CD56 (UNIQUE to NK) |
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Anergy
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Self-reactive T-cells become nonreactive without costimulatory molecule
B-cells also become anergic, but tolerance is less complete than in T-cells |
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What are bacterial toxins and what do they do?
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Superantigens (e.g. S. pyogenes and S. aureus) cross-link the beta-region of the T-cell receptor to the MHC class II on APC's
--> uncoordinated release of IFN-gamma from Th1 cells & subsequent release of IL-1, IL-6, and TNF-alpha from macrophages Endotoxins/LPS (gram-negative bacteria) - directly stimulate macrophages by binding to endotoxin receptor CD14; Th cells are not involved |
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Examples of antigen variation: bacteria
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Salmonella (2 flagellar variants)
Borrelia (relapsing fever) Neisseria gonorrhoeae (pilus protein) |
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Examples of antigen variation: ..
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trypanosomes (programmed rearrangement)
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Type I Hyper-sensitivity
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First is Fast
Anaphylactic & atopic IgE on mast cells & basophils trigger vasoactive amines (histamine) that act on postcapillary venules Reaction after Ag exposure, due to preformed Ab Test: scratch test & radioummunosorbent assay |
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Type II Hypersensitivity
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Antibody mediated - IgM, IgG b ind to fixed antigen on "enemy" cell, leading to lysis (by complement) or phagocytosis
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What are the 3 mechanisms of antibody mediated (type II) hypersensitivity?
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3 mechs:
1. Osponize cells or activate complement 2. Antibodies recruite neutrophils and macrophages that incite tissue damage 3. Bind to normal cellular receptors and interfere with functioning Test: direct & indirect Coombs |
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Which isotypes are involved with type II h.s.?
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IgM & IgG
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Type III hypersensitivity
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Immune complexes = IgG --> complement --> attract neutrophils --> release lysosomal enzymes
Serum sickness Arthus reaction |
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Serum sickness
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5 days after exposure, Ab's are formed; deposited in membranes
Fix complement --> tissue damage More common > Arthus |
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Arthus reaction
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Intradermal injection of antigen
--> Ab's, which form ag-ab compelxes in the SKIN Characterized by: edema, necrosis, and complement-activation. |
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Serum sickness
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Caused mostly by DRUGS these days. Symptoms:
Fever, urticaria, lymphadenopathy 5-10 days after antigen exposure |
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Type IV h.s
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SENSITIZED T-cells encounter antigen --> release lymphokines
--> Macrophage activation NO antibody involved 4 T's: T-lymphocytes Transplant rejections TB skin tests Touching (contact dermatitis) |
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anti-dsDNA
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SLE
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anti-centromere
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CREST
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anti-Scl-70
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Scleroderma
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Antihistone
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Drug-induced Lupus
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anti-DNA topoisomerase I
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same as anti-Scl-70
Scleroderma (diffuse) |
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Antimitochondrial
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primary biliary cirrhosis
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Anti-gliadin
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Celiac
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Anti-BM
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Goodpasture's
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Anti-desmoglein
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Pemphigus vulgaris
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Anti-microsomal
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hashiMoto's thyroiditis
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anti-thryoglobulin
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Hashimoto's thryoiditis
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Anti-Jo-1
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PolyMyositis, dermatomYositis
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Anti-SS-a
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Sjogren's (anti-Ro)
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Anti-SSb (anti-La)
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Sjogren's
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Anti-U1
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Mixed connective tissue disease
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Anti-smooth muscle
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Autoimmune hepatitis (is the liver smooth muscle?)
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Anti-glutamate decarboxylase
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Type I DM
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c-ANCA
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Wegener's
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p-ANCA
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other vasculitides
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Type I hypersensitivity & examples
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Immediate
Anaphylactic Atopic Examples: allergic & atopic disorders (e.g. rhinitis, hay fever, eczema, hives, asthma) |
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Type II
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Antibody-mediated (IgM, IgG bind to fixed antigen on "enemy" cell, leading to lysis (by complement) or phagocytosis. (Cy-2-toxic: antibody + complement --> MAC).
Examples: Hemolytic anemia Pernicious anemia Erythroblastic fetalis Idiopathic Thrombocytopenic Purpura (ITP) Acute Hemolytic Transfusion Reactions (i.e. lots of blood stuff) Rheumatic fever (molecular mimicry) Goodpasture's syndrome (anti-BM antibody) 2 weird names: Bullous pemphigous & Pemphigus vulgaris Grave's disease (B8) Myasthenia Gravis |
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Type III
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Immune complex (IgG complexes activate complement --> attach to neutrophils, which release lysosomal enzymes)
Think THREE things: Antigen-Antibody-Complement Serum sickness - immune complexes are deposited in membranes --> fix complement --> tissue damage Arthus reaction: local, subacute, intrAdermal (immune complexes in skin) Test: immunoflouresence test Examples: SLE R.A. Polyarteritis Nodosum Post-strep glomerulonephritis Serum sickness (fever, urticaria, arthralgias, proteinuria, LA - usually 5-10 days after exposure to antigen) Arthus reaction (e.g. swelling & infl. post-Tetanus vaccine) Hypersensitivity pneumonitis (e.g. Farmer's lung) |
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Type IV
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Delayed type H.S. - sensitized T-lymphocytes encounter antigen and then release lymphokines (leads to macrophage activation; no antibody involved)
4 T's: -T lymphocytes -Transplant rejections -TB skin tests -Touching (contact dermatitis) Examples: Multiple sclerosis Type I DM Guillan-Barre Hashimoto's Thyroiditis Graft-vs-Host Disease Contact dermatitis (e.g. poison ivy, nickel allergy) |