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25 Cards in this Set
- Front
- Back
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Central tolerance
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Deletion of self reactive clones
B cell receptor editing (re-rearranging receptor genes) |
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Peripheral tolerance
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Induction of anergy
T-regs (CD-25 or IL-1R α chain; Foxp3 transcription factor) Induction of apoptosis (Fas-FasL, imbalance of regulators) |
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Loss of Tolerance (Autoimmunity) Genetic predisposition
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MHC genotype and phenotype
Non-MHC genes (PTPN-22, NOD-22) |
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Loss of Tolerance (Autoimmunity) Environmental factors
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Cross reactive antigens: molecular mimicry
Excessive immune cell activation (superantigens) |
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Four Mechanisms of Hypersensitivity or Immune Mediated Damage
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Type I: Allergy, anaphylaxis
Type II: Antibody mediated cytotoxicity Type III: Immune complex disease Type IV: Cell mediated hypersensitivity |
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Type I Hypersensitivity
Who are the players? |
Th2 lymphocyte driving B cell activation; IL-4 mediated B cell class switch to IgE
Possibly M2 programmed macrophage driving B cell activation IgE producing plasma cells Mast cells that bind IgE Eosinophils Inflammatory mediators |
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Type I Hypersensitivity What is the pathologic mediators or mechanisms?
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Release of vasoactive mediators: histamine, heparin, leukotrienes (C4, D4, spasmogenic, vascular permeability); Platelet Activating Factor, Cytokines (IL3, IL5, Eosinophils)
Vasoactive mediators induce vascular leakage, tissue damage, eosinophil infiltration, vasodilation, bronchoconstriction |
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Type I Hypersensitivity Regional and systemic effects
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Hives
Rhinitis Systemic vasodilation and blood pressure decrease |
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Type I Hypersensitivity What are the classical diseases?
Local/regional |
Atopy: genetic predisposition for hypersensitivity to inhaled or ingested antigens
Allergic Rhinitis Asthma (current thoughts on asthma prevalence) Urticarial reaction Drug reactions |
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Type I Hypersensitivity What are the classical diseases?
Disseminated |
Systemic anaphylaxis (bee venom, IV proteins)
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Type II Hypersensitivity Who are the players?
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B cells that produce antibodies reacting with cell or tissue components (autoantibodies)
Neutrophils NK Cells Macrophages Complement system Receptor bearing cells |
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Type II Hypersensitivity
What is the process? Three different scenarios |
Cellular Damage (Induction of autoreactive antibodies to cells
Opsonization of cells Removal by phagocytosis Or ADCC* Or Complement Lysis ) Tissue or Membrane Damage Modification of receptor function (1-Induction of anti-receptor antibodies Engagement of receptors Receptor Activation 2-Induction of anti-receptor antibodies Engagement of receptors Receptor blockade) |
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Type II Hypersensitivity Tissue or Membrane Damage
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Induction of autoreactive antibodies to tissues
Antibodies bind tissue and activate complement or induce inflammation Inflammatory cells engage Fc and C receptors Induction of inflammation and tissue damage |
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Type II Hypersensitivity
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Proinflammatory
Antibodies bind complement, C3a, C5a, membrane attack Inflammatory cells bind antibody via Fc receptor Phagocytosis or antibody dependent cell cytotoxicity (ADCC) Reverse phagocytosis and extrusion of enzymes and mediators into membranes or tissues Linear pattern of immunofluorescence (glomeruli) Alteration of receptor function Blockade and hypofunction Activation and hyperfunction |
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Type III Hypersensitivity Who are the players?
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Vascular system and vascular system dependent filters (synovium, glomerulus)
Circulating antigen Circulating antibody Complement Neutrophils Macrophages |
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Type III Hypersensitivity What is the process?
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Circulating Antigen…..
That Persists Induction of complement fixing antibodies Condition of slight antigen excess Medium sized immune complexes Deposits in Vessels, Glomerulus, joints Complement Activation Inflammatory cell activation C3a, C5a, etc. |
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Type III Hypersensitivity What is the pathologic mediators or mechanisms
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Deposition of antigen antibody complexes activate complement and incites inflammation/tissue damage
Damaged filtration membranes Glomerulus: Lumpy bumpy immunofluoresence Synovial membranes: arthritis Damaged vessels: Fibrinoid vasculitis |
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Type III Hypersensitivity Clinical presentations
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Vasculitis: Fibrinoid vascular changes; petechiation
Glomerulitis: protein leakage Synovial: arthritis, joint pain |
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Type III Hypersensitivity Classical Experimental Pathology: Arthus Rx
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Immunize with protein antigen yielding cirulating antibody
After 10 days, inject antigen intra-dermally Induces classical fibrinoid vasculitis and necrosis |
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Type IV Hypersensitivity Who are the players?
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CD4+ Th1 lymphocytes (IL-12 driven)
CD4+ Th17 lymphocytes (IL-1, IL-6, IL-17, IL-23) Immunologic memory Macrophages (IFN-γ) Neutrophils (IL-17, IL-22) |
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Type IV Hypersensitivity What is the process? Immune based inflammation
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Antigen Exposure
(Persistence) Induction Th1 Response (memory cells) Induced CD8+ Production IFN Immune Inflammation Activated macrophages Chronic Granulomatous inflammation |
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Type IV Hypersensitivity What is the pathologic outcomes?
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Unique inflammatory patterns
Immune granulomas and granulomatous inflammation (macrophages driven by T cells) Chronic inflammation (Th1, Th17) Immune based tissue damage (cells expressing viral antigen) Delayed type hypersensitivity Classical tuberculin reaction Acute cellular graft rejection |
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Autoimmune Diseases Organ Specific – directed against specific site
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Type I diabetes (β cells of pancreas)
Multiple sclerosis (myelin) Sjögren Syndrome (lacrimal and salivary glands) |
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Autoimmune Diseases Intermediate scope
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Goodpasture syndrome
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Autoimmune Diseases Systemic
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Systemic lupus
Systemic sclerosis Polymyositis Mixed connective tissue disease |
