hypersensitivity.pdf

Hypersensitivity part II Simon Powis The Four Types of Hypersensitivity Reaction Type I Type II Immune reactant IgE IgG Antigen soluble Effector mechanism Example Mast cell activation Allergy, Asthma cell or matrix Cell surface associated receptor Complement, Ab alters FcR+ cells Dru...

Hypersensitivity part II Simon Powis The Four Types of Hypersensitivity Reaction Type I Type II Immune reactant IgE IgG Antigen soluble Effector mechanism Example Mast cell activation Allergy, Asthma cell or matrix Cell surface associated receptor Complement, Ab alters FcR+ cells Drugs signalling chronic urticaria Type III Immune reactant Antigen associated IgG soluble Type IV Th1 cells soluble Th2 cells soluble CTL cellantigen Effector mechanism Example dermatitis complement, macrophage eosinophil phagocytes activation activation arthus reaction cytotoxicity contact dermatitis chronic asthma tuberculin reaction & allergic rhinitis contact Type II Hypersensitivity • Type II reactions are the result of antibodies, usually IgG, binding to components of cell membranes or extracellular matrix. • Can be self-components, or exogenous components • Self: Goodpasture’s syndrome, antibodies bind to basement membrane collagen type IV, glomerulonephritis in kidney, pulmonary haemorrhage in lung Goodpasture’s syndrome Type II Hypersensitivity • Antibodies to substances bound to host cell surface: hemolytic anemia caused by penicillin Type III hypersensitivity • As with Type II, Type III are caused by antibody, usually IgG, but also sometimes IgM. • Type III antibodies directed to soluble antigens • Formation of antibody-antigen complexes is a normal part of immune response. • Usually cleared by reticuloendothelial system (RES): macrophages, neutrophils in liver spleen and bone marrow that ingest and degrade immune complexes • Excess immune complex deposition in tissues leads to pathology Type III Type III Type III: sites of immune complex deposition • Sites of immune complex (IC) deposition are not necessarily the sites from where the antigen is derived. • Glomeruli : kidney, filtration process makes it very common site in IC deposition, damage driven by complement activation • Blood vessel walls: IC accumulate on veins and arteries, causes vasculitis, often seen as skin lesions if close to surface • Synovial membranes: Rheumatoid arthritis, in which the IgG of the immune complexes can become an antigen itself, and IgM Rheumatoid Factor antibodies develop. • Skin: common site for IC deposition, causes rashes. • Systemic sites: in case of Systemic Lupus Erythematosus (SLE) IC deposits in kidney, joints, skin, vasculature, muscle and other organs. Type IV Hypersensitivity • Unlike I, II & III, Type IV reactions are entirely cell-mediated • Complement does not play a role in Type IV. • Most Type IV reactions are caused by CD4+ delayed type hypersensitivity (DTH) reactions. ‘Delayed’ refers to reaction occurring 2 to 4 days after antigen exposure • Macrophages that cause damage are not specific, harm infected and non-infected tissue DTH reactions • Some DTH reactions can be prolonged and damaging • Listeria, Leishmania, M. tuberculosis, M. Leprae • DTH responses can lead to walling off infectious sites, granulomas. • Remnants of granulomas are tubercles seen in longterm tuberculosis Contact sensitivities • A special category of DTH reaction in which antigen is not an infectious agent, but a chemical that binds to cell surface. • Heavy metal sensitivity • Poison Ivy, reaction in skin to catechols Autoimmune diseases can be classified in same way as Hypersensitivity reactions: Type II Syndrome Autoantigen Consequence Autoimmune hemolytic anemia Blood group antigens Destruction of rbc, anemia Autoimmune Platelet integrin Abnormal bleeding thrombocytopenic GpIIb:IIIa purpura Goodpasture’s Collagen type IV syndrome Glomerulonephritis, Pulmonary hemorrhage Pemphigus vulgaris Epidermal cadherin Skin blisters Acute Rheumatic fever Strep cell wall: Ab x-react to cardiac muscle Arthritis, myocarditis, valve scarring Autoimmune diseases can be classified in same way as Hypersensitivity reactions: Type III syndrome autoantigen consequence Mixed essential cryoglobulinemia Rheumatoid Factor- Systemic vasculitis IgG complexes SLE DNA, histones, ribosomes Rheumatoid Arthritis Rheumatoid Factor- arthritis IgG complexes Glomerulonephritis, vasculitis, rash Autoimmune diseases can be classified in same way as Hypersensitivity reactions: Type IV syndrome autoantigen consequence Insulin dependent !-cell destruction Diabetes mellitus Pancreatic !-cell antigen Rheumatoid arthritis Synovial joint antigen Joint inflammation and destruction Multiple sclerosis Myelin basic protein Nervous system damage Summary • Type II reactions: antibody mediated, cell membranes, drugs bound to cell membranes • Type III: antibody mediated, immune complex formation to soluble antigens, deposits at key sites, kidney, vessels, joints, skin • Type IV: cell mediated, DTH reactions to infectious organisms, granuloma. Contact sensitivity to reactive chemicals.