Antibody-Mediated (Type II) Hypersensitivity

Antibody-Mediated (Type II) Hypersensitivity Ab-Mediated (Type II) Hypersensitivity (Ab dependent) m ediated by antibodies directed tow ard antigens present on cell surfaces or ex tracellular m atrix . • When circulating cells (erythrocytes or platelets), are coated (opsonized) with autoantibodies, with or without complement proteins, the cells become targets for phagocytosis by neutrophils and macrophages (IgM, IgG or C3b and C4b) • phagocytes express receptors for the Fc tails of IgG antibodies and for breakdown products of the C3 complement protein, bind and ingest opsonized particles. • Opsonized cells are usually eliminated in spleen, splenectomy is of some benefit in autoimmune thrombocytopenia and hemolytic anemia. Clinical situation: 1) transfusion reactions, cells from an incompatible donor react and opsonized by antibody in the host (2) erythroblastosis fetal : an antigenic difference between the mother and the fetus, and antibodies (IgG class) from the mother cross the placenta and cause destruction of fetal RBC (3) autoim m une hem olytic anem ia, agranulocytosis, and throm bocytopenia, antibodies against own blood cells (4) certain drug reactions, antibodies against drug, attach to the surface of erythrocytes or other cells. • Ab Dependent Cell Cytotox icity (ADCC) • Inflammation induced by antibody binding to Fc receptors of • • leukocytes and by complement breakdown products. Ab binds to cellular or tissue Ags, activate the complement system by the "classical" pathway. Products of complement activation recruit neutrophils and monocytes, triggering inflammation in tissues, opsonized cells for phagocytosis, and lyse cells, especially erythrocytes Example: Good pasture syndrome, Pemphigus vulgaris • Antibody-M ediated Cellular Dysfunction •Graves disease •myasthenia gravis • Antibodies directed against cell-surface receptors dysregulate function without cell injury or inflammation. • Anti-receptor antibodies disturb the normal function of receptors. 1. Ab against the thyroid stimulating hormone (TSH receptor) activates thyroid cells in Graves disease (Hyperthyroidy) 2. Antibodies against acetylcholine (ACh) receptor damage neuromuscular transmission in myasthenia gravis (muscle weakness) • Examples of Antibody-Mediated Diseases (Type II Hypersensitivity) Disease Target Antigen Mechanisms of Disease Autoimmune Red cell membrane proteins Opsonization and phagocytosis of hemolytic anemia (Rh blood group antigens) red cells Autoimmune thrombocytopenic purpura Pemphigus vulgaris Vasculitis caused by ANCA (antineutrophil cytoplasmic Ab ) Good pasture syndrome Clinicopathologic Manifestations Hemolysis, anemia Platelet membrane proteins Opsonization and phagocytosis of (Gpllb: Illa integrin) platelets Bleeding Proteins in intercellular Antibody-mediated activation of junctions of epidermal cells proteases, disruption of (epidermal cadherin) intercellular adhesions Neutrophil granule proteins, Neutrophil degranulation and presumably released from inflammation activated neutrophils Skin vesicles (bullae) Vasculitis Noncollagenous protein in basement membranes of kidney glomeruli and lung alveoli Acute rheumatic Streptococcal cell wall fever antigen; antibody crossreacts with myocardial antigen Myasthenia gravis Acetylcholine receptor Complement- and Fc receptor– mediated inflammation Nephritis, lung hemorrhage Inflammation, macrophage activation Myocarditis, arthritis Graves disease TSH receptor (hyperthyroidism) Insulin-resistant Insulin receptor diabetes Antibody-mediated stimulation of Hyperthyroidism TSH receptors Antibody inhibits binding of insulin Hyperglycemia, ketoacidosis Antibody inhibits acetylcholine Muscle weakness, binding, down-modulates receptors paralysis Figure 13-4 Reactions of Innate Immunity • The innate immune system provides host defense by the following two main reactions: • 1. Inflammation. Cytokines and products of complement activation, as well as other mediators, are produced during innate immune reactions and trigger the vascular and cellular components of inflammation. • The recruited leukocytes destroy pathogens and ingest and eliminate damaged cells. • 2. Anti-viral defense. Type I interferons produced in response to viruses act on infected and uninfected cells and activate enzymes that degrade viral nucleic acids and inhibit viral replication. • innate immune system generates signals that stimulate the subsequent, more powerful adaptive immune response Innate lymphoid cells (ILCs) • The populations of lymphocytes that lack TCRs but • • • • produce cytokines similar to those that are made by T cells. They are classified into three groups, produce IFN-γ, IL-5, or IL-17, cytokines that are characteristic of TH1, TH2, and TH17 subsets of T cells. NK cells are related to group 1 ILCs based on their production of IFN-γ, a cytokine also made by TH1 cells. ILCs mostly reside in tissues, they are early defense against infections in the tissues, before T cells are activated and can migrate into tissues. ILCs also may be early participants in inflammatory diseases.