Types of Immune Response 3 and 4 PDF

17 Types of immune response; Types III and IV of hypersensitivity reactions. ILOs By the end of this lecture, students will be able to ▪ Distinguish pathogenesis of types III and IV of hypersensitivity reactions. ▪ Apply different reactions to clinical conditions as autoimmune diseases,...

17 Types of immune response; Types III and IV of hypersensitivity reactions. ILOs By the end of this lecture, students will be able to ▪ Distinguish pathogenesis of types III and IV of hypersensitivity reactions. ▪ Apply different reactions to clinical conditions as autoimmune diseases, granuloma, and virus infected cells and tumor cells. Type III Hypersensitivity Reaction, immune complex-mediated hypersensitivity Mediated by IgG and IgM against soluble antigens, exogenous or endogenous, 3-8 hs after exposure to antigen. Reaction may be localized or systemic. The antigen binds to the antibody forming an immune complex. Circulating antigen-antibody immune complexes deposit in postcapillary venules, with subsequent complement fixation that led to leukocyte recruitment with inflammatory reactions→ necrotizing vasculitis and fibrinoid necrosis, and tissue injury. Clinical Examples; 1- Systemic Immune complex mediated disease e.g., serum sickness. It is an acute self-limited disease that occurs 6-15 days after injection of foreign serum (e.g-horse anti-tetanus serum) for passive immunization or anti-snake venom. It is characterized by fever, skin rash, arthralgia, vasculitis and acute glomerulonephritis. 2- Localized immune complex mediated diseases: e.g., Arthus reaction: it is a localized, immune reaction-induced vasculitis leading to an area of tissue necrosis. It is elicited in the skin after injection of an antigen in sensitized individuals. 3- Autoimmune diseases; Many autoimmune diseases are mediated by this reaction. Favored sites of immune complex deposition are renal glomeruli, joints, skin, heart, serosal surfaces, and small blood vessels. Microscopically; 1. Necrotizing vasculitis 1  2. Fibrinoid necrosis 3. Inflammatory infiltrate; neutrophils Microthrombi Type IV hypersensitivity reaction. o Also known as cell mediated hypersensitivity or delayed type of hypersensitivity. A T lymphocyte mediated destruction of cells along with dendritic cells, macrophages and cytokines. o Type IV hypersensitivity occurs 24 hours after contact with an antigen, usually starting at 2 or 3 days and often last for many days [ termed as “delayed hypersensitivity”]. o Type IV hypersensitivity is unique in that, unlike the first three types of hypersensitivity which are antibody mediated, type IV hypersensitivity is cell mediated and also a delayed reaction. o CD4+ , Cytokine–Mediated Inflammation\ Delayed hypersensitivity reaction, against persistent non-degradable intracellular antigens, activated by CD+4 T-helper (T h-1 \ 17) cells lead to release of inflammatory mediators IFN → activate macrophage’s transformation to Epithelioid cells and development of granuloma. Examples; The tuberculin reaction (Mantoux test): In this reaction, a purified mycobacterial antigen administered into the skin of a previously immunized individual results in a detectable cutaneous reaction within 24 to 48 hours (hence the term delayed, in contrast to immediate hypersensitivity). It is used as the basis of a diagnostic skin test for an immune response to tuberculosis. Granuloma formation: due to inability to kill intracellular pathogens in macrophages that often results in a chronic stimulation of the pathogen specific T cells. Granuloma is a histopathologic term that refers to microscopic aggregation of epithelioid cells, usually surrounded by a collar of lymphocytes with or without the formation of multinucleated giant cells. Epithelioid cells are transformed macrophages that have abundant large and pink cytoplasm (epithelium like). 2  Allergic contact dermatitis: Environmental chemicals, metals or topical medications causing epidermal necrosis, inflammation, skin rash and blisters. o CD+8- Cell-mediated cytotoxic reaction mediated by CD+8 T cells. Activated cytotoxic cells stimulate antigen bearing-cell apoptosis. o Examples; Cytotoxic reaction against virus- infected cells, transplanted organs and tumor cells. Type-1 diabetes: The killing of the pancreatic islet cells by cytotoxic T cells resulting in insulin deficiency (an autoimmune condition). Graft-versus-host disease and Chronic transplant rejection. 3