L17 Hypersensitivity Reactions (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 tumour cells.  Apply mechanisms of hypersensitivity reactions on graft rejection process. Type III Hypersensitivity Reaction, immune complex-mediated hypersensitivity Antibodies; Mediated by Ig G and IgM against soluble antigens, exogenous or endogenous, 3-8 hours 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 lead to leukocyte recruitment with inflammatory reactions→ necrotizing vasculitis and The sequential phases in the induction of systemic immune fibrinoid necrosis, and tissue injury (as complex–mediated diseases (type III hypersensitivity). shown in the figure). Clinical Example ; 1-Systemic immune complex mediated disease e.g., serum sickness. It is an acute self-limited disease that occurs 6-8 days after injection of foreign serum (e.g., horse antitetanus serum) for passive immunization. It is characterized by fever arthralagia, 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. 1 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; 1. 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. 2. Granuloma formation: against the intracellular, non-degradable antigens as mycobacteria bacilli in the lung as in tuberculosis. It is mediated by CD+4, Th-1 activation and the production of cytokines as IFN-γ, IL-3\GMCSF that stimulate macrophage production, activation and transformation to epithelioid cells. 3. Reaction against fungal infection mediated by activated Th17 cells that secrete IL-17, IL-22, chemokines and some cytokines that recruit neutrophils and monocytes promoting inflammatory reaction. 4. Allergic Contact dermatitis, classic example is reaction mediated against poison ivy. 2  The same mechanism is responsible for most drug reactions, tattoo, black henna, Nickels and bracelets allergy as well as some occupational allergies. 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 and malignant 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