Hypersensitivity Reactions (2) Lecture Notes PDF

Lecture (30); Hypersensitivity reactions (2) Hypersensitivity reactions (2) Objectives By the end of the lecture the student will be able to;  Know the definitions of type III and type IV hypersensitivity.  Explain the underlying mechanisms of type III and typ...

Lecture (30); Hypersensitivity reactions (2) Hypersensitivity reactions (2) Objectives By the end of the lecture the student will be able to;  Know the definitions of type III and type IV hypersensitivity.  Explain the underlying mechanisms of type III and type IV hypersensitivity.  List different examples of type III and type IV hypersensitivity.  Recognize the clinical manifestations of some examples of type III and type IV hypersensitivity. www.vision.edu.sa Hypersensitivity reactions (2) Type III Hypersensitivity www.vision.edu.sa Hypersensitivity reactions (2) Type III hypersensitivity Also called immune-complex mediated hypersensitivity. Definition: A reaction in which antigen–antibody (immune) complexes are formed in the circulation and deposit in blood vessels, leading to complement activation and inflammation. www.vision.edu.sa Hypersensitivity reactions (2) Mechanism:  Ab (IgG or IgM) combines with Ag → formation of immune complexes.  Immune complexes deposit in tissue or vessel wall.  This leads to complement activation, inflammation, and tissue destruction. www.vision.edu.sa Hypersensitivity reactions (2) The antigens in these complexes may be exogenous antigens, such as microbial proteins, or endogenous antigens, such as nucleoproteins. Small amounts of antigen–antibody complexes may be produced during normal immune responses and are usually phagocytosed and destroyed. These complexes become pathogenic when produced in large amounts, persist, and deposited in tissues. Immune complex–mediated injury is systemic when complexes are formed in the circulation and are deposited in several organs, or it may be localized to particular organs (e.g., kidneys, joints, or skin) if the complexes are formed and deposited in a specific site. www.vision.edu.sa  Hypersensitivity reactions (2) Mechanism of type III hypersensitivity www.vision.edu.sa  Hypersensitivity reactions (2) Examples of Immune Complex–Mediated hypersensitivity Disease Antigen Involved Clinico-pathologic Manifestations Systemic lupus Nuclear antigens Nephritis, skin erythematosus (SLE) lesions, arthritis, others Post-streptococcal Streptococcal cell wall Nephritis glomerulonephritis antigen(s); may be “planted” in glomerular basement membrane Polyarteritis nodosa Hepatitis B virus antigens in Systemic vasculitis some cases www.vision.edu.sa Hypersensitivity reactions (2) Other examples: Acute serum sickness  It is the prototype of systemic immune complex disease. It was first described in humans when large amounts of foreign serum were administered for passive immunization (e.g., in persons receiving horse serum containing anti-diphtheria antibody).  It is now seen only rarely (e.g., in patients injected with rabbit or horse anti-thymocyte globulin for treatment of graft rejection).  Approximately 5 days after the foreign protein is injected, specific antibodies are produced; these react with the antigen still present in the circulation to form antigen–antibody complexes.  The complexes deposit in blood vessels in various tissues, triggering an inflammatory reaction. www.vision.edu.sa Hypersensitivity reactions (2) Other examples: Arthus reaction  A model of experimental local immune complex diseases, in which an area of tissue necrosis appears as a result of acute immune complex vasculitis.  The reaction is produced experimentally by injecting an antigen into the skin of a previously immunized animal (i.e., pre-formed antibodies against the antigen are already present in the circulation).  Immune complexes are formed, precipitated at the site of injection, and trigger an inflammatory reaction. www.vision.edu.sa Hypersensitivity reactions (2) Type IV hypersensitivity www.vision.edu.sa Hypersensitivity reactions (2) Type IV hypersensitivity (delayed / T Cell–Mediated): A type of hypersensitivity mediated or caused by T cells. Mechanism:  Ag stimulates T lymphocytes → sensitized T lymphocytes → secretion of cytokines → inflammation. Examples: Granulomas. Rheumatoid arthritis. Inflammatory bowel disease. www.vision.edu.sa Hypersensitivity reactions (2) Mechanism of granuloma formation; Macrophages process and present antigen (via MHC class II) to CD4+ helper T cells. Interaction leads macrophages to secrete IL-12, inducing CD4+ helper T cells to differentiate into TH-1 subtype. TH-1 cells secrete IFN-γ, which converts macrophages to epithelioid histiocytes and giant cells. www.vision.edu.sa Hypersensitivity reactions (2) Diagram of granuloma formation www.vision.edu.sa Thank You www.vision.edu.sa