Immunopathology Dr JG Lawrenson

Immunopathology Hypersensitivity Autoimmunity Immunodeficiency © Dr JG Lawrenson 2001

Hypersensitivity Hypersensitivity reactions are exaggerated or inappropriate immune responses that lead to tissue damage Four types of hypersensitivity reaction are recognised: Type I, II, III and IV © Dr JG Lawrenson 2001

Type I Hypersensitivity Type I (immediate type) reactions include: asthma, hay fever, food allergy Also referred to as atopy Triggered within minutes of exposure to a variety of environmental antigens e.g. pollen, house dust mite Strong genetic link Caused by an overproduction of IgE © Dr JG Lawrenson 2001

Type I Mechanism Mast cells display a high affinity receptor for IgE IgE is synthesised in response to certain antigens (allergens) Allergens are deposited on mucous membranes and taken up and processed by antigen presenting cells (e.g. Dendritic cells or B cells) © Dr JG Lawrenson 2001

Type I Mechanism Allergen presented to TH2 cells which provide cytokine signals to B cells to produce IgE Ig E binds to mast cells Cross linking of IgE by subsequent exposure to allergen causes mast cell degranulation © Dr JG Lawrenson 2001

Type I Mechanism Mast cell degranulation is the major initiation of the acute allergic reaction Mast cell mediators include histamine, heparin and other factors These cause, mucus secretion, vasodilation and oedema © Dr JG Lawrenson 2001

Mast cell mediators Mast cell mediators include pre-formed and newly formed mediators Pre-formed mediators include : histamine, heparin and neutral protease Newly formed mediators include leukotrienes, prostaglandin D2 and platelet activating factor © Dr JG Lawrenson 2001

Type II Hypersensitivity Antibody mediated hypersensitivity Antibody directed against membrane and cell surface antigens (autoantibodies) Antigen-antibody reactions activate complement producing membrane damage Examples include: transfusion reactions and haemolytic disease of the newborn © Dr JG Lawrenson 2001

Type II Mechanism Antibodies bind to cell surface Phagocytes bind to the antibody via their Fc receptor Phagocytosis of target cell Antibody binding also activates complement via the classical pathway Complement mediated cell lysis © Dr JG Lawrenson 2001

Haemolytic disease of the newborn © Dr JG Lawrenson 2001

Type III Hypersensitivity Immune complex mediated Excessive formation of immune complexes e.g. pesistent low-grade infection, repeated inhalation of antigens Examples of Type III hypersensitivity include: Farmers lung, immune complex glomerulonephritis © Dr JG Lawrenson 2001

Type III Mechanism Normally immune complexes are degraded by phagocytosis, particularly in the liver and spleen Excessive immune complex formation results in deposition in the tissues, particularly arterioles, kidney and joints © Dr JG Lawrenson 2001

Type III Mechanism Complexes induce platelet aggregation and complement activation Attempted phagocytosis causes enzyme release and results in tissue damage © Dr JG Lawrenson 2001

Type IV Hypersensitivity Delayed type hypersensitivity Takes more than 12 hrs to develop after antigenic challenge Examples include: contact dermatitis and tuberculin reaction Antigens include large molecules or small molecules (haptens) linked to carrier molecules © Dr JG Lawrenson 2001

Type IV Mechanism APC resident in the skin process antigen and migrate to regional lymph nodes where they activate T cells Sensitised T cells migrate back to the the skin where they produce cytokines which attract macrophages which cause tissue damage © Dr JG Lawrenson 2001

Autoimmunity Autoimmunity is a reaction of the immune system to the bodies own tissues Self molecules are recognised as antigens due to a breakdown of self-tolerance Antibodies (autoantibodies) react against these components Includes organ-specific and non-organ specific diseases © Dr JG Lawrenson 2001