Immunopathology Dr JG Lawrenson. Immunopathology Hypersensitivity Autoimmunity Immunodeficiency © Dr JG Lawrenson 2001

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


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


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)


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


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



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


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


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


Haemolytic disease of the newborn


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


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


Type III Mechanism

• Complexes induce platelet aggregation and complement activation

• Attempted phagocytosis causes enzyme release and results in tissue damage


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




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




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


Documents

Immunopathology Dr JG Lawrenson. Immunopathology Hypersensitivity Autoimmunity Immunodeficiency © Dr JG Lawrenson 2001