Objective 17 Hypersensitivity Hypersensitivity (allergy): an inappropriate or over exaggerated humoral or cell mediated response that causes tissue damage in the host allergen: antigen that triggers a hypersensitive reaction

Categories of Hypersensitive Reactions: Immediate and subacute hypersensitivities, delayed hypersensitivity Immediate (acute; type 1; reaginic, in common terms “allergies”) Time Course: begins within seconds of contact and lasts for about 30 minutes

Mechanism: Anaphylaxis Type:  Allergens elicit IgE secretion; IgE attaches to mast cell/basophil surfaces  Subsequent entry of allergen causes cross linking of IgE on mast cell and basophil surfaces  cross linking induces degranulation and release of chemical mediators of anaphylaxis; leads to:  vascular dilation and increased permeability leads to edema  increased mucus production  smooth muscle contraction leads to bronchiolar constriction

Atopy:. like anaphylaxis, but in these genetically Atopy: like anaphylaxis, but in these genetically susceptible people, no prior sensitization is needed  atopy usually involves environmental antigens, such as dust mites and pollen

Local Reaction:. limited to a specific area, such as the Local Reaction: limited to a specific area, such as the respiratory tract, or digestive tract Systemic: anaphylactic shock (bee stings, spider bites, drug reactions)

Subacute Hypersensitivities Time Course: reactions occur within 1-3 hours of exposure) Cytotoxic (Type II) reactions  IgG or IgM antibodies bind to antigens on cell surfaces and stimulate complement activation (phagocytosis, cell lysis, inflammation, etc..)  Examples include transplant rejection, autoimmune diseases (myasthenia gravis, autoimmune hemolytic anemia)

Immune Complex Disease (Type III)  IgG or IgM antibodies react with antigens and form large insoluble complexes that get stuck in various tissues and in basement membranes; complement activation causes tissue damage  Examples include rheumatoid arthritis, chronic glomerulonephritis, systemic lupus erythematosus (SLE)

Delayed Hypersensitivity (Type IV): Time Course: occurs within 1-3 days of exposure Mechanism: cell mediated reaction involving Th and Tc cells, followed by inflammation and tissue damage Examples include viral related skin rashes, tubercular leprosy, shistosomal cirrhosis, tuberculin skin test, reactions to hair dyes, metals, cosmetics, latex, poison ivy

Objective 18 Autoimmunity Autoimmunity: the generation of antibodies (autoantibodies) and/or cytotoxic T cells that attack self antigens found on cells or in tissues Immunologic Tolerance: nonresponsiveness to molecules that are normally recognized by the IS; tolerance is acquired during late fetal life and in the few months after birth

Theories Used To Explain Loss Of Tolerance: Appearance of New Antigens  structural changes in existing antigens  mutations that create new antigens  exposure to the IS of antigens from avascular tissue  new antigens that appear during development 2. Ineffective Lymphocyte Programming  self reactive lymphocytes should have been removed early in the development of the IS, for proteins that are unavailable to the IS in early life Introduction of new antigens that are structurally similar to Self Antigens Rheumatic fever

Objective 19 Immunodeficiencies Immunodeficiency: a state of suppressed immunity; related to defects in immune cells (B or T lymphocytes), phagocytes, or complement A. SCID (Severe Combined Immunodeficiency Disorder) Cause: genetic defects that lead to defective B and T lymphocytes Effects: lack of protection from a range of pathogens fatal if untreated David Vetter

Acquired Immune Deficiency Syndrome (AIDS) Cause: Human Immunodeficiency Virus (HIV) infects and destroys Th cells, macrophages, dendritic cells and monocytes Pathology loss of cell mediated immunity and marked deficit in antibody production patients develop cancers, opportunistic infections, dementia and death