2/18/2014 Objectives Foundations of Public Health • Describe the hypersensitivity reaction to Immunology antigen exposure • Identify and explain the similarities and differences in the mechanism of the four types of hypersensitivity reactions Hypersensitivity • Identify selected disorders for each type of hypersensitivity reaction (selected disorders of autoimmunity) Type I hypersensitivity • Identify and explain the mechanisms of sepsis reactions can be caused by a variety of allergens Hypersensitivity Hypersensitivity • Normally beneficial immune responses that • Four types of occur in an exaggerated or inappropriate hypersensitivity form diseases • Results in inflammation, tissue damage or other problems known as immunopathology • Mechanism of • Hypersensitivity reaction only occur on the immune injury second or subsequent exposure to an is different in allergen • The host must first be sensitized to the allergen!! each type Characteristics of Hypersensitivity Type I: Immediate Hypersensitivity • Also know as: • Allergy • Atopy • Anaphylaxis • Most severe form of Type I reaction • Examples of Type I reactions • Asthma • Hay fever • Some food and drug allergies 1 2/18/2014 Type I Hypersensitivity Type I Reaction cont’d Reaction • Cross‐linking induces • IgE is produced in 1st degranulation of the exposure to an antigen involved mast cells and basophils‐ on 2nd & later • IgE proteins bind to Fc exposures receptors on mast cells • Mediators are released (on both the connective during degranulation tissue and in the mucosa) • Trigger the symptoms of Type I hypersensitivity and basophils • One mediator released during • Repeat exposure to the this reaction is histamine • Anaphylatoxins, C3a & C5a, antigen then cross‐links also released in complement the IgE molecules cascade triggered by released mediators. Process of the cross-linking of IgE with the antigen Type I: Immediate Hypersensitivity • Th2 cytokines promote Type I hypersensitivity • Genetic predisposition for allergen which appears to be Human Leukocyte Antigen (HLA)‐linked • Environmental pollutants can promote allergies • These pollutants can act as IgE adjuvants 2 2/18/2014 Th2 Mediation of Type I Hypersensitivity Type I: Immediate Hypersensitivity Type I: Latex Allergy • Allergies can be diagnosed by • Occurs when the immune system reacts the Skin Prick Test to proteins in natural rubber latex • “Wheal & Flare” is characteristic • of an allergic reaction An estimated 1 –6% of general population has been sensitized to latex • Common allergens include pollen, foods, dander • 5 – 10% of healthcare workers are • A variety of medication and sensitized! treatments are used to control • Should substitute synthetic gloves allergies for latex • Hyposensitization • Products that commonly cause reactions (Desensitization) therapy included gloves, balloons & condoms • Person is exposed in increasing levels of the antigen until • May also react to rubber bands, erasers, tolerance develops rubber parts of toys, pacifiers, etc. Ascaris (Roundworm) Type 1: Asthma • Effects of an asthmatic reaction • Strong immune response to larval stage can occur both Ascaris lumbridoides infestation immediately and • Ascaris allergen is the most potent of all allergens over a prolonged or parasitic origin time period • • Results in both an Bronchial asthma, urticaria (hives), early & late angioedema (diffuse swelling and hives) response during an frequently occur with the larval stage parasite asthmatic attack • However, the immune system is frequently from inflammatory response tolerant of adult Ascaris intestinal infestation 3 2/18/2014 Dracunuliasis Type 2: Cytotoxic Hypersensitivity • Also known as Guinea Worm • With Type 2 reactions, the reaction is against an disease antigen located on a cell surface • The female worm forms a painful • blister on the skin (usually the The antigen being attacked is an integral part of the cell!! feet) and when the foot is placed • IgM and IgG antibodies bind to the cell surface or in water, the female worm tissue antigens in conjunction with complement releases numerous eggs activation • The worm can be removed by • The complement activation results in: winding it slowly around a stick over many days (see photo w/ • Chemotaxis match stick) • Inflammation • If worm ruptures during removal, • Opsonization it will release numerous antigens • Cellular activation & produce a severe allergic reaction. Type 2 Mediated Immunopathology Type 2: Blood Immunopathologies • Blood transfusion reactions • Hemolytic Disease of the Newborn • RhD factor • Reaction involves IgG • Also called erythorblastosis fetalis Erythroblastosis fetalis 4 2/18/2014 Bleeding under the skin due to low platelets. Type 2: Autoimmune Blood Reactions • Spontaneous reactions that destroy erythrocytes • Warm antibody hemolytic anemia involve autoantibodies that attach to and destroy erythrocytes at temperatures above normal body temperature • Cold antibody hemolytic anemia involve autoantibodies that attach to and destroy erythrocytes at temperatures below normal body temperature • Thrombocytopenia (low platelet count) Type 2: Adverse Drug Reactions • Drug‐induced reactions involving drug‐Ab immune complex and erythrocyte antigens • Steven‐Johnson Syndrome (SJS) • Affects people of all ages, but more child cases • If untreated, can result in death • Toxic Epidermal Necrolysis Syndrome • Another form of SJS Toxic Epidermal Necrosis Type 2: Autoimmune Diseases Type 2: Autoimmune Diseases • Goodpasture’s syndrome • Pemphigus vulgaris • Involves IgG and complement • • Lungs & kidneys are effected Involves antibodies against • Results in kidney basement chromosome proteins, skin membrane damage and mucous membranes • May be triggered by viral • Results in blistering respiratory infections or inhaling hydrocarbon solvents • Exact cause is unknown • Treat with immunosuppressive • Disease is uncommon, drugs and plasmapheresis (to occurs mostly in middle‐aged remove harmful autoantibodies from the blood) (or older) patients 5 2/18/2014 Type 2: Autoimmune Diseases Type 3: Immune Complex Hypersensitivity • Myasthenia Gravis • With type 3 hypersensitivity, damage occurs to tissues • Involves IgG and at sites of immune complex deposition complement against • Antigens involved in Type 3 reactions are insoluble, acetylcholine receptors small immune complexes which have not been on muscle cell removed by phagocytes, the liver, or the spleen membranes • Results in muscle • Involves the deposited antigen, antibodies (IgG), weakness and fatigue complement deposition & effector cells • Thymus abnormalities • The antigen‐antibody often present complexes induce • Thymic tumors found in complement activation 10% of patients & result in • Changes in germinal inflammation mediated centers found in 70% of patients by neutrophils Factors Contributing to Deposition of Immune Complexes • Complement • Increased vascular deficiencies permeability (due to • Low affinity antibodies vasoactive amines) • Antibody isotype • High blood pressure • Ineffective phagocytois and turbulence (for example in the • Abnormal carbohydrate glomerular capillaries of on antibody molecules the kidneys) • Size of immune complex • Affinity of the antigen and the antibody for specific tissues isotype Type 3 Hypersensitivity • Three General Groups: • Persistent infection involving microbial antigens and the kidneys • Autoimmune disease against self antigen • Damage can occur to the kidneys, joints, & arteries etc. • Extrinsic antigens • Inhaled antigen –(mold) lung • Serum Sickness • Arthus Reaction 6 2/18/2014 Type 3: Autoimmune Disease Types 1 - 3 • Systemic Lupus Erythematosus • Antibody Mediated (SLE) Hypersensitivity • Formation of immune complexes cause inflammation & tissue • Different effector injury mechanisms that cause • Affects many parts of the body (joints, skin, kidneys, heart, pathology lungs, brain, blood vessels) • Autoantibodies are • Characterized by periods of illness (flares) & times of health antibodies specific for self (remission) antigens • More common in young women • Damage cells & tissues • Present in excess in many autoimmune diseases (including SLE) Autoimmune Diseases: Autoantibodies Autoantibody Tests • Not always a direct • Antinuclear antibody (ANA): may be found in autoimmune hypersensitivity link, but disorders [especially lupus, scleroderma, Sjorgren’s formation of autoantibodies can syndrome, polymyositis, certain types of chronic active cause autoimmunity hepatitis] • Graves disease & Hashimoto’s • Anti‐DNA antibody: may be present in lupus thyroiditis are 2 disease where • Titers will decrease when treatment is successful autoantibodies target a single • Usually not found in other autoimmune diseases organ – the thyroid • Antiphospholipid antibody: may be found in lupus and • Rheumatoid arthritis is a certain other conditions systemic autoimmune disorder – • Associated with miscarriages and clots high levels of circulating autoantibodies target multiple • Rheumatoid factor: often found in blood and joint synovial organs but most commonly affect fluid in rheumatoid arthritis patients the joints Type 4: Delayed Hypersensitivity T Cell Mediated Hypersensitivity • Type 4 reactions are regulated by cell‐mediated reactions • Type 4 reactions usually take longer than 12 hours to develop due to mediation via T‐cells Granuloma formation around a schistosome • Protective immunity does not egg (center) destroys always occur with Type 4 the liver tissue. reactions • Three varieties of Type IV Hypersensitivity: • Contact