HYPERSENSITIVITY

ALLERGIC REACTIONS IN HUMAN BODIES

1. IMMUNOLOGY DONE BY : NIVETHA.M 1 st M.Sc ZOOLOGY

2. INTRODUCTION: Hypersensitivity refers to excessive, undesirable reactions produced by the normal immune system. This reaction leads to damage, discomfort and sometimes fatal to the body. It is an appropriate response of repeated exposure to antigen . The immune response becomes injurious to the host. Hypersensitivity reactions develop in the course of either a humoral or a cell mediated immune response.

3. Factors causing hypersensitivity Factors causing hypersensitivity – allergens In clinical terms ,hypersensitivity is called allergy Extrinsic factors & intrinsic factors Drugs – Penicillin, Aspirin, Sulphamide Airborne particles – Pollen grains, spores, animal dander's Food stuffs – Shell fish, vegetables, peanut Blood transfusion of mismatched blood Infectious organisms – bacteria, viruses, fungi, parasite

4. Hypersensitivity Reactions Hypersensitivity reactions divided into two types Local reactions – When the symptoms appear in a restricted area. Systemic reactions – When the symptoms affect all the organ systems of the body.

5. TYPES OF HYPERSENSITIVITY

6. BASED ON TIME TAKEN FOR THE REACTION 1) IMMEDIATE HYPERSENSITIVITY When the immune reactions manifest in a short duration of time ,within minutes. E.g.: Most of hypersensitivities to drugs (penicillin) Inflammatory responses occurs in a few minutes. This immune reaction appears and disappears rapidly. It involves the interaction of antigen and antibody. It is handled by B-cells by the production of antibodies . It is inhibited by antihistamine drugs.

7. Cont… 2) DELAYED HYPERSENSITIVITY When the immune reactions manifest slowly from 24 hours to 72 hours. It appears slowly & lasts longer. It produces erythema, indurations and lymphocyte infiltration. They involves the reaction between antigens & T cells. Cell mediated immunity. They are suppressed by corticosteroids.

8. BASED ON THE DIFFERENT MECHANISMS OF PATHOGENESIS Coombs & Gell proposed 5 types of hypersensitivity. Type 1 – Anaphylactic hypersensitivity Type 2 – Antibody dependent cytotoxic hypersensitivity Type 3 – Immune complex mediated hypersensitivity Type 4 – Cell mediated hypersensitivity Type 5 – Stimulatory hypersensitivity

9. Type 1 – Immediate or Atopic or Anaphylactic Hypersensitivity Type I hypersensitivity is an allergic reaction provoked by re-exposure to a specific antigen . Exposure may be by due to ingestion, inhalation, injections or direct contact. The reaction is mediated by IgE antibodies and produced by the immediate release of histamine, tryptase , arachidonate and derivatives by basophils and mast cells . This causes an inflammatory response leading to an immediate (within seconds to minutes) reaction . The reaction may be either local or systemic. Symptoms vary from mild irritation to sudden death from anaphylactic shock. Treatment usually involves epinephrine, antihistamines and corticosteroids

10. MECHANISM OF TYPE 1 HYPERSENSITIVITY When a person receives the allergens it get attached to the B cells . The allergens stimulate the B cells to change into plasma cells . The plasma cells make IgE antibodies . These antibodies are called reagins . The IgE antibodies produced for the first time, get attached to the surface receptors of mast cell with the help of their Fc segment.

11. Allergen cross reacting with IgE on mast cell

12. The next time the allergen enters the body, it cross-links the Fab portions of the IgE bound to the mast cell. This triggers the mast cell to degranulate , that is, release its histamine and other inflammatory mediators. The inflammatory mediators are now able to bind to receptors on target cells which leads to dilation of blood vessels, constriction of bronchioles, excessive mucus secretion, and other symptoms of allergy.  

13. Cont .. As this initial contact with antigens leads to the priming of the B cells , it is known as sensitizing or priming dose. Subsequent contact with the allergen causes manifestation of hypersensitivity – shock dose . When the animal get exposed to the second antigen for the second time ,the IgE antibodies attached to the surface of mast cells ,bind the antigen. The allergens cross link the IgE antibodies attached to the mast cells. This triggers the mast cells where a series of enzymatic reaction occurs.

14. This results in the mast cells to release the granules – degranulation. These granules contain substances like histamine, serotonin ,heparin etc .. These substances are the primary cause for anaphylactic hypersensitivity. The manifestation of anaphylaxis are due to mediators. These are of 2 types Primary mediators Secondary mediators The primary mediators include :- histamine, serotonin, heparin.

15. Secondary mediators are produced by leucocytes upon the stimulation of mast cells. These include :- slow reacting substance of anaphylaxis (SRS-A) ,prostaglandins ,platelet activating factor. Some examples are Allergic asthma Allergic conjunctivitis Allergic rhinitis ("hay fever") Anaphylaxis Angioedema Urticaria (hives )

16. Type II - antibody-dependent cytotoxic hypersensitivity In type II hypersensitivity, the antibodies produced by the immune response bind to antigens on the patient's own cell surfaces. The antigens recognized in this way may either be intrinsic ("self" antigen, innately part of the patient's cells) or extrinsic (absorbed onto the cells during exposure to some foreign antigen, possibly as part of infection with a pathogen).

17. Cont.. IgG and IgM antibodies bind to these antigens to form complexes that activate the classical pathway of complement activation for eliminating cells presenting foreign antigens (which are usually, but not in this case, pathogens). As a result mediators of acute inflammation are generated at the site and membrane attack complexes cause cell lysis and death. The reaction takes hours to a day.

18. These reactions are classified into 2 types, ISOIMMUNE REACTION AUTOIMMUNE REACTION ISOIMMUNE REACTION Reaction brought about by the antigen and antibody of two individuals belonging to the same species. 1. Transfusion reaction 2. Erythroblastosis foetalis 3. transplant rejection reaction

19. Cont.. AUTO IMMUNE REATION Reaction brought about by the interaction of antigen and antibody of the same individual. It include autoimmune hemolytic anaemia. The individuals produces antibodies against his own RBC antigens. The red cell coated with antibodies are destroyed in the spleen and liver.

20. MECHANISMS OF CYTOTOXIC REACTION In this reaction the cell damage occurs in following steps, 1) PHAGOCYTOSIS The antibodies are attached to the cell surface antigen Then the macrophage bind to the antibody coated cells The macrophages engulf the antibody coated cells 2) LYSIS The antibody coated cells bind to the phagocytic cells through their receptor for C3b They move continue to fix in sequence up to the lytic c8 and c9 components to cause damage to the cells by the mechanisms similar to that in lysis 3) KILLING The antibody coated cells may be attacked by cytotoxic killer cells which carry receptor for C3b and Fc portion of IgG

21. EXAMPLES Autoimmune haemolytic anaemia Pernicious anemia Immune thrombocytopenia Transfusion reactions Hashimoto's thyroiditis Graves' disease Myasthenia gravis Farmer's Lung Hemolytic disease of the newborn

22. TYPE 3 HYPERSENSITIVITY It is mediated by immune complexes essentially of IgG and IgM antibodies with suitable antigens. Antibody – antigens complexes form in proper concentration of antigen and antibody. Depending on the size of these complexes they may be cleared efficiently by phagocytic cells.

23. MECHANISMS OF TYPE 3 HYPERSENSITIVITY When enormous amount of soluble antigens enter the body , antibodies are produced by B cells. This result in antigen – antibody complex. The immune complexes then get attached to in and around minute capillaries. And they bind to complement. The compliment 3(C3) and 5(C3) produce active factors called anaphylotoxin and chemotoxin . Anphylotoxin triggers the mast cells to release vasoactive amines. The amines increases the tissue permeability. Chemotoxin attracts the polymorphs and promote phagocytosis resulting in the release oh hydrolytic enzymes.

24. Examples: Immune complex glomerulonephritis Rheumatoid arthritis Serum sickness Subacute bacterial endocarditis Symptoms of malaria Systemic lupus erythematosus Arthus reaction

25. TYPE 4 HYPERSENSITIVITY It is caused by the interaction between antigens and sensitized T cells. Lead to inflammatory reaction result in tissue damage. Antibodies are not involved here. As T cells are involved – cell mediated hypersensitivity. Also delayed hypersensitivity. T cells on contact with the antigens produce a soluble protein – lymphokine .

26. MECHANISMS OF TYPE 4 HYPERSENSITIVITY When T cells primed to an antigen come in contact with the same antigen for the second time the cell release lymphokines. This activates macrophages to kill intra cellular bacteria. It involves: TUBERCULIN REACTION It is due to the interaction of sensitized T cells and tuberculin bacterium. It is a delayed hypersensitivity. CONTACT DERMITITIS It is the inflammation of the skin due to contact with a substances to which the person is allergic.

27. Some clinical examples: Contact dermatitis (poison ivy rash, for example) Temporal arthritis Symptoms of leprosy Symptoms of tuberculosis Transplant rejection

28. TYPE 5 HYPERSENSITIVITY It is caused by the interaction of antibodies with cell surface antigen leading to stimulation of cells. While comparing with type 2 ,instead of stimulation destruction of cell occurs. This phenomenon occurs in Graves disease. Stimulation of thyroid cells by TSH is another example.