Hypersensitivity or allergic reactions

hypersensitivity reactions, type I, type II, type III, type IV, hay fever

1. HYPERSENSITIVITY or ALLERGIC REACTIONS By Lalita Shahgond M . Pharm Sem II Pharmacology

2. What Is Hypersensitivity A condition in which the immune system reacts abnormally to a foreign substance. Unwanted immune responses, termed as allergic or hypersensitivity  reactions, are generally classified into four types.

3. Types of hypersensitivity

4. Type I hypersensitivity Also called immediate or anaphylactic hypersensitivity. Often known  simply as ‘allergy’. Type I hypersensitivity occurs in individuals  who predominantly exhibit a th2 rather than a th1 response to  antigen. 

5. In type I hypersensitivity individuals, substances that are not inherently  noxious such as:  -Grass pollen -House dust mites -Certain foodstuffs  or drugs -animal fur  Provoke the production of IgE  antibodies. Such individuals are said to be atopic (out of place).

6. These fix on mast cells, in the lung, and also to  eosinophils.  Subsequent  contact  with  the  substance  causes  the  release of histamine, PAF, eicosanoids and cytokines. The effects  may be  localised  to the nose (hay fever), the bronchial tree (the initial  phase of asthma), the skin ( urticaria ) or the gastrointestinal tract.

7. Hay fever: -pollens -running nose -watery eyes -sneezing

8. Hives or urticaria

9. Common types of allergy Drug allergy : an abnormal reaction of the immune system to a medication. Food allergies : an unpleasant or dangerous immune system reaction after a certain food is eaten. Contact dermatitis : a skin rash caused by contact with a certain substance. Latex allergy : an allergic reaction to certain proteins found in natural rubber latex.

10. Allergic asthma : asthma triggered by exposure to the same substances that trigger allergy symptoms. Seasonal allergies : an allergic response causing itchy, watery eyes, sneezing and other similar symptoms. Animal allergy : an abnormal immune reaction to proteins in an animal's skin cells, saliva or urine. Anaphylaxis : a severe, potentially life-threatening allergic reaction. Allergy to mold : an abnormal allergic reaction to mould spores.

11. Diagnostic test Skin (prick and intradermal) tests Measurement of total IgE and specific IgE antibodies against the suspected allergens by a enzyme immunoassay (ELISA ). Increased IgE levels are indicative of an atopic condition A genetic predisposition for atopic diseases.

12. treatments Antihistamine which block histaminic receptors. Chromolyn sodium inhibits mast cell degranulation by inhibiting Ca 2+ influx. Leukotriene receptors blockers or inhibitors of the cyclooxygenase pathway. Bronchodilators (inhalants) for bronchoconstriction.

13. Inhibitors for cAMP phosphodiesterase. Use of IgG antibodies that binds to mast cells block mast cell sensitization. Hypo-sensitization (immunotherapy or desensitization) to insect venom and pollens.

14. Type II hypersensitivity Also called antibody-dependent cytotoxic hypersensitivity Type II  hypersensitivity occurs when the mechanisms outlined in type I hypersensitivity are  directed against cells within the host that are (or appear to be)  foreign.  For example, host cells altered by drugs are sometimes  mistaken by the immune system for foreign proteins and evoke  antibody formation.

15. The antigen–antibody reaction triggers complement activation (and its sequelae) and may promote attack by NK  cells.  Examples include alteration by drugs of neutrophils, leading  to agranulocytosis or of platelets, leading to thrombocytopenic purpura. These type II reactions are also implicated  in some types of autoimmune thyroiditis (e.g. Hashimoto’s disease)

16. Diagnosis Detection of circulating antibody against the tissue that are involved in hypersensitivity. The presence of antibody and complement in the lesion (biopsy) by immunofluorescence.

17. Treatment Anti inflammatory agents immunosuppressive agents

18. Type III hypersensitivity Also called complex-mediated hypersensitivity, type III hypersensitivity  occurs  when  antibodies  react  with  soluble  antigens.  The  antigen–antibody complexes can activate complement or attach to  mast cells and stimulate the release of mediators.

19. Arthus reaction that occurs if  a foreign protein is injected subcutaneously into a rabbit or guinea  pig with high circulating concentrations of antibody.  Within 3–8  hours  the  area  becomes  red  and  swollen  because  the  antigen– antibody complexes precipitate in small blood vessels and activate  complement.   Type III hypersensitivity is also implicated in lupus erythematosus (a  chronic, autoimmune inflammatory disease).

20. Neutrophils are attracted and activated (by c5a) to  generate toxic oxygen species and to secrete enzymes. Mast cells are also stimulated by c3a to release mediators.  Damage  caused by this process is involved in serum sickness, caused when  antigen persists in the blood after  sensitisation , causing a severe  reaction, as in the response to  mouldy  hay (known as farmer’s lung),  and in certain types of autoimmune kidney and arterial disease. 

21. diagnosis Tissue biopsies for deposits of Ig and complement by immunofluorescence. The presence of immune complexes in serum and depletion in the level of complement. Polyethylene glycol mediated turbidity to detect immune complexes. Treatment Anti inflammatory agents

22. Type IV hypersensitivity Also known as cell mediated or delayed hypersensitivity The prototype of type IV hypersensitivity is the tuberculin reaction, a local  inflammatory response seen when proteins derived from cultures of  the tubercle bacillus are injected into the skin of a person who has  been  sensitised  by a previous infection or  immunisation . 

23. An ‘inappropriate’ cell-mediated immune response is stimulated, accompanied by infiltration of mononuclear cells and the release of various  cytokines. Cell-mediated hypersensitivity is also the basis of the  reaction seen in some other infections (e.g. Mumps and measles), as  well as with mosquito and tick bites. 

24. It is also important in the skin  reactions to drugs or industrial chemicals, where the  chemical (termed a  hapten ) combines with proteins in the skin to  form the ‘foreign’ substance that evokes the cell-mediated immune  response. In essence, inappropriately deployed t-cell activity underlies  all  types  of  hypersensitivity,  initiating  types I,  II   and  III,  and  being  involved  in  both  the  initiation    and the effector phase in type IV.  These reactions are the  basis of the clinically important group of autoimmune  diseases. 

25. Immunosuppressive drugs and/or glucocorticoids are routinely employed to treat such  disorders. In essence, inappropriately deployed t-cell activity underlies  all  types  of  hypersensitivity,  initiating  types  I ,  II   and III,  and  being  involved  in  both  the  initiation    and the effector phase in type IV.  These reactions are the  basis of the clinically important group of autoimmune  diseases. Immunosuppressive drugs and/or glucocorticoids are routinely employed to treat such  disorders.

26. Classification Of Type IV Hypersensitivity

27. Diagnostic and treatment In vivo include: delayed cutaneous reaction ( montoux test) and patch test (for contact dermatitis) In vitro include: mitogenic response, lympho- cytoxicity , and IL-2 production. Treatment: Corticosteroids and other immunosuppressive agents

28. Reference: Rang HP, Ritter JM, flower RJ, H enderson G. Rang & dale's pharmacology. Chapter 6: cellular mechanism : host defence . Elsevier health sciences; 8 th edition 2016 dec 2; pg : 88-89.