1. and Immunity

3.  Coombs and Gell classification 1-Type I - immediate ( atopic, or anaphylactic) 2-Type II - antibody-dependent 3-Type III - immune complex 4-Type IV - cell-mediated or delayed

4. Type I - immediate (or atopic, or anaphylactic)  Type I hypersensitivity is an allergic reaction provoked by re-exposure to a specific antigen. antigen  Exposure may be by ingestion, inhalation, injection, or direct contact. ingestioninhalationinjection  The reaction is mediated by IgE antibodies and produced by the immediate release of histamine, tryptase, arachidonate and derivatives by basophils and mast cells.. IgEantibodies histamine tryptasearachidonate basophils mast cells

5.  This causes an inflammatory response leading to an immediate (within seconds to minutes) reaction. inflammatory  The reaction may be either local or systemic. Symptoms vary from mild irritation to sudden death from anaphylactic shock. anaphylactic shock  Treatment usually involves epinephrine, antihistamines, and corticosteroids epinephrine antihistamines corticosteroids

6. Some examples:  Allergic asthmaasthma  Allergic conjunctivitisconjunctivitis  Allergic rhinitis ("hay fever") Allergic rhinitis  Anaphylaxis Anaphylaxis  Angioedema Angioedema  Urticaria (hives ) Urticaria

7.  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

8.  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). IgGIgMclassical pathway complement  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.membrane attack complexes

9.  Autoimmune haemolytic anaemiaanaemia  Pernicious anemia Pernicious anemia  Immune thrombocytopenia Immune thrombocytopenia  Transfusion reactions Transfusion  Hashimoto's thyroiditis Hashimoto's thyroiditis  Graves' disease Graves' disease  Myasthenia gravis Myasthenia gravis  Farmer's Lung Farmer's Lung  Hemolytic disease of the newborn Hemolytic disease of the newborn

10. In type III hypersensitivity :  soluble immune complexes (aggregations of antigens and IgG and IgM antibodies) form in the blood and are deposited in various tissues (typically the skin, kidney and joints )bloodskin kidneyjoints  This may trigger an immune response according to the classical pathway of complement activation.  The reaction takes hours to days to develop

11. Examples:  Immune complex glomerulonephritisglomerulonephritis  Rheumatoid arthritis Rheumatoid arthritis  Serum sickness Serum sickness  Subacute bacterial endocarditisendocarditis  Symptoms of malariamalaria  Systemic lupus erythematosuslupus erythematosus  Arthus reaction Arthus reaction

12. Type IV Hypersensitivity  Type IV hypersensitivity is often called delayed type as the reaction takes two to three days to develop.  Unlike the other types, it is not antibody mediated but rather is a type of cell- mediated response.

13. Some clinical examples:  Contact dermatitis (poison ivy rash, for example) Contact dermatitis  Temporal arteritis Temporal arteritis  Symptoms of leprosyleprosy  Symptoms of tuberculosistuberculosis  Transplant rejection Transplant rejection

14. The hypersensitivity reactions

16.  Type I hypersensitivity is also known as immediate or anaphylactic hypersensitivity.anaphylactic  The reaction may involve skin (urticaria and eczema), eyes (conjunctivitis), nasopharynx (rhinorrhea, rhinitis), bronchopulmonary tissues (asthma) and gastrointestinal tract (gastroenteritis)

17.  The reaction may cause a range of symptoms from minor inconvenience to death.  The reaction usually takes 15 - 30 minutes from the time of exposure to the antigen.  sometimes it may have a delayed onset (10 - 12 hours).

18.  Immediate hypersensitivity is mediated by IgE.  The primary cellular component in this hypersensitivity is the mast cell or basophil.  The reaction is amplified and/or modified by platelets, neutrophils and eosinophils.  A biopsy of the reaction site demonstrates mainly mast cells and eosinophils.

19.  The mechanism of reaction involves preferential production of IgE, in response to certain antigens ( allergens ).  IgE has very high affinity for its receptor on mast cells and basophils.  A subsequent exposure to the same allergen cross links the cell-bound IgE and triggers the release of various pharmacologically active substances  Cross-linking of IgE Fc-receptor is important in mast cell triggering. Mast cell degranulation is preceded by increased Ca ++ influx, which is a crucial process; ionophores which increase cytoplasmic Ca++ also promote degranulation, whereas, agents which deplete cytoplasmic Ca++ suppress degranulation. ionophoresdegranulation

21.  Type II hypersensitivity is also known as cytotoxic hypersensitivity and may affect a variety of organs and tissues.  The antigens are normally endogenous, although exogenous chemicals (haptens) which can attach to cell membranes can also lead to type II hypersensitivity.haptens Examples: - Drug-induced hemolytic anemia -Granulocytopenia -Thrombocytopenia

22.  The reaction time is minutes to hours.  Type II hypersensitivity is primarily mediated by antibodies of the IgM or IgG classes and complement

24.  Also known as immune complex disease  occurs when immune complex (Ag-Ab) are not removed from circulation  These complexes are deposited in various tissues and organs such as: - Kidneys - Joints - Lung - Skin

25.  Immune complex formation may occur as a result of : Autoimmune diseases (RA) Persistence infection (Hepatitis virus) Repeated inhalation of antigenic materials

26. Large quantities of soluble antigen- antibody complexes form in the blood and are not completely removed by macrophages.

27. These antigen- antibody complexes lodge in the capillaries between the endothelial cells and the basement membrane.

28. These antigen- antibody complexes activate the classical complement pathway leading to vasodilatation.

29. The complement proteins and antigen-antibody complexes attract leukocytes to the area.

30. The leukocytes discharge their killing agents and promote massive inflammation. This can lead to tissue death and hemorrhage.

32.  Type IV hypersensitivity is also known as cell mediated or delayed type hypersensitivity.  The classical example of this hypersensitivity is tuberculin (Montoux) reaction  Reaction peaks 48 hours after the injection of antigen (PPD or old tuberculin). The lesion is characterized by induration and erythema

34.  Type IV hypersensitivity is involved in the pathogenesis of many autoimmune and infectious diseases:  Tuberculosis  Leprosy  Blastomycosis  Histoplasmosis  Toxoplasmosis  Leishmaniasis  Granulomas due to infections and foreign antigens.

36.  Another form of delayed hypersensitivity is contact dermatitis (poison ivy (figure 6), chemicals, heavy metals, etc. ) in which the lesions are more papular  Type IV hypersensitivity can be classified into three categories depending on the time of onset and clinical and histological presentation

37. T ype R eaction time C linical appearance H istology A ntigen and site contact48-72 hreczema lymphocytes, followed by macrophages; edema of epidermis epidermal ( organic chemicals, poison ivy, heavy metals, etc. ) tuberculin48-72 hr local induratio lymphocytes, monocytes, macrophages intradermal (tuberculin, lepromin, etc. ) granuloma21-28 dayshardening macrophages, epitheloid and giant cells, fibrosis persistent antigen or foreign body presence (tuberculosis, leprosy, etc. )

38.  The mechanism includes T lymphocytes and monocytes and/or macrophages.  Cytotoxic T cells (Tc) cause direct damage whereas helper T (TH1) cells secrete cytokines which activate cytotoxic T cells, recruit and activate monocytes and macrophages, which cause the bulk of the damage  The delayed hypersensitivity lesions mainly contain monocytes and a few T cells.

39.  Diagnostic tests in vivo include delayed cutaneous reaction ( e.g. Montoux test )  In vitro tests for delayed hypersensitivity include mitogenic response, lympho- cytotoxicity and IL-2 production.  Corticosteroids & other immunosuppressive agents are used in treatment.

41.  Immunity is the body's ability to fight off harmful micro-organisms –PATHOGENS- that invade it.  The immune system produces antibodies or cells that can deactivate pathogens.  Fungi, protozoans, bacteria, and viruses are all potential pathogens.

42. 1. INNATE:SPECIFIC NON SPECIFIC.SPECIES.RACIAL.INDIVIDUAL 2.ACQUIRED:.ACTIVE -NATURAL AND ARTIFICIAL.PASSIVE-NATURAL AND ARTIFICIAL

43. It is due to genetic and constitutional make- up of an individual

44. Nonspecific immunity – It indicates a degree of resistance to infections in general. Species immunity – Refers to the resistance to a pathogen shown by all members of a species for example all human beings are totally unsusceptible to plant pathogens. Racial immunity – Different races within a species, may show differences in susceptibility to infections for example in some parts of Africa resistance to Plasmodium falciparum malaria is seen

45. Individual immunity – It is the difference in innate immunity shown by different individuals within a race. Several factors such as age, hormones and nutrition influence the level of innate immunity in an individual

46. Age: The very young and very old are more prone to infectious diseases than the rest. The fetus in utero is normally protected by placental barrier. But some pathogens cross this barrier. Some, such as rubella virus, herpes viruses, cytomegaloviruses and parasite Toxoplasma gondii, can lead to congenital infections. The increased susceptibility of the fetus to infection is due to immaturity of its immune system. Old persons are more susceptible to infections due to their waning immune responses and other factors, like enlarged prostate leading to stasis of urine

47. Nutrition: Both cell mediated and antibody mediated immune responses are depressed when there in malnutrition. Cell mediated immune responses such as Mantoux test for tuberculosis becomes negative in severe protein deficiency, as in kwashiorkor. Specific immunity – It refers to the resistance to a particular pathogen.

48. Species Racial Individual MECHANISM OF INNATE IMMUNITY Epithelial surfaces: The intact skin and mucous membrane covering the body protect it against invasion of microorganisms. The bactericidal activity of skin secretions can be illustrated by frequent fungal and bacterial infections in individuals who immerse their hands in soapy water for long periods of time occupationally for example washer men

49. Hormonal influences: Endocrine disorders like diabetes mellitus are associated with increased risk of infections. The increased risk may be related to increased levels of carbohydrate in tissues. Corticosteroids depress the individuals resistance by its anti inflammatory and anti phagocytic effects. The effect of stress in increasing susceptibility to infections may be due to release of steroids.