Hypersensitivity

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hypersensitivity,hypersensitivity, pathophysiology, pathology, pharmd, vels, hypersensitivity reactions, immunoglobulin e, immunoglobulin g, hypersensitivity types

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Hypersensitivity

  1. 1.  Hypersensitivity refers to undesirable reactions produced by the normal immune system, including allergies and autoimmunity  These reactions may be damaging, uncomfortable, or occasionally fatal.
  2. 2.  TYPE I – IMMEDIATE, ATOPIC, ANAPHYLACTIC  TYPE II – ANTIBODY DEPENDANT  TYPE III – IMMUNE COMPLEX  TYPE IV – CELL MEDIATED / DELAYED TYPE OF HYPERSENSITIVITY
  3. 3.  Type I hypersensitivity is also known as immediate or anaphylactic hypersensitivity.  The reaction may involve skin (urticariaand eczema), eyes (conjunctivitis), nasopharynx (rhinorrhea, rhinitis), bronchopulmonary tissues (asthma) and gastrointestinal tract (gastroenteritis).
  4. 4.  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, although sometimes it may have a delayed onset (10 - 12 hours).
  5. 5.  Mediated by IgE antibody to specific antigens  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.  Mast cells stimulated and release histamine
  6. 6.  ALLERGEN:Allergens are nonparasite antigens that can stimulate a type I hypersensitivity response.
  7. 7.  Atopy is the term for the genetic trait to have a predisposition for localized anaphylaxis.  Atopic individuals have higher levels of IgE and eosinophils.
  8. 8.  Initial introduction of antigen produces an antibody response. More specifically, the type of antigen and the way in which it is administered induce the synthesis of IgE antibody in particular.  Immunoglobulin IgE binds very specifically to receptors on the surface of mast cells, which remain circulating.
  9. 9.  Reintroduced antigen interacts with IgE on mast cells causing the cells to degranulate and release large amounts of histamine, lipid mediators and chemotactic factors that cause smooth muscle contraction, vasodilation, increased vascular permeability, broncoconstriction and edema. These reactions occur very suddenly, causing death.
  10. 10.  Histamine  Cytokines TNF- , IL-1, IL-6.  Chemoattractants for Neutrophils and Eosinophils.  Enzymes tryptase, chymase, cathepsin.  Changes in connective tissue matrix, tissue breakdown  Leukotrienes  Prostaglandins
  11. 11.  Diagnostic tests for immediate hypersensitivity include skin (prick and intradermal) tests , measurement of total IgE and specific IgE antibodies against the suspected allergens.  Total IgE and specific IgE antibodies are measured by a modification of enzyme immunoassay (ELISA).  Increased IgE levels are indicative of an atopic condition, although IgE may be elevated in some non-atopic diseases (e.g., myelomas, helminthic infection, etc.).
  12. 12.  Drugs. › Non-steroidal anti-inflammatories › Antihistamines block histamine receptors. › Steroids › Theophylline OR epinephrine -prolongs or increases cAMP levels in mast cells which inhibits degranulation.  Immunotherapy › Desensitization (hyposensitization) also known as allergy shots. › Repeated injections of allergen to reduce the IgE on Mast cells and produce IgG.
  13. 13.  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.  Drug-induced hemolytic anemia, granulocytopenia and thrombocytopenia are such examples. Pencillin allergy also belong to this class.
  14. 14.  The reaction time is minutes to hours.  Type II hypersensitivity is primarily mediated by antibodies of the IgM or IgG classes and complement .  Phagocytes may also play a role.  The lesion contains antibody, complement and neutrophils.
  15. 15. Rh factor incompatibility  IgG abs to Rh an innocuous rbc antigen › Rh+ baby born to Rh- mother first time fine. 2nd time can have abs to Rh from 1st pregnancy. › Ab crosses placenta and baby kills its own rbcs. › Treat mother with ab to Rh antigen right after birth and mother never makes its own immune response.
  16. 16.  Diagnostic tests include detection of circulating antibody against the tissues involved and the presence of antibody and complement in the lesion (biopsy) by immunofluorescence.  The staining pattern is normally smooth and linear, such as that seen in Goodpasture's nephritis (renal and lung basement membrane)  Treatment involves anti-inflammatory and immunosuppressive agents
  17. 17.  Antigen antibody immune complexes. IgG mediated  Large amount of antigen and antibodies form complexes in blood.  If not eliminated can deposit in capillaries or joints and trigger inflammation.
  18. 18.  The reaction may be general (e.g., serum sickness) or may involve individual organs including skin (e.g., systemic lupus erythematosus, Arthus reaction), kidneys (e.g., lupus nephritis), lungs (e.g., aspergillosis), joints (e.g., rheumatoid arthritis) or other organs.  This reaction may be the pathogenic mechanism of diseases caused by many microorganisms.
  19. 19.  The reaction may take 3 - 10 hours after exposure to the antigen .  It is mediated by soluble immune complexes.  They are mostly of the IgG class, although IgM may also be involved.  The antigen may be exogenous (chronic bacterial, viral or parasitic infections), or endogenous (non-organ specific autoimmunity: e.g., systemic lupus erythematosus, SLE).  The antigen is soluble and not attached to the organ involved
  20. 20.  PMNs and macrophages bind to immune complexes via FcR and phagocytize the complexes. BUT  If unable to phagocytize the immune complexes can cause inflammation via C’ activation ---> C3a C4a, C5a and "frustrated phagocytes".
  21. 21.  Diagnosis involves examination of tissue biopsies for deposits of immunoglobulin and complement by immunofluorescence microscopy.  The presence of immune complexes in serum and depletion in the level of complement are also diagnostic.  Treatment includes anti-inflammatory agents.
  22. 22.  Reaction involves sensitized T cells and release of its lymphokines as mediators and amplifiers  Mediated by cells rather than antibodies  Clinical states: Contact dermatitis, , Transplant rejection, Granuloma
  23. 23.  Th1 cells release cytokines to activate macrophages causing inflammation and tissue damage.  Continued macrophage activation can cause chronic inflammation resulting in tissue lesions, scarring, and granuloma formation.  Response starts after 48 -72 hrs
  24. 24. Delayed hypersensitivity reactions Type Reaction time Clinical appearance Histology Antigen and site Contact dermatitis 48-72 hr eczema lymphocytes, followed by macrophages; edema of epidermis epidermal ( organic chemicals, poison ivy, heavy metals, etc.) tuberculin 48-72 hr local induration lymphocytes, monocytes, macrophages intradermal (tuberculin, lepromin, etc.) granuloma 21-28 days hardening macrophages, epitheloid and giant cells, fibrosis persistent antigen or foreign body presence (tuberculosis, leprosy, etc.)
  25. 25.  Diagnostic tests in vivo include delayed cutaneous reaction (e.g. Montoux test and patch test (for contact dermatitis).  In vitro tests for delayed hypersensitivity include mitogenic response, lympho- cytotoxicity and IL-2 production.  Corticosteroids and other immunosuppressive agents are used in treatment.
  26. 26. Comparison of Different Types of hypersensitivity characteris tics type-I anaphylactic type-II (cytotoxic) type-III (immune complex) type-IV (delayed type) antibody IgE IgG, IgM IgG, IgM None antigen exogenous cell surface soluble tissues & organs response time 15-30 minutes minutes-hours 3-8 hours 48-72 hours appearan ce weal & flare lysis and necrosis erythema and edema, necrosis erythema and induration histology basophils and eosinophil antibody and complement complement and neutrophils monocytes and lymphocytes transferred with antibody antibody antibody T-cells examples allergic asthma, hay fever erythroblastosis fetalis, Goodpasture's nephritis SLE, farmer's lung disease tuberculin test, poison ivy, granuloma

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