HYPERSENSITIVITY REACTIONS Flashcards
What are Hypersensitivity reactions? What are the types?
- Hypersensitivity refers to excessive, undesirable (damaging, discomfort-producing and sometimes fatal) reactions produced by the normal immune system.
- Hypersensitivity reactions require a pre-sensitized (immune) state of the host.
- Hypersensitivity reactions can be divided into four types: type I (A-anaphylactic) , type II (C-cytotoxic), type III (I-immune-complex) and type IV (D- delayed), based on the mechanisms involved and time taken for the reaction.
What is Type I hypersensitivity?
What do symptoms include and how long do they usually take to manifest?
What antibody is it mediated by and what is it’s primary cellular component?
Type I hypersensitivity is also known as immediate or anaphylactic hypersensitivity.
It may involve skin (urticaria and eczema), eyes (conjunctivitis), nasopharynx (rhinorrhea, rhinitis), bronchopulmonary tissues (asthma) and gastrointestinal tract (gastroenteritis).
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).
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.
What is the mechanism of Type I Hypersensitivity?
The mechanism of reaction involves preferential production of IgE, in response to certain antigens (often called allergens).
The precise mechanism as to why some individuals are prone to type-I hypersensitivity is not clear. However, it has been shown that such individuals preferentially produce more TH2 cells that secrete IL-4, IL-5 and IL-13 which in turn favour IgE (from IgM) class switch.
The naive T helper cells first comes in contact with the allergen through APC’s and it then primed and differentiates into TH2 (IL-4 from APC enables this conversion)
TH-2 releases IL-4 (and IL-13) which activates the class-switch of the B-cell to cause it to become a plasma cell whihc produces IgE antibodies.
IgE has very high affinity for its receptor (Fcε; CD23) on mast cells and basophils.
A subsequent exposure to the same allergen, the allergen cross links the cell-bound IgE and triggers the release of various pharmacologically active substances (degranulation).
Cross-linking of IgE Fc-receptor is important in mast cell triggering.
Mast cell degranulation is preceded by increased Ca2+ influx, which is a crucial process; ionophores (a class of compounds that form complexes with specific ions and facilitate their transport across cell membranes) which increase cytoplasmic Ca2+ also promote degranulation, whereas, agents which deplete cytoplasmic Ca2+ suppress degranulation
What are the Preformed mediators in granules of immediate hypersensitivity and what do they cause? [THEK]
Histamine: Bronchoconstriction, mucus secretion, vasodilatation, vascular permeability
Tryptase: Proteolysis
Kininogenase: Kinins and vasodilatation, vascular permeability, edema
ECF-A (tetrapeptides): Attract eosinophil and neutrophils
What are the Newly formed mediators in granules of immediate hypersensitivity and what do they cause? [L2P2]
Leukotriene B4: Basophil attractant
Leukotriene C4, D4: Same as histamine but 1000x more potent
Prostaglandins D2: Edema and pain
PAF & Heparin: platelet aggregation and heparin release: microthrombi
What are the Diagnostic tests for immediate hypersensitivity?
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.).
What is the symptomatic treatment of Type I Hypersensitivity?
Symptomatic treatment is achieved with
- Anti-histamines which block histamine receptors.
- Chromolyn sodium inhibits mast cell degranulation, probably, by inhibiting Ca2+ influx.
- Late onset allergic symptoms, particularly bronchoconstriction which is mediated by leukotrienes, are treated with leukotriene receptor blockers (Singulair, Accolate) or inhibitors of the cyclooxygenase pathway (Zileutoin).
- Symptomatic relief from bronchoconstriction is provided by bronchodilators (inhalants) such as isoproterenol derivatives (Terbutaline, Albuterol).
- Theophylline elevates cAMP by inhibiting cAMP-phosphodiesterase and inhibits intracellular Ca2+ release is also used to relieve bronchopulmonary symptoms.
- The use of IgG antibodies against the Fc portions of IgE that binds to mast cells has been approved for treatment of certain allergies, as it can block mast cell sensitization.
- Hyposensitization (immunotherapy or desensitization) is another treatment modality which is successful in a number of allergies, particularly to insect venoms and, to some extent, pollens.
What is Type II hypersensitivity and examples?
Reaction time?
Mediated by which antibodies?
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.
The reaction time is minutes to hours.
Type II hypersensitivity is primarily mediated by antibodies of the IgM or IgG classes and complement. Phagocytes and K cells may also play a role.
The lesion contains antibody, complement and neutrophils.
What are the Diagnostic tests for Type II hypersensitivity?
Diagnostic tests include detection of circulating antibody against the tissues involved and the presence of antibody and complement in the lesion (biopsy) by immunofluorescence.
What is the Treatment of Type II Hypersensitivity?
Treatment involves anti-inflammatory and immunosuppressive agents
What is Type III hypersensitivity? What is it mediated by?
Type III hypersensitivity is also known as immune complex hypersensitivity.
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), blood vessels (e.g., polyarteritis), joints (e.g., rheumatoid arthritis) or other organs.
This reaction may be the pathogenic mechanism of diseases caused by many microorganisms.
The reaction may take 3 - 10 hours after exposure to the antigen (as in Arthus reaction).
It is mediated by soluble immune complexes 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.
Primary components are soluble immune complexes and complement (C3a, 4a and 5a).
How is damage caused (mechanism of damage) in Type III Hypersensitivity?
The damage is caused by platelets and neutrophils with lesion containing neutrophils and deposits of immune complexes and complement.
Macrophages infiltrating in later stages may be involved in the healing process.
The affinity of antibody and size of immune complexes are important in production of disease and determining the tissue involved.
What is the diagnosis for Type III Hypersensitivity?
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.
What is the treatment for Type III Hypersensitivity?
Treatment includes anti-inflammatory agents.
What is Type IV Hypersensitivity and examples?
Type IV hypersensitivity is also known as cell mediated or delayed type hypersensitivity.
The classical example of this hypersensitivity is tuberculin (Montoux) reaction which peaks 48 hours after the injection of antigen (PPD or old tuberculin).
The lesion is characterized by induration and erythema.
Type IV hypersensitivity is involved in the pathogenesis of many autoimmune and infectious diseases (tuberculosis, leprosy, blastomycosis, histoplasmosis, toxoplasmosis, leishmaniasis, etc.) and granulomas due to infections and foreign antigens.
Another form of delayed hypersensitivity is contact dermatitis (poison ivy, chemicals, heavy metals, etc.) in which the lesions are more papular
