Hypersensitivity Reactions Flashcards
Define Allergy and anaphylaxis (Type I)
Rapidly progressing immune reaction through antigen binding to surface of IgE-coated basophils or mast cells
- -> “immediate hypersensitivity”
- -> e.g. respiratory allergies, allergic asthma, hives, food allergies, anaphylaxis
Define Anaphylaxis
Induced by insect venoms, penicillin, seafood, nuts, etc
–> Allergens - directly into bloodstream or rapidly absorbed fro gut (systemic mast cell activation
Define Atopy
Atopic = increased tendency to develop allergies
- -> usually IgE response to parasites, but atopic individuals make IgE to allergens
- -> Th2 responses = absence of inflammation (which allergens DONT elicit)
- -> physiologic responses to parasites usually in skin, airways and gut are the same places as most allergic responses
Define Hygiene hypothesis
deceases exposure to pathogens early in life leads to Th2-mediated immunity and IgE
Define Respiratory allergen
small molecules carried on larger particles (pollen grains or mite feces)
- -> soluble allergen elutes and diffuses into the mucosa at very small doses
- -> transmucuosal delivery in very low doses = effective at eliciting Th-2 mediated IgE response
Describe Basophils
- contain basophilic granules that contain lots of histamine
- NON-phagocytic
- related to tissue mast cells
- -> PROMINENT role in allergies and anaphylaxis
Describe the development of anaphylaxis
- 1st exposure to allergen –> IgE (no anaphylaxis on 1st exposure)
- Penicillin is hapten –> must couple to self proteins to stimulate IgE
- IgE binds to Fc receptors on basophils + mast cells
- Subsequent exposure to allergen binds to surface-bound Ige –> cells release granule contents (histamine)
- Granule contents contain vasoactive compounds –> edema and smooth muscle contraction –> symptoms and possibly death (trouble breathing, and lungs filling up with fluid)
Describe the effects of Histamine
Bronchial smooth muscle contraction + increased vascular permeability
Describe Leukotrienes (LT)
Most potent substances known that cause smooth muscle contraction and increased vascular permeability
- -> released more slowly (synthesized) + longer effect
- -> in contrst: histamine = released quickly + shorter effect
Describe eosinophils
Accumulate in nasal and bronchial mucosa in respiratory allergies and in intestinal mucosa during certain worm infestations:
–> attach to worms and release granules containg hydrolytic enzymes
Describe Late phase response
2nd phase of smooth muscle contraction
–> sustained edema
–> recruitment of eosinophils and Th2 Cells
Remodeling of tissue –> eg smooth muscle hypertrophy + hyperplasia
May lead to chronic asthma and associated airways hyperactivity
Describe treatments of type I
- Enjections of epinephrine
- repeated subcutaneous allergen injections –> IgE levels decrease and IgG levels increase
- Humanized mouse anti-IgE antibodies –> binds IgE to prevent binding to IgE receptors
Describe Non-cytotoxic reactions (both are autoimmune diseases)
Graves disease = antibodies to TSH receptor causes overproduction of thyroid hormones –> hyperthyroidism
Myasthenia gravis = antibodies to acetylcholine receptor blocks nerve impulse transmission to muscles
Describe Type III - immune complex diseases
Pathogenesis: Antigen + antibody = immune complexs
- -> antigen must persist for long periods for disease to develop
- -> optimal proportions of antibody and antigen are required
Pathogenic process:
- immune coplexes lodge in tissues (skin/kidney etc)
- complement activation –> C5a –> neutrophil accumulation
- lysosomal enzymes damage tissue
Define Serum sickness
Protoype immune complex disease = serum sickness
–> occurs as a consequence of repeat injection of foreign serum
Foreign serum = horse anti-tetanus serum etc
Describe Delayed type hypersensitivity (Type Iv)
Manifests 24-72 hours after exposure to antigen
- -> tuberculin reaction, contract dermatitis, delayed graft rejection
- -> cell mediated immune response, therefore mediated by Th1 cells
- -> memory response: requires prior sensitization to antigen
Define Contact dermatitis
skin exposure to nickel, chromium, cosmetics, hair dye, poison oak, etc
- -> small molecules complexed with skin proteins are presented on antigen presenting cells to T helper cells
- -> ex: poison ivey leaf oil is lipid soluble and crosses cel membrane to modify intracellular proteins that are experssed on class I MHC for recognition by CTL’s
- -> CD4 and CD8 cells secrete inflammatory cytokins, including IFN-gamma
Describe granuloma formation in Typic IV
Antigen not eradicted –> DTH –> granuloma (walled off bacteria)
- -> small basic DTH mechanism, but different outcome
- -> macrophages ingest organism, surrounded by other macrophages
- -> CD4 lymphocytes surround macrophages to maintain macrophage activation + structural integrity of the granuloma
Describe type I immunity
Immediate
Immune mechanism = IgE and Th2 cells
–> Mast cells, eosinophils and their mediators involved
Describe type II immuity
Antibody mediated
Immune mechanism = IgM and IgG antibodies against cell surface or ECM antigens
- -> Osonization, Phagocytosis of cells
- -> complement- and Fc Receptor mediated recruitment and activation of leukocytes
Describe Type III immunity
Immune complex mediated
Immune mechanism = immune complexes of circulating antigens and IgM or IgG antibodies
–> complement and Fc receptor mediated recruitment and activation of leukocytes
Describe Type IV immunity
T-cell mediated
Immune mechanism = CD4 T cells and CD8 CTL’s
- -> cytokine-mediated inflammation
- -> direct target cell killing
