USMLE Step 1 Web Prep — Failures of the Immune System: Hypersensitivity
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Types of Hypersensitivity
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There are four major types of hypersensitivity. Three are mediated by antibody, and
the fourth is mediated by cellular mechanisms.
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Type I Hypersensitivity
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Common allergens in immediate-hypersensitivity reactions causing respiratory
symptoms include:
i.
Tree, grass, and weed pollens
ii.
Cat antigen and other animal dander antigens
iii.
Dust mite fecal pellet antigens
iv.
Mold spores
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In a Nutshell: Type I Immediate Reaction Hypersensitivity
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First exposure sensitizes host
Macrophages and B cells present epitopes to Th2 cells, which produce interleukin
(IL)-4
IL-4 causes class switch to IgE
Mast cells and basophils bind IgE to high-affinity receptors
IgE cross-linking initiates granule release
These granules contain histamine, heparin, and proteases that induce edema,
increased mucus secretion, and smooth muscle contraction; this is the immediate
reaction that occurs
The cells also synthesize prostaglandins and leukotrienes LTC4 and LTD4, which
mediate the late-phase (4-6 hours later) inflammatory response
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Clinical Correlate: Diagnosis of Atopic Disease
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In vivo skin testing with batteries of allergens
In vitro RAST test (quantitate specific IgE levels)
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Therapies for immediate hypersensitivities
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Avoidance
Antihistamine (Benadryl)
Cromolyn sodium
Epinephrine
Theophylline (xanthines)
Immunotherapy by injecting small amounts of allergen
Corticosteroids
-Adrenergic agonists
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Cytotoxic Type II Hypersensitivity
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Antibody-mediated hypersensitivity against our own cells or receptors or membranes
Type II or cytotoxic hypersensitivity is mediated by IgG or IgM antibodies against
tissue antigens. The result is organ-specific antibody production. Antibody binds to
cells or tissues and causes local complement activation, influx of leukocytes, and
tissue destruction because of ADCC, degranulation by phagocytes, and production of
oxygen radicals.
An example is hemolytic disease of the newborn.
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Noncytotoxic Type II Hypersensitivity
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Also due to the production of tissue-specific IgG autoantibody.
Instead of causing cytotoxic tissue destruction, the antibody in these cases alters
cellular structure or function
An example is Graves’ disease
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Other examples of type II hypersensitivity
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Myasthenia gravis: An autoantibody against the patient’s own acetylcholine receptors
in which the antibody removes and internalizes the receptors.
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Clinical Correlate: Cytotoxic Antibody Disease
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Erythroblastosis fetalis
Transfusion reactions
Hyperacute graft rejection
Acquired hemolytic anemia: autoimmune, drug-induced
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Other examples of type II hypersensitivity
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Goodpasture syndrome: An autoantibody produced against the patient’s own type IV
collagen present in basement membranes of kidney and lung.
Autoimmune hemolytic anemia: An autoantibody produced against the patient’s own
red blood cell antigens (eg. I antigen).
Autoimmune thrombocytopenic purpura: An autoantibody produced against the
patient’s own platelet integrin.
Hyperacute graft rejection: The recipient of a graft already has preformed antibody
against the graft; after receiving the graft it is rejected within hours.
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Clinical Correlate: Therapy for Type II (and III) Hypersensitivities
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Withhold allergenic drug
Remove antibodies
i.
Exchange transfusion
ii.
Plasmapheresis
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Use immunosuppressive agents:
i.
Corticosteroids
ii.
Cytoxan
iii.
Cyclosporin A
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Type III: Immune complex hypersensitivity
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Caused by high levels of circulating, soluble immune complexes containing IgG or IgM
antibody.
Circulating immune complexes overwhelm the ability of the mononuclear phagocyte
system to remove them and deposit in various tissues (eg. skin, glomeruli, blood
vessels, synovium, lungs) and activate complement.
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Examples of type III hypersensitivity immune complex diseases
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Arthus reaction
Serum sickness
Hypersensitivity pneumonitis
Post-streptococcal glomerulonephritis
Lupus
Rheumatoid arthritis
Certain infectious diseases, eg. hepatitis B, HIV, and mycobacterium
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Type IV: Delayed-type hypersensitivity (DTH)
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T-cell-mediated response that gets its name from the long time (48-96 hours) that it
takes for a skin reaction against the antigen to develop.
Th1 cells recognize the antigenic peptide presented by an antigen-presenting cell and
secrete cytokines (interferon-) that activate macrophages. Macrophage mediators then
produce the damage in tissues. Antibody and complement play no role in DTH.
Antigens may be intracellular bacterial pathogens (Mycobacterium tuberculosis,
Mycobacterium leprae), viruses, fungi, or intracellular parasites; they also may be
environmental antigens (eg. poison ivy and nickel) that bind to, and alter, host cell
surfaces, resulting in contact dermatitis.
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Common contact allergens
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Poison ivy (catechols)
Nickel
Formaldehyde
Latex
Chromium
Dyes in clothing and cosmetics