Post on 07-Nov-2014
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Immune Disorders
Chapter 21
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HYPERSENSITIVITY
IMMEDIATE DELAYED
TYPE I Ig E - mediated
TYPE IICytotoxic
TYPE IIIImmune Complex
TYPE IVCellular
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• Type I Hypersensitivity Is Induced by Allergens• The sensitizing dose is
the first dose of antigen• The immune system
responds as it would a pathogen
• The person is sensitized as IgE antibodies attach to mast cells and basophils
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• On subsequent allergen exposure, IgE antibodies are cross-linked
• This causes degranulation, which releases mediator substances:• Histamine is released
into the blood and causes smooth muscle cell constriction
• Leukotrienes are potent smooth muscle constrictors
• Prostaglandins can constrict bronchial tubes
• Cytokines can also stimulate/inhibit inflammation
• IL4, IL5, TNF-£
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• Is the Most Dangerous Form of a Type I Hypersensitivity
• Allergens in the bloodstream can trigger mast cell degranulation that contracts smooth muscle
• Small veins constrict and capillary pores expand, forcing fluid into the tissues• A drop in blood pressure, edema, and rash
occur
• Contractions in the gastrointestinal tract and bronchial muscles cause cramps and shortness of breath
• The lungs fill with carbon dioxide• This can cause death by asphyxiation in
10-15 minutes
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• Atopic Disorders Are the Most Common Form of a Type I Hypersensitivity
• Atopic disease is a common (seasonal) allergy caused by the inhalation of pollen
• Year-round allergies can result from chronic exposure to allergens
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• Food allergies can cause symptoms like:• swollen lips, abdominal cramps,
nausea• Diarrhea, hives (urticaria),
anaphylaxis
• Involvement of eosinophils, neutrophils and T helper cells
• Physical factors that can cause allergies include: extreme temperatures, sunlight, sweating
• Exercise can cause allergies in the form of an asthma attack
• ECZEMA : atopic dermatitis; reddened skin rash with intense itching
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• Allergic Reactions Also Are Responsible for Triggering Many Cases of Asthma
• Asthma can be caused by airborne allergens, exercise, or cold temperature
• Degranulation of mast cells releases mediators in the lower respiratory tract, causing:• brochoconstriction• vasodilation• mucus buildup
• Recruitment of eosinophils and neutrophils into the lower respiratory tract can cause:• tissue injury • airway blockage
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• Atopic people may lack sufficient IgA-secreting lymphocytes to block antigen stimulation in IgE
• Atopic people may have defective suppressor T cells, allowing for more IgE production
• Allergies may help expel pathogens through:• sneezing • gastrointestinal tract contractions
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• Desensitization therapy involves a series of injections of allergens which may:
• Cause gradual reduction of granules in sensitized mast cells
• Cause production of IgG antibodies that neutralize allergens (blocking antibodies)
• Monoclonal antibodies can be used to dislodge IgE from mast cells and basophils
• Antihistamines block the effect of histamine
• Corticosteroids are inhaled through the nose to relieve symptoms; some also block mediator release
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• Type II Cytotoxic Hypersensitivity Involves Antibody-Mediated Cell Destruction• It occurs when IgG reacts
with antigens, often activating complement
• Cell damaging reaction – Ig reacts with antigen on cell surface
• Cells affected are “target cells”
• TRANSFUSION REACTION
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• If incompatible blood types are mixed, agglutination occurs and complement is activated• Rh disease can lead to stillbirth or jaundice
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• In myasthenia gravis, antibodies react with receptors on muscle fiber membranes,• This causes a loss of muscle
activity
• In Graves disease, antibodies bind unto thyroid gland cells• This causes overproduction
of thyroxine
• Hashimoto’s disease: antibodies attack thyroid gland cells leading to thyroxine deficiency
• In type I diabetes, pancreatic beta cells are destroyed• A lack of insulin production
results
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• THROMBOCYTOPENIA – results from antibodies produced against aspirin, antibiotics or antihistamines
• AGRANULOCYTOSIS – destruction of neutrophils by antibodies
• GOOD PASTURE SYNDROME – antibodies combine with antigens on the membranes of glomeruli in kidneys
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• Type III Immune Complex
Hypersensitivity Is Caused by
Antigen-Antibody Aggregates
• Develops when antibody combines with antigen and form aggregates that accumulate in the blood vessels or tissue surface
• Complement is activated (C3a and C5a)
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• Serum sickness occurs when IgG is produced against residual proteins in a serum• This can cause:
• kidney damage • symptoms of type I anaphylactic hypersensitivity:
hives and swelling in the face, neck and joints
• In the Arthus phenomenon, very large amounts of IgG complex with antigens • This can lead to thromboses in blood vessels
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• In systemic lupus erythematosus (a.k.a. SLE, lupus), nuclear components of disintegrating white blood cells elicit IgG production• Immune complexes
aggregate in the skin and organs, causing rash and lesions
• Rheumatoid arthritis (RA) is an inflammatory condition resulting in accumulation of immune complexes in joints
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• Hemorrhagic shock – which may accompany dengue fever
• Subacute Sclerosing Panencephalitis – which follows a case of measles
• Lymphocytic Choriomeningitis – slow-forming kidney disease
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• Is Mediated by Antigen-Specific T Cells• Cellular hypersensitivity is an
exaggeration of cell mediated immunity
• It is a delayed reaction characterized by:• thickening and drying of skin tissue
(induration)• surrounding by erythema
• Infection allergy occurs when the immune system responds to certain microbial agents• Sensitized lymphocytes remain in
the tissue to provide immunity to subsequent infection
• Sensitivity can be determined by injection of a purified microbial sample and observation for induration (Mantoux test)
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• Contact dermatitis develops after exposure to a variety of allergens• Repeated
exposures cause drying to skin with erythema and scaling
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• Immunodeficiencies Can Involve Any Aspect of the Immune System
• Primary immunodeficiency is the result of a genetic abnormality
• Secondary immunodeficiency is acquired later in life
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• X-linked (Bruton) agammaglobulinemia is a congenital humoral immunodeficiency• B cells fail to develop so patients lack mature B cells,
plasma cells, and antibodies• It is a sex-linked trait, more common in males than
females
• In DiGeorge syndrome, the thymus fails to mature in the embryo so T cells do not develop
• Patients with ataxia-telangiectasia:• have malfunctioning B and T cells • are deficient in IgA and IgE• Paralysis and dementia lead to death by age 30
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• Severe combined immunodeficiency disease (SCID) involved lymph nodes deficient in B and T cells• One form is caused by an
enzyme deficiency that can be corrected using gene therapy
• In Chédiak-Higashi syndrome, lysosome within phagocytes cannot release their contents to kill microbes
• In chronic granulomatous disease, phagocytes do not produce substances to kill microbes
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• Transplantation of Tissues or Organs Is an Important Medical Therapy • An autograft is a graft taken
from one part of the body and transplanted to another part of the same body
• An isograft is a graft from one identical twin to the other twin
• Allografts are grafts between genetically different members of the same species
• Xenografts are grafts between members of different species (rarely successful)
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• Rejection of transplants becomes more vigorous as the difference in genetic makeup of donor and recipient increases
• If the recipient body sees the transplanted tissue as “non-self,” the tissue is rejected• Cytotoxic T cells attack and destroy
transplanted cells• Phagocytes secrete lysosomal enzymes that
digest the tissue
• In bone marrow transplants, the transplanted marrow can form immune products against the host’s suppressed immune system• Graft-versus-host-reaction (GVHR) can be
fatal to the host
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• MHC genes are believed to exist on chromosome 6 in humans
• 2 types of MHC proteins:• Class I – nucleated cells• Class II – important in the
recognition of non self antigens when T lymphocytes combine with macrophages in CMI.
• The nature of MHC proteins is a key element in transplant acceptance or rejection.
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• Rejection is stimulated by recognition of MHC proteins on the surface of graft cells
• The closer the match between donor and recipient MHC proteins the greater the chance of successful transplantation
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• Rejection is inhibited by immunosuppression in the host using:• steroids that suppress the inflammatory response
• antilymphocyte antibodies
• antimitotic drugs
• drugs to suppress cell mediated immunity
• monoclonal antibodies
• radiation
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• Four major immunotherapies:
• Chemotherapy and radiation
• Cytokines as immunostimulants• Interferon alpha, IL – 2, TNF - £
• Monoclonal antibodies
• Cancer vaccines