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