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IgE causes immediate (type I) hypersensitivities › Characterized by immediate reaction of the sensitized individual Generally within minutes of exposure

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Page 1: IgE causes immediate (type I) hypersensitivities › Characterized by immediate reaction of the sensitized individual  Generally within minutes of exposure
Page 2: IgE causes immediate (type I) hypersensitivities › Characterized by immediate reaction of the sensitized individual  Generally within minutes of exposure

IgE causes immediate (type I) hypersensitivities› Characterized by immediate reaction of the

sensitized individual Generally within minutes of exposure

Tendency to have type I hypersensitivities is inherited› Reactions occur in at least 20% to 30% of

population

Page 3: IgE causes immediate (type I) hypersensitivities › Characterized by immediate reaction of the sensitized individual  Generally within minutes of exposure

Sensitization occurs when antigen makes contact with some part of body and induces response

IgE antibodies bind to receptors on mast cells and basophiles› Antigen readily bonds to cells fixed with IgE

antibodies Within seconds, mast cells degranulate releasing

mediators that initiate immune reaction including hives, hay fever and anaphylaxis

Page 4: IgE causes immediate (type I) hypersensitivities › Characterized by immediate reaction of the sensitized individual  Generally within minutes of exposure

Localized anaphylaxis› Most allergic reactions are local

anaphylaxis Hives

Allergic skin condition characterized by formation of wheal and flare rash

Hay fever Allergic condition caused by inhaled

antigen Condition marked by itching teary eyes,

sneezing and runny nose Asthma

Respiratory allergy Allergic mediators attracted to inflamed

respiratory tract Results in increased mucous

secretion and bronchi spasm

Page 5: IgE causes immediate (type I) hypersensitivities › Characterized by immediate reaction of the sensitized individual  Generally within minutes of exposure

Generalized anaphylaxis› Rare, but more serious› Antigen enters bloodstream and becomes

widespread Reactions affect almost entire body Can induce shock

› Massive release of mediators causes extensive blood vessel dilation and fluid loss Causes fall in pressure leading to blood flow

insufficiency

Page 6: IgE causes immediate (type I) hypersensitivities › Characterized by immediate reaction of the sensitized individual  Generally within minutes of exposure

Immunotherapy› General term for

techniques used to modify immune system for favorable effect

› Procedure is to inject individual with extremely dilute suspension of allergen Called desensitization or

hyposensitization› Concentration of

allergen gradually increased over time Individual gradually

becomes less sensitive

Page 7: IgE causes immediate (type I) hypersensitivities › Characterized by immediate reaction of the sensitized individual  Generally within minutes of exposure

Immunotherapy› Second therapeutic procedure is injection

of antibodies to bind IgE Essentially anti-IgE antibodies

› Most IgE are bound to mast cells and basophiles

Engineered anti-IgE created rhuMab = recombinant human Monoclonal antibody

Page 8: IgE causes immediate (type I) hypersensitivities › Characterized by immediate reaction of the sensitized individual  Generally within minutes of exposure

Complement-fixing antibodies react with cell surface antigens causing cell injury or death

Cells can be destroyed in type II reactions through complement fixation and antibody-dependent cellular cytotoxicity (ADCC)

Examples of type II hypersensitivities are› Transfusion reactions› Hemolytic disease of the newborn

Page 9: IgE causes immediate (type I) hypersensitivities › Characterized by immediate reaction of the sensitized individual  Generally within minutes of exposure

Transfusion reactions› Normal red blood cells have different surface

antigens Antigens differ from person to person

People are designated type A, B, AB or O

› Transfused blood that is antigenically different can be lysed by recipient immune cells

› Cross-matching blood is used to ensure compatibility between donor and recipient

› Antibody-coated cells removed by phagocyte system

› Symptoms include low blood pressure, pain, nausea and vomiting

Page 10: IgE causes immediate (type I) hypersensitivities › Characterized by immediate reaction of the sensitized individual  Generally within minutes of exposure

Hemolytic disease of the newborn› Basis of disease is incompatibility of Rh

factor between mother and child Rh factor RBC cell surface antigen

Rh positive = Rh antigen present Rh negative = Rh antigen missing

Anti-Rh antibodies form in Rh negative mother pregnant with Rh positive fetus First Rh positive fetus unharmed Second Rh positive fetus provokes

strong secondary immune response IgG antibodies of secondary

response cross placenta causing extensive damage to fetal red blood cells

Page 11: IgE causes immediate (type I) hypersensitivities › Characterized by immediate reaction of the sensitized individual  Generally within minutes of exposure

Immune complexes consist of antigen and antibody bound together

Usually adhere to Fc receptors on cells› Complexes are destroyed and removed

Certain instances complexes persist in circulation or at sites of formation› Initiate blood clotting mechanism› Activate complement contributing to inflammation

Complexes commonly deposited in skin, joints and kidney

Complexes also cause disseminated intravascular coagulation (DIC)› Clots in small vessels

Leads to system failure

Page 12: IgE causes immediate (type I) hypersensitivities › Characterized by immediate reaction of the sensitized individual  Generally within minutes of exposure

Delayed hypersensitivities caused by cell-mediated immunity› Slowly developing response to antigen

Reactions peak in 2 to 3 days instead of minutes

T cells are responsible for reactions› Reactions can occur nearly anywhere in the

body Delayed hypersensitivity reactions

responsible for contact dermatitis, tissue damage, rejection of tissue grafts and some autoimmune diseases

Page 13: IgE causes immediate (type I) hypersensitivities › Characterized by immediate reaction of the sensitized individual  Generally within minutes of exposure

Tuberculin skin test› Test involves

introduction of small quantities of protein antigens from tubercle bacillus into skin

› In positive skin test injection site reddens and gradually thickens Reaction reaches peak

in 2 to 3 days

› Reactions result from sensitized T cells, release of cytokines and influx of macrophages

Page 14: IgE causes immediate (type I) hypersensitivities › Characterized by immediate reaction of the sensitized individual  Generally within minutes of exposure

Contact hypersensitivities› Mediated by the T cells

T cells release cytokines Cytokines initiate inflammation

that attracts macrophages Macrophages release

mediators to add to inflammation

› Common examples of contact allergies include Poison ivy and poison oak Nickel in metal jewelry Chromium salts in leather Latex products

Page 15: IgE causes immediate (type I) hypersensitivities › Characterized by immediate reaction of the sensitized individual  Generally within minutes of exposure

Major drawback to graft transplantation is possible immunological rejection› Differences between donor and recipient tissues basis

for rejection› Rejection is predominantly type IV reaction

Killing of graft cells occurs through complex combination of mechanisms› Contact with sensitized cytotoxic T cells and natural

killer cells Combination of agents commonly used to

prevent graft rejection› Cyclosporin A› Steroids› Basiliximab

Monoclonal antibody preparation Blocks binding of immune mediators

Page 16: IgE causes immediate (type I) hypersensitivities › Characterized by immediate reaction of the sensitized individual  Generally within minutes of exposure

Body usually recognizes self antigens› Destroys lymphocytes that would destroy self› Malfunction in immune recognition basis for

autoimmunity Autoimmune diseases may result from reactions

to antigens that are similar to self antigens Autoimmunity may occur after tissue injury

› Self antigens released from injured organ Autoantibodies form and interact with injured tissues and

cause further damage

Page 17: IgE causes immediate (type I) hypersensitivities › Characterized by immediate reaction of the sensitized individual  Generally within minutes of exposure

Spectrum of autoimmune diseases› Reactions occur over spectrum

Organ-specific to widespread responses› Organ-specific

Thyroid disease Only thyroid is affected

› Widespread response Lupus

Autoantibodies made against nuclear constituents of all body cells

Rheumatoid arthritis Immune response made against collagen in

connective tissue Myasthenia gravis

Autoantibody-mediated disease Antibody to acetylcholine receptor proteins

Page 18: IgE causes immediate (type I) hypersensitivities › Characterized by immediate reaction of the sensitized individual  Generally within minutes of exposure

Treatment of autoimmune diseases› Treatment aimed at:

Killing dividing cells Immunosuppressant

Controlling T cell signaling Cyclosporin

Anti-inflammatory medications Cortisone-like steroids

Replacement therapy Insulin

Page 19: IgE causes immediate (type I) hypersensitivities › Characterized by immediate reaction of the sensitized individual  Generally within minutes of exposure

Immunodeficiency disorders are marked by the body’s inability to make and sustain an adequate immune response

Two basic types of disorders› Primary or congenital

Inborn as a result of genetic defect or developmental abnormality

› Secondary or acquired Can be acquired as result of infection or

other stressor

Page 20: IgE causes immediate (type I) hypersensitivities › Characterized by immediate reaction of the sensitized individual  Generally within minutes of exposure

Primary immunodeficiencies› Generally rare› Examples

Agammaglobulinemia Few or no antibodies produced Occurs in 1 in 50,000 people

Severe combined immunodeficiency disorder (SCID) Neither B nor T lymphocytes are functional Occurs in 1 in 500,000 live births

Selective IgA deficiency Little or no IgA produced Most common disorder

One in 333 to 700 people

Page 21: IgE causes immediate (type I) hypersensitivities › Characterized by immediate reaction of the sensitized individual  Generally within minutes of exposure

Secondary immunodeficiencies› Result from environmental, rather than genetic

factors Malignancies, advanced age certain infections,

immunosuppressive drugs and malnutrition are just a few

› Often results from depletion of certain cells of the immune system Syphilis, leprosy and malaria affect T-cell population and

macrophage function Malignancies of lymphoid system decrease antibody-

mediated immunity

› Most serious widespread immunodeficiency is AIDS Destroys helper T cells

Inhibits initiation of cellular and antibody-mediated immunity