Transcript Immunologic Disorders


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
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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
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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
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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
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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

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
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

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
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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
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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
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Complexes commonly deposited in skin, joints and
kidney
Complexes also cause disseminated intravascular
coagulation (DIC)
› Clots in small vessels
 Leads to system failure
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Delayed hypersensitivities caused by cellmediated immunity
› Slowly developing response to antigen
 Reactions peak in 2 to 3 days instead of minutes
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T cells are responsible for reactions
› Reactions can occur nearly anywhere in the
body
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Delayed hypersensitivity reactions
responsible for contact dermatitis, tissue
damage, rejection of tissue grafts and
some autoimmune diseases
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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
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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
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Poison ivy and poison oak
Nickel in metal jewelry
Chromium salts in leather
Latex products
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Major drawback to graft transplantation is possible
immunological rejection
› Differences between donor and recipient tissues basis for
rejection
› Rejection is predominantly type IV reaction
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Killing of graft cells occurs through complex
combination of mechanisms
› Contact with sensitized cytotoxic T cells and natural killer
cells
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Combination of agents commonly used to prevent
graft rejection
› Cyclosporin A
› Steroids
› Basiliximab
 Monoclonal antibody preparation
 Blocks binding of immune mediators
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Body usually recognizes self antigens
› Destroys lymphocytes that would destroy self
› Malfunction in immune recognition basis for autoimmunity
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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
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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
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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
Immunodeficiency disorders are marked
by the body’s inability to make and
sustain an adequate immune response
 Two basic types of disorders
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› 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
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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
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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 antibodymediated immunity
› Most serious widespread immunodeficiency is AIDS
 Destroys helper T cells
 Inhibits initiation of cellular and antibody-mediated immunity