Immunologic Disorders

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Immunologic Disorders

• Chapter 18

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Type I HypersensitivitiesImmediate IgE-Mediated

• IgE causes immediate (type I) hypersensitivities
• Characterized by reaction the sensitized
  individual immediately
• Generally within minutes of exposure
• Tendencies to have type I hypersensitivities is
  inherited
• Reactions occur in at least 20 to 30 of
  population
• Type I reactions can be classified as local
  anaphylaxis or generalized anaphylaxis
• Anaphylaxis name given for IgE mediated allergic
  reaction

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Type I HypersensitivitiesImmediate IgE-Mediated

• Sensitization occurs when antigen makes contact
  with some part of body and induces response
• IgE antibodies bind to receptors on mast cells
  and basophils
• Antigen readily binds 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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Type I HypersensitivitiesImmediate IgE-Mediated

• 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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Type I HypersensitivitiesImmediate IgE-Mediated

• Generalized anaphylaxis
• Rare but more serious
• Antigen enters bloodstream and becomes widespread
• Reactions affects almost entire body
• Can induce shock
• Shock is state in which blood pressure too low to
  supply required blood flow
• Massive release of mediators causes extensive
  blood vessel dilation and fluid loss
• Causes fall in pressure leading to flow
  insufficiency

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Type I HypersensitivitiesImmediate IgE-Mediated

• 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

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Type I HypersensitivitiesImmediate IgE-Mediated

• Immunotherapy
• Second therapeutic procedure is injection of
  antibodies to bound IgE
• Essentially anti-IgE antibodies
• Most IgE are bound to mast cells and basophils
• Binding of anti-IgE would cause massive release
  of allergic mediators that could be detrimental
  to patient
• Engineered anti-IgE created
• rhuMab recombinant human Monoclonal antibody

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Type II Hypersensitivities Cytotoxic

• 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

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Type II Hypersensitivities Cytotoxic

• 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
• IgM antibodies cause type II reactions
• Symptoms include low blood pressure, pain, nausea
  and vomiting

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Type II Hypersensitivities Cytotoxic

• 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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Type III HypersensitivitiesImmune
Complex-Mediated

• 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

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Type IV HypersensitivitiesDelayed Cell-Mediated

• 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 disease

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Type IV HypersensitivitiesDelayed Cell-Mediated

• 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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Type IV HypersensitivitiesDelayed Cell-Mediated

• 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

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Transplant Immunity

• 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 Blocks binding
  sites of T cells
• Prevents formation of antibodies

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Autoimmune Diseases

• Body usually recognizes self antigens
• Destroys cells that would destroy self
• Malfunction in immune recognition basis for
  autoimmunity
• Autoimmune diseases may result from reaction to
  antigen that are similar to MHC self antigens
• Autoimmunity may occur after tissue injury
• Self antigens released from injured organ
• Autoantibodies form and interact with injured
  tissues

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Autoimmune Diseases

• 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
• Autoantibody to acetylcholine receptor proteins

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Autoimmune Diseases

• Treatment of autoimmune diseases
• Treatment aimed at
• Kill dividing cells
• Immunosuppressant
• Controlling T cell signaling
• cyclosporin
• Anti-inflammatory medications
• Cortico steroids
• Replacement therapy
• insulin

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Immunodeficiency Disorders

• Immunodeficiency disorders are marked by the
  bodys 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

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Immunodeficiency Disorders

• Primary immunodeficiencies
• Generally rare
• Examples
• Agammaglobulinemia
• Few or no antibodies produces
• Occurs in 1 in 50,00 people
• Sever 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

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Immunodeficiency Disorders

• 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 effect 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 humoral
  immunity