Disorders in Immunity

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• Chapter 16
• Disorders in Immunity

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Immunopathology

• Allergy, hypersensitivity an exaggerated,
  misdirected expression of immune responses to an
  allergen (antigen)
• Involves the same types of immune reactions as
  those at work in protective immunities
• Autoimmunity abnormal responses to self Ag
• Immunodeficiency deficiency or loss of immunity
• Cancer results from a lack of surveillance (?)

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Type I Hypersensitivity

• Two levels of severity
• Atopy any chronic local allergy such as hay
  fever or asthma
• Anaphylaxis a systemic, often explosive
  reaction that involves airway obstruction and
  circulatory collapse

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Contact With Allergens

• Generalized predisposition to allergies is
  familial not to a specific allergy
• Allergy can be affected by age, infection, and
  geographic area.
• Atopic allergies may be lifelong or may be
  outgrown may also develop later in life.

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Nature of Allergens and Their Portals of Entry

• Allergens have immunogenic characteristics.
• Typically enter through epithelial portals
  respiratory, gastrointestinal, skin
• Organ of allergic expression may or may not be
  the same as the portal of entropy.

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Mechanism of Type I Allergy

• Develop in stages
• Sensitizing dose on first contact with
  allergen, specific B cells form IgE which attache
  to mast cells and basophils generally no signs
  or symptoms
• Provocative dose - subsequent exposure with the
  same allergen binds to the IgE-mast cell complex
• Degranulation releases mediators with
  physiological effects such as vasodilation and
  bronchoconstriction.
• Symptoms are rash, itching, redness, increased
  mucous discharge, pain, swelling, and difficulty
  breathing.

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Role of Mast Cells and Basophils

• Mast cells are located in the connective tissue
  of virtually all organs high concentration in
  lungs, skin, GI and genital tract.
• Basophils circulate in blood and migrate into
  tissues.
• Each cell can bind 10,000-40,000 IgE.
• Cytoplasmic granules contain physiologically
  active cytokines, histamine and other chemicals.
• Cells degranulate when stimulated by allergen.

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Chemical Mediators and Allergic Symptoms

• Act alone or in combination account for scope of
  allergic symptoms
• histamine, serotonin, leukotriene,
  platelet-activating factor, prostaglandins,
  bradykinin
• General targets include skin, upper respiratory
  tract, GI tract, and conjunctiva.
• responses rashes, itching, redness, rhinitis,
  sneezing, diarrhea, shedding tears
• Systemic targets smooth muscles, mucous glands,
  and nervous tissue
• responses vascular dilation and constriction
  resulting in change in blood pressure and
  respiration

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• Histamine most profuse and fastest acting
  stimulator of smooth muscle, glands, and
  eosinophils
• response to chemical depends on the muscle
  location constricts smooth muscles of small
  bronchi, intestines relaxes vascular smooth
  muscles

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Specific Diseases

• Atopic disease hay fever, rhinitis seasonal,
  inhaled plant pollen or mold
• asthma severe bronchoconstriction inhaled
  allergen
• eczema dermatitis ingestion, inhalation, skin
  contact
• Food allergy intestinal portal can affect skin
  and respiratory tract
• vomiting, diarrhea, abdominal pain possibly
  severe
• eczema, hives, rhinitis, asthma, occasionally
  anaphylaxis
• Drug allergy common side effect of treatment
  any tissue can be affected reaction from mild
  atopy to fatal anaphylaxis

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Systemic Anaphylaxis

• Sudden respiratory and circulatory disruption
  that can be fatal in a few minutes
• Allergen and route are variable.
• Bee stings, antibiotics or serum injection

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Diagnosis of Allergy

• Important to determine if a person is
  experiencing allergy or infection
• Skin testing

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Treatment and Prevention

• General methods include
• Avoiding allergen
• Use drugs that block the action of the
  lymphocytes, mast cells, chemical mediators
  antihistamines.
• Desensitization therapy injected allergens may
  stimulate the formation of high-levels of
  allergen-specific IgG that act to block IgE mast
  cells dont degranulate

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Type II Hypersensitivity

• Reactions that lyse foreign cells
• Involve antibodies, complement, leading to lysis
  of foreign cells
• Transfusion reactions
• ABO blood groups
• Rh factor hemolytic disease of the newborn

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Human ABO Antigens and Blood Types

• 4 distinct ABO blood groups
• Genetically determined RBC glycoproteins
  inherited as 2 alleles of A, B, or O
• 4 blood types A, B, AB, or O
• named for dominant antigen(s)
• type O persons lack both A and B antigens
• Tissues other than RBCs also carry A and B
  antigens.

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Antibodies Against A and B Antigens

• Serum contains pre-formed antibodies that react
  with blood of another antigenic
  type-agglutination potential transfusion
  complication
• Type A contains Abs that react against B
  antigens.
• Type B contains Abs that react against A
  antigens.
• Type O contains Abs that react against A and B
  antigens.
• Type AB contains no Abs that react against A or B
  antigens.

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Rh Factor and Hemolytic Disease of the Newborn

• RBC antigen type results from combination of 2
  alleles
• Inheriting one dominant gene results in the
  production of the Rh antigen no pre-formed
  antibodies exist must have exposure.
• Hemolytic Disease of the Newborn (HDN) an Rh-
  mother forms antibodies to her Rh fetus usually
  requires subsequent exposure to the antigen to be
  hemolytic
• Prevention requires the use of passive
  immunization with antibodies against the Rh
  antigen prevents sensitization of mother.

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Type III Hypersensitivity

• A large quantity of soluble foreign Ag stimulates
  Ab that produce small, soluble Ag-Ab complexes.
• Immune complexes become trapped in tissues and
  incite a damaging inflammatory response.
• arthus reaction local reaction to series of
  injected Ag to same body site
• serum sickness systemic disease resulting from
  repeated injections of foreign proteins

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Type IV Hypersensitivity

• T cell-mediated
• Delayed response to Ag involving activation of
  and damage by T cells
• Delayed allergic response skin response to
  allergens tuberculin skin test, contact
  dermititis from plants, metals, cosmetics
• Graft rejection reaction of cytotoxic T cells
  directed against foreign cells of a grafted
  tissue involves the recognition of foreign HLA

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T Cells and Organ Transplantation

• Graft/transplantation rejection host may reject
  graft graft may reject host
• MHC markers of donor tissue (graft) are
  different T cells of the recipient recognize
  foreignness.
• Release interleukin-2 which amplifies helper and
  cytotoxic T cells which bind to donor tissue and
  release lymphokines that begin the rejection

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Classes of Grafts

• Classified according to the degree of MHC
  similarity between donor and host
• autograft recipient also serves as donor
• isograft tissue from identical twin is grafted
• allograft genetically different individuals but
  of the same species (humans)
• xenograft individuals of different species
• Rejection can be minimized by tissue matching HLA
  antigens, immunosuppressive drugs, and use of
  tissue that does not provoke a type IV response.

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Autoimmunity

• In certain type II III hypersensitivities, the
  immune system has lost tolerance to autoantigens
  and forms autoantibodies and sensitized T cells
  against them.
• More common in females
• Disruption of function can be systemic or organic
  specific
• systemic lupus erythematosus
• rheumatoid arthritis
• endocrine autoimmunities
• myasthenia gravis
• multiple sclerosis

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Type I Diabetes (Juvenile/Insulin dependent
Diabetes)
Individual develops antibodies to islet cells of
the pancreas that produce insulin. The cells are
damaged and insulin is not produced in sufficient
quantities for the bodys needs. Insulin is
required to maintain normal blood sugar levels.
Insulin has be injected to accomplish this.
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Myasthenia Gravis
Individual develops antibodies to the
acetylcholine receptors which bind the
neurotransmitter , acetylcholine, which is needed
for skeletal muscle contraction.
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Immunodeficiency Diseases

• Components of the immune response system are
  absent. Deficiencies involve B and T cells,
  phagocytes, and complement.
• 2 general categories
• primary immunodeficiency congenital usually
  genetic errors
• secondary diseases acquired after birth caused
  by natural or artificial agents

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• Primary immunodeficiency - lack of B-cell and/or
  T cell activity
• B cell defect agammaglobulinemia patient
  lacks antibodies
• T cell defect thymus is missing or abnormal
• severe combined immunodeficiency (SCID) - both
  limbs of lymphocyte system are missing or
  defective no adaptive immune response

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• Secondary diseases - due to damage after birth
• caused by infection, organic disease,
  chemotherapy, or radiation
• AIDS most common T helper cells are targeted
  numerous opportunistic infections and cancers

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The Immune System and Cancer

• Overgrowth of abnormal tissue arises due to
  malfunction of immune surveillance.
• Tumors may be benign (nonspreading)
  self-contained or malignant that spreads from
  tissue of origin to other sites.
• Cancers occur in nearly every cell type.
• Appear to have genetic alteration that transforms
  a normal cell
• Possible causes include errors in mitosis,
  genetic damage, activation of oncogenes, or
  retroviruses.

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