Applications of Immune Responses

1
Applications of Immune Responses

• Chapter 17

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Principles of Immunization

• Immunizationis the process that an individual's
  immune system becomes fortified against an
  agent.
• Active immunity
• Passive immunity

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Principles of Immunization

• Active immunity
• exposure to an antigen
• naturally
• Following illness
• artificially
• vaccine

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Principles of Immunization

• Passive Immunity (transfer of antibody)
• naturally
• during pregnancy
• Breast feeding
• Artificial
• Artificial passive immunity
• Can be used to prevent disease before or after
  likely exposure

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Vaccine

• Vaccine is a preparation of pathogen or its
  products used to induce active immunity.
• Inactivated vaccine
• Attenuated vaccine

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Vaccines and Immunization

• Attenuated vaccines
• Weakened form of pathogen
• Generally unable to cause disease or mild
  symptoms
• Strain replicates in vaccine recipient
• Results in long lasting immunity

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Vaccines and Immunization

• Attenuated vaccines
• Advantages
• Single dose
• Vaccine as added potential for being spread
• Disadvantages
• Potentially cause disease
• Not for Pregnant women
• Attenuated vaccines in use include
• Sabin polio vaccine
• MMR
• Yellow fever

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Vaccines and Immunization

• Inactivated vaccines
• Unable to replicate (multiple doses).
• Retains immunogenicity
• Has two categories
• Whole agents
• Contain killed organisms or inactivated virus
• Does not change epitopes
• Cholera, plague, influenza and Salk polio are
  whole agents
• Fragments
• Portions of organisms or agents including toxins
  proteins and cell wall components
• Includes toxoids, protein subunit vaccines and
  polysaccharide vaccines

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Immunological Testing (assay)

• Utilize the specific interaction between antibody
  and antigen to
• detect the presence of a specific antigen or
  antibody.
• Quantify the amount of antigen or antibody.

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Using Labeled Antibodies to Detect Interactions

• Enzyme Linked Immunosorbant Assay
• Employs antibody that has been labeled with
  detectable enzyme
• Commonly horseradish peroxidase
• Labeled antibody binds to antigen
• Binding can be direct or indirect
• Antigen location is determined using colormetric
  assay

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Pregnancy tests measure hCG
http//www.bbc.co.uk/parenting/images/300/test_blu
eline.jpg
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Enzyme-Linked Immunosorbent Assay (ELISA)

• ELISA is a widely-used method for measuring the
  presence and concentration of a particular
  molecule (e.g., a hormone, drug, virus) in a body
  fluid (blood serum or urine)
• The molecule (hCG) is detected by anti-hCG
  antibodies

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• Molecular basis of pregnancy test

T
C
R
Zones Antibody Dye substrate?
Reaction anti-hCG (type 1) Soluble, labeled with E no
Test anti-hCG (type 2) Bound yes
Control Antibody that binds anti-hCG (type 1) Bound yes
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• Animation of hCG pregnancy test (ELISA)

T
C
R

• Basics (if the woman is pregnant)
• hCG in urine will react with anti-hCG (type 1)
  antibody in Reaction zone
• The anti-hCG/hCG (type 1) complex will move
  through capillary action to the Test zone
• The bound anti-hCG antibody (type 2) will bind
  the anti-hCG/hCG (type 1)complex
• The binding of this bulky complex will activate
  the dye substrate, causing a line to appear
• Excess anti-hCG/hCG (type 1) complex will
  continue to move towards the Control zone
• Control zone has bound antibody that binds
  anti-hCG (type 1) antibody
• The binding of this bulky complex will activate
  the dye substrate, causing a line to appear

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Animation of the molecular basis of the hCG
ELISA pregnancy test

• http//www.whfreeman.com/kuby/content/anm/kb07an01
  .htm

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Immunologic Disorders

• Chapter 18

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Immunological Disorders

• Hypersensitivities (allergies)
• 4 types of hypersensitivities
• Autoimmune disease.
• Immunodeficiency

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Type I Hypersensitivities

• IgE mediated
• Immediate response
• Generally within minutes of exposure
• Inherited
• Reactions occur in at least 20 to 30 of
  population
• Can be local anaphylaxis or generalized
  anaphylaxis
• Anaphylaxis for IgE mediated allergic reaction

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Type I HypersensitivitiesImmediate IgE-Mediated
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Type I HypersensitivitiesImmediate IgE-Mediated

• Localized anaphylaxis
• Hives
• skin
• Hay fever
• inhaled antigen
• Asthma
• Respiratory allergy
• Allergic mediators attracted to inflamed
  respiratory tract
• Results in increased mucous secretion and bronchi
  spasm
• Bronchodilating drugs and steriods

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Type I HypersensitivitiesImmediate IgE-Mediated

• Generalized anaphylaxis
• more serious
• Antigen enters bloodstream
• Affects entire body
• Can induce shock
• Massive release of mediators causes extensive
  blood vessel dilation and fluid loss
• Causes fall in pressure leading to flow
  insufficiency
• Bee sting and peanuts, penicillin

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Type I HypersensitivitiesImmediate IgE-Mediated

• Immunotherapy
• Use techniques to modify immune system for
  favorable effect
• desensitization or hyposensitization
• IgG replace IgE

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Type I HypersensitivitiesImmediate IgE-Mediated

• Immunotherapy
• Anti-IgE Fc antibody
• Engineered anti-IgE created
• rhuMab recombinant human Monoclonal antibody

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Type II HypersensitivitiesCytotoxic

• Complement-fixing antibodies react with cell
  surface antigens
• Cells can be destroyed through complement system
  and antibody-dependent cellular cytotoxicity
  (ADCC).
• Blood transfusion reactions
• Hemolytic disease of the newborn

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Type II Hypersensitivities Cytotoxic

• Transfusion reactions
• Normal red blood cells surface antigen
• type A, B, AB or O
• Transfuse different type of blood can be lysed by
  recipient immune cells
• IgM antibodies can 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 (incompatibility
  of Rh factor)
• Rh factor on RBC surface
• Rh mother and Rh baby
• IgG mediated

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Type III HypersensitivitiesImmune
Complex-Mediated

• Caused by small antigen and antibody immune
  complexes
• Inflammation by activate complement
• blood clotting
• disseminated intravascular coagulation (DIC)
• Deposit in skin, joints and kidney
• Joint pain, rashes, glomerulonephritis

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Type IV HypersensitivitiesDelayed Cell-Mediated

• Delayed cell-mediated immunity
• Slowly developing response to antigen
• Reactions peak in 2 to 3 days
• T cells mediated
• nearly anywhere in the body
• contact dermatitis, tissue damage, rejection of
  tissue grafts and some autoimmune disease

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Type IV HypersensitivitiesDelayed Cell-Mediated

• Contact Hypersensitivities
• T cells release inflammation cytokines and
  attracts macrophages
• Macrophages release mediators to add to
  inflammation
• Common examples
• Tuberculin skin test
• sensitized T cells release cytokines trigger
  influx of macrophages
• Poison ivy and poison oak
• Nickel in metal jewelry
• Chromium salts in leather
• Latex products

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Transplant Immunity

• Immunological rejection
• Differences between donor and recipient tissues
  (MHC)
• Mainly type IV reaction combination of Tc cells
  and NK cells
• Drugs to prevent graft rejection
• Cyclosporin A calcineurin inhibitorprevent
  IL-2 prodction
• Steroids prevent cytokines including IL-2
  production
• Basiliximab
• Monoclonal antibody preparation to IL-2 receptor
• Blocks binding of immune mediators such as IL-2

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Autoimmune Diseases

• Recognition of self antigen
• Tissue injury cause self antigens released.
• Viral or bacterial infection.

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Autoimmune Diseases

• Organ-specific
• Thyroid disease
• Only thyroid is affected
• Widespread response
• Type I diabetes
• Cytotoxic T cell against insulin producing
  beta-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
• Controlling T cell signaling/immunosuppressant
• cyclosporin
• Anti-inflammatory medications
• steroids
• Replacement therapy
• insulin

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Immunodeficiency Disorders

• Inadequate immune response
• 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
• 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
• 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