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Applications of Immune Responses
Chapter 17
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Principles of Immunization
• Immunization:is 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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• 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
Vaccines and Immunization
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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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http://www.bbc.co.uk/parenting/images/300/test_blueline.jpg
Pregnancy tests measure hCG
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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
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
R T C
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Animation of hCG pregnancy test (ELISA)
R T C
Basics (if the woman is pregnant)1. hCG in urine will react with anti-hCG (type 1) antibody in
Reaction zone2. 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 appear3. 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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http://www.whfreeman.com/kuby/content/anm/kb07an01.htm
Animation of the molecular basis of the hCG ELISA pregnancy test
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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 Hypersensitivities:Immediate IgE-Mediated
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Type I Hypersensitivities:Immediate 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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• 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
Type I Hypersensitivities:Immediate IgE-Mediated
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Type I Hypersensitivities:Immediate IgE-Mediated
• Immunotherapy– Use techniques to modify
immune system for favorable effect
– desensitization or hyposensitization
• IgG replace IgE
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• Immunotherapy– Anti-IgE Fc antibody
– Engineered anti-IgE created» rhuMab = recombinant human Monoclonal antibody
Type I Hypersensitivities:Immediate IgE-Mediated
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Type II Hypersensitivities:Cytotoxic
• 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 Hypersensitivities:Immune 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 Hypersensitivities:Delayed 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 Hypersensitivities:Delayed 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 inhibitor—prevent 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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– 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
Autoimmune Diseases
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• Treatment of autoimmune diseases• Controlling T cell signaling/immunosuppressant
– cyclosporin
• Anti-inflammatory medications– steroids
• Replacement therapy– insulin
Autoimmune Diseases
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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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• 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
Immunodeficiency Disorders
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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
• 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
Immunodeficiency Disorders