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Applications of Immune Responses Chapter 17 Principles of Immunization • Immunization:is the process that an individual's immune system becomes fortified against an agent. – Active immunity – Passive immunity Principles of Immunization • Active immunity – exposure to an antigen • naturally – Following illness • artificially – vaccine 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 Vaccine • Vaccine is a preparation of pathogen or its products used to induce active immunity. – Inactivated vaccine – Attenuated vaccine 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 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 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 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. 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 Pregnancy tests measure hCG http://www.bbc.co.uk/parenting/images/300/test_blueline.jpg 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 Molecular basis of pregnancy test R T C Zones Antibody Reaction anti-hCG (type 1) Dye substrate? no •Soluble, labeled with E Test anti-hCG (type 2) yes •Bound Control Antibody that binds “anti-hCG (type 1)” •Bound yes 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 zone 2. 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 antihCG/hCG (type 1)complex • The binding of this bulky complex will activate the dye substrate, causing a line to appear 3. 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 Animation of the molecular basis of the hCG ELISA pregnancy test http://www.whfreeman.com/kuby/c ontent/anm/kb07an01.htm Immunologic Disorders Chapter 18 Immunological Disorders • Hypersensitivities (allergies) – 4 types of hypersensitivities • Autoimmune disease. • Immunodeficiency 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 Type I Hypersensitivities: Immediate IgE-Mediated 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 Type I Hypersensitivities: Immediate 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 Type I Hypersensitivities: Immediate IgE-Mediated • Immunotherapy – Use techniques to modify immune system for favorable effect – desensitization or hyposensitization • IgG replace IgE Type I Hypersensitivities: Immediate IgE-Mediated • Immunotherapy – Anti-IgE Fc antibody – Engineered anti-IgE created » rhuMab = recombinant human Monoclonal antibody Type II Hypersensitivities: Cytotoxic • Complement-fixing antibodies react with cell surface antigens • Cells can be destroyed through complement system and antibodydependent cellular cytotoxicity (ADCC). – Blood transfusion reactions – Hemolytic disease of the newborn 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 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 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 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 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 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 Autoimmune Diseases • Recognition of self antigen – Tissue injury cause self antigens released. – Viral or bacterial infection. 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 Autoimmune Diseases • Treatment of autoimmune diseases • Controlling T cell signaling/immunosuppressant – cyclosporin • Anti-inflammatory medications – steroids • Replacement therapy – insulin 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 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 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 antibodymediated immunity – Most serious widespread immunodeficiency is AIDS • Destroys helper T cells – Inhibits initiation of cellular and humoral immunity