Applications of Immune Responses

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

http://en.wikipedia.org/wiki/Immune_system


• Active immunity– exposure to an antigen

• naturally– Following illness

• artificially– vaccine


• 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


• 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

• 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

http://www.bbc.co.uk/parenting/images/300/test_blueline.jpg

Pregnancy tests measure hCG

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

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

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

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

Animation of the molecular basis of the hCG ELISA pregnancy test

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


• 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

• 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



• Immunotherapy– Use techniques to modify

immune system for favorable effect

– desensitization or hyposensitization

• IgG replace IgE

• 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 antibody-dependent cellular cytotoxicity (ADCC).– Blood transfusion reactions– Hemolytic disease of the newborn


• 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


• 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.

– 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

Autoimmune Diseases

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

• 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


• 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


Applications of Immune Responses

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