Transcript Immunologic Disorders

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
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•
•
•
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