Immunologic Disorders

Chapter 18

Type I Hypersensitivities:Immediate IgE-Mediated

IgE causes immediate (type I) hypersensitivities Characterized by reaction the sensitized individual

immediately Generally within minutes of exposure

Tendencies to have type I hypersensitivities is inherited Reactions occur in at least 20% to 30% of population

Type I reactions can be classified as local anaphylaxis or generalized anaphylaxis Anaphylaxis name given for IgE mediated allergic reaction

Sensitization occurs when antigen makes contact with some part of body and induces response

IgE antibodies bind to receptors on mast cells and basophils Antigen readily binds to cells

fixed with IgE antibodies Within seconds mast cells

degranulate releasing mediators that initiate immune reaction including, hives, hay fever and anaphylaxis

Type I Hypersensitivities:Immediate IgE-Mediated

Type I Hypersensitivities:Immediate IgE-Mediated

Localized anaphylaxis Most allergic reactions are local

anaphylaxis Hives

Allergic skin condition characterized by formation of wheal and flare rash

Hay fever Allergic condition caused by inhaled

antigen Condition marked by itching teary eyes,

sneezing and runny nose Asthma

Respiratory allergy Allergic mediators attracted to inflamed

respiratory tract Results in increased mucous

secretion and bronchi spasm

Generalized anaphylaxis Rare but more serious Antigen enters bloodstream and becomes

widespread Reactions affects almost entire body Can induce shock

Shock is state in which blood pressure too low to supply required blood flow

Massive release of mediators causes extensive blood vessel dilation and fluid loss

Causes fall in pressure leading to flow insufficiency

Type I Hypersensitivities:Immediate IgE-Mediated

Type I Hypersensitivities:Immediate IgE-Mediated

Immunotherapy General term for techniques

used to modify immune system for favorable effect

Procedure is to inject individual with extremely dilute suspension of allergen

Called desensitization or hyposensitization

Concentration of allergen gradually increased over time

Individual gradually becomes less sensitive

Immunotherapy Second therapeutic procedure is injection of

antibodies to bound IgE Essentially anti-IgE antibodies

Most IgE are bound to mast cells and basophils

Binding of anti-IgE would cause massive release of allergic mediators that could be detrimental to patient

Engineered anti-IgE created rhuMab = recombinant human Monoclonal antibody

Type I Hypersensitivities:Immediate IgE-Mediated

Type II Hypersensitivities:Cytotoxic

Complement-fixing antibodies react with cell surface antigens causing cell injury or death

Cells can be destroyed in type II reactions through complement fixation and antibody-dependent cellular cytotoxicity (ADCC)

Examples of Type II hypersensitivities are Transfusion reactions Hemolytic disease of the newborn

Type II Hypersensitivities:Cytotoxic

Transfusion reactions Normal red blood cells have different surface

antigens Antigens differ from person to person

People are designated type A, B, AB or O Transfused blood that is antigenically different

can be lysed by recipient immune cells Cross-matching blood is used to ensure

compatibility between donor and recipient IgM antibodies cause type II reactions Symptoms include low blood pressure, pain,

nausea and vomiting

Type II Hypersensitivities:Cytotoxic

Hemolytic disease of the newborn Basis of disease is incompatibility of

Rh factor between mother and child Rh factor RBC cell surface antigen

Rh positive = Rh antigen present Rh negative = Rh antigen missing

Anti-Rh antibodies form in Rh negative mother pregnant with Rh positive fetus

First Rh positive fetus unharmed Second Rh positive fetus provokes

strong secondary immune response IgG antibodies of secondary

response cross placenta causing extensive damage to fetal red blood cells

Type III Hypersensitivities:Immune Complex-Mediated

Immune complexes consist of antigen and antibody bound together

Usually adhere to Fc receptors on cells Complexes are destroyed

and removed Certain instances complexes

persist in circulation or at sites of formation Initiate blood clotting

mechanism Activate complement

contributing to inflammation

Complexes commonly deposited in skin, joints and kidney

Complexes also cause disseminated intravascular coagulation (DIC) Clots in small vessels

Leads to system failure

Type IV Hypersensitivities:Delayed Cell-Mediated Delayed hypersensitivities caused by cell-mediated

immunity Slowly developing response to antigen

Reactions peak in 2 to 3 days instead of minutes

T cells are responsible for reactions Reactions can occur nearly anywhere in the body

Delayed hypersensitivity reactions responsible for contact dermatitis, tissue damage, rejection of tissue grafts and some autoimmune disease

Type IV Hypersensitivities:Delayed Cell-Mediated

Tuberculin skin test Test involves introduction of

small quantities of protein antigens from tubercle bacillus into skin

In positive skin test injection site reddens and gradually thickens

Reaction reaches peak in 2 to 3 days

Reactions result from sensitized T cells, release of cytokines and influx of macrophages

Type IV Hypersensitivities:Delayed Cell-Mediated

Contact Hypersensitivities Mediated by the T cells

T cells release cytokines Cytokines initiate inflammation

that attracts macrophages Macrophages release

mediators to add to inflammation

Common examples of contact allergies include

Poison ivy and poison oak Nickel in metal jewelry Chromium salts in leather Latex products

Transplant Immunity

Major drawback to graft transplantation is possible immunological rejection Differences between donor and recipient tissues basis for

rejection Rejection is predominantly type IV reaction

Killing of graft cells occurs through complex combination of mechanisms Contact with sensitized cytotoxic T cells and natural killer cells

Combination of agents commonly used to prevent graft rejection Cyclosporin A Steroids Basiliximab

Monoclonal antibody preparation Blocks binding of immune mediators Blocks binding sites of T cells

Prevents formation of antibodies

Autoimmune Diseases

Body usually recognizes self antigens Destroys cells that would destroy self Malfunction in immune recognition basis

for autoimmunity Autoimmune diseases may result from

reaction to antigen that are similar to MHC self antigens

Autoimmunity may occur after tissue injury Self antigens released from injured organ

Autoantibodies form and interact with injured tissues

Spectrum of autoimmune diseases Reactions occur over spectrum

Organ-specific to widespread responses Organ-specific

Thyroid disease Only thyroid is affected

Widespread response Lupus

Autoantibodies made against nuclear constituents of all body 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 Treatment aimed at:

Kill dividing cells Immunosuppressant

Controlling T cell signaling cyclosporin

Anti-inflammatory medications Cortico steroids

Replacement therapy insulin

Autoimmune Diseases

Immunodeficiency Disorders

Immunodeficiency disorders are marked by the body’s inability to make and sustain an adequate immune response

Two basic types of disorders 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

Agammaglobulinemia Few or no antibodies produces Occurs in 1 in 50,00 people

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

Syphilis, leprosy and malaria effect T cell population and macrophage function

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