Immunological disorders Flashcards
Immunologic Disorders
1) Hypersensitivity
2) Autoimmunity
3) Immunodeficiency
Type I Hypersensitivities: Immediate IgE-Mediated
– IgE causes immediate (type I) hypersensitivities
– Characterized by immediate reaction of the sensitized individual
* Generally within minutes of exposure
* Tendency 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
Type I Hypersensitivities: Immediate IgE-Mediated
Sensitization occurs when?
antigen makes contact with some part of body and induces response
* IgE antibodies bind to receptors on mast cells and IgE antibodies bind to receptors on mast cells and basophiles
– Antigen readily bonds to cells fixed with IgE antibodies
* Within seconds, mast cells degranulate releasing mediators that initiate immune reaction including hives, hay fever and anaphylaxis
Localized anaphylaxis
– Most allergic reactions are local anaphylaxis
1) Hives
– Allergic skin condition characterized by formation of wheal and flare rash
2) Hay fever
– Allergic condition caused by inhaled antigen
– Condition marked by itching teary eyes, sneezing and runny nose
3) Asthma
– Respiratory allergy
– Allergic mediators attracted to inflamed respiratory tract
* Results in increased mucous secretion and bronchi spasm
Type 1 hypersensitivity: Generalized anaphylaxis
– Rare, but more serious
– Antigen enters bloodstream and becomes widespread
* Reactions affect 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
- Immunotherapy
– General term for techniques used to modify immune system for favorable effect 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
Type I Hypersensitivities: Immediate IgE-Mediated
Immunotherapy– Second therapeutic procedure is injection of?
antibodies to bound IgE antibodies to bound IgE
* Essentially anti-IgE antibodies
– Most IgE are bound to mast cells and basophiles
* 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 II Hypersensitivities: Cytotoxic
Complement-fixing antibodies react with cell surface antigens causing cell injury or death
* Cells can be destroyed in type II reactions 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 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 diseases
Type IV Hypersensitivities: Delayed Cell-Mediated
-Tuberculin skin test
– Test involves introduction of small quantities of protein
antigens from tubercle 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
1) Poison ivy and poison oak
2) Nickel in metal jewelry
3) Chromium salts in leather
4) 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 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
