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Flashcards in Immunological disorders Deck (21):
1

Immunologic Disorders

1) Hypersensitivity
2) Autoimmunity
3) Immunodeficiency

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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

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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

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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

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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

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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

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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

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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

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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

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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

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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

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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

13

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

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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

15

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

16

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 reactions to antigens 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

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Autoimmune Diseases: Spectrum of autoimmune diseases

– Reactions occur over spectrum
* Organ-specific to widespread responses
– Organ-specific
* Thyroid disease
– Only thyroid is affected
– Widespread response
* Lupus
– Auto antibodies made against nuclear constituents of all body cells
* Rheumatoid arthritis
– Immune response made against collagen in connective tissue
* Myasthenia gravis
– Autoantibody-mediated disease
* Auto antibody to acetylcholine receptor proteins

18

Autoimmune Diseases:Treatment of autoimmune diseases

– Treatment aimed at:
* Killing dividing cells
– Immunosuppressant
* Controlling T cell signaling
– Cyclosporin
* Anti-inflammatory medications
– Cortico steroids
* Replacement therapy
– Insulin

19

Immunodeficiency disorders are marked by the?

body’s inability to make and sustain an adequate immune response immune response
* Two basic types of disorders
1) Primary or congenital
* Inborn as a result of genetic defect or developmental
abnormality
2) Secondary or acquired
* Can be acquired as result of infection or other stressor

20

Immunodeficiency Disorders: Primary immunodeficiencies

– Generally rare
– Examples
* Agammaglobulinemia
– Few or no antibodies produced
– Occurs in 1 in 50,000 people
* Severe 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 people

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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 affect 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 antibody-mediated immunity