Disorders in immunity
Name the two major categories of immune dysfunction
Identify the four types of overreaction to antigens.
-type I: immediate reactions - B cells (IgE)
-type II: antibody-mediated - B cells (IgG & IgM)
-type III: immune complex reactions - B cells (IgG & IgM)
-type IV: delayed/cell mediated - T cells & macrophages
Gives examples of disorders for each type of reaction.
Type 1: anaphylaxis, hay fever, asthma
type 2: hemolytic dz of newborn, myasthenia gravis
type 3: lupus, RA, arthus reaction, serum sickness
type 4: TB skin test, poison ivy, graft rejection
Define allergen and distinguish among inhalant, ingestant and contactant types. Give examples of each category.
Allergen – an antigen which allergic individuals are sensitive to
-Inhalant: allergens which enter the respiratory tract (dust, dander, pollen)
-Ingestant: allergens which enter the gastrointestinal tract (food, drug)
-Injectant: allergens which enter via a shot or venom from stings (drugs injected, bee venom) -Contactant: allergens which enter via the skin (chemicals, dyes, latex)
Describe the sequence of events after secondary exposures to allergens.
Primary exposure – also called the “Sensitizing Dose”
-Allergen is phagocytized, processed, and presented to a T-helper cell.
-T-cell is activated and presents allergen (or secretes cytokines) to activate a B-cell.
-B-cell proliferates and differentiates in to Plasma cells (which produce IgE antibodies rather
than IgM or IgG antibodies) and Memory cells
-IgE antibodies attach via the Fc portion of the Ab to the cell membrane of a mast cell.
Secondary exposure – also called the “Shocking Dose”
-Allergen is encountered for the second time and binds to Memory cells – which “re-sensitize” the body (see Sensitizing Dose) to the allergen
-Allergen also binds to the free Fab (antigen binding) region of IgE Ab on sensitized Mast cells.
-When several adjacent Ab are bound with allergen, the cell degranulates.
-Degranulation releases chemical mediators which cause allergic symptoms (hives, itchy, red, watery eyes, nasal congestion, puffiness around eyes, sneezing, headache, and sometimes difficulty breathing).
Explain why systemic anaphylaxis is so serious.
Systemic anaphylaxis involves a severe, systemic reaction which affects the respiratory and circulatory systems. Persons with a severe anaphylactic reaction can go into anaphylactic shock and stop breathing. Death can occur within 15 minutes if not treated.
Briefly describe two methods for diagnosing allergies.
-In vivo (in the living organism) - Skin test – small amounts of allergen are injected or scratched
into the skin and monitored for wheal response (bumps)
-In vitro (in the living tissue outside the body)
o Serological tests – for IgE levels (RAST, radioallergosorbent test)
o Leukocyte histamine release test
o Differential blood cell count
o Elevated blood levels of tryptase (released by mast cells during allergic response)
Discuss the mechanism of action of “allergy shots”.
-Desensitization - controlled injections of allergen (small but increasing doses every two
o Produces IgG antibodies which block the allergen from binding IgE on mast cells
-Drugs which block allergies –
o Corticosteroids (inhibit lymphocytes)
o Antihistamines – block histamine
o Aspirin – blocks prostaglandin
o Cromolyn – prevents degranulation of mast cells o Epinephrine – opens airways in an asthma attack o Leukotriene inhibitors – ie., Advair
List the major immune system components involved in Type II hypersensitivity.
-IgG and IgM antibodies tag cells (or target cells) for destruction
-Complement Activation – causes lysis of targeted cells
Explain the basis for the ABO blood groups, and what type of antibody to the ABO antigens different individuals might have
-“A” type blood cells have A antigens and B antibodies
-“B” type blood cells have B antigens and A antibodies
-“O” type blood cells have neither A nor B antigens and both A and B antibodies
-“AB” type blood cells have A and B antigens and no antibodies
Identify which blood types are considered universal donors and universal recipients.
-AB is considered the “Universal Recipient”
-O is considered the “Universal Donor”
Explain under what circumstance the Rh factor can be problematic for newborn babies.
If the mother is Rh- and the fetus is Rh+ and the mother has already been sensitized to the Rh+ antigen by a previous pregnancy
Specify how Type III hypersensitivity is similar to, and also differs from, Type II hypersensitivity.
-Type II targets cells using antibodies attached to the targeted cell – targets the cells for destruction
-Type III targets cells using antigen-antibody (Ag/Ab) complexes which are of intermediate size and which cause neutrophils to migrate to the area that they get caught in and degranulate – causing damage to tissues.
Provide highlights about the Arthus reaction and serum sickness.
-Arthus reaction: localized reaction at the site of injection due to inflamed blood vessels in the
vicinity of any injected antigen
-Serum sickness: systemic reaction throughout the blood and settle into various tissues causing destruction at the site (due to neutrophils degranulating)
-Similar, but different from anaphylaxis because
o Depend on IgG, IgM, IgA rather than IgE
o Require large doses of antigen
o Symptoms are delayed rather than immediate
Describe the pathogenesis of contact dermatitis.
o Allergen enters the skin and is engulfed by macrophages just under the skin
o Macrophages engulf, process, and present antigen to T-helper cells which proliferate and differentiate into many T-helper1 cells (Sensitized)
o Allergen is processed and presented by macrophages to T-helper cells
o T-helper cells proliferate and differentiate into T-helper1 cells and memory cells
o T-helper 1 cells activate macrophages
o Macrophages secrete cytokines which cause the contact dermatitis (delayed hypersensitivity reaction on the skin)
Provide the names for four different sources of graft material.
-isograft: identical twin
-allograft: close match from same species
-xenograft: different species
List the target cells for the following autoimmune diseases.
3.Type I diabetes
5.RA and Ankylosing spondylitis
1. Thyroid Stimulating Hormone (TSH) receptors
2.(ACh) receptors on postsynaptic membrane of synapse of the neuromuscular junction
3.T-cells attack insulin producing cells in the pancreas
4. T-cells and antibodies attack myelin sheath
5. Immune complexes collect in the joints
6. Immune complexes collect in various organs
Distinguish between primary and secondary immunodeficiencies.
-Primary Immunodeficiencies: present at birth (congenital) and usually stemming from genetic errors
-Secondary immunodeficiencies: acquired after birth caused by natural or artificial agents
Explain severe combined immunodeficiency. What type of cells are people with SCID lacking?
-Complete absence of lymphocyte stem cells in the bone marrow
-Loss of both B-cells and T-cells (not just immature, but all forms of lymphocytes)
Name four conditions that can cause secondary immunodeficiencies.
-Organic/Non-infectious Metabolic Disease (liver, diabetes, kidney disease)