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Lecture 10
Thyroiditis & Blood Antigens
37
Immunology
Professional
01/31/2011

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Term
Graves' Disease
Definition
Agonistic antibody that stimulates the TSH receptor
Results in overproduction of thyroid hormone
Term
Hashimoto's Lymphocytic Thyroiditis
Definition
3-4% (High) Prevalence
Antibodies against thyroglobulin and thyroid peroxidase (TPO) block thyroid hormone production
HYPOthyroidism
Inflammation, Maybe also CTL-mediated damage
Term
Postpartum Thyroiditis
Definition
5-8% Incidence within 6 mo. post-partum
Not as common as Hashimoto's
Complement-fixing anti-Thyroid Peroxidase antibodies
Results in Hypothyroidism
Term
Describe the thyroid in Hashimoto's Disease
Definition
Many infiltrated lymphocytes
Difficult to see thyroid follicles
Enlarged lymphatics expand thyroid size = goiter
Germinal centers form in the lymphatics - B cell proliferation - produce IgG
Thyroid Gland "becomes a lymph node"
Probably a type II and IV mixed reaction
Term
What antibody class recognizes carbohydrate antigens?
Definition
IgM
Term
What type of antigen is T cell independent? What does this mean?
Definition
Carbohydrate antigens
(If polyvalent) can activate B cell without T cell help
Ex = ABO blood groups
Term
What acutely mediates a type IV Hypersensitivity reaction?
Definition
CTLs, Inflammatory Cytokines
Term
What is the type IV hypersensitivity called the "delayed type"?
Definition
Happens 24-48 hours after skin exposure
Time required for T cells to accumulate and mediate the reaction
Term
How long does it take for a type III arthus reaction to happen?
Definition
8-12 hours for immune complexes to form in situ
Term
Epitope
Definition
the chemical structure that forms (non-covalent) bonds with the antigen receptor
Term
What limits the maximum size of an epitope?
Definition
Size of the antigen binding site of a variable region
6 amino acids OR 6 hexoses
Term
How is an antigen receptor different from a ligand receptor?
Definition
An antigen receptor has a variable binding site that can bind a wide variety of different antigens.
Term
What is the size of the smallest molecule recognized by an antibody? How do we take advantage of this in medicine?
Definition
Smallest thing = 1 benzene/1hexose
Put in very small synthetic molecules that won't be recognized
Term
What antibody class recognizes protein antigens?
Definition
IgG
Term
Why can Rhesus Factor cause medical problems in pregnant women?
Definition
As a (t cell dependent) protein antigen, it is recognized by IgG, which can cross the placental barrier.
Term
What kind of cell induces class switching in B cells?
Definition
T cells (working with T-dependent protein antigens)
Term
Why do we have natural antibodies against the different blood group types that we don't have?
Definition
The ABO antigens resemble sugars found in common enteric bacteria. We make the natural IgM antibodies against the enteric bacteria.
Term
What is best practice during blood transfusions?
Definition
1. Use packed RBCs, not whole blood
2. Test for compatibility before transfusion
Term
What happens if you transfuse O whole blood into a B patient?
Definition
Anti-A antibodies in the recipient can't bind to donor RBCs, so there is no reaction.
Term
What percentage of the population is Rh-negative?
Definition
15%
Term
Where is rhesus (Rh) antigen found?
Definition
a protein in an ion channel on the RBC
Term
How do Rh-negative mothers develop anti-Rh IgG?
Definition
Rh-negative mothers are exposed to Rh+ fetus, especially during birth
Term
Describe Hemolytic Disease of the Newborn.
Definition
Rh-negative mother transfer her anti Rh-IgG via FcRn to the subsequent fetus, this will attack the Rh+ fetus.
Term
Describe hydrops fetalis.
Definition
Result of hemolytic disease of the newborn (HDN).
Edema, fetal anemia, heart failure, death
Term
RhoGam
Definition
Passive immunity blocks active immunity
Give IM injection of IgG anti-Rh to FIRST TIME MOMS
Give @ 26 weeks and within 72 hours of birth
Coats/lyses fetal cells in maternal circulation and blocks immune response
Term
Coombs Test Titers
Definition
Higher concentration if the 2nd number is higher
(1:8 is less concentrated than 1:128)
Term
What are other consequences from Rh incompatibility besides hydrops fetalis?
Definition
Brain damage from hyperbilirubinemia (from RBC destruction)
Life-threatening anemia
Term
What are the treatments for infants with hemolytic disease of the newborn?
Definition
1. Fluorescent irradiation of jaundiced infants.
2. Intrauterine or post-partum transfusion.
Term
What is the rationale behind the amount of RhoGam given to first time mothers?
Definition
Give 300 ug of RhoGam (anti-Rh antigen antibodies)
This is enough to neutralize 30 mL of fetal serum that might get into maternal blood.
Term
Why does RhoGam fail 0.1% of the time?
Definition
Because more than 30 mL of fetal serum has gotten into the maternal circulation.
Term
Direct Coombs Test
Definition
Are the RBCs coated with a particular antibody?
Combine RBCs with an antibody to a certain type of antibody - see if it agglutinates?
Term
Indirect Coombs Test
Definition
Does the serum in question contain antibodies that could react with the test RBCs?
Term
Does free immunoglobulin bind to Fc receptors?
Definition
No. antibodies must have bound antigen before they can bind Fc receptors on macrophages, etc.
Term
Name 2 ways of activating the macrophage to lead to destruction of a bacterium.
Definition
1. Aggregate the immunoglobulin on the bacterial surface to allow binding to Fc receptors.
2. Conformational change in immunoglobulin on binding to antigen may expose Fc-binding site.
Term
Follicular B Cells
Definition
Receptors: IgD, IgM
Bind with: protein antigen + helper T cells
Undergo a germinal center reaction
Produce: isotype-switched, high-affinity antibodies, long-lived plasma cells (IgG, IgA, IgE)
Term
Marginal zone B Cells
Definition
Receptors: IgM
Location: marginal zones of splenic white pulp, respond to blood-bourne polysacharides
Bind with: polysaccharides, lipids, etc.
Produce: mainly IgM and short lived plasma cells
Term
B-1 B Cells
Definition
Receptors: IgM, CD5
Bind with: polysaccharides
Found in: mucosal tissue and peritoneum
Produce: mainly IgM, short-lived plasma cells
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