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Immunology Exam 2, Part 2
Immunogenetics; Antibody-Mediated Immunity
41
Immunology
Professional
02/13/2012

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Term
An individual can generate 10^8 different antibody specificity. How is the genome large enough for this level of information?
Definition
The genes present aren't big enough for that many possibilities.

Diversity instead results from differences in heavy and light chains, during joining of chains, somatic mutation, etc
Term
On a Kappa Chain gene, how many segments are there before any processing?
Definition
3 light chain loci and 1 heavy chain loci
Term
What gene segments does a single expressed kappa chain contain?

How many possibilities can result from their combination?
How many possibilities are possible for these combinations?
Definition
Vk + Jk +Ck

40 x 5 x 1 = 200 possibilities
Term
For the V, J, D, and C gene segments, what do each of these letters stand for?
Definition
V= variable
J= joining
D= diversity (only on heavy)
C= constant
Term
On a Lamda Chain gene, how many segments are there before any processing?
Definition
3 light chain loci and 6 C1 exons representing each subtype
Term
What gene segments does a single expressed lamda chain contain?

How many possibilities can result from their combination?
Definition
Vl + Jl +Cl

30 x 4 x 1 = 120 possibilities
Term
How many possible variable regions can result from light chain gene combinations?
Definition
320 (120 from lamda and 200 from kappa)
Term

Which chromosome are light chain genes on?

 

Which chromosome are heavy chain genes on?

Definition

Kappa- chromosome 2

Lamda- chromosome 22

Heavy chain- chromosome 14

Term
What gene segments does a single expressed heavy chain contain?

How many possibilities can result from their combination?
Definition
Vh + Jh +Ch

65x 27 x 6 = 10,530
Term
How many possible idiotypes can result from heavy and light chain combination?
Definition
10,530 x 320 = more than 3 million (10^6) possible idiotypes

Other processes such as imprecise joining can increase diversity
Term
List and describe the steps of V/(D)/J recombination
Definition
1. Regions of DNA between V and J sequeces are recognized by RAG (recombinase) enzymes

2. Two of the RAG complexes are brought together, forming a stem loop structure that excises out and is deleted

3. This creates another level of diversity when the two unlike DNA is brought together, TdT adds nucleotides to allow base pairing and exonucleases remove unpaired ones
Term
Once VDJ recombinase has combined the gene segments in a B or T cell, is the idiotype permanent?
Definition
Essentially permanent.

An exception is for memory B cells which undergo somatic hypermutation, which leads to affinity maturation in order to recognize an antigen
Term
Which gene segment determines an Ig secondary biological characteristics?
Definition
CH (A constant gene on the heavy chain)
Term
List qualities of the B Stem Cell stage
Definition
-Develop under bursal equivalent
-Located in bone marrow and blood
Term
List qualities of the Pro-B cell stage
Definition
-Most primitive recognizable stage
-Assembly of heavy chain
-Located in bone marrow and blood
Term
List qualities of the Pre-B cell stage
Definition
-Heavy chain expressed
-Assembly of light chain (k or l)
-Located in periphery
Term
For any given B cell, how many possible light chains could be chosen?
Definition
4 possible (1 kappa and 1 lamda from each parent)

1 chosen during Pre-B cell stage, other 3 silenced
Term
List qualities of the Immature B cell stage
Definition
-Cell begins to express complete IgM
-Idiotype completely determined
-Responses negatively to self immunogens, for tolerance
Term
List qualities of the Mature B cell stage
Definition
-Surface IgD and IgM expressed
-Surface molecules acquired
Term
How many B cells are produced in the body per day? What happens if they are never stimulated by antigen?
Definition
About 10^9 made a day, but die in several weeks if not stimulated by antigen.

About 1 in 100,000 could react to any given epitope
Term
How long do plasma cells life in the body?
Definition
About 4 days

But memory cells can reside in lymphoid tissue for years
Term
Define isotype (class) switching
Definition
Upon antigen stimulation, memory cells provide antibody of the same specificity but different secondary activity

A similar process to VJ binding, irreversible splicing
Term
Define somatic hypermutation
Definition
-Occurs in V/J and V/D/J exons during an immune response

-Results in antibodies of increased or decreased affinity

-Cells of higher affinity receptors are selected to "mature" the immune response
Term
Describe the system to limit antibody synthesis once an effective immune response has been launched
Definition
Antigen-antibody complexes bind to B cells via Fc receptors to suppress the B cells via negative feedback
Term
What two events in B cell development are reversible?
Definition
1. Coexpression of IgM and IgD

2. Change of synthesizing secreted antibody instead of membrane Ig
Term
When do B cells first start being produced in an individual?

Where are they first seen?
Definition
B cells first appear in the fetal liver 8 weeks after conception

They are produced in the bone marrow during the second trimester
Term
List the isotypes in the order that they appear in a fetus
Definition
IgM, IgD, IgG, IgA
Term
How and when does a fetus get immunity?
Definition
Active transport of maternal IgG begins about the 16th week, but mostly after 34th week
Term
What can indicate intrauterine infection?
Definition
Presence of IgM and IgA in the cord blood

(IgG is normal since it is transferred through barriers)
Term
How long does a baby have maternal IgG?
Definition
Up to six months after birth

(Also, IgA is transmitted through breast milk)
Term
When should routine pediatric immunizations be started?
Definition
Within the first two months of life
Term
When is a person's immune response reasonably mature?
Definition
By 2-3 years of age, but inexperienced
Term
When is serious congenital immunodeficiency usually detected?
Definition
At 3-6 months of age, after maternal immunity wanes

Often detected during a reaction to a live vaccine
Term
How does puberty affect immunity?
Definition
1. New exposures due to new experiences
2. Thymus reaches maximum size
Term
Describe the size of the thymus throughout life
Definition
Maximum size (~35g) during puberty then begins involution until a small mass (~6g) remains in later adulthood

But shriveled thymus works just as well
Term
How many acute infections does a normal adult contract a year?
Definition
2-5 common infections

Usually determined by environmental factors
Term
Does immunity decrease with age?
Definition
No, there's no evidence of this.

However, autoimmune and neoplastic diseases are correlated with age
Term
What is the effector function of SIgA?
Definition
To bind to organisms in external secretions and prevent their attachment to mucous membranes
Term
Define opsonin

Give an example
Definition
A substance that enhances phagocytosis

IgG, complement proteins via Fc receptors
Term
Define toxin neutralization
Definition
Physical binding of an antibody (usually IgG) to prevent a toxin binding to its receptor
Term
Define virus neutralization
Definition
Physical binding of an antibody (usually IgG) to prevent a virus binding to its cell receptor
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