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Test 2 Immunology Expression of Ig Genes and Ab Diversity
Test 2 Immunology Expression of Ig Genes and Ab Diversity
81
Immunology
Graduate
03/07/2015

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Term
The current accepted theory for specificty of immune response and Ab formation is
Definition
Clonal selection theory
Term
clonal selection theory explains what about Ab and Ag relationship
Definition
Its specificity!
Term
What is the issue with any theory and the Ab structure and how its relates to the large # variation of Ab
Definition
Well since we know Ab are very diverse then one has to try and figure out what exactly makes each Ab so diverse. Initial people thought each diverse antibody had its own unique gene. But then it was quickly realized this would be impossible since there are over 10^10 different kinds of Ab
Term
Since theory of one gene for each different Ab was found impossible. Then what explains why we can have so many different kinds of AB
Definition
Diversity of Ab is directly related to the variable and constant regions of each Ab. Slight changes in this configuration generates an enormous degree of diversity.
Term
What is the current explanation for diversity of Ab 3x main parts
Definition
1. All or parts of germline
2. somatic-variation
3. two gene theories.
Term
what is Germline theories
Definition
DNA coding for Ab comes from germ cells since they have large quantities of genes.
Term
What are germ cells
Definition
From egg and sperm
Term
What is the somatic variation theory and how it relates to Ab diversity
Definition
The genes from germline theories can futher undergo recombination or mutation in somatic cells such as lymphocytes or other no-germ cells
Term
What two ways do somatic cells in somatic variation theories contribute to the diversity of AB
Definition
1. Somatic recombination of genes
2. Mutation of genes
Term
What did germline and somatic variation theories not explain
Definition
how Ab could have a large diversity of VARIABLE REGIONS and have Constatn regions that remain constant
Term
What did the two gene theory say
Definition
There is one gene for the variable region and one for the constant region. There is more diversity of variable genes that contribute to the variable region.
Term
in the 1970's what was finally proved regarding genes and Ab diversity. What did it prove about gene segments for Ab
Definition
Evidence finally confirmed there are separate gene segments for variable and constant regions of each L and H chain of Ab. L chains have 3 gene segments and H chains have 4 gene segments that code for it.
Term
When do immunoglobin gene segments rearrange
Definition
during B cell differentiation into mature B cell
Term
Do all cells have allelic exclusion? What is this?
Definition
NO specific to lymphocytes. B cells use genes from just one parental chormosome. It insures just one type of Ab is made.
Term
germline cells are also called
Definition
stem cells
Term
define what a gene segment is in regards to its DNA and sequence
Definition
Gene segments are regions of DNA which do not contain all the coding sequences need to code for light or heavy chains. They are not arranged into functional genes and indivdiual DNA
Term
The majority of gene segments code for _____ in the ____ region of the AB
Definition
Gene segments code for amino acids in the variable region of the Ab
Term
Noncoding regions of the Ab are calledi
Definition
introns
Term
Are coding gene segments of the variable region in close proximity to the coding gene segments of the constant region?
Definition
NO
Term
what kind of region of DNA has the ability to code for the variable portions of light and heavy chains?
Definition
A single FUNCTIONAL reigon of DNA codes for the variable light and a single FUNCTIONAL codes for the variable heavy chains.
Term
which gene segments code fo amino acids in the variable reigon of the light chain
Definition
V and J gene segments
Term
Which gene segment codes for amino acids in the constant region of the light chain
Definition
C gene segment
Term
How many gene segments code for amino acids production to make the light chain
Definition
3x.
V and J for VR of L chain
C gene segment for CR of L chain
Term
V, J , and C gene segments stand for? Code for what?
Definition
V: Variable gene segment codes for the variable region of light chain
J: Joining gene segment codes for variable region of the light chain
C: Constant gene segment codes for constant region of light chain
Term
How many V gene segments in human kappa light chain
Definition
40 V segments on kappa
Term
What is ahead of each V gene segment that codes for amino acids necessary to get L and H chain peptides into endoplasmic reticulum
Definition
Signal or L (leader) Genes
Term
What two gene segments are in germline DNA for light chains
Definition
V and J
Term
how many J gene segments are there in Kappa light chains
Definition
5 functional J gene segments
Term
If the variable light chain is 110 amino acids long than what portions of that are made up of the three gene segments?
Definition
V gene segment (40 versions in Kappa) makes up amino acids 1-97.

J Segment (5x in Kappa L Chains) makes up 13 amino acids at positions 98-110.

C segment: (1 C geen seg for kappa) Codes for CONSTANT NOT VARIAble part of LIght chain and does so for amino acids 111-214.
Term
How many amino acids make up the light chain and where is the breakdown of amino acids in the variable portion of this and constant portion
Definition
214 amino acids. Out of which amino acids 1-110 are in the variable region and 111-214 are in the constant region.
Term
Gene rearrangement and recombination that takes place with B cell differentiation involves what with regards to the individual gene segments
Definition
Goal is to join 1x of the 40 V gene segments to 1x of the five J gene segments.
Term
a___ is an expressed region of DNA that has codes for proteins. While Intron's are noncoding regions of DNA
Definition
Exon = expressed region of DNA, has code for protein
Term
___ Are enzymes that cleave DNA, then join V and J gene segments
Definition
V(D)J recombinase enzymes
Term
These proteins aid in DNA cleavage and recombination process of light chains segments
Definition
REcombination activating genes (RAG)
1. RAG-1
2. RAG-2
Term
how many gene segments code for the Heavy Chain
Definition
4 gene segments (VDJ-Variable region & C-Constant Region)
Term
Which gene segments code for the variable region of the heavy chain and which for the constant region
Definition
C gene segment: constant region of heavy chain

V,D, J gene segments code for V region of H chain.
Term
how many V gene segments are there in heavy chains? What amino acids does it code for
Definition
38 V gene segments, each gene segment codes for amino acids 1-101
Term
What is the name for the gene ahead of V gene segment of Heavy chain that codes for amino acids that get peptide thorugh endoplasmic reticulum
Definition
L (Leader) Genes
Term
How many D gene segments, what amino acids does it code for
Definition
D=diversity gene segments. There are 30 D gene segments. Each D gene codes for amino acids 102-106
Term
What region is between the V and J segment amino acids of the Variable Heavy chain
Definition
D Gene segment! Amino acids 102-106
Term
how many J gene segments are there in the variable heavy chains
Definition
6 J funcitonal gene segments which code for amino acids 107-123
Term
for B cell DNA which gene segments of variable heavy chain join first? Then which after
Definition
D + J then D-J + V = D-J-V
Term
during the ____ phase of _____ non coding sequences of the primary RNA transcript are spliced out to make a funcitonal mRNA
Definition
During transcription phase of PROTEIN SYNTEHSIS
Term
how many types of C segments are there on the heavy chain
Definition
8x types of Constant Segments on the heavy chains
Term
add P Nucleotides does what
Definition
When DNA is spliced it is not always even so body adds a P nucleotide to replace missing piece = more diversity
Term
Addition of N Nucleotides does what
Definition
added to heavy chains
Term
What is junctional flexiblity
Definition
just refers to variation as a result of having mulitple different types of V,D,J combinations
Term
what is combinatorial diveristy
Definition
Heavy chains can COMBINE with different LIGHT chains
Term
Where does H and L chains combine
Definition
Endoplasmic reticulum
Term
adding P and N nucleotides changes what on the DNA? Which means
Definition
changes the tripliet code which means its changes the amino acids in the variable reigon and the Ag binding pocket shape.
Term
when does somatic hypermutations occur? Before or after variable gene region rearrangement
Definition
AFTER!!
Term
Higher affinity of Ab to a specific Ag may occur as a result of what process
Definition
Somatic hypermutation. Which comes AFTER the intial Rearrangement of variasble gene segments
Term
Somatic hypermutation results in what two important characteristics of B cells
Definition
1. allows for higher affinity of Variable region of Antibody
2. Creates different Ab binding specificities
Term
what region of the Ig is where somatic hypermutation is most evident
Definition
CDR (Complementarity determining regions)
Term
describe protein syntehsis steps to make Ab
Definition
1. transcription of DNA to primary RNA
2. RNA transcript processed to make functional messenger RNA (mRNA)
3. Translation of mRNA at ribosomes to make Ig light and heavy chains
4. Light and heavy chains combined in endoplasmic reticulum
Term
If class switching occurs and Ab changes to a different isotype does that new Ab detect the same antigen
Definition
Antigen specificity does not CHANGE
Term
Does class switching occur in naive or mature B cells? Doe sit occur before or after V-D-J gene segment rearrangement
Definition
Class switching occurs AFTER initial arrangement of the VDJ segment
Term
what induces class switching of Ab
Definition
DEPENDENT ON INITIAL Ag which then stimulates cells such as T cells and other cells to secrete Cytokines.
Term
What cytokines from T cells tell Ab to class switch? What non T cell cytokine also tells Ab to class swtich
Definition
Tcells secrete IL-4, IL-5, IFN Gamma
Non T cells secrete TGF-Beta
Term
Chromosome # has the kappa, has the lambda, has the heavy chain
Definition
Kappa: Chromosome 2
Lambda: Chromosome 22
Heavy Chain: Chromosome 14
Term
during ____ the introns are removed from the RNA and whats left is
Definition
During splicing the introns are removed from the RNA whats left is mRNA and ready for protein synthesis
Term
Light chains have no ____
Definition
No Diversity genes
Term
are ABO blood antibodies present in new borns
Definition
No, they develop after first year or more of life
Term
The precursor to the ABO blood group antigens, present in people of all common blood types, is called the
Definition
H antigen
Term
Individuals with the rare ____ (hh) do not express antigen H on their red blood cells. 
Definition
Individuals with the rare Bombay phenotype (hh) do not express antigen H on their red blood cells. 
Term
patients with bombay phenotype of their blood are of special concern with regards to donating or receiving blood b/c?
Definition
The precursor to the ABO blood group antigens, present in people of all common blood types, is called the H antigen. Individuals with the rare Bombay phenotype (hh) do not express antigen H on their red blood cells. As the H antigen serves as a precursor for producing A and B antigens, the absence of the H antigen means that the individuals also lack A or B antigens as well (similar to O blood group). However, unlike O group, the H antigen is absent, hence the individuals produce isoantibodies to antigen H as well as to both A and B antigens. If they receive blood from someone with O blood group, the anti-H antibodies will bind to the H antigen on the red blood cells ('RBC') of the donor blood and destroy the RBCs by complement-mediated lysis. Therefore, people with Bombay phenotype can receive blood only from other hh donors (although they can donate as though they were type O).
Term
The ABO locus, which is located on chromosome 
Definition
chromosome 9,
Term
How many alleles does blood have
Definition
3x - A-B-O
Term
Blood that is Rh- (positive or negative) can be transfused into a person who is Rh-positive
Definition
does not matter. but an Rh-negative individual can create antibodies for Rh-positive RBCs.
Term
blood type is called the "universal donor"; since its red blood cells have no A or B antigens and are Rh-negative, no other blood type will reject it.
Definition
O
Term
blood type is referred to as the "universal recipient", as it possesses neither Anti-B or Anti-A antibodies in its plasma, and can receive both Rh-positive and Rh-negative blood.
Definition
AB +
Term
ABO Blood type is determined by how many genes? How many alleles in that gene?
Definition
1 gene with 3 alleles
Term
which allele in ABO is recessive?
Definition
o is recessive. So if you get A from mom and O from dad then you will be type A blood. If you get O from mom and dad then you are O.
Term
which blood is codominant and what does that mean
Definition
AB blood is Co dominant because A and B are dominant alleles while O is a recessive allele. So if you get A from mom and B from dad both are equally dominant and therefore both are expressed = AB blood.
Term
Rh disease sensitization is about 10 times more likely to occur if the fetus is ABO compatible or incompatible with the mother?
Definition
Rh disease sensitization is about 10 times more likely to occur if the fetus is ABO compatible with the mother than if the mother and fetus are ABO incompatible
Term
How does Rhogram work
Definition

The idea is giving this shot to women within 72 hours of birth (birth is hte most likely time that red blood cells from baby with Rh + RBCs will cross into mother circulation from all that trauma of labor). This shot is active immunity and Immunoglobulins that will directly kill Rh + RBCs from baby hopefully before the mother's own immune system has time to recognize them and make memory cells. 

 

REMEMBER the first mother exposure to Rh+ Is usually not that bad for the baby, IgM starts to form and some IgG. But as a result of Memory cells, any subsequent pregnancy to Rh + fetuses will result in stronger and more deadly responses by Mom's IgG antibodies which are now formed as a result of exposure. 

Rhogram is IgG

Term
In sexually reproducing organisms, cells that are not in the germline are called
Definition
In sexually reproducing organisms, cells that are not in the germline are called somatic cells.
Term
germline cells are?
Definition
In biology and genetics, the germline in a multicellular organism is that population of its bodily cells that are so differentiated or segregated that in the usual processes of reproduction they may pass on their genetic material to the progeny
Term
main benefit of monoclonal antibodies
Definition
The main advantages of isolating monoclonal antibodies are that (a) they are a homogeneous population that (b) they can be produced in essentially unlimited quantities.
Term
The main weakness of monoclonals is
Definition
The main weakness of monoclonals is that they recognize only a single epitope, so there is always the possibility that an epitope that is shared by two antigens can confuse the experimentalist. An antigen directed against a carbohydrate can be shared by many proteins and even glycolipids.
Term
What do scientist do with mice when making monoclonal antibodies
Definition
In the case of MAbs, animals are given injections of antigen or antigen/adjuvant mixtures to induce specific B cells that are obtained from the spleen or lymph nodes to establish hybridomas.
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