0108101330 - Mfm Ii - Diversity Of Antigen Receptors (Alley)

Front 1

immunological diversity

Back 1

number of different in Abs is limitless and is generated by gene rearrangement

Front 2

immunological specificity

Back 2

each Ab is specific for single Ag/epitope

Front 3

relative to antigen exposure, when does lymphocyte development/diversity take place?

Back 3

before Ag exposure

Front 4

variable region is composed of what?

Back 4

variable fragment (V) + diversity fragment (D) + joining fragment (J)

Front 5

how many different types of recombinatorial D and J fragment types exist?

Back 5

D ~ 12 different types
J ~ 4 different types

Front 6

somatic recombination

Back 6

process by which B and T cell immunoglobulin and TCR (T cell receptors) diversity is achieved

Front 7

what fragment types compose the Ig heavy chain and TCR beta-chain?

Back 7

V, D, J

Front 8

what fragment types compose the Ig light chain and TCR alpha-chain?

Back 8

V, J

Front 9

What are the general steps for recombination of light and heavy chains?

Back 9

light - V, J made from gene separately
V attaches to J
VJ combo is translated into a functional light chain protein

heavy - V, D, J are generated
D combines with J = DJ
DJ combines with V = VDJ
protein translation provides function VDJ protein for heavy chain

(pic)

Front 10

from gene to functional Ig chain, how is diversity achieved?

Back 10

there are only pieces of the gene (loci) that encode for a variable type of V, a variable type of D, and a variable type of J. only one type will end up in the functional Ig chain.

(pic)

Front 11

combinatorial diversity

Back 11

VDJ rearrangement

Front 12

how are recombination of gene segments in somatic recombination achieved?

Back 12

RSS - recombination signal sequences
1) provide recognition sites for recognition enzymes that cut and rejoin DNA
2) ensure gene segments are joined in the correct order

Front 13

what is the 12-23 rule?

Back 13

there are portions of the genetic RSS sequence that provide direction on either side of a V, J, or D fragment. The 12-23 rule is that any two adjacent fragments must complement a 23 nucleotide spacer with a 12 nucleotide spacer. So space sequences will be one of two organizations:
1) 7-12-9-9-23-7
2) 7-23-9-9-12-7

this guarantees that there will be 1 V, 1 D, and 1 J

(pic)

Front 14

what is VDJ recombinase?

Back 14

a collection of enzymes that in general will recombine V, D, J

ex.
1) RAG-1, RAG-2
2) TdT (terminal deoxynucleotidyl transferase)

Front 15

What are is the function of recombination activating genes (RAG-1 and RAG-2)?

Back 15

RAGs attach to the RSSs on nearest sides of sequence specific fragments (V and J or V and D or D and J) that come together forming a hairpin loop of unwanted fragments allowing VDJ recombinase to ligate the unwanted segments and join the wanted fragments

(pic)

Front 16

epitope

Back 16

Ag that which an Ab is specific and attaches

Front 17

how does junctional diversity work?

Back 17

junctional diversity is done by other enzymes that are part of the VDJ recombinase collection.
1) RAG binds to and cleaves
2) RAG generates palindromic P-nucleotides (P nucleotides are not complementary)
3) N-nucleotides are generated by TdT (N nucleotides are complementary)
4) Strands pair, attach
5) extra nucleodies that don't match the palindromic sequence are exised by exonuclease
6) complete DNA sequence is formed to complete the junction between two diversity fragments

(pic)

Front 18

second type of combinatorial diversity

Back 18

random combination of heavy and light chains

Front 19

what is the TCR equivalent to the heavy and light chains?

Back 19

heavy - beta-chain
light - alpha-chain

Front 20

allelic exclusion

Back 20

in a single cell there will only be the expression of one heavy chain and one light chain. to maintain that consistency and specificity, one of the two alleles that represents a gene in a single cell will always be repressed.

Front 21

somatic hypermutation

Back 21

rapid increase in mutation rates that offers greater specificity after antigen exposure in B lymphocytes. this occurs in heavy and light chain variable regions.

this provides a better second response to an Ag

Front 22

What three diversification events occur before antigen exposure?

Back 22

1) allelic exclusion
2) somatic recombination
3) junctional diversity

Front 23

What diversification events occur after antigen exposure?

Back 23

somatic hypermutation in B cells lymphocytes (Ig) only!

Front 24

what's the difference between the transmembrane Ig and the secreted Ig?

Back 24

the poly AAA tail is different and the transmembrane type has a transmembrane specific poly AAA tail and respectively for the secreted Ig

Front 25

what is the purpose of the B cell?

Back 25

to secrete antibodies... it's what it lives to do

Front 26

antibodies can opsonize a pathogen cell. what does that do?

Back 26

opsonization leads to the activation of complement

Front 27

isotype switching

Back 27

the process of switching between isotypes of the same Ig such as IgM monomer to IgM pentamer. this happens with IgM and IgG

Front 28

why is isotype switching necessary?

Back 28

IgM pentamer cannot move from blood to tissue, so it must be switched after it gets to the target antigen

Front 29

how does isotype switching occur?

Back 29

differential splicing of the same primary RNA transcript. this is a arrangement of germline DNA. very similar to the somatic recombination process.

Front 30

What is the first produced Ig in an immune response?

Back 30

IgM in its pentomeric form

Front 31

What should we think of when we think of IgA

Back 31

snot - mucosal secretions

Front 32

IgE significance

Back 32

allergies and parasites

Front 33

IgG significance

Back 33

the most prolific Ig in the blood

Front 34

What are the two reversible actions in diversification of Igs?

Back 34

1) change from membrane bound to secreted forms of Ig
2) switch between IgM expression and IgD expression and coexpression

both depend on poly AAA tail cleavage positions

Front 35

IgD significance

Back 35

coexpressed with IgM by differences in poly AAA sites. IgD is just a cell surface marker during development with no other functional significance.

Front 36

what is the difference concerning gene splicing to produce IgD vs IgM?

Back 36

IgD - poly AAA tail is cleaved at the second poly AAA site on the end of the delta gene (longer)

IgM - poly AAA tail is cleaved at the second poly AAA site on the end of the mu gene (shorter)

(pic)