Immunology Unit 11

common lymphoid progenitor

bone marrow B cells, T cells, and NK cells are produced by these stem cells

bone marrow

pre-B cells mature here

thymus or intestinal cryptopatches

pre-T cells mature here

stromal cells

stimulates that pre-lymphocyte to stay alive and undergo rearrangement of the BCR/TCR genes

RAG-1 and RAG-2

two genes that work together to catalyze the recombination events necessary for rearrangement of the heavy and light chain or TCR genes

D genes

heavy chain, TCR beta, and TCR delta

V and J genes

light chain, TCR alpha, amd TCR gamma

germ line theory

cells contain genes for each antibody specificity

somatic mutation theory

each cell contains a small number of antibody genes, and multiple mutations during maturation would produce B-cells able to make a diverse range of antibodies

V(D)J recombinase

also known as RAG complex; binds to recombination signal sequences so the DNA is looped out and the two regions that are to be joined are brought next to each other

12/23 rule

can only occur between recombination signal sequences (RSSs) that have different spacer lengths; crucial for ensuring proper gene assembly and preventing aberrant rearrangements

DNA dependent protein kinase

cuts one of the strands one or two bases from the end and unfolds the strand leaving a two or four base overhang on both peices of DNA

terminal deoxynucleotidyl transferase

attaches additional bases to both pieces of DNA until there is a match between the two pieces of DNA

p-nucleotides

palindromic nucleotides; derived from the hairpins; are the opposite on both end of the junction

n-nucleotides

random nucleotides; these are added by the Tdt and usually result in random 1-20 amino acuds being inserted

combinational diversity

diveristy due to the combination of the different possible variable regions

junctional diversity

diversity due to the process of linking the possible variable regions; random and leads to insertion of 1-3 amino acids; sometimes there are deletions instead

allelic exclusion

is the process whereby only one allele is recombined at a time; important to make sure that only one kind of antibody is produced at a time

negative selection

really strong positive selection; too much signal to survive or death signal from an antigen presenting cell will lead to death of the lymphocyte

transcriptional changes

irreversible and lymphocyte is now either know as a memory or effector lymphocyte

CD45R

expression of this is one of the earliest steps in B cell development; all B cells present this

pro B cell

does not express the heavy chain and is in process of rearranging the heavy chain

pre B cell

expresses the heavy chain with a surrogate light chain; in the process of rearranging the light chain

immature B cell

expresses only IgM and undergoes negative selection; will leave the bone marrow and only lives for a few days unless it makes it to the spleen

transitional 1B cell

short lived cell that has not yet arrived in the spleen

transitional 2B cell

short lived; can migrate to lymphoid tissue; express IgM and IgD

mature B cell

developed in the lymphoid tissue and can be activated by the T cells; expresses both IgM and IgD; stable for extended period of time and rarely migrate throughout the body

anergic B cell

naive B cell that ran into a dendritic cell and a T cell and was inactivated

lambda5 and Vpre5

substitute light chain consists of these two proteins

bone marrow screening

immature B cells are screened before leaving the bone marrow for reaction with stromal cells

negative selection

BCR on surface of immature B cell and interacts with host antigens; if it leads to a signal production development is stopped

tolerance

deletion of auto-reactive antibodies

receptor editing

rearrangement of the light chain alleles to make a BCR that does not lead to production of those signals

BAFF cytokine

transitional 2B cells respond to this; also known as B cell activating factor

ignorant B cells

midly autoreactive B cells that will not undergo anergy; do not bind to host antigens strongly enough to induce anergy; could cause an autoimmune reaction if activated

central tolerance

occurs in the bone marrow in thymus

peripheral tolerance

after B and T cells migrate to the tissue; if they respond to antigens in the absence of inflammation can be permanently inactivated

B-1 B cell

innate like B cell that mostly found in the peritoneum; produces a lot of IgM antibodies to capsular antigens; does not require T cell activation; can be induced to class switch with T cell activation

marginal zone B cell

innate like B cell responsible for presenting lipid antigens; found in the spleen and does not appear to require T cell activation