Chapter 3: Lymphocyte Development and Selection Flashcards
The mature naive B lymphocyte expresses what 2 isotypes within its surface membrane?
IgM and IgD
What receptor on the B cell does EBV bind to?
CD 21
mRNA molecules are created which join variable domains to what type of constant domains in B cell heavy chains?
mu or delta
Order with which VDJ combination takes place in heavy chains?
- D-J joining
- V-DJ joining
What does VDJ stand for?
variable, diversity, joining
Order VDJ recombination takes place in light chains?
V-J joining thats it really
Which chain on T cell receptor is synonymous with the B cell heavy chain?
beta
Which on TCR is synonymous with the B cell light chain?
alpha
What type of constant chain domains do the light chain bind to?
kappa or lamda
Purpose of Tdt?
While heavy chain gene segments undergo recombination, this enzyme, terminal deoxyribonucleotidyl transferase, randomly inserts bases (without a template on the complementary strand) > junctional diversity
Allelic exclusion?
When recombination has generated a functional product then allele on homologous chromosome is turned off.
Difference between N-nucleotide addition in B and T cells?
B cells (only heavy chains)
T cells (all chains)
RAG 1 and RAG 2
2 proteins found within recombinase, a protein complex
Resoposbile for B and T cell rearrangment to create functioning receptors on the surface
What is the inheritance pattern of Omenn Syndrome?
AR
Inheritance pattern of SCID?
severe comibined immunodeficiency is an AR condition can also be X-linked
Omenn Syndrome molecular defect?
- missense mutation in RAG genes
- the RAG enzymes have only partial activity
Symptoms of Omenn Syndrome?
- Lack of B cells (below limits of detection)
- marked decrease in predominantly Th2
*characterized by early onset, failure to thrive, red rash (generalized), diarrhea, and severe immune deficiency
What is the molecular defect in SCID?
- null mutations in RAG1 or RAG 2 genes
- no RAG enzyme activity
What are the symptoms of SCID?
- total lack of B and T cells
- total defects in humoral and cell-mediated immunity
Is bone marrow considered a primary or secondary lymphoid organ?
primary lymphoid organ
B lymphocytes whose idiotypes have too great an affinity for normal cellular molecules go through what processes?
- They are either deleted in the bone marrow (clonal deletion)
- They are inactivated in the periphery (clonal anergy)
How does clonal anergy take place?
anergic B cells express high levels of IgD on their surface rendering them inactive
Which B cells are released to the periphery?
only those cells which are selectively unresponsive (tolerant) to self antigen
Label Cell differentiation picture. (B Cells)
Is the thymus a primary of secondary lymphoid organ?
primary
Pre-thymic T cells are referred to as double negative or double positive T lymphocytes? Why?
double negative ; since they do not express CD4 or CD8 on their surface
Cortex of the thymus contains immature or more mature T cells?
Packed with immature T cells
Thymic T cells undergoing rearrangement of beta and alpha chains and coexpressing CD3 complex as well as CD4 and CD 8 co-receptors are collectively referred to as what?
double positive
MHC stands for?
major histocompatibility complex
Overall describe MHC genes and location?
collection of highly polymorphic genes on the short arm of chromosome 6 in the human
Another name for MHC gene products?
HLA (human leukocyte antigen)
What are class I MHC gene products?
HLA-A, HLA-B, HLA-C
What are the class II MHC gene products?
HLA-DP, HLA-DQ, HLA-DR, HLA-DM
Why is HLA-DM different from the other MHC II gene products?
HLA DM is not a cell surface molecule but functions as a molecular chaperone to promote proper peptide loading
Where are Class I molecules expressed?
all nucleated cells in the body, as well as platelets
How are class I MHC molecules expressed on the nucleated cells of the body?
in a codominant fashion, meaning that each cell expresses 2 A, 2 B, and 2 C products (one from each parent)
What is the purpose of the second light chain, B2- microglobulin in the MHC function?
is not encoded within the MHC and functions in peptide-loading and transport of the class I antigen to the cell surface)
Where is Class II MHC presentation usually found?
codominantly on the professional APCs of the body (primarily macrophages, B lymphocytes, and dendritic cells)
Describe positive selection of T cells.
- In thymus, each of these MHC products are loaded with normal self peptides are presented to developing double positive thymocytes
- Those that have TCRs capable of binding with low affinity will receive a positive selection signal to divide and establish clones that will eventually mature in the medulla
Describe failure of positive selection of T cells?
those that fail to recognize self MHC at all will not be encouraged to mature (failure of positive selection)
Describe negative selection of T cells?
those that bind too srongly to self MHC molecules and self-peptide will be induced to undergo apoptosis (negative selection) because the cells will have potential to cause autoimmune disease
CD4 cells recognize which class of MHCs to become “helper T cells?
MHC II
CD8 cells recognize which class of MHCs to become cytotoxic T lymphocytes?
MHC I
What is the function of T regs?
inhibit self reactive Th1 cells in the periphery
How are T regs selected?
While most self- reactive T cells will be deleted in the thymus a small population will differentiate into T regs
How are Tregs identified? What markers?
by their constitutive expression of CD25 on the surface and by the expression of the transcription factor FoxP3
What do T regs secrete to inhibit inflammation?
IL-10 and TGF-B
What is a major function of T regs?
shown to be critical in prevention of autoimmunity
Stages/location of T cells?
Pre-thymic > thymic cortex > thymic medulla > circulating T cells
What are the stages Tdt is found in Human T cell differentiation?
pre-thymic > early thymic medulla
What stages is rag expression of T cells?
thymic cortex
What stages is CD2 expressed in development of T cells?
thymic cortex stage to when it becomes a circulating T cells
What stage is CD3 expressed in development of the T cells?
thymic cortex to when it becomes a circulating T cell
What stage is the TCR found in the development of the T cell?
thymic cortex to when it becomes a circulatory T cell
When does double expression of CD4 and CD8 on T cells become expression of one or the other?
late thymic cortex stage
