T-Lymphocytes Flashcards
TCR variable region genes form by…
chromosomal rearrangements.
a chains are 2 gene segments and b chains are 3 gene segments.
T-cell receptor complex
TCR, and 2 CD3 molecules
alpha chain TCR variable region is made of…
one V and one J genes are paired together.
beta chain variable region of TCR contain…
one V, one D, and one J gene.
TCR variability
there are 10^18 possible TCR variable regions
TCR part of TCR complex
recognizes antigenic peptides bound to MHC molecules
CD3 part of TCR complex
transmits the recognition signal to the cytoplasm & nucleus
Types of TCR
TCRalpha-beta
TCRgamma-delta
Severe Combined Immunodeficiency (SCID)
inherited immunodeficiency in Arabian foals due to inability to splice chromosomes together after strand breaks like the ones needed to create functional variable region genes.
Foals can’t make Ag receptors & lack T & B cells
How can you diagnose a large lymph node as a lymphoma or leukemia?
- PCR-amplification of lots of lymphocytes’ genes which are varied in size.
- PCR-amplification of lymphoma or leukemia give ONE PCR product from every cell.
- Running PCR through gel electrophoresis can let you determine which one it is.
Lymphocyte precursors commit to become NK, T or B cells in..
bone marrow
T & B cell precursors do….
- Migrate to their unique primary lymphatic tissue
- Rearrange their TCR or Ig genes
- Express the Ag receptor on their plasma membrane.
When are T & B cell precursors considered “immature” lymphocytes
Once they express their rearranged Ag receptor on their plasma membrane
In primary lymphoid tissues, T cells
Precursor T cells differentiate into Tgamma-delta and Talpha-beta cells.
AND
Talpha-beta cells differentiate into Th and Tc cells
T-cells mature and becoming “immature” T-cells
BEFORE seeing antigen
in bone marrow and thymus
In secondary lymphoid tissues, Th cells..
differentiate into Th1, Th2, Th17, Tfh, and Treg cells
Differentiation of Th cells occurs
AFTER seeing Ag
T Cell maturation in Thymus
- Rearrange TCR genes
- Positive Selection
- Negative Selection
Rearrangement of TCR genes involves…
rearranging gamma chain and delta chains Tgamma-delta cells OR rearranging of alpha and beta genes and become Talpha-beta cells
Positive Selection
recognition = survival
Tab cells selected for ability to recognize self-antigens + MHC
Rules of Positive Selection
- Tab doesn’t recognize self MHC molecules at all = DEATH
- Tab recognizes self MHC I => mature CD8 T cell
- Tab recognizes self MHC II => mature CD4 T cell
Negative Selection
T cells DELETED if affinity for self antigens + MHC is too high
CHECKS AFFINITY
Rule for immature lymphocytes in primary lymphatic tissue
T cell recognizes antigen in primary lymphatic tissue it is probably a self-antigen, and T cell dies cause it MIGHT be dangerous.
Possible effect of having high affinity for self antigens
- CD4 and CD8 cells die
2. CD4 become natural Treg cells
Moderate affinity means
T cell binding affinity for self antigens presented by MHC is too weak for activation
General features of Lymphocytes responses to Ags
- Recognition
- Activation
- Proliferation
- Differentiation (effector or memory cells)
Recognition
done via Ag receptors in cell membranes
SIGNAL 1
Signal 1 in T-cell Responses to Ags
Ag Recognition
location of Signal 1
diffuse lymphoid tissues
Important cells for Signal 1
Dendritic cells for presenting Ag to naive T-cells
Signal 1 Mechanism
T cell enters lymph nodes via high endothelial venules & scan dendritic cells. When it recognizes its Ag, it stops scanning and forms longer term interaction with DC
Signal 2 is what step in T cell response to Ags
Activation
Activation of T cell occurs
via costimulatory signals received from another cell
Signal 2 involves…
activation of DCs by PAMPs, DAMPs & inflammatory cytokines
Signal 2’s activated DCs
express new cell-surface molecules (B7 family) required for T-cell activation
What occurs if Signal 2 is absent?
T cell recognizes Ag but isn’t activated.
T cell becomes anergic