T cell maturation

hematopoietic stem cells

what is the origin of T cells?

thymus

where do T cells mature?

thymocytes

what are lymphocyte precursors referred to as?

60-80%

what percent of T cells are lymphocytes in peripheral blood?

Thymus

where does T cell differentiation occur?

85%

what percent of lymphocytes are in the cortex of the thymus?

• cortex

• medulla

what are the two sections of the thymus?

3 weeks

how long does it take for cells to filter through the thymus?

>97%

how many T cells fail during the maturation process? (die)

weak recognition of class I + peptide or class II MHC + peptide

what is positive selection?

strong recognition of either class I or class II MHC + peptide

what is negative selection?

CD4

what is the T helper cell marker?

CD8

what is the T cytotoxic cell marker?

CD2

which CD marker is an important T-cell marker that is involved in T cell activation?

CD3

which CD marker is a complex of proteins that delivers the signal to cell interior upon TCR-AGN recognition, ⍺ and β chains?

CD5

which CD marker is the T-cell maker?

MHC II

what is present in APCs that associate antigen to present to T helper cells?

MHC I and CD 45R

what is present in all cells?

sheep RBCs

what is CD2 a receptor for?

rosettes—flower like formation

what does it look like when sheep RBCs are mixed with T cells?

detect and identify T cells

what is the purpose of mixing sheep RBCs with T cells?

CD3:TCR complex

what forms when CD3 attaches to the TCR?

alpha and beta chains

what is TCR composed of?

binds MHC

what is the function of TCR?

delta, epsilon, gamma, and tau chains

what is CD3 composed of?

intracellular signaling

what is the function of CD3?

variable areas for antigen recognition

what does TCR contain?

β chain rearrangement

what occurs first in the TCR?

CD3 delivers the signal to cell interior

what happens when TCR recognizes the antigen?

1. double negative

2. double positive

3. either CD4 or CD8

what is the sequential steps of T cell maturation?

thymocytes (immature cells)

what cells are the double negative T cells?

CD4 and CD8

what do double negative T cells lack?

rearrangement of genes that code for TCR

what do double negative T cells undergo?

several CD markers

what is the appearance of double negative T cells?

CD4 and CD8 antigens are expressed

what occurs in double positive T cells?

co-receptors that bind to MHC

what is the function of CD4 and CD8 antigens in double positive T cells?

double-positive thymocytes

what is another name for double positive T cells?

CD3:TCR complex is complete

what occurs in double-positive T cells?

preservation of self MHC-restricted T cells

what is the process of positive selection?

they live

what happens when T cells recognize the peptide presented by MHC molecules?

they die by apoptosis

what happens if T cells don’t bind to MHC molecules?

fix class I and class II MHC restrictions

what does positive selection also do?

the expression of CD4

what is lost when cells have TCRs that recognize class I MHC molecules while preserving the expression of CD8?

the expression of CD8

what is lost when cells have TCRs that recognize class II MHC molecules while preserving the expression of CD4?

tolerance to self

what does negative selection determine?

they die

what happens to cells that bind strongly to the self proteins displayed by the MHC molecules?

that mature T cells are tolerant to many self antigens

what does negative selection ensure?

helper cells

what are CD4 cells?

about 2/3 of T cells

what fraction of T cells are helper cells?

recognizes antigen in association with MHC class II molecules

what is the function of CD4 cells?

cytotoxic cells

what are CD8 cells?

about 1/3 of T cells

what fraction of T cells are CD8 cells?

recognizes antigen in association with MHC class I molecules

what is the function of CD8 cells?

circulate into secondary lymphoid organs

where do CD4 and CD8 cells go after being released from thymus?

when T cell interacts with specific antigen

when do T cells become activated?

antigen-dependent

what type of lymphopoiesis do activated T cells undergo?

cell proliferates and differentiates into effector cells

what happens after a T cell becomes activated?

• Th

• Tc

what are the T cell effector cells?

cytokine producing lymphocytes

what are Th cells?

cytotoxic T lymphocytes

what are Tc cells?

CD4 memory cells

what are T helper cells also known as?

CD8 memory cells

what are T cytotoxic cells also known as?

to proliferate sooner and express a broader array of cytokines

what ability do memory T cells have?

months to years

how long do memory T cells circulate for?

5-10%

what percent of CD4 cells become T regs?

CD4 and CD25

what CD markers do T regs possess?

self-tolerance and exert active immune suppression

what do T regs maintain?

paracortex

where are T cells located in the lymph node?

central PALS (periarteriolar lymphoid sheath)

where are T cells located in the spleen?

cortex

where are B cells located in the lymph node?

marginal PALS (periarteriolar lymphoid sheath)

where are B cells located in the spleen?

T or B cell markers

what do NK cells typically not have?

large granular lymphocytes

what is the morphology of NK cells?

10-15%

what percent of peripheral blood lymphocytes are NK cells?

double negative thymocytes with γ and δ chains

where are NK cells believed to be derived from?

the ability to kill cells without prior exposure to them

where do NK cells get their name from?

bridges natural to acquired response

what is another function of NK cells?

CD16 and CD56

what CD markers do NK cells have?

receptor for Fc portion of IgG

what is CD16?

NKs have a higher cytotoxic activity

what happens when NK cells have high CD16?

main NK marker

what is CD56?

NKs produce more cytokines and help support antibody production

what happens when NK cells have high CD56?

CD4&CD8 markers

what do NK cells lack?

microenvironment

what influences whether an immature thymocyte turns into a T cell or a NK cell?

IL2

what also activates NK cells?

kill diseased/infected, cancerous cells

what is the function of NK cells?

activate macrophages

why do NK cells produce cytokines?

• antibody-independent cytotoxicity

• antibody-dependent cytotoxicity

what are the mechanisms NK cells have to kill cells?

NK cells kill cells with reduced MHC class I expression

what is antibody-independent cytotoxicity?

NK cell releases substances that create channels in the target cell membrane and lyse cells

what occurs during antibody-independent cytotoxicity?

recognize and lyse antibody-coated cells

what is antibody-dependent cytotoxicity?

through the CD16 receptor for IgG

how does binding occur in antibody-dependent cytotoxicity?

target cells coated with IgG is bound and destroyed

what occurs during antibody-dependent cytotoxicity?

• monocytes

• macrophages

• neutrophils

what other cells can perform antibody-dependent cytotoxicity?