Handout 10: Differentiation and Functions of CD4+ T cells Flashcards
How many T cells have a specific TCR that can recognize a given pathogen? What do these T cells with specific TCRs that recognize pathogens do?
1 in 10^6 T cells
These T cells are mobilized and activated
Specific T cells are made by the immune system _____
On demand
Most of the T cells in ciruculation (90-95%) have what type of TCRs?
They have alpha beta TCRs
What do alpha beta TCRs recognize/bind to? What kind of co-receptors do they express?
They recognize/bind to both peptides presented within the MHC molecules and MHC itself
They express either CD4 or CD8 co-receptors
alpha Beta T cells are ______
MHC restricted
Ag recognition involves _______
clustering of TCRs
How is activation of T cells initiated?
By a signaling cascade after TCRs (at least two) recognize a specific Ag
Which parts of the alpha beta TCR signals and which parts are not long enough to signal?
The alpha and Beta chains have only a very short intracellular domain so signaling is mediated by other proteins comprising the TCR complex. CD3 proteins (gamma, delta, epsilon and zeta) have cytoplasmic tail that is long enough to signal
What components are required to activate a T cell?
TCR, CD4 or CD8, and CD3 to activate a T cell. CD4 is needed for T helper cells while CD8 is needed for cytotoxic T lymphocytes (CTLs)
What marker is used for counting total numbers of T cells (CD4 + CD8 T cells)
CD3
What is required to interview naive T cells? How many T cells can in interview per hour?
Activated DC required. Interviews about 500 naive T cells per hour
______ are immature dendritic cells that do not express high levels of B7
Langerhans’ cells
What is the process by which dendritic cells stimulate naive T cells?
- Ag uptake by Langerhan’s cells in the skin
- Langerhan’s cells leave the skin and enter the lymphatic system
- Langerhan’s cells enter the lymph node to become dendritic cells expressing B7
- B7-positive dendritic cells stimulate naive T cells
After the TCR is engaaged and activates T cell, what must the T cell receive?
Co-stimulatory signal
What are the co-stimulatory molecules expressed on professional APC?
B7 proteins (CD80/CD86)
B7 molecules plug into _____ expressed on T cells
CD28 receptor
What is the purpose of co-stimulation?
It’s an amplifier that improves the signal; with co-stimulation, we need about 100 fewer clustered TCRs for activation
What does CD80-CD26 Co-stimulation lead to?
Leads to proliferation and differentiation of T cells specific for a bacterial protein
What happens after T cell activation is completed?
The T helper cell and the APC are separated, and the APC goes on to activate other T cells. The T cells proliferate to increase their numbers.
What is required for the proliferation of T cells and is also called T cell growth factor?
IL-2
Do all T cells have IL-2 receptors (IL-2R) expressed on their surface? If not, which which T cells express IL-2R and which do not?
No, naive T cells do not have IL-2R expressed on their surface. Activated T cells, in contrast produce large amounts of IL-2 and express IL-2R.
Aside from T cell proliferation, what is another function of IL-2?
It enhances resistance of activated T cells to apoptosis
What are the steps in T cell proliferation?
- T cell is activated by Ag and costimulator
- IL-2 is secreted
- IL-2R alpha chain is expressed which results in formation of a high-affinity IL-2R alpha-beta-gamma complex (without the alpha chain, there is low affinity for the T cell)
- IL-2 induced T cell proliferation occurs
What are the phenotypic subsets of CD4 + T cells? These are all what kinds of cells?
Th1, Th2, & Th17 cells. These are all CD4 positive helper cells