Lecture 5: Activation of T Lymphocytes

T Lymphocytes

perform many functions in defending against infections in the intracellular environment

-major role is within cell-mediated immunity of the adaptive immune response

humoral, cell-mediated, phagocytes, communicate, killing, B cells

Functions of T Lymphocytes:

• Direct role in enhancing both ______ and ___-_______ immunity

• Activation of ___________

• _______ with other cells through the release of cytokines, chemokines, and interleukins

• ________ of infected and tumor cells

• Help for _ ____

Recognition, proliferation, differentiation, and effector

Phases of T Cell Response:

• _______ of cell associated microbes by naive T-cell

• Expansion of antigen-specific clones via ________, stimulated by IL-2

• _______ of progeny into either ______ T cells or memory T cells

Endosome

Where does recognition of class II MHCs occur?

stabilize, APC

Adhesion molecules on T cells _______ the binding of T cells to the ___

Integrin

most important adhesion molecule, found on the T-cell

helps direct migration of T-cells to where they need to be

T cells, APCs

Integrin mediated adhesion is critical for the _ _____ to bind to ____ displaying microbial antigens

co-stimulators

Full activation of T cell is dependent on the recognition of __-___________ on APC in addition to antigen

B7

Best defined co-stimulator that binds to CD28

B7, CD28

__ on APCs and ____ families on T-cells stimulate or inhibit immune response

CD40L

______ on activated T cells and CD40 on APC also helps with T cell responses

Activates, expression, differentiation

CD40L:CD40 Interactions

• _______ APCs

• Increased APC __________ of B7 costimulators/cytokines

• Enhanced T cell _________

These help APCs get better at stimulating T cells

Critical

Inhibitory Receptors are _______ for limiting/terminating immune responses, help prevent autoimmune conditions

CTLA-4

inhibitory receptor that recognizes B7-1 and B7-2 on APCs

PD-1

inhibitory receptor that recognizes two different, structurally related ligands

cytosolic, cross-presented

Initiation of CD8 T cell often requires _______ antigen from one cell to be ______-__________ by dendritic cells. Ensures all microbes are being screened and caught

CD4

Differentiation of naive CD8 T cells may require concomitant activation of ___ helper Tcell

T Cell

Antigen recognition activates several biochemical mechanisms that lead to _ ____ responses, like: activation of kinase enzymes, recruitment of adaptor proteins, production/activation of transcription factors

Immune Synapse

created when T-cell recognizes MHC: the region of contact between APC, T cell, and redistributed membrane proteins

-where a cascade of events occurs

NFAT

nuclear factor activated T cells

-transcription factor in cytosol of T cells

Ca+, PLCy

Activation of the Calcium-NFAT pathway is dependent on the ____ concentration and _____

Calcineurin

_________ inhibitors act on the Calcium-NFAT pathway, suppressing NFAT and causing decreased proliferation of T Cells or activation of T cell.

AP-1

transcription factor found in the RAS- and RAC-MAC kinase pathway, enhances the transcription of T cell genes

signaling, NF-kB

PCK0 (aka Protein Kinase C) is essential for T-cell ________ in the PKC0-NF-KB pathway, where it activates __-___

mTOR, rapamycin

_______ is an enzyme that can cause Graft vs Host disease in transplant patients. To prevent this condition, ________ is given.

cytokines, clonal, effector, memory

The functional responses of T lymphocytes to antigen and co-stimulation are:

1. Secretion of _______ and expression of cytokine receptors.

2. ________ expansion

3. Differentiation of Naive T cells into _______ cells

4. Development of ________ T cells

Dendritic cells, macrophages

Primary cytokine producers of the innate immune system

CD4+ T Cells

What cells are the main producer of cytokines in adaptive immunity?

Yc

X-Linked SCID is caused by a mutation in the __ gene, which is a common subunit in several cytokine receptors. Only males can be affected by this condition, 50% of cases

IL-2

Activated T-Cells produce __-_

alpha

Naive T cells have a low binding affinity to IL-2 + B and y signaling chains because they lack an _______ chain

IL-2

interleukin that stimulates the survival, proliferation, and differentiation of T cells

High

Maturation causes T-cells to switch to ______ affinity binding, which allows them to proliferate and differentiate

1-2

Activated T lymphocytes begin to proliferate in _-_ days, with the expansion of antigen-specific clones happening later

CD8+

The majority of cloned T-cells are ____, for they can directly kill microbes. They aren’t just intermediate cells.

cytokines

Some proliferating T cells differentiate into effector cells, depending on what _______ are being expressed. This helps eradicate infections/some cancers.

Memory T Cells

• can be either CD4+ or CD8+

  • very small fraction of these cells are made and differentiate into long term ones

infection, cytokines, antigen, lymphoid organs, not, may

Memory Cells:

1. Survive after _________

2. May rapidly produce ________ → kill infected cells upon _______ recognition

3. Found in ______ ______ and various peripheral tissues

4. Activation does ___ require high co-stimulation and ___ be activated by various APCs

FK 506

drug that suppresses T cell activation

Cyclosporine A

used as a calcineurin inhibitor in the calcium-NFAT pathway, suppressing NFAT and causing decreased T cell proliferation and stop T cell activation