Objectives and Vocabulary for Week # 11 Flashcards
Where does activation of naive T lymphocytes occur?
Typically in the secondary lymphoid organs, when they come in contact with APCs, specifically DCs.
What is the role of effector CD4+ and CD8+ effector cells?
CD4+ cells activate macrophages, B Cells, and other cells; CD8+ cells kill infected cells and activate macrophages.
What are the first and second signal in T lymphocyte activation?
1) Antigen recognition by the T cell receptor (specifically dendritic cells) 2) Co-stimulation
What happens to T cells that have signal 1, but not signal 2?
1) Die by apoptosis or 2) enter into a state of prolonged unresponsiveness.
CD28
T cell surface marker that binds to B7-1/2 (CD80 and CD86), which is present on the surface of APCs.
B7 molecules
(CD80 = B7-1 and CD86 = B7-2); expressed on the surface of APCs (DCs, Macrophages, and B lymphocytes); upregulated by TLR recognition of pathogen and the secretion of IFNg (Example of innate aiding adaptive); B7-2 is expressed constitutively at all levels and is then upregulated quickly after APC activation.
Bcl-2 and Bcl-Xl
anti-apoptotic proteins, promote survival; enhanced proliferation; increased metabolic activity; production of IL-2; and the differentiation of the naive T cells into effector and memory cells.
ICOS
(inducible co-stimulator, CD278); ligand is ICOS-L (CD275), which is expressed on dendritic cells, B cells, and other cell populations; responsible for the development and activation of follicular helper T cells, which is needed to create high affinity B cells.
CTLA-4
Cytotoxic T Lymphocyte antigen 4; inhibitory receptor; recognize B7 molecules just like CD28, but instead of activating T cell, it inactivates T cells by competitively inhibits CD28, remove B7 molecules from the surface of APCs, or deliver inhibitory signals that block activating signals from the TCR and CD28
PD-1
Programmed death 1; inhibitory receptor; PD-ligand interactions inhibit the activation of effector cells, especially in peripheral tissues.
CD40L
Present on the surface of T cells. Interacts with CD40 on the surface of APCs. Activates APCs to make them more potent by enhancing their expression of B7 molecules and secretion of IL-12 that promotes T cell differentiation.
Licensing
Activated T cells enable APCs to become more powerful stimulators; CD40L and CD40 interaction Activates APCs to make them more potent by enhancing their expression of B7 molecules and secretion of IL-12 that promotes T cell differentiation.
Describe the changes in outer surface of the T cell as it is activated. What are their purposes?
1) CD69 expression increased, causing decreased amounts of S1PR1 (sphingosine 1-phosphate receptor aids in migration out of lymph node) which keeps the lymphocyte in the cell. 2) CD25 (IL-2RA) Increased expression allows for T cell to respond to IL-2 3) CD40L enables CD4+ T cells to interact with macrophages and B cells. Enables APCs to become better APCs 4) CTLA-4, increased expression to regulate T cell response. 5) reduced expression of CCR7 and L- selectin (both are responsible for migration into the lymph nodes) 6) Increased expression of LFA-1 and VLA-4 receptors for E and P selectin respectively, responsible for migration to peripheral sites of infection 7) Increased expression of CD44 a receptor for the extracellular matrix molecule Hyaluronan, helps retain effector T cells in the tissues at sites of infection and tissue damage.
IL-2 and its role in T lymphocyte activation
1) Role: growth, survival, and differentiation factor for T lymphocytes 2) Produced by: mainly T cells (autocrine/paracrine function) 3) IL-2R receptors: present briefly on naive and effector T cells, while regulatory T cells always express high affinity IL-2 receptors;
How does IL-2 stimulate the survival, proliferation, and differentiation of antigen-activated T cells?
Aids in the production of anti-apoptotic protein Bcl-2; increases the production of effector cytokines IFNg IL-4
What cytokine is required for the survival and function of regulatory T cells?
IL-2; IL-2 has also been shown to stimulate proliferation and differentiation of NK cells and B cells.
Roles of effector T cells (CD4+ and CD8+)
CD4+: Activated B lymphocytes, Macrophages, and Dendritic cells CD8+: cytotoxic and kill infected cells
Blimp-1
Transcription factor that promotes the differentiation of memory cells.
Memory cells
Integral part of the adaptive immunity, characterized by their ability to survive in environments with little to no available antigen and mounts enhanced responses to pathogens previously encountered.
What proteins are released that keep memory T cells alive, even without survival signals?
Bcl-Xl and Bcl-2 are anti-apoptotic proteins, which prevent the release of cytochrome c from the mitochondria, which prevents apoptosis due to the lack of survival signals.
What cytokine is most important for the maintenance of memory CD4+ and CD8+ T cells?
IL-7, which is also important in early lymphocyte development and survival of naive T cells
Which cytokines induce the expression of anti-apoptotic proteins?
IL-7 and IL-15
What receptors are up-regulated in response to T cell recognition of antigen, to keep the T cells at the site of infection? What are their ligands?
1) VLA-4/5 and CD44 2) Fibronectin/(VCAM-1) and hyaluronan are the ligands respectively.