Flashcards in Objectives and Vocabulary for Week # 10 Deck (27):
The process by which Naive lymphocytes migrate from the thymus to the secondary lymphoid tissues (homing). If they do not recognize antigen, then they drain into the blood stream through the lymphatic system. Once in the blood, lymphocytes cycle back to secondary lymphoid organs.
How does inflammation relate to lymphocyte re-circulation?
Inflammation increases the rate at which blood flows to lymph nodes, which means increased movement of lymphocytes
What APC is best adapted to activate T Cell immunity?
Through what structure does homing of T Cells occur through?
Homing of naive T cells into lymph nodes and mucosal associated lymphoid tissues occurs through specialized post-capillary venules called high endothelial venules (HEV) located in the T cell zones.
What role does lymphotoxin play in homing?
Lymphotoxin is a cytokine that is important in HEV development.
Native T cells migrate from the blood, through HEVs and into the _____ of the lymph node
What molecules are important for naive T lymphocyte rolling in HEVs in the lymph node?
L-Selectin (on lymphocyte); Peripheral node addresin "PNad" on HEVs. (PNad can be displaced by GlyCAM-1 and CD34)
What molecules are important for naive T lymphocyte rolling in peyer's patch?
Specifically Peyer's patches in the intestinal wall; L-selectin (CD62L ) (still on the lymphocytes); Ligand (MadCAM-1 mucosal addresin cell adhesion molecule - 1)
Firm adhesion of lymphocytes to HEVs is caused by
LFA-1 (on lymphocytes); ligand (ICAM-1 on HEV)
What are the chemokines that activate naive T cell integrins to a high affinity state?
CCL19 - constitutively expressed and CCL21 (source: Fibroblast reticular cells within the T cell zone; ligands for CCR7); Receptor on lymphocytes CCR7
What receptor and ligand are responsible for lymphocyte exit out of lymph nodes?
Chemo-attractant sphingosine 1- phosphate; receptor sphingosine 1-phosphate receptor 1
How is S1P exit mediated?
S1P is at higher concentrations in the blood (S1P lyases are present in the tissues so the concentration is lower); S1P gradient mediates movement of Lymphocytes. In the blood, high amounts of S1P cause internalization of S1PR1 on T lymphocytes; if a lymphocyte is activated by an antigen, S1PR1 is downregulated keeping lymphocytes in the lymph nodes or other secondary lymphoid organs.
What cytokines downregulate the expression of S1PR1?
Type I interferons; antigenic stimulation and Type I interferons increase the expression of CD69 (T cell membrane protein) which binds to S1PR1 and reduces its cell surface expression; This allows T lymphocytes to proliferate and differentiate. Once done, CD69 is downregulated and effector cells can migrate.
Signal # 1
Signal # 1 is the antigen recognition in the context of MHC for T cells.
Signal # 2
Signal # 2 are membrane bound molecules of APCs (B7-1, B7-2) Co-stimulators
Products of pathogens or something that mimics pathogens that enhance the expression of costimulators and cytokines.
CD40 and CD40L
CD40L is expressed by activated CD4+ cells; binds to CD40 on DCs, macrophages, and the T cells that secrete cytokines such as IFNg; the combination of IFNg and CD40 signals activates APCs increasing their ability to process antigens, increased expression of costimulators, and secretion of cytokines that activate T cells.
Transportation of antigens to the lymph nodes
Antigens are transported from site of infection to lymph nodes, through lymphatic ducts, by APCs (primarily DCs). Free floating antigens also enter the lymph nodes by draining into lymphatic ducts.
Where do antigens that are present in the blood processed by T cells?
develop from embryonic precursors; take up residence in the skin prior to birth; populate epidermis
(also called conventional DCs); most numerous in lymphoid organs, characterized by their ability to stimulate strong T Cell responses; present self antigens to T cells in draining lymph nodes. Function may be to eliminate self reactive T cells or produce Treg cells; TLRs 3 and 11; major cytokines produced (IL-12, IL-23, TNF, IL-6)
Only have dendritic cell functional properties after activation; arise from bone marrow precursors; found in the blood; are poorly phagocytic; secrete large amounts of type I interferons in response to viral infections; also present viral antigens to virus specific T cells; have TLRs 7 and 9;
The process by which dendritic cells uptake samples of their environments independent of receptors.
Chemokine receptor on the surface of dendritic cells and T cells; specific for chemokines CCL19 and CCL21; help to home T cells and dendritic cells into lymph nodes. Increases the probability that the two will interact
How are soluble antigens presented to Naive T cells?
Soluble antigens can be uptaken by DCs, BCs, or other APCs; soluble antigens can also travel into the lymph node and interact with APCs there.
Why are Dendritic Cells the most efficient APC for initiating primary T cell response?
1) Have receptors that help them capture and respond to microbes 2) Location: at sites of entry or at areas where microbes reproduce 3) They migrate from areas where infection is probable to lymph nodes 4) have a high amount of MHC, costimulators, and cytokines needed to activate T lymphocytes.