12. Effector Lymphocytes Flashcards
(38 cards)
Primary activation of naive T cells requires Ag:MHC (signal 1) and costimulatory molecules (signal 2). what does hte effector function require?
Ag:MHC (signal) 1 only!
stimulation of cells within the node increases the expression of certain cell surface molecules on the blood vessels associated with the lymph nodes. These vessels are called what?
high endothelial venules (HEV)
lymphocytes circulating the in blood bind to the HEV surface primarily through what?
selectins and integrins on cell surface (and the migration of lymphocytes REGARDLESS OF ANTIGEN SPECIFICITY) into the node is greatly enhanced - this is why draining lymph nodes get large with infection
what type of cells are in the lymph node follicles?
B cells and FDC (follicular dendritic cells)
In T cell zones, what cells are present?
T cells and class II-expressing DCs (the professional APCs)
CD4 can be further divided into T helper subsets (Th1, Th2, Th17, etc) which are discriminated primarily by what?
cytokines they secrete after activation and during effector function
where does the effector function of T cells occur? (CD4 and CD8)
site of infection (requires only Signal 1!)
when are antigen-specific lymphocytes released from the lymph node?
after activation (3-5 days after antigen exposure)
what are the important T cell Lymph node homing receptors?
LFA-1 (binds to ICAM) or VLFA-4, CD62L (L-selectin), and CCR7 (binds to CCL19/CCl21)
activated T cell shave _____ which is capable of binding to CXCL10 that allow T cells to leave the blood stream and to go out into tissue to exert the immune response.
CXCR3
____ allows for rolling/tethering.
selectin
_____ allows for simulation/signaling.
chemokines
_____ allows for firm adhesion.
integrin
4 steps of leukocyte trafficking
- tethering (selectins)
- activation (chemokines)
- adhesion/arrest (integrin/CAM)
- transendothelial migration (diapedesis)
how do chemokines affect adhesion?
inside-out signaling
chemokines signal from the inside to change the conformation of integrins (make them high affinity) on the outside of lymphocytes
migration of lymphocytes is dictated by their combination of what?
selectin, chemokine receptor, and integrin
lymph node-homing cells (naive and central memory cells) can be identified by their expression of what?
CD62L (L-selectin) and CCR7
CD8 cells require activation from D cells and help from CD4 cells - what are the two models for this requirement?
- CD4 cells and CD8 cells recognize antigen on the same DC
- armed CD4 cells (ie CD40L-expressing CD4 cells) activate quiescent DC to upregulate costimulatory molecules, a phenomenon known as DC licensing
For effector cell function, no 2nd signal is required just the recognition of the antigen/MHC class I complex by the killer T cell. Therefore, only naive T cells that have recognized antigen in the presence of a 2nd signal gain effector function - why go through all of this trouble to activate cells?
to preserve self tolerance
(Recall that class I molecules are expressed by almost all cells of the body and thus can display peptides—mainly derived from viruses or other cytosolic pathogens (or any self protein !) - for recognition by activated CD8 cells, especially at epithelial surfaces. Any self antigen that can be presented by self MHC is a potential target and not all self antigens are expressed by the thymus for selection. By requiring Signal 2 for proper activation, one can avoid responses by self-reactive mature T cells in the periphery since recognition of Signal 1 in the absence of Signal 2 induces anergy (inactivation) of naïve T cells. )
when CTLs bind their targets, they lyse them by one of what pathways?
- a molecule found in granules called perforin (which is homologous to complement C9) polymerizes upon release from CTL onto an infected cell and effects osmotic lysis of the infected cell, but this is a minor pathway
- a molecule found in granules, granzyme B, can enter the infected cell (through perforin pores) and induce programmed cell death cascades in those cells, which is considred the major pathway
- CTL expressing a molecule called FAS-Ligand can bind to FAS on other cells and induce programmed cell death
- cytotoxic cytokines such as TNF and lymphotoxin (LT) secreted by CTL in close proximity to infected cells can induce lysis
CD8 cells also mediate immune response to what type of pathogens and give examples?
intracellular pathogens: mycobacteria, listeria, cryptococcus, rickettsia by producing some inflammatory cytokine alpha (IFN-gamma)
perforin deficiency causes what?
Hematophagocytic lymphohistiocytosis (HLH)
- genetic or acquired (infection)
- fever, splenomegaly, haemophagocytosis, hypertriglyceridaemia, and hypofribrinogenaemia
- high serum levels of IFN-gamma, TNF-alpha, IL-6, IL-10, and M-CSF
anti-IFNgamma is a a proposed treatment for what?
HLH (reverses the toxicity associated with the loss of perforin)
how specific is CTL killing of targets?
one CTL can kill multiple targets
