T-Cell Effector Mechanisms Flashcards
Processes 1. Homing to Lymph Tissue, High Endothelial Venules i. Rolling Adhesion: L-selectin ii.. Rolling Adhesion: CCR7 iii. Stationery Adhesion: general integrins (LFA-1) Diapedesis: S1P leads a cell out of lymph nodes 2. Homing to infected peripheral tissue i. Rolling Adhesion: E and P selectin ligand ii. Stationery Adhesion: LFA-1 and VLA-4 (integrins) iii. diapedesis 3. TH1 Response- classic macrophages activation a. macrophages present antigen b. CD4 cells express CD40 li
selectins
f(x): rolling adhesion
cell: expressed by endothelial cells
wh: cell adhesion molecules that bind to selectin ligands expressed on Tcells during homing
integrins
f(x): stationery adhesion during lympohcyte homing in inflammation
cells: expressed by T cells
wh: cell adhesion molecules
examples: LFA-1 (general), VLA-4 (peripheral tissue)
chemokines
small cytokines that can induce chemotaxis
L selectin
f(x): cause rolling adhesion
cells: endothelium of high lymphatic venules
wh: endothelial cells/ tissue express L-selectin and CC-L19 and CC-L21to attract naive lymphocytes.
LFA-1
F(x): an integrin that promotes stationery adhesion
cell: expressed by Tcells
wh: expressed by lymphocytes during rolling, it binds to ICAM and VCAM ligands expressed on enothelial cells/ tissues cells
CC-R7
f(x): homing to lymphatic tissue
cell: expressed by naive lympohcytes
wh: expressed by naive lymphocytes. They bind to its ligand, CC-L-19 and CC-2, during they enter rolling due L-selectin expressed on resident cells
E and P selectin ligand
F(x): rolling adhesion
cells: activated T-cells
Wh:cytokines at sites of inflammation induces expression of E/P selectin ligands. Causes rolling, the first step in adhesion
VLA-4 / LFA-1
F(x): stationery adhesion
cells: activated T-cells
Wh: cell adhesion molecules (integrins) that are expressed on rollng
CXC-R3
F(x): homing/ adhesion
cells: activated T-cells
Wh: one of many receptors that cause homing of activated T-cells to infected tissue. They bind to their respective ligand, CXC-L10
L selectin ligand
F(x): rolling adhesion
cells: high endothelial venules
Wh: expressed to cause rolling adhesion in Naive T-lymphocytes
ICAM-1 or VCAM-1
F(x): stationery adehsion
Cells: Endothelial Cells/ Resident Cells
Wh: Ligand for integrins (LFA-1/VLA-4) expressed during rolling by Tcells
CCL19 or CCL21
F(x): homing/ adehsion Cells: Endothelial Cells Wh: ligands for CC-R class receptor expressed on Tcells and other cells during homing
E or P selectin
F(x): rolling adehsion
cells: endothelial cells
Wh: bind to E and P ligands expressed on activated T lymphocytes and lead to weak binding (rolling) at sites of inflammation
CXCL10
F(x): homing/ adhesion
Whr: endothelial cells
Wh: ligand for homing chemotaxis receptors
VLA-4 and LFA-1 are also known as
Integrins
IL-12
induces differentiation of naive CD4 cells to mature T cells
produced by macrophages during bidirectional interaction with T cells
IFN gamma
Effector T1H cells secrete IFN gamma and express CD40L to promote microbicidal activities of macrophages
T1H cells: what are their primary effector mechanisms?
activation of macrophages with IFN gamma and CD40L
Effector Mechanisms of Macrophages
- killing of phagocytosed bacteria
- secretion of cytokines (TNF, IL-1, IL_12, chemokines)
- increased expression of MHC and costimulators
TH2 effector mechanisms
- helminth defense: IL-4 and IL-5 production stimulates eosinophils and mast cells
- inhibition of classic macrophages activation: IL-4, IL10
- alternative macrophage activation: IL4, IL13
Th17 cells effector mechanisms
- inflammation recruits monocytes and neutrophils
2. defensins: function like locally produced endogenous antibiotics
classically activated macrophages
stimulation with IFN-gamma, usually through a TH1 pathway
alternative activation of macrophages
TH2 mediated with IL-4, and IL-13
a. causes tissue repair and fibrosis
b. balances effects of TH1 cells
IL-4
stimulates the production of IG3 antibody which binds to Fc receptors on mast cells and eosinophils
Il-13
works with IL4 to produce alternative macrophage activation
fun fact: lepromatous leprosy
destructive, associated with a defective in TH1 activation
fun fact: tuberculoid leprosy
less destructive, intact TH1 activation
Fas Ligand
f(x): execution of infected cells
cells: expressed on cytotoxic t cells
wh: ligand for death receptor on infected cells , causes a signaling cascade that causes apoptosis without perforation. *likely plays a minor role compared to granzyme mediated death
Fas aka
CD95
whr: infected cells
wh: receptor for Fas ligand on cytotoxic T cells
f(x): leads to apoptosis without granules being shed. *likely plays a minor role compared to granzyme mediated death
Granzymes
cleave and activate capsases in target cells
perforin
makes cell membranes less stable and allows rapid diffusion of granzymes
NK cells
recognize an absence of MHC I and kill cells
