Effector Mechanisms of T Cell-Mediated Immunity Flashcards
ways t cells can become activated
phagocytes with ingested microbes or infected cells, both present Ag to naive t cells via MHC I/II
Discovery of Cell-Mediated Immunity
immunity transferred from one lab animal to a naïve animal only by cells (T-cells)
T cells transferred, but macrophages become activated to kill
Subsets of CD4+ helper T lymphocytes distinguished by?
cytokines produced
subsets of Th
Th1
Th2
Th17
Th1
Th2
Th17
general properties of t cell cytokines always produced? act over what distances? only one action per cytokine? redundancy?
transiently produced in response to Ag
acts in autocrine/paracrine way
each cytokine has multiple possible actions
redundant: some may share same actions
transient cytokine production significance
only made when needed for a response
auto/para significance if cytokines
if not accomplsihed?
localizes the effect, if not=autoimmuine or severe infection
multi effect of cytokines function
provides diverse actions but can limit clinical utility of cytokines (redundancy)
redundancy of cytokine significance
blocking one cytokine may not produce desired effect
action and source of: IL-2 IFN-gamma IL-4 IL-5 IL-17 IL-22 TGF-B
Th1 cells basic
induced with microbes in APC, presentation via MHC II to CD4 cells
Th1 produced: IFN-gamma released to cause classical macrophage activation
Activation of macrophages by Th1 lymphocytes
classical activation
MHCII binds TCR of CD4 cell/Th1, induced signal for CD40L to CD40 on APC which causes costim for IFN-gamma from Th1 to macrophage receptor to activate killing functions, increased MHC and costimulator production and secretion of cytokines
macrophage responses in classical immunity and their role in cell-mediated immunity
killing?
cytokines?
t cells?
w
Th1 cell development
IL-12 from APC and IFN-gamma from NK cells drive cell expression to become Th1
REQUIRES AN AG ACTIVATED CD4 CELL
Th2 cells basic
induced by?
signature cytokines?
Induced by parasitic worm infections
Signature cytokines: IL-4, IL-5, IL-13
Th2 cell activation and effector pathways
note the Tfh cell working on b cell: IgE produced, works w mast cells and eosinophils at the Fc receptors
IgE- and eosinophil-mediated killing of helminths
IgE binds Fc receptors on the eosinophils which allow cell to recognize Ag of the worm and target it
IL-5 activates the eosinphil to degranulate causing the killing of the worm
Classical and alternative macrophage activation compared/relation
Th1 cytokine IFNgamma inhibits Th2 and Th17 developmental possibilities
Th2 cytokines IL-4 & IL13 inhibit classicalmacrophage activation (M1)
events of hypersensitivity/allergies
Immediate hypersensitivity reactions are initiated by the introduction of an allergen, which stimulates TH2 reactions and immunoglobulin E (IgE)
production.
IgE binds to Fc receptors (FcΕRI) on mast cells, and subsequent exposure to the allergen activates the mast cells to secrete the mediators that are responsible for the pathologic reactions of immediate hypersensitivity.
. Balance between Th1 and Th2 cell activation determines?
outcome of intracellular infections, want more Th1 to activate killing function
Th2 cell
development
REQUIRES AG ACTIVATED T CELL EXPOSED TO IL-4 TO INITIATE TFS FOR GENE EXPRESISON TO TH2
Th17 major cytokines and functions
IL-17, IL-22
Recruitment of neutrophils and resulting in inflammation to combat bacterial/fungal infections
Th17 response pathway
Th17 cell
development
STILL REQUIRES AG-ACTIVATED T CELL, USES IL-1, IL-6, IL-23, AND TGF-B TO INDUCE THE TFS
function of CD8+ cytotoxic T lymphocytes with infected cell
TCR complex?
enzymes?
m
. Cooperation between CD4+ and CD8+ T cells in eradication of
intracellular infections
mycobacteria counter to immunity
prevent phagolysosome formation
HSV counter
inhibits TAP/Ag presentation
CMV counter
prevents Ag presentation with removal MHC molecules from the ER
EBV counter
inhibition Ag presentation with proteasomal inhibition
AND
IL-10 production causes the inhibition of macrophage and dendritic cell activation
pox virus counter
production soluble cytokine receptor to prevent effector cell activation
Host counter defense to reduced MHC class I display on cell surfaces:
activation of natural killer cells
HIV effect
infects/kills CD4 cells