T-Cell Activation Flashcards
T- cell co stimulatory molecules in T-cell activation
CD4, CD28, CD2, LFA-1, CD40: (CD154)
Dendritic cell co-stimulatory molecules in T-cell activation
HLA class II peptide, HLA class II, B7-1(CD80), B7-2(CD86), LFA-3, ICAM-1, ICAM-2, CD40
Thp Activation
Expression of IL-2R, Secretion of IL-2, Autocrine and paracrine, clonal expansion of THP differentiation to TH0
Th0
secretes IL-2, IL-4, IFN gamma,
IL-2 is a growth factor for
T-cells
IL-4 polarizes
response to TH2,
IFN gamma polarizes
response to Th1
IL-4 likely source is
mast cell
IFN gamm source is
IL-12 activated NK cells.
CTLA-4 is also known as
CD152
CD152 has a higher affinity for
CD80 and CD86 than CD28
CD200R is located on
Activated T-cells
Signaling via CD200R is
inhibitory
nTregs come from
thymic differentiation
a/i Tregs differentiate from
Th0
nTregs go after
self reactive T cells that have escaped negative selection
both nTregs and a/i Tregs suppress
various immune responses
IL-10 down regulates
secretion of IL-12 by dendritic cells
IL-12 secreted by Dendritic cells affects
INF gamma secretion by NK cells and hence Th1 and Th1 cytokines
nTregs contain
CD4+, CD25+, and FOXP3+
nTregs also negatively control
immune responses to allo/non-self antigens
Depletion of nTregs enhances
immune response to pathogens
Depletion of nTregs leads to
tumor rejection
Genetic mutations in FoxP3 result in
deficiency or dysfunction of Tregs
Mutations Tregs=
disorder, IPEX (immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome.
a/i Tregs arise
in periphery following activation of Thp and Th0 cells
a/i tRegs differentiation requires
TGF Beta
Phenotype for a/i Tregs is
CD4+, CD25+, FOXP3+
FOXP3 is a transcription factor that
is essentatil for development and function of regulatory T cells
a/i Tregs control
immune response to both foreign and to self antigens by down regulating the function of effector CD4+ and effector CD8+
three stages of Th17 differentiation
–differentiation which involves IL-1/IL6 and TGF Beta –stabilization(IL12 from dendritic cells and macrophages) –amplification (secreted by TH17 cells growth factor)
Role in the immune response against extracellular pathogens not
eliminated by the CD4+ Th1 and CD4+ Th2 effector cells
Th17 is effective in
eliminating fungal infections
Th17 cells secrete
proinflammatory cytokines IL-17, IL-21, IL-22
Th17 induce
the secretion of inflammatory mediators from macrophages and other cells that play a role in inflammation
Inflammatory mediators include
various cytokines, chemokines and matrix metalloproteinases
memory cells immunosurvey since they
have been presensitized to the immunizing agent that induced their differentiation
re-exposure results in
secondary responses in a rapid 1-2 days
conditions for memory T cell activation are
less stringent in requirements for adhesion and costimulatory molecules
Antigen presenting cells (other than dendritic cells) can serve in
in the capacity of adhesion and costimulatory molecules early in response to antigen reexposure
memory cell activation can occur at
the site of antigen contact, rather than in secondary lymphoid tissues.
Memory CD4+ T cells secrete
cytokines.
Type 2 Cytokines
IL-4,5,6,10,13 and TFG beta – they support B cell differentiation to plasma cells. –support isotype switching to IgG1 and IGE
Thp cells differentiate to
Th1, Th2, a/iTregs, Th17
activation of T-cells requires that the antigen
be displayed on the surface of an antigen presenting cell in association with Class II MHC
the most effecient antigen presenting cell is
the dendritic cell.
The antigen presenting dendritic cell expresses both
MHC class II and costimulatory molecules whose countermolecules are present on the T cell
When a T cell interacts with peptide/MHC complexes in the absence of these costimulatory interactions then
the T cell becomes unresponsive
ThP express receptors
IL-2 receptors and secrete the cytokine IL-2 that function in both autocrine and paracrine manner
interaction with IL-2 and its receptors induces
clonal expansion of antigen stimulated T cells which increase the number of T cells with specificity uniquely recognizing the peptide/MHC class II complex that induced the initial differentiation
critical signal in Tcell activation leading to clonal expansion is
CD28- CD80/86 interaction
CD28-CD 80/86 interaction triggers
signal transduction events that lead to the stabilization of mRNA for IL-2
Type 1 cytokines
IL-2 TNF, IFN gamma, support responses in which macrophages, NKC and CD8+tcells are effectors responsible for delayed type hypersensitivity responses that are manifestations of actibation of memory CD4+ Th1 cells. REQUIRED for immunity against viruses, parasites, fungi and intracellular bacteria
Isotype switching requires contribution of
both type 1 and type 2 cytokines
6 downregulators of T-cell activation
–elimination of infection –reciptorcal regulation (Th1 and Th2) – CTLA-4 CD152 interaction –CD200-CD200R interaction –apoptosis – Tregs
CTLA-4 is not expressed
constitutively but peaks two days after the initial T cell activation and disappears by day 4
CD200R is expressed primarily on
the cells of the myeloid lineage and on some T cells. 9higher on CD4 and higher on memory than naive.
CD200R expression is upregulated on
both CD4+ and CD8+ after stimulation
