T Cell Mediated Immunity Flashcards
CD4+ T cell broad function
Help activate B cells and macrophages
CD8+ T cells broad function
Initiate cell death of infected or transformed cells
Which type of cell can DCs activate?
Mature naive T cells
Which type of cell can B cells and macrophages activate?
Memory T cells
Characteristics of activated peripheral DCs
Lose adhesive markers and upregulate CCR7 expression (lymphatic endothelium)
Increase expression of MHC, CD80 (B7) and LFA-1
Mature as they migrate to regional secondary lymphoid tissue
Home by chemokines
Present Ag to mature naive T cells circulating in lymph tissue
Which cytokines are secreted by DCs in order to promote T cell subset differentiation?
IL-12: Th1
IL-23: Th17
IL-10: Tregs
What do T cytotoxic cells express on their surface?
TCR/CD3 signaling complex including zeta
CD8+, MHC class I
CD28+, CCR7
LFA-1 and L selectin
What do T helper cytokine secreting cells express on their surface?
TCR/CD3 signaling complex including zeta
CD4+, MHC Class I
CD28+, CCR7
LFA-1 and L-selectin
Describe naive T lymphocyte trafficking
Naive T cells enter the LNs across HEV in the cortex
Slow down - L selectin and CCR7
Stable arrest - LFA
T cells sample the Ag presented by APCs and will either proliferate and differentiate into effector cells or wont encounter the Ag and leave the LN through the lymph and travel down the chain to the next LN
Describe the immunological synapse for CD4 T cells
CD4 —> MHC class II TCR —> peptide presented on the MHC class II CD3 ITAM CD28 and CTLA4 —> B7-1/-2 (CD80) PD1 ITIM —> PD-L1/L2 LFA-1 —> ICAM1 (adhesion)
What is the first signal for T cell activation?
Binding of MHC/peptide complex displayed by DC to TCR on the T cell
What is the second signal for T cell activation?
Recognition of the Ag is critical for the upregulation of co-stimulatory molecules
Binding of the co-stimulator molecules provides second signal to the cell
What other cellular changes occur when the TCR/HLA recognizes an Ag?
Recognition changes integrin conformation on T cells from low affinity to high affinity
Integrin avidity increases upon Ag recognition by T cells: LFA-1
Allows for clustering of adhesion molecules and firm adhesion for immune synapse
What happens upon binding of the TCR to MHC/peptide complex during T cell activation?
Upon binding of TCR to MHC/peptide complex the T cell increases CD40L expression and CD28 expression is constitutive
DC has CD40 constitutive expression while B7/CD80 expression and cytokine secretion is increased
Why is T cell activation a two pronged approach?
Clonal selection
First signal: recognition of antigenic epitope by TCR
Second signal: maintains the specificity of the response to the specific epitope
This results in a large number of Ag-specific effector cells from rare Ag-specific naive T cell
When does induction of anergy occur?
T cells recognizing Ag without binding of co-stimulators ligands or cytokine support will not become activated
Instead they become unresponsive to additional stimulus (anergic and tolerant)
Describe T cell activation
Formation of the immune synapse initiates the intracellular signaling leading to complete T cell activation and occurs through activation of ITAMs
Kinase associated with coreceptors CD4 and CD8 phosphorylates and activates the tyrosine kinase ZAP-70 associated with the zeta chain
Activation of ZAP-70 on the zeta chain is necessary for all downstream signaling
Describe the cascade of protein production that occurs after activation of T cells?
Substantial proliferation of activated lone to expand population of Ag specific lymphocytes
Activated CD4+ Th cells start expressing CTLA4 and PD1 for immune regulation
Activated CD8 T cells start expressing PD1 for immune regulation
Explain the order of receptor expression during an immunological response
C-Fos —> CD40 ligand —> IL-2 —> IL-2a (CD25) receptor —> DNA synthesis
IL-2 is an
Autocrine survival signal for newly activated T cells and is not produced until T cell activation
IL-2R-beta-gamma-c is constitutively expressed on what?
Mature a naive T cells as a low affinity receptor minimizing proliferation
What happens when IL-2 binds to its receptor?
Upon activation upregulation of additional high affinity chain in IL-2R alpha chain occurs (IL-2R-alpha-beta-gamma-c
Binding of IL-2 to high affinity IL-2R promotes T cell differentiation and proliferation
Within two days of an Ag appearing in a LN it has been bound by its
Naive Ag specific T cell
5 days after the arrival of the Ag, activated
Effector cells emigrate from the LN into the periphery
Where is S1P highly present in the body?
Blood and lymphatic
Explain the role of CD69 in T cell sequestering
Naive T cells express S1PR that directs their migration through the circulation
Newly activated T cells will transiently express CD69
CD69 binds to S1PR on T cell surface and sequesters it
Leaves the T cell unable to respond to S1P migration signals
Ensures activated T cell has time to provide help to other lymphocytes
New effector cells lose CCR7 and upregulate S1P —> effector cells cross endothelial barrier and enter circulation in response to S1P