T Cell-Mediated Immunity – Activation of T Cells by Cell-Associated Antigens Flashcards
types of intracellualr microbes combated by t cells
those in phagocytes and those in non-phagocytes
examples of microbes in phagocytes
examples of microbes in non-phagocytes
Induction and effector phases of cell-mediated immunity diagrammed
where does Ag recognition occur?
peripheral LN
do all effector T cells leave the LN?
some stay to simulate B cells
Steps in the activation of T lymphocytes diagrammed
locations of these steps?
what happens to effector cell population when infection cleared?
die off aside from memory cells (contraction/homeostasis)
what are CD4/8
coreceptors to help recognize the MHC complexes
Antigen recognition and costimulation
just TCR and MHC?
helps with?
occurs with TCR complex not just MHC to TCR and CD4/8, required interactions for stimulation
help with adhesion and signal transduction
TCR complex interactions diagrammed
first activating signal of t cells
Ag recogniton via TCR and CD4/8 to MHC causing the signal transduction in the t cell with phos/dephos pathways to induce TFs and gene expression for expansion and effector function
Adhesion molecules on T cells that stabilize binding to APCs
LFA-1 is an integrin protein expressed on t cell mem that binds the ICAM ligand on APC to stabilize adhesion
table with TCR receptor complex components and their ligands and functions and where they occur CD3 CD4 CD8 CD28 CTLA-4 PD-1 LFA-1
Role of costimulation in T cell activation:
signals/ligands from activated APC
without these?
B7 ligand on APC will bind CD28 on the T cells
this is required for a t cell response, only activated APC express B7 (due to innate immunity response or microbes), WITHOUT B7 NO RESPONSE/ TOLERANCE
activated APC also secrete IL-2
BOTH ACTIONS CAUSE THE T CELL TO SECRETE IL-2 AND ACTIVATE (IL-2 TO IL-2R ON T CELL=AUTOCIRNE), CAUSES PROLIF AND DIF
Inhibitory receptors of T cells, why needed? interactions causing this?
necessary for limiting/terminating immune responses
B7 to CTLA-4 receptor=inhibitory, mediates function of Ts
PD-L2 to PD1=inhibition
MHC I and II dual action
APCs that engulf virus-infected cells (source of class II MHC peptides) and also are infected themselves (source of class I MHC peptides) will have antigens presented by both classes I and II MHC molecules.
These APCs engage both CD4+ T cells (via Class II MHC) and CD8+ T cells (via Class I MHC).
In this case the CD4+ T cell helps activate the CD8+ T cell
important with some viral infections
T cell expression following recognition of antigens and costimulators
graph of proteins produced and their functions
cascade of gene expressions will drive the prolif and dif of t cells
Signal transduction pathways in T lymphocytes
TCR complex will phos adaptor proteins via CD3 and ITAM to cause signal transduction into the cytoplasm via cascades of phos/dephos producing intermediates and ultimately active enzymes to produce TFs that activates genes for genes for cytokines, cytokine receptors, cell cycle inducers, and other effector molecules
active enzymes and TFs of Tcell signal transduction
cyclosporine and rapamycin actions
used in grafting procedures to prevent reject
cyclo will inhibit calcineurin to prevent T cell expanse/ function and rapamysin will inhibit Akt/ mTOR to do the same
Secretion of cytokines and expression of cytokine receptors with t cell activation/ role of IL-2 and IL-2R in proliferation
principal function IL-2
survival and proliferation of antigen-specific T cells
Expansion and decline of T cell responses
both Ag-specific Th and Tc rapidly expand (from relatively small naive population) in infection but then decline once infection cleared to restore homeostasis (memory cells remain)
why would more CD8 effectors be needed?
these take the pathogen on one on one whereas the CD4 uses cytokines and plays a less direct role on defenses
immunodominant Ag’s, why would we need many types of receptors due to these?
these bind very strongly to MHC complexes, need a variety of receptors so we can survey for other Ag too
Development of effector CD4+ T cells
some also become memory cells to induce a rapid response with future exposures
Roles of CD40L and cytokines in effector functions of CD4+ helper T cells
CD40 is ligand found on active Th that can activate macrophages and b lymphocytes
binding to receptors on either will stimulate cytokine production and the effector functions of each cell
Migration of naïve and effector T lymphocytes molecule classes used
selectin
integrin
chemokine receptor
where a naive t cells
peripheral LN
naive t cell basic migration pattern
migrate between blood/lymphoid tisse back and forth until exposed to Ag, then activated/ migrates to site of infection for effector function
exit molecule of t cell migration from LN (responsible for the back an forth)
S1P: higher con. in blood> causes lower con. receptors on t cells in blood and migration to the LN where S1P is low, this increases the receptor con. and they move back into blood
naive t cells: homing receptors, ligand on endothelial cell and the function of the binding of the two (for each class of molecules involved)
activated t cells (effector and memory): homing receptors, ligand on endothelial cell and the function of the binding of the two (for each class of molecules involved)
