13. activation of naive t lymphocytes

where does T-cell activation occur?

• localized infection → draining/local lymph node

• systemic infection → spleen (+ lymph nodes)

how is dendritic cell migration directed to the paracortex?

chemokines CCL19 and CCL21 (produced in the paracortex)

CCR7

receptor for chemokines (CCL19 & CCL21) expressed by activated dendritic cells

what 3 things are required for initiation of T-cell responses?

• specific antigen recognition

• stable adhesion of T cells to APCs

• transduction of activation signals

accessory molecules

T cell surface receptors that are not involved in antigen recognition

• signal transduction

• adhesion

co-receptors

• CD4/CD8

• function with TCR in antigen reception and signal transduction

what makes up the TCR complex?

TCR, CD3, and ζ (zeta chain)

what is the function of CD3 & ζ (zeta chain)?

signal transduction

how are integrins involved in T cell activation?

• mediate adhesion between T cells and APCs

• switch from low-affinity state to high-affinity state when antigen recognition occurs between APCs and T cells

what is the two signal model of naive T-cell activation?

activation of naive T cells requires simultaneous delivery of antigen specific and costimulatory signals → ONLY professional APCs can initiate T cell responses

how is the co-stimulatory signal produced?

CD28 (on T cells) binds to co-stimulatory B7 molecules (B7.1 and B7.2) expressed on professional APCs

what happens if there is no co-stimulation signal?

the T cell either has no response or becomes tolerant (self-antigens)

how does co-stimulation affect T-cells?

• necessary for production & secretion of IL2 → autocrine signaling

• T cells start expressing high affinity IL2-R (receptor)

  • (at rest, express low affinity IL2-R)

what is IL2?

a growth factor/cytokine that drives T cell proliferation

CD4 T-cell independent activation of CD8 T-cells

microbes infect dendritic cells

CD4 T-cell dependent activation of CD8 T-cells

microbes do not infect dendritic cells (ex. viral infection, tumor cells)

• cross-presentation

• one DC can present to both CD4 and CD8 T cells

how do adjuvants enhance immunogenicity of antigens?

activate APCs to express costimulatory molecules

what are the T cell co-inhibitory receptors?

• CTLA-4

• PD-1

when are the inhibitory receptors expressed?

when T cells become activated → function to inhibit activation (brakes)

how does CTLA-4 inhibit activation?

• interacts with B7 molecules on APCs

• has a higher affinity for B molecules → outcompetes CD28 (activator)

what does PD-1 interact with?

PD-L1/2 on APCs

how are co-inhibitory receptors relevant to cancer treatment/treatment of persistent infections?

• drugs can have anti PD-1 / anti CTLA-4 effects

• remove T cell inhibition → allow T cell to kill tumor cell

• controlled autoimmunity

how do superantigens interact with T cells?

• cause uncontrolled, nonspecific activation of T cells

• ↑↑ T cell activation → lethal shock