Exam 2 Lecture 8: Naive T Cell Activation

Question 1

How do dendritic cells take up antigens and bring them to T cells
Fix this?

Answer 1

CD4+ cells use MHC II
-receptor mediated endocytosis (bacteria)
-macropinocytosis (bacteria/virus)
CD8+ use MHC I
-cross presentation of exogenous viral antigens

Question 2

How does dendritic cells migration and activation change their morphology

Answer 2

Antigen capture: internal MHC
Migration: mix
Lymph: external MHC

Question 3

How do T cells arrive in the lymph nodes

Answer 3

1: Through high endothelial vesicles
Similar to PMN extravasation
Rolling adhesion, tight binding, extravasation, migration
2: From an upstream lymph node through the afferent lymphatics (which attach to downstream efferents)

Question 4

Cognate match

Answer 4

TCR + peptide:MHC + co-receptor interactions

Question 5

What are the molecular interactions that allow dendritic cells and T cells to find their cognate match

Answer 5

Naive T cell binds dendritic cell with low affinity with LFA-1 to ICAM-1 interactions
No match: leaves via efferent lymphatics following S1P gradient
Match: upregulates CD69 blocks S1P. stays in lymph node

Question 6

What are Signal 1 and Signal 2

Answer 6

Signal 1:
T cell: TCR + CD3 + co-receptor
DC: peptide-MHC

Signal 2:
T cell: co-stimulatory receptor (CD28)
DC: co-stimulator (B7)

Question 7

What is the purpose of a T cell synapse and what are the components

Answer 7

Leads to receptor clustering and promotes intracellular phosphorylation
Consists of c-SMAC and p-SMAC

Question 8

What is a c-SMAC and a p-SMAC

Answer 8

c-SMAC: central supramolecular activation complex
contains Signal 1 and 2

p-SMAC: peripheral supramolecular activation complex
contains LFA-1 and ICAM-1

creates bullseye interaction to activate T cell

Question 9

What are the sequence of steps from MHC-TCR interaction to activation of transcription factors

Answer 9

1. T cell synapse leads to receptor clustering and promotes intracellular phosphorylation
   ITAM: immunoreceptor
   a) Lck: kinase that phosphorylates ITAMs on CD3 complex
   b) ZAP70: kinase that docks to phosphorylated sites on CD3 ζ-chain and becomes phosphorylated
2. Triggers downstream signaling which leads to activation of transcription factors NF-kB, NFAT, AP-1
3. Cell division, proliferation, differentiation

Question 10

How does a cognate match signal a T cell to survive and proliferate

Answer 10

Secrete IL-2 and express high affinity to IL-2 receptor leading to T cell proliferation

Question 11

What is anergy

Answer 11

irreversible state of non-reactivity, defined for T cells by failure to make IL-2

Question 12

What induces T cell anergy

Answer 12

T cells that didn’t find their cognate match
Signal 1 without Signal 2

Question 13

What is the difference between direct and indirect CD8+ T cell activation

Answer 13

Direct (autoctine): DCs present virus derived peptides to naive CD8 T cell > activated CD8 cells make IL-2 that drives division and development to form clone of cytotoxic CD8

Indirect (paracrine): DCs present virus derived peptides to CD4 effector cells > IL-2 from the CD4 drives proliferation and differentiation of virus specific CD8 to form clone of cytotoxic CD8

Question 14

What are the 5 main CD4+ Effector T cell subsets and their polarization signals

Answer 14

TH1: IL-2, IFNγ, activate macrophages
TH2: IL-4, IL5, activate cellular and antibody response to parasites
TH17: IL-17, IL-22, enhance neutrophil response
TFH: IL-21, activate B cells to refine antibody response
Treg: TGF-β, IL-10 suppress other effector T cells

Question 15

How does T cell polarization determine the outcome of leprosy disease

Answer 15

CD4+ T cell polarization determines disease outcome
Tuberculoid: low bacterial load, low infectivity, normal immunogloblulin levels
produces IL-2, IFNγ, LT
TH1 polarized

Lepromatous: high bacterial load, high igm levels, low T cell response
Produce IL-4, IL-5. IL-10
TH2 polarized