T-Cells Flashcards
CD8+ T-cells
cytotoxic T-cells
kill intracellular pathogens
MHC I receptors expressed on all cells
CD4+ T-cells
helper T-cells
kill extracellular pathogens (or can recruit)
MHC II receptors expressed on APCs
3 APCs
macrophages
dendritic cells
B-cells
What cells express CD28?
both CD4 and CD8 T-cells
ITAM: structure, function and location
contains 2 tyrosines
helps with signaling
located on CD3 / zeta chain of TCR
3 steps of TCR signaling cascade
1) CD4 or CD8 TCR binds to MHC
2) activate Lck which phosphorylates the tyrosine residues in CD3 ITAM
3) Zap-70 (another tyrosine kinase) binds the now phosphorylated ITAM and triggers phosphorylation cascade
NFAT
transcription factor that increases gene expression for cytokines (IL-2)
activated by dephosphorylation (calcineurin)
calcineurin
dephosphorylates NFAT to activate
Ca2+ dependent
What drugs block calcineurin? What is their effect?
cysclosporin + FK506
prevents NFAT / IL-2 production and dampens immune system
leads to decreased autoimmunity but increases risk of infection
What 2 signals are required for full T-cell activation?
TCR - MHC
CD28 - B7
What happens when a cell does not have B7?
you have anergy
CTLA-4 can bind B7 to prevent immune response
CTLA-4
dampens the immune response
present on T-reg always (sometimes on other T-cells after activation)
binds to B7 molecules to prevent immune response
Cancer and CTLA-4
cancer upregulates CTLA-4 to dampen the immune system and continue to grow
How are T-cells trafficked?
through the lymph
How do T-cells proliferate? (2 ways)
produce IL-2 and upregulate receptor for IL-2 (CD25)
What are Th subsets distinguished by? (2 features)
- cytokines produced
- pathogen targeted
What cytokine does Th1 differentiation require?
IL-12
What cytokine does Th2 differentiation require?
IL-4
How do Th1 and Th2 antagonize each other? (one example)
Th1 produces IFN-gama to activate macrophages
Th2 produces IL-4 to inhibit macrophages
Two types of leprosy
1) tuberculoid leprosy: Th1 activates cell-mediate response to stop spread
2) lepromatous leprosy: Th2 prevents cell-mediated immunity which makes spread worse
How does Th17 work?
produces IL-17 and IL-22 which act on epithelial cells to attract neutrophils and increase barrier protection
Does MS affect CNS or PNS?
CNS
Which cytokine is involved with MS?
IL-17
(remember that Th17 and Th1 produce autoimmunity)
list 3 environmental factors for MS
1) EBV
2) smoking
3) Northern countries
Genetic factor for MS
MLA-DR2
immunopathology of MS
T-cells (Th1 and Th17) specific for myelin proteins are activated in periphery lymph node
then, they enter the CNS
cells make IL-17 and IFN
difference between naïve T-cells and activated T-cells
only activated T-cells have CD25 receptors expressed
naive T-cells could differentiate into any Th subtype
list 4 T-cell mediated autoimmune diseases
MS
T1DM
RA
Crohn’s
Psoriasis
What does IL-10 do?
suppresses the T-cell response
prevents autoimmunity
What interleukins work with extracellular pathogens?
IL-4 and IL-17
What interleukins work with intracellular pathogens?
IFN-gama
