Cascades and Communication Flashcards
What are immunological synapses? What are their function?
A mechanism to redistribute receptor signalling on the cell surface. They promote the concentration of receptors and co-receptors into lipid rafts which contain signalling enzymes. Rafts called MTOCs.
What are MTOCs?
What are their functions?
In what cell-cell interactions are they used?
Micro Tubule Organizing Centers
They require receptor interaction with actin filaments, reorganize digestive/secretory organelles, promotes clustered MHC presentation towards target cell, and promotes cytokine secretion towards target cell.
They are used in DC-T, T-B, NK-B cell interactions, etc.
Describe how TLR signalling primes the BcR for IS formation.
The increased BcR mobility allows more frequent BcR-BcR interactions/collisions and enhace a microcluster formation when APC bound Ags are present.
The TLR priming allows BcRs to drift across cell surfaces.
How are B cell IS formations initiated?
What do these signals activate?
What does the activation of these signals do?
LYN and SYK
Activates actin polymerization
Polarization of MTOC allows for the recruitment of MHC II and lysosomes.
Define the following and briefly describe their functions:
cSMAC
pSMAC
dSMAC
cSMAC: central supramolecular activation cluster - BcRs concentrate when activated with Ag
pSMAC: peripheral SMAC w contains adhesion molecules
dSMAC: distal SMAC where actin is enriched
Briefly describe a BcR signalling cascade.
LYN and SYK activate signalling cascade
AKT leads to NFAT activation which allows proliferation and survival. NFkB activation leads to cytokine production.
What is the goal of TcR ligation?
What signals initiate TcR signalling cascades?
Survival, proliferation, differentiation, and NFkB secretion.
LCK and ZAP70 initiate cascade
What does CD28 in T cell signalling do?
What does CTLA-4 in T cell signalling do?
promotes activation of the T cell
inhibits activation of the T cell by inhibiting AKT.
Why do specific transcription factors activate T cell phenotype/effector profile?
The context in which they differentiate is likely the context in which they will have to work so the cytokines that define them are likely going to be the ones they need to secrete.
What is a second function of the MTOC?
It can be an immunological synapse as well as a viral synapse.
In HTLV-1 the capsid protein (Gag) is polarized and MTOC alpha tubulin filaments reorient to lie adjacent.
Define cytokine... Pleiotropy Redundancy Synergy Antagonism
Varied responses in cell target
Different cytokines induce same response
Cytokines cooperate in inducing specific response
One blocks activity of another
Name the 5 classes of cytokine receptors.
Ig-type ectodomain TNF homotrimeric ectodomain Cytokine type I and II receptors (ectodomains) Chemokine receptors (typical and atypical) one end ecto, one end endo.
What are the four types of cytokine receptor families?
What cytokines are in each family?
IL type I family: IL-2, IL-6, IL-12
IL type II family: IFN, and IL-10
TNFR: TNF
Ig family: IL-1
IL-2 is produced by whom?
What does IL-2 respond to on a cell surface?
What pathways does it initiate?
What cells have these receptors?
T/DCs
IL-2Ralpha, IL-2R beta, and gamma c
Initiates JAK/STAT pathway
T, B, and NK cells
What cytokines induce the following? What do the following initiate the secretion of? By whom are they stimulated? What does their exaggerated stimulation cause? Th1 Th2 Th17 Treg
IFNalpha/beta and IL-12 – IFNgamma and TNF alpha – Viruses/ intracellular bacteria – autoimmunity.
IL-4 – IL-4, IL-5, and IL-13 – Parasites – asthma/allergy
IL-G, TGFbeta, IL-21, and IL-23 – IL-17 – extra cellular bacteria/fungi – autoimmunity/fibrosis
TGFbeta and RA – IL-10 and TGFbeta – ?? CD4? –Tumours
