9 + 10 Flashcards
TCR antigen binding specificity is
random
only TCR that recognizes _ can be activated
self MHC
Walk me through t cellin the thymus
start w acquiring the TCR
- TCRb first w placeholder TCRa just like heavy and light chains
then aquire both CD4+,CD8+
then go through positive selection
then lose on of the +’s
then go through negative selection
DN (corticomedullary junction to cortex to subspapsular cortex) at the subcapsular cortex TCR rearrangement happens
in the cortex we acquire CD4+8+ and do positive selection there
negative selectino in the medulla
lethal x irradiation
destroy bone marrow
didnt have an effect along w bone marrow graft on what cells recognized self MHC in mice experiment
T cells w low TCR affinity for self
fail to be positively selected
where does negative selection occur
in medulla by thymic mTECs and thymic dendritic cells
what carries superantigens
bacteria and viruses
superantigens result
activate 5% of peripheral t cells and lead to massive negative selection and deletion in the thymus
gamma delta T cells expressedin association w _ but not _
CD3 but not CD4,8+
GAMMA DEELTA T CELLS DEFENSE
primary defense
variability of y D t cells
less variable than a B
the two signals for t cells can
come from two different cells or mimmicked using ab but this isnt the normal case
what makes up the psmac
adhesion molecules and bound ligands
what activates macrophages
PAMPS and t cell help (ifn y)
what activates dendritic cells
PAMPs and cytokines
what activates b cells
ag
what inc the likelihood of T cell meeting its right ag
the ability of t cells to recirculate the lymph system and meet DC that go to the lymph node w the ag
what allows for paracrine IL2 to have an effect
if the non self cells also upregulated high affinity IL2 receptor
what is the result of IL2 and IL2R
many genetically identical memory and efector T cells
what does cyclosporin do
prevents calcineuring dephosphorylating NFATc
wgat is the purpose of B7/CD28 and ICOS
ahesive interactinos
cytokine effect on B cells
allows them to progress through the cell cycle
what induces cytokine secrection by APCs
binding to PAMPs
IFNY in TH1
activates macrophages which turns on thier microbicidal activity and secretes IL12 further skewing to TH1
class switch B cells to igG
cytokines in deciding the Th cell subset
positive feedback
activates master regulator for one type and inhibits master regulatro for another type
Th17 polarizing cytokines
il17, TGFB il6 il23
function of il17
autoimmune
dual protective and pathogenic role
mutated in HIES due to STAT3 mutation
protects against bacteria and funghi
peripheral t reg function
differ from thymic t reg
important in pregnancy
il10 and TGFb inhibit APC activity by targettingother t cells
peripheral treg cytokines`
TGFB
il10
il2
retinoic acid/ vit a
plays a role in inducing Treg polarization
TGFB
upregulates both FOXP3 and RORYT both of which miportant at balacing and at barrier tissues
Tfh master regulator
Bcl6
Tfh cytokines
il4
il21
il6
Tfh purpose
imortant for germinal centre
high CD40L
express CXCR5 (and ICOS) which draws it to CXCL13 in germianal centre
afffinity maturation
BCL2
inhbitis
tbet
gata3
RORYT
what th cell important for b and t cell help
b cell help- tfh
t cell help- th1
what also induces anergy
inhibitory costimulatory receptors/ signlas
CTLA 4 instead of CD28- induced within 24 of t cell activation- binds w higher affinity than CD28
PD 1 binding to PDL1
- important for cancer therapy
anti PD1 mAB cancer therapy
nivolumab
pembrolizumab
anti CTLA4 cancer therapy
ipilumab
what induces apoptosis
actiavtion of Fas recetpro on activated T cells
trimerization when Fas interacts w its receptor
brings in FADD
activates pro apoptotic caspace proteases
apoptosis
B cell only getting signal 1
apoptosis
b cell only getting signal 2
neglect
t cell only getting signal 1
anergy
t ecll only getting signal 2
nothing
where are niave b cells found
in the spleen
where are memory b cells found
BM
LN
spleen
abs in naive b cells
IGM
IGD
low
abs in memory b cells
all of them
high
how are memory CTLs activated
can be w/o t cell help
how are memory b cells activated
still need Th cell help
generation of tc cells
either sequentially or simultaneously
Th allows DC to use the cross presentation pathway to express an endogenous antigen on MHCI to activate Tc cells
how does a CTL functino
lethal hit and delivery system
forms congugate w target cell and cytoplasm rearranges
CTL granule exocytosis (perforins and granzymes in FasL)
CTL dissociation
CTL recycling
pathways used by CTLs and NK cells to induce apoptosis
2 pathways
caspase 3
Fas L- perforins and granszymes
NK cells vs CTLS
have the same cytotoxic machienery but different ways of target recognition and regulation
loss of MHC molecule expression on APC
promotes killing of altered self cel
up regulation of stress induced ligands
promotes killing of altered self cell
presence of MHC I but a little of activating stress indued ligand
NK cell inhibited
NK cell memory
exists
