Cytokines, receptors and signaling Flashcards
these are heritable and each cell in body expresses same one
germline encoded
PRR, cytokine receptors and MHC are examples of
germline encoded
BCR and TCR are examples of
somatic recombination
these are mediated by cytokines and act in paracrine/endocrine or autocrine manner
cell contact independent
these occur and are located in 2nd lymphoid organs, allow for increased contact time and interaction
cell contact dependent
Pathogens have or make these so PRRs recognize them
PAMPs
PRR recognize ______ and are part of which immunity branch
PAMP
innate
TLR and Nod are expamples of
PRR’s
TLR can recognize ____ and _____ PAMPS
cell contact depent or indepent PAMPS
One PRR:PAMP comes into contact, we get
intracell signal cascade foor pro-inflamatories regardless if PAMP is attached or unattached to pathogen
Membrane PRRs recruite adaptor proteins that…
activate NFkB path to make more pro-inflmamatories
What three cytokines are secreated downstream of NFkB?
TNF-a, IL-1 and IL-6
this guy will activate inflammation, neutrophil activation, cause fever in hypothal, APP of liver
TNF alpha
TNF-a made by
macrophages and T cells
IL-1 does:
activates inflamation
causes fever
causes liver synthesis of Acute phase proteins
IL-1 released by
macrophages, endothelial cells and so epi
IL-6 causes
liver to make acute phast proteins
Cause B CELL TO PROLIFERATE ANTIBODY PRODUCING CELLS
IL-6 gives us a mix of…
antB secreating B cells via causing proliferation
what 2 cytokines cause fever
TNF-a and IL-1
what do G-CSF and GM-CSF do
induce proliferation in bone marrow; egress of PMS from bone marrow during neutrophil influx
induce proliferation in bone marrow; egress of PMS from bone marrow during neutrophil influx
granulocyte and granulomonocyte colony stim factor
G-CSF and GM-CSF
where do G-CSF and GM-CSF come from
macrophages mostly and Theper and secreated at sight of infection
This is causes ciruculating PMNS (chemotactic)
IL-8
IL-8 is really great
at triggering leukocytes
IL-8 made by
macrophages, endothelial cells, ep cells
Chemokines are good at
cauusing leukocytes to hhave increased integrin affinity, chemotaxis or activation of stuff
How are chemokines classified
based on number and location of N-terminal cysteine residues
CC, CXC, C and CX3C are secreated by ______ to promote migration of ______ to infectedsites
macrophates (or other epithelial/endothelial cells)
PMNS to site of infecion
Chemokines are cell contact dependend/independent
INDEPENDENT
Chemokines promote four stages of PMN extravasation
- rolling
- integrine activation by chemokines
- stable adhesion
- migration through endothelium
T cell activation requires contact ind/dependend
DEPENDENT
T cell activation is mediated by VDJ, VJ or both
both, needs both alpha and betta chain to function as a receptor
MHC, CD28, CD80 and CD86 are all exaples of
germline genes the T cell needs to get activated
CD28 on T cell binds to
B7 on APC
T cell expression of CTLA-4 results int
negatively regulating activation and competes with B7 to provide a ‘stop’ signal by binding to CD28
CTLA-4 are ____inflamatory and are contact dependent/indepentdent
ANTI inflammator
DEPENDENT
negatively regulating activation and competes with B7 to provide a ‘stop’ signal by binding to CD28
CTLA-4
Once TCR binds it will upregulate expression of:
CD40L expression (for B cell Ig class switching)
IL2 and IL12 receptor
DNA synthesis of NFAT and NFkB
Why does TCR upregulate CD40L once activated
key for B cell Ig class switching
cytokine that provides autocrine cell-contact INDEPENDENT, pro-proliferative feeback to Th cell producing it
IL-2
Why does TCell upregulate IL2-R once activead
because it will also release IL-2 once activated and IL-2–IL-R will cause pro-proliferaction…. autofeedback
This is directed by several cell-contact IND. signals produced by both APCs and Th cells themselves
Th cell differenctiation
APC–> IL-12 to promote Th1 expression of
IFN-gmma
IL-12 and IFN-gmma cause Th–>
Th1
TGFB makes by lots of cell types and cauaes induction to Th–>
Tregs (Th17)
IL-10 promotes the
Treg pathway
If there are no APC cytokines present, our Th default path is
Th2
Suppresses Th1 and Th2 devo
TGF-B to stop inflammation
inhibits IL-12 production and reduces expression of costims and class II MHC
IL-10
tarkets NK cells and T cells to increase INF-gmma produciton, increase cytotoxic activity and Th1 differentiation
IL-12
provides autocrine signal to promote more Th1 gene expression and upregulate it’s own expression
IFN-gmma
these two provide autocrine signal to prmore more Treg devo
TGF-B and IL-10
these promote skewing towards Th2 cells
IL-4 and IL-5
INF-ggm inhibits expression of
IL-4… and vise versa
this causes a class switch to IgA and prmotes eosinophilia
IL-5 released from Th2 cells
This causes macrophage activation, class swithc to IgG2a, suppresses Th2 devo
INF-gamma
Causes a class switch IgG1, and IgE, suppresses Th1
IL-4 from Th2 cells
too much of this Th will cause autoimmunity and suspetibility to bacterial infection
Th17
Although TFGB is usually anti-infl, when combinded with IL-6 and IL-23… it promotes this subset
Th17
IL-17 effect on epithelial cells
anti-microbial peptides and increases barrier function
IL-17 effect on leukocytes, tissues cells
increaes neutorlphil response
Th1 is a master regulator of
T-bet transcription factor
Th2 is master regulator of this subset
GATA-3 transcription factor
TGF B alone or wth IL-10 promote _____
which is master regulator of _____-
T reg
Foxp3
TGFB with IL6 and IL23 prmote _____
which is master regulator of ______
Th17
RORyT
what drives the expression of genes necessary for each lineages function
master regulators
What is our only FDA approved adju
alum
what does ALUM do
promotes APC IL-4 expression to upregute Th2 devo thus increase antiB production
B cells process and present Ag to
Th cells
AntiG induced clustering of memrane Ig receptors triggers signals that are…
transduced by receptor-associated signal molecules
—we get tryosine phosphorylation events
What enhances the signaling pathway of B cells once they are activated
binding of complement: C3d
C3D on microbe will bind to what on B cell and whats teh results
binds to CR2 and increases signaling pathway
How do T cells help B cells mediate interaction and cytokines?
via CD40:CD40L interation
Once a B cell presents and antiG to T helper, what does T helper do
gets activated (MHC:TCR) and will express CD40ligand and secreate cytokines to the B cell
B cell activated and releases IgM causes
complement activation
Thelp releaseing IFN-y (Th1) causes B cell to isotype switch to
IgG subclasses….IgG1 and 3
IgG’s are good at
Fc-receptor dependent phagocyte reponses; compleent activation, neonatal immunity
Ig responsible for: Fc-receptor dependent phagocyte reponses; compleent activation, neonatal immunity
IgG via
via IFN-y from Th1
complementn activation by which Ig?
IgM
IL-4 released from Th2 causes B cell isotype switch to:
IgE
IgE responsible for
immunity against helminths
mast cell degranulation
immunity against helminths
mast cell degranulation
IgE
TGF-B, cytokines and BAFF cause release of
IgA
responsible for mucosal immunity and transport of this Ig through epithelia
IgA
IgG binds to what receptors on macrophages to cause opsonization
FcyRI
What do Fc receptor signals do?
activate phogocytosis and killing of ingested microbe
Opsonization is done by what Ig and receptora
IgG to FcyRI
NK celsl express
FcyRIIIA (CD16) for IgG
why do NK cells expres FcRIIIA?
because gets coated with IgG and that will turn on antibody dependent cellular cytotoxicity (ADCC)
What regulates granulocyte degredation?
Fc-e-R1 being bound by IgE
Granclocyte activtion depends on what part of IgE
Fab part binds to the Ag whiles it’s Fc portion binds to the Fc-e-R2 receptor on granulocyte
This response is cell contact dependent or independent
both
free floating allergens or Ag bound to surface of helmith that the Fab part of the IgE binds to then it’s Fc portion wil l bind to granulocyte
Bindng of complement proteins to Fc regions of antiB on microbial cell surface is:
FcR-independent
Antibody directed phagocytosis depends on:
Fc-gamma-R1 recognitoin of IgG
Antibody directed cyytotoxicity or ADCC depends on
Fc-g-RIIIA-reconition of IgG
What two cytokines are associated with NK cell lysis
IL-15 and IL-18
What cytokine are associated with CD8T cell cytotoxicity
INF-alpha, INF-B… will increase MHC I expression and activate NK cells
What cytokines are associated with activating macrophages?
INF-gamma coming from NK cells and T cells activates macrophage to phagocytize and destroy
