review class Flashcards
how do IFN responses promote a feed-forward loop
4
FDCs are the main secreters of IFN
IFN increase the cytotoxicity of CTLs, which will kill infected cells and increase more local debris which can be utaken by APCs
maybe talk about first and second wave IFN signalling here?? idkidk
How does the innate immune system react to PRR activaiton
NFkb IRF IFNS pro-inflammatory cytokines ISGs (and resttriction factors)
First wave IFN
happens inside an infected cell
when a cell is infected
PRR activaiton
second wave IFN
ifn produciton in initial infected cell and neighbouring cells
IRF3
in the cytoplasm, when it dimerizes it activates the transcription of interferons alpha and beta, as well as other interferon-induced genes.[8]
IRF3 plays an important role in the innate immune system’s response to viral infection.
IRF7
IRF7 regulates many interferon-alpha genes.[5] Constitutive expression of IRF7 is largely restricted to lymphoid tissue, largely plasmacytoid dendritic cells,
has been shown to play a role in the transcriptional activation of virus-inducible cellular genes, including the type I interferon genes
Outcomes of IFN signalling cascades
???
Redundancy
multiple moleucles have the same effects
Exosomes
how do they stimulate immunity
2
extracellular vesicles deliver bioactive molecules
-> can supress or activate immune activities
effect on APC activation
Effect of Cytokines
Effect on cellular cytotoxicity
all depends on the cargo they hold
(look at examples in the text)
Which forms of cell death drive inflammarion
3
which drive inflammation and which dont
NETosis, Necrosis = inflammaotry
Autophagy and apoptisis are non-inflammatory
Apoptotic bodies taken up by phagocytes
Autphagy = self degredations and autophaic grannules uptaken by phagocytes
necrosis lysis and release damps
pyrotosis releases cellular contents
silent clearence of apoptotic bodies
cell lysis drive prr activation through damps
phagocytes clear apoptotic bodies
two stages:
recruitment and engulfment
Compare and contrast the function of neutrophils and macrophages in the progress and resolution of inflammation
????
What is NETosis
3
PROINFLAMMATORY
utalization of DNA as a trap for pathogens
decondensation of chromatin
ruptures the neutrophile or small release of DNA
What is NETosis
3
PROINFLAMMATORY
utalization of DNA as a trap for pathogens
decondensation of chromatin
ruptures the neutrophile or small release of DNA
has pathogen toxin grannules inside the chromatin
benifit = trap and has antimicrobial enz
cons= proinflammatory and may lead to autoimmunity
what is in NETs
granule protiens bind extruded DNA
elastase and cathepsis G
myeloperoxidase
DNA and Histones
prevents dissemination of microbes
Dendritic cells, PRR activaiton and antigen presentation
innate immune response and apc, trafficking and maturation
6
???
antigen processing in DC
MHC1 present endogenous peptides (intracellular)
= self proteins or viral and or cancer peptides
=loaded into the ER by tap proteins after degredation by the proteasome
=loaded onto the MHC1
=recognized by CD8+ T cells as well as NK cells (recall this is an inhibitory signal for these bad bois)
-> this happens in all cells of the body
-> essential such that cytotoxic cells can recognize strange or the lack of self peptides
-> smaller peptides (closed pocket)
MHC2 present exogenous peptides
-> expressed only on APCS like DCs, monocytes, macrophages, B cells and eosinophils
=brought into the endosome where is it digested
=vesicle fused with another that had MHC2 within, exchage with CLIP and then presented to CD4+ cells
-> biggerpeptides becasue there is an open pocket
cross presentaion
in autophagy
= consumption of peptides and transfer to and MHC 2
DC can uptake exogenous antigen and present it to a type 1 pathway
= exogenous antigen to a ensogenous pathways
only happens in specific cell types
-CD8+ DC
CD8+ T cells are not the same as CD*+_ DC
What activates a DC
PRR activaiton leads to increased antigen uptake and processing
=> DC starts to mature and presents antigen on it surfaces, presentation of co-stimulatory ligands and the capacity to activate a T cell
stages of DC activaiotn
Myeloid vs plasmacytois DC
first stage is differentation from their precursors
seconds stages is increased rate of antigen uptake
thrid is antigen processing
fourth is phenotype maturation
=cell surface markers are CD CD80/86, CD83
functional maturation
=the capacity for a DC to actually activate a T cell
=secretion of cytokines like IL-13 and TNF
`DC migration to the lymph node
diffedrend DCs resides as teh barrier sites
=skin and mucosla surfaces
upregulation of migratory capacity after antigen uptake
= upreg of CCR7 to home towards a lymph node ( just like the T cells do)
no longer uptakes any new antigen
snap shot of the site of infection
how do you activate a Th17 cell
3
three signal activaiotn
want to expand and differentie
Il-2 for proliferation (clonal expansion) and polarizing cytokines
Th17 requires IL-6 and TGHbeta causes the upreguatio of RORgt which causes differentaiton to an effector cell
= leads to the secreation of mediatiors Il-17A, IL-17F and Il-22
why is clonal expansion so important
multiple cells that all share the same specificity to a given MHC-peptide complex
lots of effectors targeted to the same outcome
more than one cell is requred to fight an infection
not all cells surrvive after an infeciton
=we need memory cell!!
What motivates cells to traffic to organs and move into vessicles
know where cells develop from, and which organs the cell move to and traffic inbetween
3
chapter 14
511-533
go over those figures boisss
thymocytes reside in the thymus for 4-5 days undergoing negative selection
CCR7 and S1PR1
CCR7 is essential for T cell homing to the lyumph nodes and the thymus
S1PR1 sensitivity recruits T cells abck to circulation and lymph
more CCR7 = will move to the lymph node
more S1PR1 = more likley to move towards circulation
four key steps of immune cell extravasion from vasculatore into tissues
rollin, activaiton, arrest/ adhesion/ and transmigration
four key steps of immune cell extravasion from vasculatore into tissues
rollin, activaiton, arrest/ adhesion/ and transmigration
what is the fuction of cTECs and MTECs
4
purple thymus slides
know potive and negative selection in the thymus
cTECS
postive
=T cells need to recognize selfg MHC, otherwise if they dont revognize MHC they are usless
(because they need to see peptides in the context of MHC)
negative
=if they recognize MHC too strongly in the absene of peptides they are killed off because they are autoreactive
mTECS
= special because they express the transcription factore AIRE and express tissue specific antigen
=loses up chroimatin and allows the transcription of normally silenced genes
Tregs
autoreactive
bind MHC stoo strongly
help to supress immune response of other immune cells
help to maintain tolerance
How does antigen traffic through a lymph node
4
there is two ways
free flowing and fDCs
Organization of lymph nodes
??
Where does antigen enter the lymph node
via and afferent lymph and enter the B cell zone
is uptaked by resident Subcapular sinus macrophaged and fDCS
B cell interact with intake antigen through their BcR and processed antigen like T cells
Lymphocyte migration alone the firbroblast reticular cells
guided by 3d netword
FRC network surround the HEVs and naive T cells exit from HEVs
________IDKk
What are the products of an effective GC response
4
what the inital cells that are aftivation to undergo mutation = affintiy maturation
classical T cell B cell interactions
Tfh cells are CD4 that provide something
classical T cell B cell interactions
Tfh cells are CD4 that provide something
?????
AID
important enzymne in SHM
mutates cytosine to uracil
= leads to DNA repair and mutation in the DNA sequence
trial and error processs
differentiate light and dark zone of the GC
do it
What does it mean to be a memory cell
3
what happens after the collapse of a immune response
Memory cells live
they are the first cells to be activated upon secondaary exposure to an antigen
differnt type of memory cells
T effector
Tem
CCR7 long lived
Trm memory celkls
not all reside in the same areas, lifespans or capacity to become memory cells
Chemokine receptors
Typical vs atypical receptores
typical = DRYLAV motif, and are G protein coupled receptors
atypical =substituiton int he DRYLAVmotif and are not G protien coupled receptors
= can help to scavengw chemokines and are immunomodulatory
Complement proteins
MAC complex
forms holes and pores in the target cell membrane
leads to lysis of the target cell
Chapter 12 437-438
know the purpose of the signalling cascade
-> and what C1 does as well as outcomes
C5a
is a chemoattractant for inflammatory cells and is a part of the complement cascade
antibody mediated immune reactions
know three effector mechanism for the final
neutralization, agglutination, precipitation
complemetn fixation, opsonizationa nd actiaviton of NK cells
