Ppt 3 antigen capture and presentation Flashcards
How are the adaptive immune responses initiated?
When in presence of antigen
Do lymphocytes of adaptive immunity recognize same antigen?
no
What to antigen receptors on B lymphocytes recognize?
all types of molecules of antigen: carbs/lipids/protein
what do antigen receptors on T lymphocytes recognize?
only peptide antigen
What is used by dendritic cells topresent peptide antigen to T lymphocytes?
MHC
Do all dendritic cells need to use MHC molecules to present peptide antigen to T lymphocytes?
yes
what is the MHC?
a genetic locus that works by binding peptide antigen
what is MHC restriction?
T cells will recognize peptides only when they are presented by your own MHC molecules
Why do T cells have dual specificity?
because they recognize theMHC molecule doing the presentingand the peptide being presented
How do peptides bind to the MHC molecule?
through anchor residues
blood borne antigen are taken where?
captured by APC ‘s and taken to the spleen
antigen in epithelium or connective tissue are taken where?
lymph nodes
What cell mainly captures antigen and where does it take it?
dendritic cell and it takes and accumulates it in the lymph nodes
dendritic cells capture antigen and present it to whom?
Naive T cells
Once Naive T cells have been presented the antigen by dendritic cells, what happens to them?
they will start clonal expanssion and effector differentiation
where do we find immature dendritic cells?
in the epithelium
where do we find mature dendritic cells?
in the paracortex
once a naive t cell has differentiated and divided, it leaves the lymph organ and now has to find what?
the same antigen peptide it was presented by the dendritic cell
Give an example of a immature dendritic cell
langerhans cell
why are immature dendritic cells “immature”?
They are inefficient at stimulating T cellsbecause they do not have the necessary things required to stimulate T cells
Immature dendritic cells express this receptor to bind microbes
receptor for terminal mannose residues
how do microbes stimulate the innate immunity?
by stimulating Toll-like receptors in dendritic cells, resident macrophages and epithelial cells, leading to secretion of TNF and IL-1 (inflammation)
what activates dendritic cells?
cytokines and toll-like receptors
what do mature dendritic cells express on their surface?
MHC and co-stimulators (B7)
When dendritic cell encounters and binds antigen, where do they go? what is expressed in order for the dendritic cell to go there?
they go to the lymph nodes by expressing CCR7
What do macrophages do in the cell mediated immunity?What do effectorT cells tell macrophages to do?
they phagocytose microbes and display the antigens to effector T cellsthe effector t cells tell the macrophage to kill the microbe
What do B cells do in the cell mediated response?
they ingest microbes and present them to helper T cells
What cells present antigen to CD8+ (CTL’s)?
all nucleated cells
How do Naive CD8+ cells react whena virus infects a host cell causing it to not produce the signals needed to initiate T cell activation?What is this process called?
using the mechanism wheredendritic cells ingest the infected cells and display theantigens present in the infected cells for recognitionby CD8+ T lymphocytethis is cross-presentation
can both, CD8 and CD4 cells use cross presentation mechanism?
yes
what are MHC molecules?
they are membrane proteins in APC’s that display peptide to T cells
what is the most important molecule when doing a tissue graft?
MHC
on what chromosome are the MHC locus?
Ch.6
What genes are in MHC 2 locus?
HLA- DP, DR, DQ
What are the genes in the MHC 1 locus?
HLA-ABC
What are the 2 sets of highly polymorphic genes found in the MHC locus?
1) MHC 12) MHC 2
how are the MHC locus genes (very characteristic)?
highly polymorphic
what subunits in the MHC 2 are nonpolymorphic?
alpha and beta subunits
what does the invariant portion of MHC 1 bind?what is the invariant portion of the MHC 1 molecule?
CD8 co-receptorthe alpha 3 domain
what does the MHC 1 structure share with the MHC 2 structure?
they both have a peptide binding cleft
what is different about the globulin composition in MHC 1 and MHC 2?
MHC 1 has a beta 2microglobulin and 3 alphasMHC 2 has alpha 1 and 2 bound and beta 1 and beta 2 bound
what alpha sub-units in the MHC 1 structure form the peptide binding cleft?
alpha 1 and alpha 2
what is the invariant chain in the MHC 2 molecule?what does the MHC 2 invariant chain bind to?
beta 2 domainbind to the CD4 co-receptor
what chains in the MHC 2 molecule form the peptide binding cleft?
the alpha 1 and beta 1
what domain is nonpolymorphic in the MHC 2 molecule?
the beta 2 domain
how are the MHC genes expressed?
codominantly because they are inherited from both parents
What cells express MHC 2?
dendritic cells, macrophages, monocytes and B cells
what are the 3 polymorphic MHC 1 genes?
HLA- A/B/C
What are the 3 polymorphic MHC 2 genes?
1) HLA-DQ A1, HLA-DQ A22) HLA-DP A1, HLA-DP B13) HLA-DR A1, HLA-DR B1/B2/B3/B4/B5
Many peptides arepresented by each MHC molecule?Why? what kind of molecule can the MHC bind?
1 because there is only 1 peptide cleft and only bind peptide
when do MHC’s get their peptide cargo?
during their biosynthesis inside the cell
MHC molecules will display peptides from microbes that are found inside host cells, with this in mind, what cell mediates the immunity to intracellular microbes?
MHC restricted T cells
from where do MHC 1 molecules get their peptide?
from cytosolic proteins that get transported to the ER
from where do MHC 2 molecules get their peptide?
from intracellular vesicles
dendritic cells, B cells, and macrophages will put extracelullar proteins that get internalized where?
in intracellular vesicles to later be processed
how will B cells, dendritic cells, and macrophages internalize extracellular proteins?
by having microbe bind to :- receptor specific of microbial product- Fc receptor- products of comlement activation attached to the microbe already (C3b or CR1)
what molecules do MHC 2 cells use to transport peptides or load the MHC molecule?
Ii or invariant chain
what molecules do MHC 1cells use to transport peptides or load the MHC molecule?
TAP
MHC 2 processing of internalized vesicular antigens
- take up intracelluar peptide and put into a vacuole- then degradedin lysosome; (at the same time the MHC 2 molecule is synthesized in ER and put on an endosome with the cleft boud to CLIP)- CLIP is removed using HLA-DM- the peptide then binds to the MHC 2 molecule- complex is now transported to surface
When the newly synthsized MHC 2 molecule does not bind to the broken down peptide, what happens?
it is degraded
peptide fragments that bind to the MHC molecule are called what?
immunodominant epitopes of the antigen
What another name for CLIP?
Ii, invariant chain
class I MHC pathway of processing cytosolic antigen
- virus in cytoplasm makes protein or the protein gets taken up through phagocytosis of the microbe itself- the protein is unfolded in the cytoplasm and ubiquinated, then degraded by proteosome- the peptides produced get transported to the ER by TAP- Peptides get trimmed and bound to newly made MHC 1- MHC 1 bound to peptide gets moved to cell surface
how do viruses evade MHC 1 presentation?
- Removing newly synthesized MHC molecules from the ER2. Inhibiting the transcription of MHC genes3. Blocking peptide transport by TAP
What is the consequence of MHC 1 reduction by a virus?
CD 8+ (CTL’s) can’t detect these cells to kill the virus
What ensures that T cells respond only to cell-associated antigens?
the need to recognize the MHC molecule associated with the antigen’s peptide
what benefit does it have to segregate between MHC 1 and 2?
It allows the ability to respond to intracelullar as well extracellular antigens
Who will present antigen taken up from the extracellular environment?What will macrophages do once they have it?
Macrophages and B cells (both have MHC 2)macrophages will present it to T helper cells who will activate the macrophage to destroy the microbe and activate B cells to produce antibodies against all other extracellular microbes
What happens to microbes that are in the cytoplasm of an infected host? (intracellular microbe)
Cytotoxic T cells will eradicate it
