Lecture 1- Antigen processing, presentation and co-stimulation Flashcards
5 steps if you mix an e. coli with macrophage?
- binding
- engulfment
- phagosome formation (acidification via respiratory burst)
- phagosome fuses with lysosome to form phagolysosome
- membrane disruption
T cell does NOT recognize: (4)
soluble Ag
cell surface Ag
soluble peptides of Ag
Cell surface peptides of Ag
T cell WILL recognize:
Cell surface peptides of Ag presented by cells that express MHC antigens
Antigen processing and presentation is the process of taking up a …., processing the… and presenting it to a ….
- microbe
- antigens
- naive T cell
Which cells can process and present antigens?
- dendritic cells
- monocytes/macrophages
- B cells
Dendritic cells are the primary….. and are a link between….
- APC
- innate and adaptive immunity
Dendritic cells are…. cells
phagocytic
Dendritic cells typically express….. molecules
MHCII
Dendritic cells …. and…. antigen
internalize and process
Dendritic cells present…. within …. on surface
- antigen peptides
- MHCII
Dendritic cells are important for …. and….
- presenting Ag to T cells
- activating T cells
Dendritic cells are a minor population in the …. but are found in….
- minor in blood
- skin, mucosa, LN, spleen, thymus
…. are extremely important for antigen processing, they have a characteristic large nucleus, produce chemotactic agents for other leukocytes, contain arsenal of lysozymes and antimicrobial proteins. Extremely important for clearance of dead cells and debris
monocytes/macrophages
5-10% of blood leukocytes
B cells can… but do not….
present
process
B cells are a lymphocyte part of the… immunity and can activate…
- adaptive
- T cells
Antigen presentation is a way to concentrate the… in areas most likely to come in contact with…
antigen
T and B cells
Process of antigen presentation (getting the antigen to area that will most likely come into contact with B and T cells)
4 steps:
- microbe infects host
- microbe taken up by APC at s.o.i.
- APC enters lymph circulation and into LN
- Naive T and B cells enter LN from circulation
… was linked to graft rejection but later found to be critical importance to all immune responses involving proteins Ags
Major histocompatibility complex
…. is found on all nucleated cells, is recognized by CD8+ T cells and can have cytoplasmic protein bound to it
MHCI
….. is found on APCs, extracellular proteins will be bound to it and it is recognized by CD4+ T cells
MHCII
…. is the process by which antigens are digested and placed on the cell surface with the correct MHC molecule
antigen processing
There are … pathways for processing antigens
2
Pathway 1 for processing antigens is when:
Extracellular proteins are internalized by professional APCs into vesicles, processed and displayes by …. molecules
MHCII
Pathway 2 for processing antigens is when:
Proteins in the cytosol of nucleated cells are processed and displayed by … molecules
MHCI
Often cytosolic proteins are… proteins
viral
In pathway 2 (cytosolic), …. binds to proteins which targets them for degradation
ubiquitin
In pathway 2 (cytosolic proteins):
Ubiquinated proteins are cleaved into smaller peptides by the…
These peptides are transported to ER by…. and then trimmed to correct size by…. so that it can bind to the binding groove of…
Once … binds ag, released from ER, packed in golgi, trafficked to surface, expressed so…. can recognize it
proteosome TAP transporters ERAP MHCI MHCI CD8+ T cell
In pathway 1 (extracellular proteins):
Extracellular are taken up into vesicular compartments of… then there is formation of the…. as well as degradation of the microbe by…. and…
The… is syn. in ER, packed in golgi and then transported to phagolysosome where it fuses and the ag binds to binding groove before it goes to the surface and is expressed so that … can recognize it
- APC
- phagolysosome
- ROS/NO and enzymes
- MHCII
- CD4+
Antigen processing and presentation is essential for activation of naive T cells but…
that alone is not sufficient to activate them. Multiple receptors on T cellss need to be engaged as well
CD8+ are… restricted and recognize…
MHCI
cytosolic proteins
CD4+ are… restricted and recognize….
- MHCII
- extracellular/intravesicular proteins
Recognition of antigen ( and MHC) in the absence of …. fails to activate T cell, in fact it leads to …. of the T cekk
- co-stimulation
- anergy
Multiple receptors on T cell need to be engaged in order to activate it, these receptors together are referred to as the…
immunological synapse
The immunological synapse:
- TCR recognizing….
- CD4 recognizing…
- CD28 on T cell recognizing…
- LFA-1 on T cell recognizing…
same in CD8
except CD8–>MHCI
- TCR–> antigen
- CD4–> MHCII
- CD28 on T cell–> B7 on APC
- LFA-1 on T cell–> ICAM-1 on APC
At the termination of the immune response, …. replaces CD28 and downregulated T cell function
CTLA-4
Absence of co-stimulatory molecules, T cell will…
not be activated (anergy)
Absence of antigen-TCR interaction, …
T cell will not be stimulated (no efffect)
B7 receptors play a role in … and…
activating T cells AND terminating the T cell response
B7 is bound by CD28 but then is bound by … at termination of immune response
CTLA-4
CTLA-4 can … CD28 binding to B7
competitively inhibit
CTLA-4, when bound to B&, will actively block signals from the… and from the…
TCR
CD28
