antigen processing and presentation histocompatibility Flashcards
MHC
major histocompatibility complex
MHC function
-chop up and present antigens to T cells (this can be the cause of rejection or an organ during a transplant)
describe MHC genes
polygenic, polymorphic and tend to be codominantly expressed
MHC class I
- present peptides to CD8 + T cells
made up of alpha and beta subunits - present on all nucleated cells (not Red blood cells)
- displayed on endogenous peptides
alpha subunit
large and contains entire peptide binding cleft
beta subunit
helps maintain structure of MHC class I
MHC Class II
- presents peptides to CD4 +T cells
- expressed on professional antigen presenting cells
- display exogenous peptides
- more symmetrical than class I
what are the differences between class I and II peptide binding regions
class I: u shaped curve of 8-10 amino acids, doesn't have to make full contact with the MHC just needs two ends to be anchored on Class II: binds in a wavy pattern to 13-18 amino acids, almost all amino acids touching MHC
antigen processing definition
the breaking down of macromolecules into smaller fragments in order to prepare them for presentation to a t cell
one b cell per
one epitope
4 major pathways of Ag processing
- exogenous
- endogenous
- cross-presentation
- autophagic
exogenous
internalize antigens and present on cell surface via MHC II. Recognizes external pathogens and only for CD4+T cells
endogenous
cell recycling. recognize intracellular pathogens. presented on cell surface of MCH I only presents to CD8+T
which cells are best at presenting antigens to T cells because they have high MHCII
dendritic cells
which cells can present to either CD4+T and CD8+T
dendritic cells
3 types of antigen presenting cells
mature dendritic cells, macrophages and B cells
which cells can activate naive t cells
dendritic cells
autophagic
recognize internal pathogenic then activate CD4+T cells; present as MCH II
cross-presentation
recognize external pathogens and then activate CD8+T cells
which cells have highest level of MCH II
dendritic cells
Naive t cell activation
by dendritic cells. clonal expansion and differentiation into effector T cells
effector t cell activation
can be done by macrophages and b cells. (b cells in the blood and strictly for extracellular pathogens)
cells put out to look for antigens
dendritic cells
tissue resident resting dendritic cells function
antigen capture
activate dendritic cell function
antigen presentation to t cells
no ____ peptides go into MHCII
self binding
invariant chain
important for exogenous pathway. blocks binding to MHC class II molecules in the ER
steps to exogenous pathway
- substance ingest by APC into endosome. and antigen is degraded via lysosome enzymes
- MHC II molecules are assembled in ER, Golgi, endosome. Invariant chain keeps alpha and beta chains stable and prevents self Ag binding.
- MHC II and peptide travel via endosome to cell surface to present Ag to CD 4 cell
CLIP
molecule left behind after lysozyme enzymes break down invariant change.
HLA-DM
helps to remove CLIP so Ag can bind
endogenous pathway steps
- internal proteins are degraded via the proteasome then transported to ER via TAP
- MHC I is synthesized and loaded in the ER
- MHCI/Ag transported to golgi, then the plasma membrane to present to a CD8 T cell
TAP
transports internal proteins to the ER during endogenous pathway
cross presentation steps
- APC ingests and processes virally infected cell. (exogenous)
- Viral proteins enter the cytosol and is processed via endogenous pathway to activate a CD8T cell via MHCI
two classes of T-cell receptors
alpha and beta chains (90% of T cells) an γδ (10%)
alpha and beta t cells function and location
recognize MHC.AG and reside in secondary lymph tissue
γδ t cells function and location
recognizes processed and unprocessed ligands. found in intraepithelial tissue
b receptors vs t receptors
b: y shaped
t: linear
CD8 is a _____ t cell while CD4 is a ____ t cell
cytotoxic, helper
TCR cells undergo what type of recombination
VDJ recombination
when t cell receptors undergo ____ recombination it creates greater genetic diversity for T cells
variable region recombination
4 ways t cell development is similar to b cell development
- begins in the bone marrow
- VDJ recombination of variable region of TCR leads to antigen diversity
- at one point cells express both CD4 and CD8 (double positive)
- undergo positive and negative selection
4 ways t cell development is different from b cell development
- begins with NK/T precursor cells
- after leaving the bone marrow thymocytes move to the thymus to finish development
- MHC molecules are involved in the establishment of central tolerance
- No possibilities for somatic hypermutation (only undergo positive or negative selection once)
CD44
cell adhesion molecule for t cell development
CD25
Il-2 receptor for t cell development
where must a t cell be to become fully mature
thymus
there are 2 times as many ____ t cells in the body
CD4+
single positive t cels
the cell has gone through distinction and now it can leave and go to the periphery lymph tissue
3 types of t lymphocytes periphery
CD8+-killers
CD4+-helpers
Treg- suppressors
3 signals when a cell meets an antigen presenting cell
- Ag recognition
- costimulation
- cytokines
what is needed for survival, proliferation and differentiation of t cells
IL-2
during differentiation t cell can become
an effector cell or a memory cell
IFNy t cell function
t help for Tc responses against intracellular pathogens Th1.
IL-4 function
T help for B cell response against extracellular pathogens Th2
IL-17 function
combats infection of skin and mucosae. autoinflamtiaon Th17
IL-10 function
peripheral tolerance. iTreg
Th1 effector function
classical macrophage activation
Th2 effector function
humoral activation of antibodies for extracellular pathogens.
Th17 effector functions
inflammation and recruiting neutrophils for barrier functions
why do cytotoxic t lymphocytes make many contacts with their targets
to exert effector functions
