MHC Flashcards
What do antigen receptors of B cells recognize?
- macromolecules
- proteins
- polysaccharides
- lipids
- nucleic acids
- small chemicals in soluble form
what do antigen receptors of T cells recognize
- peptide fragments of protein antigens
- only when present on MHC cells
T-cell mediated immune responses only against
- protein antigens
- produced in host cells
- taken up by host cell
antigens can only be recognized in the proper context
- location (anatomic)
- setting (micranatomic/molecular)
where does antigen presentation occur
- lymph node collects antigen from epithelium and connective tissues
- blood-borne antigens are captured by antigen-presenting cells in the spleen
langerhans cells
- dendritic cells in the skin
- as they capture antigen, they get signals to travel to T cell areas within lymph nodes
where are proteins displayed or recognition by T lymphocytes
- peripheral lymphoid organs
- lymph nodes
- spleen
major location of conventional dendritic cells
- tissues
major location of plasmacytoid dendritic cells
- blood
- tissues
major cytokines produced by conventional dendritic cells
- pro-inflammatory
- TNF
- IL-6
- IL-12
major cytokines produced by plasmacytoid dendritic cels
- type I interferons
major functions of conventional dendritic cells
- induction of T cell responses against most antigens
major functions of plasmacytoid dendritic cells
- antiviral innate immunity
- induction of T cell responses against viruses
after dendritic cells capture microbial antigens
- activated
- and leave their location
- migrate to draining lymph nodes
what attracts dendritic cells to the lymph nodes
- chemokines produced in the lymphatics and nodes
how to the dendritic cells mature and acquire the ability to present antigen
- in response to signals induced by the microbe such as Toll like receptor signals and cytokines
immature dendritic cells express
- surface receptors that capture microbial antigen
mature dendritic cells express
- high levels of MHC molecules and costimulators
- to stimulate T cells
dendritic cell class II MHC - constitutive or inducible
- constitutive
dendritic cell class II MHC increases with
- maturation
dendritic cell class II MHC increases by (cytokine)
- interferon gamma
dendritic cells costimulators - constitutive or inducible
- constitutive
dendritic cells costimulators increases with
- maturation
dendritic cells costimulators inducible by
- TLR ligands
- interferon gamma
- CD40-CD40L interactions
dendritic cells principle function
- initiation of T cell responses to protein antigens
macrophages class II MHC - constitute or inducible
- inducible by interferon gamma
INTERFERON GAMMA MAKES MACROPHAGES HUGE AF
macrophages costimulators - constitutive or inducible
- inducible by:
- TLR ligands
- interferon gamma
- CD40-CD40L interactions
macrophages principal function
- effector phase of cell-mediated immune responses
B lymphocytes class II MHC - constitutive or inducible
- constitutive
B lymphocytes class II MHC increased by
- IL-4
B lymphocytes costimulators induced by
- CD40-CD40L interactions
- antigen receptor cross linking
B lymphocytes function
- antigen presentation to CD4+ helper T cells in humoral immune responses
MHC I pathway (intrinsic or extrinsic)
- intrinsic
MHC II pathway (intrinsic or extrinsic)
- extrinsic
3 processing pathway
- intracellular
- intrinsic
- extrinsic
3 presentation pathways
- extracellular/surface
- multi-molecular
- multi-cellular
MHC gene products in humans are called
- human leukocyte antigens
- HLAs
most important HLAs
- Class I and Class II
HLA gene and haplotypes
- certain haplotypes can determine if you are protected or predisposed to certain autoimmune diseases
MHC gene expression
- codominantly expressed
MHC genes and diversity
- highly polymorphic
co-dominant expression
- both parental alleles of each MCH gene are expressed
significance of codominant expression for MHC
- increases the number of different MHC molecules that can present peptides to T cells
significant of polymorphous genes for MHC
- ensures that different individuals are able to present and respond to different microbial peptides
Class II MHC found on
- dendritic cells
- macrophages
- B cells
Class I MHC found on
- all nucleated cells
MHC Class I chains
- alpha chain
- beta-2 microglobulin (not coded in MHC)
MHC Class I binding cleft
- alpha 1 and alpha 2 domains
size of peptide MHC Class I can bind
- 8-11 AA in size
part of Class I MHC that binds CD8
- alpha 3
polymorphisms in MHC Class I
- mostly alpha 1 and 2
MHC II chains
- alpha and beta chains
size of peptide MHC II can bind
- 10-30 AA
part of MHC II that binds CD4
- beta 2
number of antigens MHC can present at a time
- only one peptide at a time
- peptides only
how many MHC molecules on the surface
- 10^5
how what percentage of MHC must be bound to be activated
- less than 1%
significance of slow off rate of MHC molecule
- displays bound peptide for long enough to be located by a T cell
CD4 T cell responses
- classic T helper
- cell mediated immunity
- humoral responses
- T regulatory cells
CD8 cell responses
- classically CTL responses
- kills infected cells
- antiviral immunity
MHC II enzymes responsible for peptide generation
- endosomal and lysosomal proteases
MHC I enzymes responsible for peptide generation
- cytoplasmic proteasome
site of peptide loading MHC II
- specialized vesicles
site of peptide loading MHC I
- endoplasmic reticulum
molecules in volved in transport of peptides and loading of MHC molecules on MHC II
- invariant chain
- DM
molecules in volved in transport of peptides and loading of MHC molecules on MHC I
- TAP
MHC II Pathway
- uptake of EXTRACELLULAR proteins into vesicular compartments of APC
- processing of internalized proteins in endosomal/lysosomal vesicles
- biosynthesis and transport of class II MHC molecules to endosomes
- association of processes peptides with class II MHC molecules in vesicles
- DM provides the switch
- expression of peptide MHC complexes on cell surface
MHC Class I pathway
- production of proteins in cytosol or phagosome bringing in
- proteolytic degradation of proteins by proteasome
- transport of peptides into ER by TAP for assembly
- packaged in Golgi
- released in exocytic vesicle for surface expression
dendritic cells can also present to
- CD8 T cells
- through MHC1 expression
how dendritic cells present to CD8 T cells
- infected cells and viral antigens picked up by APC
- cross-presentation of viral antigen
roles of APC
- co-stimulators
- secrete cytokines
- present a context for immune regulation
- may limit immune responses
important chromosome for human HLA
- chromosome 6