Antigen processing, presentation, and co-stimulation (Stiner-jones) Flashcards
What is the general flow of how lymphocytes are activated?
- Microbe infects the host
- Antigen presenting cell engulfs microbe
- APC exits circulation and enters a lymph node
- Naive T and B cells are schooled by APC
- Schooled T and B cells exit lymphatic circulation and head to infection site
What is an effector T-cell?
It is an armed T-cell that is ready to destroy
CD8+ T cells are _____ restricted and recognize _____ _____.
MHC I
cytosolic proteins
CD4+ T cells are _____ restricted and recognize _____ and ______ ______.
MHC II
Extracellular and intravesicular pathogens
What is the bridge between antigen recognition and the initiation of a full-blown immune response?
Antigen presentation
T-cells _____ and B-cells _____ _____.
Kill
produce antibodies
Antigen presentation is modulated by what?
Co-stimulatory molecules
The most common antigen presenting cell is the what?
Dendritic cell
Which cell is the professional APC?
Dendritic cells
Macrophages must be activated by _____ before presenting antigens.
Phagocytoses
Are APC’s limited to dendritic cells, macrophages, and B cells?
Nope
What other cells can be APC’s?
All nucleated cells can present endogenous antigens in association with MHC I molecules
What happens in pathway 1 of antigen processing?
Pathway 1: exogenous antigens are taken into the cell (8-13 amino acids) and are presented to T helper cells together with MHC II molecule
What happens in pathway 2 of antigen processing?
Pathway 2: for endogenous antigens- they are digested to small peptides (13-18 amino acids) and presented to CD8+ T cells
What is the pathway of degradation for intracellular proteins?
Cytoplasmic proteins are degraded by proteosomes into peptides. Exopeptidase turns the peptides into amino acids
Endocytic proteins are degraded in the lysosome into peptides. Exopeptidase turns the peptides into amino acids
Endogenous antigens- the cytosolic pathway: how does it work?
- Proteins that need to be degraded are tagged for degradation by ubiquitin
- Degradation of ubiquitin-protein complex occurs within the central channel of the proteosome
- Peptides generated via degradation are transported to the lumen of the RER by the TAP protein
- Newly synthesized MHC I within the RER membrane binds to the antigen peptide
- Antigen-MHC I complex is released and transported to the cell surface
Where are MHC I and MHC II made?
Endoplasmic reticulum
Exogenous antigens- the endocytic pathway: how does it work?
- Antigens are internalized in endosomes
- Antigens are digested first in the endosomes and then further in the lysosomes to 13-18 amino acids
- Class II molecules are produced in the RER
- MHC II molecules are associated with the invariant chain protein, which prevents their binding to endogenous antigens.
- Class II-invariant chain complex moves into endocytic compartments
- Invariant chain protein will be digested to a short fragment (CLIP)
- HLA-DM triggers the exchange of CLEP and the antigen peptide
- HLA-DO blocks the activity of HLA-DM
What three things can the MHC haplotype influence?
How an individual responds to certain pathogens
Susceptibility to certain diseases
Transplant success
T/F MHC genes are highly polymorphic?
True
MHC genes are the most polymorphic genes in the human genome- what implications does this have?
Difficulty finding transplant donors that match, even among first degree relatives
The set of MHC alleles on an individual chromosome is termed what?
The MHC haplotype
What combination of MHC and antigen does the T-cell recognize?
Self MHC + foreign antigen