HRR: antigen capture and presentation Flashcards
Describe cell mediated immunity
a division of the adaptive immune system that utilizes T cells that secrete cytokines and kill other cells. It is effective against intracellular microbes and tumors
Describe humoral immunity
A division of the adaptive immune system that utilizes antibodies made by B cells. It is effective against extracellular microbes, debris, and toxins.
Describe the basic function of MHC
MHC proteins present peptide antigens on the surface of cells.
How do T cells recognize antigens?
T cells have antigen receptors that interact with the MHC+peptide complex.
Describe the basic structure of MHC class I
has one polymorphic chain (alpha chain), one invariant chain (b2 microglobulin) that does not change from person to person. It is a chaperone protein and is not covalently linked the alpha chain
Describe the basic structure of MHC class II
has two polymorphic chains, alpha and beta.
Describe how MHC interacts with T cell receptors
The MHC has a pocket that the peptide lays in. the T cell receptor has a contact point for the peptide as well as contact points for residues of the MHC molecule. The T cell recognizes the combination of these 2, not just the peptide alone
Describe MHC restriction
A T cell recognizes the combination of MHC and peptide and will not recognize the same peptide if it is presented by a different MHC
What kind of T cells does MHC I present to?
CD8+ cytotoxic T cells
What kind of T cells does MHC II present to?
CD4+ helper T cells
Describe peptide binding in MHC’s
Peptide binding to MHC is noncovalent. MHC can bind one peptide at a time and can bind many potential peptides.
What happens if you do not have an MHC for a given peptide?
You cannot generate T cell immunity to it; therefore, MHC alleles you inherit determine which antigenic peptides your immune system can respond to
How do MHC genes tend to be inherited?
They’re inherited as a haplotype, meaning they’re inherited as a unit. This inheritance follows Mendelian genetics
What are the genotypes for MHC classes I and II?
Class I: HLA A, B, and C
Class II: HLA DP, DQ, and DR
Describe MHC codominance
we express each MHC allele from each parent on the cell surface equally. This means we have 6 different MHC class I molecules on all cells. There are about 12 possibilities for class II molecules on APC (3 classes, 2 chains, 2 from each parent in each class)
What are the two situations in which antigen presentation to T cells is required?
1.Naïve T cells require antigen presentation in order to undergo clonal expansion and maturation. This is done with dendritic cells
2.Effector T cells require antigen presentation to activate their functions, as T cells require MHC to ‘see’ peptide antigens
Which MHC is usually found on phagocytes?
MHC II
What kind of antigens to MHC I and II present?
MHC I: cytoplasmic antigens
MHC II: antigens collected from the extracellular environment
What are the 3 professional antigen presenting cells?
Dendritic cells, macrophages, B cells
Describe the function of dendritic cells in terms of antigen presentation
Present antigen to naïve T cells in secondary lymphoid organs (lymph node or spleen)
Describe the 2 types of dendritic cells
Classical: induce inflammatory response and secrete inflammatory cytokines
Plasmacytoid: activate antiviral response and make type I interferons
Describe the function of macrophages in terms of antigen presentation
Present antigen to stimulate effector T cell function in peripheral tissue
Describe the function of B cells in terms of antigen presentation
Present antigen to CD4 helper cells in order to receive their help to facilitate antibody production
Describe the two ways that antigen end up being transported to T cells
Antigens are transported to naïve T cells by either entering blood or lymph and get trapped by dendritic cells. In lymph they will be captured by lymph nodes, in the blood they’ll be captured by the spleen
Describe what happens to dendritic cells upon capturing an antigen
- dendritic cell captures antigen, which activates it
- DC loses its adhesiveness and expresses CCR7 to travel to the lymph node
- DC’s mature as they migrate through lymphatic vessels
- DC’s present to naive T cell in lymph node
what is CCR7
a receptor for chemokines secreted by T cell zones in lymph nodes; DC’s will express this upon antigen capture in order to travel to the naive T cells
What is the most important co-stimulatory molecule for T cells? where are these expressed?
B7; APC’s
Explain how antigen presenting cells, which are part of the innate immune system, steer the adaptive immune system toward humoral vs. cell-mediated responses
With an intracellular pathogen, an APC will induce a cell-mediated response by presenting with MHC I. with an extracellular pathogen, an APC will induce humoral response by presenting with MHC II
When do MHCs obtain a peptide in relation to their synthesis?
MHC molecules acquire the peptide they present during their synthesis; they require the peptide to fold into their stable conformation
MHC class I synthesis is present in ___ cells, and MHC class II synthesis is present in ___ cells
All nucleated; antigen presenting
Describe the MHC class I synthesis pathway
oProteins in the cytoplasm are targeted for ubiquitination
oProtein enters the proteasome and gets cleaved into peptides
oPeptides produced by the proteasome are transported to the ER.
oThe ribosomes make class I MHC a and b2 chains. TAP, a transporter for antigen presentation, transports the peptides from the proteasome into the ER.
oThe peptide can associate with the class I MHC and bind to the cleft.
oThe proteins exit to the golgi, leave the cell via exocytosis, and the MHC I is then presented on the cell surface
Describe the MHC Class II synthesis
oExtracellular antigens enter APC via phagocytosis.
oThe internalized protein is processed in an endosomal/lysosomal vesicle, forming peptides.
oRibosomes make and assemble class II molecules and their invariant chain in the ER
oThe MHC II goes to the golgi for processing, then buds off the golgi in a vesicle
oThe exocytotic vesicle with MHC II fuses with the endosome/lysosome containing peptides.
oThe invariant chain in cleaved and leaves behind the clip. This clip can exchange with the peptide, joining the peptide and the MHC. This is mediated by HLA DM.
oThe MHC II-peptide complex will be released via exocytosis, and then expressed on the cell surface.
What elements are exclusive to MHC I synthesis? MHC II synthesis?
TAP; clip and HLA DM
Describe cross-presentation
Cross presentation is when class I and class II presentations cross. Cytoplasmic proteins can end up on class II, and ingestion of whole cells can form a double membrane structure that call allow for escape of proteins into the cytoplasm. That allows viruses to be presented on class I.
Describe epitopes
parts of biomolecules that are targets of the immune response. They are found on the antigen and will bind to a paratope on the antibody. most antigens have many potential epitopes
Why can T cells only recognize linear peptide epitopes?
due to the MHC requirement
