HRR: antigen capture and presentation

Question 1

Describe cell mediated immunity

Answer 1

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

Question 2

Describe humoral immunity

Answer 2

A division of the adaptive immune system that utilizes antibodies made by B cells. It is effective against extracellular microbes, debris, and toxins.

Question 3

Describe the basic function of MHC

Answer 3

MHC proteins present peptide antigens on the surface of cells.

Question 4

How do T cells recognize antigens?

Answer 4

T cells have antigen receptors that interact with the MHC+peptide complex.

Question 5

Describe the basic structure of MHC class I

Answer 5

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

Question 6

Describe the basic structure of MHC class II

Answer 6

has two polymorphic chains, alpha and beta.

Question 7

Describe how MHC interacts with T cell receptors

Answer 7

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

Question 8

Describe MHC restriction

Answer 8

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

Question 9

What kind of T cells does MHC I present to?

Answer 9

CD8+ cytotoxic T cells

Question 10

What kind of T cells does MHC II present to?

Answer 10

CD4+ helper T cells

Question 11

Describe peptide binding in MHC’s

Answer 11

Peptide binding to MHC is noncovalent. MHC can bind one peptide at a time and can bind many potential peptides.

Question 12

What happens if you do not have an MHC for a given peptide?

Answer 12

You cannot generate T cell immunity to it; therefore, MHC alleles you inherit determine which antigenic peptides your immune system can respond to

Question 13

How do MHC genes tend to be inherited?

Answer 13

They’re inherited as a haplotype, meaning they’re inherited as a unit. This inheritance follows Mendelian genetics

Question 14

What are the genotypes for MHC classes I and II?

Answer 14

Class I: HLA A, B, and C
Class II: HLA DP, DQ, and DR

Question 15

Describe MHC codominance

Answer 15

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)

Question 16

What are the two situations in which antigen presentation to T cells is required?

Answer 16

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

Question 17

Which MHC is usually found on phagocytes?

Answer 17

MHC II

Question 18

What kind of antigens to MHC I and II present?

Answer 18

MHC I: cytoplasmic antigens
MHC II: antigens collected from the extracellular environment

Question 19

What are the 3 professional antigen presenting cells?

Answer 19

Dendritic cells, macrophages, B cells

Question 20

Describe the function of dendritic cells in terms of antigen presentation

Answer 20

Present antigen to naïve T cells in secondary lymphoid organs (lymph node or spleen)

Question 21

Describe the 2 types of dendritic cells

Answer 21

Classical: induce inflammatory response and secrete inflammatory cytokines

Plasmacytoid: activate antiviral response and make type I interferons

Question 22

Describe the function of macrophages in terms of antigen presentation

Answer 22

Present antigen to stimulate effector T cell function in peripheral tissue

Question 23

Describe the function of B cells in terms of antigen presentation

Answer 23

Present antigen to CD4 helper cells in order to receive their help to facilitate antibody production

Question 24

Describe the two ways that antigen end up being transported to T cells

Answer 24

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

Question 25

Describe what happens to dendritic cells upon capturing an antigen

Answer 25

- 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

Question 26

what is CCR7

Answer 26

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

Question 27

What is the most important co-stimulatory molecule for T cells? where are these expressed?

Answer 27

B7; APC's

Question 28

Explain how antigen presenting cells, which are part of the innate immune system, steer the adaptive immune system toward humoral vs. cell-mediated responses

Answer 28

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

Question 29

When do MHCs obtain a peptide in relation to their synthesis?

Answer 29

MHC molecules acquire the peptide they present during their synthesis; they require the peptide to fold into their stable conformation

Question 30

MHC class I synthesis is present in ___ cells, and MHC class II synthesis is present in ___ cells

Answer 30

All nucleated; antigen presenting

Question 31

Describe the MHC class I synthesis pathway

Answer 31

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

Question 32

Describe the MHC Class II synthesis

Answer 32

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.

Question 33

What elements are exclusive to MHC I synthesis? MHC II synthesis?

Answer 33

TAP; clip and HLA DM

Question 34

Describe cross-presentation

Answer 34

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.

Question 35

Describe epitopes

Answer 35

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

Question 36

Why can T cells only recognize linear peptide epitopes?

Answer 36

due to the MHC requirement