2T 10:00Am - L17 & 18: Cell-Mediated Immunity I & Ii

Front 1

What are the 2 distinct components of the adaptive immune response and what are they mediated by?

Back 1

1. Humoral immunity
Mediated by: antibodies produced by B lymphocytes

2. Cellular immunity
Mediated by: T lymphocytes and components of the innate immune system (macrophages)

Front 2

Describe the structure of an MHC class I molecule

Back 2

Heavy chain: α1, α2, α3

Light chain: β2-microglobulin (β2m) - has Ig folds

The heavy and light chain interacts noncovalently.
Heavy chain is polymorphic, but light chain is not.

Front 3

Identify the functional regions in an MHC class I molecule

Back 3

Peptide-binding region: α1, α2 - has β-pleated sheets and parallel walls of α helices

Immunoglobulin-like domain: part of α3 and β2m

(Hydrophobic) transmembrane region: part of α3

Cytoplasmic region: part of α3

Front 4

Describe the structure of an MHC class II molecule

Back 4

α chain: α1, α2

β chain: β1, β2

Both α and β chains are polymorphic.

Front 5

Identify the functional regions in an MHC class II molecule

Back 5

Peptide binding region: α1 and β1
Immunoglobulin-like region: part of α2 and β2
Transmembrane region: part of α2 and β2
Cytoplasmic region: part of α2 and β2

Front 6

What are the differences in the binding of MHC I and MHC II

Back 6

MHC I: binds peptides 8-9 residues long
(bc antigen binding cleft is closed)

MHC II: binds peptides 13-20 residues long
(bc antigen binding cleft is open at both ends)

Front 7

Bacteria such as Staphylococcus and viruses such as murine mammary tumor virus release superantigens, which do not bind to the MHC peptide groove. How do they work?

Back 7

Superantigens directly bind to the outer surface of specific MHC II molecules (without antigen processing) and the Vβ region of the T cell receptor (irrespective of the Vα chain).

This induces massive production of cytokines and functionally inactivates responding T cells, causing general immunosuppresion.

Front 8

What are the loci encoding the MHC class I genes in humans?

Back 8

HLA-A, HLA-B, HLA-C

Front 9

What are the loci encoding the MHC class II genes in humans?

Back 9

HLA-DPα, HLA-DQα, HLA-DRα
HLA-DPβ, HLA-DQβ, HLA-DRβ1, HLA-DRβ2

Front 10

What do the MHC class III genes encode for?

Back 10

Components of the complement system

Front 11

Other than restriction elements for T cells, what other genes are encoded in the human MHC region?

Back 11

Heat shock proteins
Cytokines (eg: TNF)
Gene products involved in antigen processing:
- TAP
- LMP
- tapasin
- DM

Front 12

List 3 properties of the MHC genes that contribute to the diversity of MHC molecules expressed by an individual

Back 12

1. polymorphism
2. co-dominant expression
3. polygeny

Front 13

A human cell may express as many as how many Class I molecules?

Back 13

6

3 heavy chain genes (A, B, C) inherited from mother;
3 heavy chain genes inherited from father

Front 14

A human cell may express as many as how many Class II molecules?

Back 14

15

3 α chain genes (DPα, DQα, DRα) and 4 β chain genes (DPβ DQβ, DRβ2, DRβ1) from mother

3 α chain genes (DPα, DQα, DRα) and 4 β chain genes (DPβ DQβ, DRβ2, DRβ1) from father

That makes 14. And some maternal and paternal α and β chains can bind with each other.

Front 15

The genes that encode the MHC class I α chains and the MHC class II α and β chains are the most polymorphic of all known genes.

Where are polymorphic residues within MHC molecules clustered at?

Back 15

In the MHC molecule's antigen-binding site

Front 16

What does it mean that the block of MHC genes is a haplotype?

Back 16

MHC molecules are inherited as an entire block of genes.

Front 17

On which cells are MHC I molecules expressed?

Back 17

All nucleated cells (ie: not on RBCs)

Front 18

Considering that the function of MHC II is to communicate with other cells, on which cells are MHC II molecules expressed?

Back 18

Most hematopoietic cells in lymphoid tissues:
- B cells
- Macrophages
- Other antigen-presenting cells
- Epithelial cells of the thymus
(Not really T cells)

Front 19

How are endogenous antigens (proteins synthesized in the cytoplasm, such as those derived from a virus that has infected the cell, or those being made by tumor cells) processed?

Back 19

Endogenous antigens in the cytoplasm are processed and presented on Class I molecules to be recognized by CD8+ T cells

Front 20

How are exogenous antigens (those derived from bacteria, viruses) processed?

Back 20

Exogenous antigens are endocytosed and presented on Class II molecules to be recognized by CD4+ T cells, which will activate macrophages to destroy the intracellular microorganisms

Front 21

Summarize the steps in MHC class I-restricted antigen presentation

Back 21

1. virus replicates
2. cytoplasmic viral protein is degraded by proteasome
3. TAP1/2 transport degraded peptides into the ER
4. peptide in ER binds to new MHC I molecules, helped by
- calnexin, tapasin, and calreticulin (chaperones)
- ERp57 (a thioloxidoreductase - opens and closes disulfide bonds)
5. The Class I-peptide complex is exocytosed onto the cell surface and presented to CD8+ T cells

LMP = low molecular weight protein (proteasome subunits)
TAP = transporter associated with antigen processing
(LMP2, LMP7, TAP1/2, tpn are encoded within the MHC)

Front 22

Processing of antigens by MHC I and II occurs for both foreign antigens and self antigens. Is this a problem?

Back 22

No. T cells do not recognize self antigens complexed with self MHC because T cells are tolerant against them. T cells learn to ignore self antigens during their selection in the thymus

Front 23

Summarize the steps in MHC class II-restricted antigen presentation before the peptide-containing endosomes fuse with MHC II/Ii-containing vesicles

Back 23

1. Antigens are endocytosed
2. Antigen-containing endosomes fuse with lysosomes; antigens are degraded by lysosomal protases called cathepsins
Meanwhile:
1. New MHC II molecules in the ER are complexed with a 3rd chain, an Invariant chain (Ii)
2. The MHC II/Ii complex is targeted to the endocytic pathway

The Ii has 2 functions (1) transport signaling (2) the CLIP (class II-associated invariant chain peptides) region shields the antigen binding groove of MHC II from peptide binding while it's still in the ER and Golgi

Front 24

Summarize the steps in MHC class II-restricted antigen presentation after the peptide-containing endosomes fuse with MHC II/Ii-containing vesicles

Back 24

3. Fusion of endosome and vesicle
4. Lysosomal proteases degrade the Ii until only the CLIP fragment is left intact
5. DM, which looks like MHC II, binds to MHC II to catalyze the release of CLIP and the loading of high-affinity peptides. This happens in the MHC class II compartment (MIIC)
6. The MIIC fuses with the plasma membrane, allowing peptide presentation to CD4+ T cells

Front 25

T cell receptors resemble antibody molecules in that they have both variable and constant regions. What are some differences?

Back 25

T cell receptors
- are never secreted
- have a single antigen-binding domain
- recognize antigen in the context of self-MHC molecules

Front 26

Describe the structure of a T cell receptor

Back 26

α and β chains covalently linked by disulfide bonds.
Each chain has a variable and constant region.

1-5% of T cells in blood are γδ T cells - they're made of γ and δ chains.

Front 27

Expressed on?
Ab: ____
TCR: ___

Back 27

Ab: B cells
TCR: T cells

Front 28

Has cell surface forms?
Ab: ____
TCR: ___

Back 28

Ab: Yes
TCR: Yes

Front 29

Has secreted forms?
Ab: ____
TCR: ___

Back 29

Ab: Yes
TCR: No

Front 30

What kind of chains?
Ab: ____
TCR: ___

Back 30

Ab: 2 heavy, 2 light
TCR: α and β,
or γ and δ

Front 31

Members of Ig superfamily?
Ab: ____
TCR: ___

Back 31

Ab: Yes
TCR: Yes

Front 32

Has isotypes with distinct functions?
Ab: ____
TCR: ___

Back 32

Ab: Yes
TCR: No

Front 33

Number of antigen binding sites?
Ab: ____
TCR: ___

Back 33

Ab: 2
TCR: 1

Front 34

Antigens recognized?
Ab: ____
TCR: ___

Back 34

Ab: protein, sugar, lipid, etc
TCR: MHC+peptide

Front 35

Diversity generated by DNA rearrangement?
Ab: ____
TCR: ___

Back 35

Ab: Yes
TCR: No

Front 36

Diversity generated by somatic hypermutation?
Ab: ____
TCR: ___

Back 36

Ab: Yes
TCR: No