Lec #1 (Wk 3): Cell Mediated Immunity

Question 1

What do we mean by cell mediated immunity?

Answer 1

This is AKA T-cell mediated immunity where the T-cells are the main agents of cellular immunity.

(Humoral immunity refers to the B-cells, since antibodies are made and ONLY released into fluid like serous fluid, plasma etc hence the name humoral meaning fluid).

Question 2

What are T-cells & the types?

Answer 2

T-cells mature in the thymus & have a T-cell Receptor (TCR) on their surface. There are 2 main types:
- CD4+
- CD8+

Question 3

What is the structure of the T-cell receptor?

Answer 3

T-cell receptor contains 2 chains: alpha & beta. This T-cell receptor is composed of:
- Variable region
- Constant region
- Transmembrane region
- Cytoplasmic tail
- Disulfide link.

Question 4

What is the TCR complex?

Answer 4

As you can see in the picture below, T-cell receptor doesn’t go deep into the cell thus cannot really promote signal transduction thus the TCR is surrounded by CD3 complex made up of:
- gamma
- delta
- 2 epsilon
- 2 Zeta (at bottom)

so in total there are 8 peptides making up the TCR complex (1 alpha, 1 beta, 1 gamma, 1 delta, 2 zeta, & 2 delta).

Question 5

What are the differences between TCR & BCR?

Answer 5

1- BCR has 2 antigen binding sites whereas TCR only has 1.

2- BCR can be secreted whereas TCR canNOT be secreted.

3- The antigen for TCR is always a linear epitopes made of amino acids which are 8-20 aa’s with MHC only. Whereas BCR can bind to linear epitopes just like TCR AND to 3D macromolecules like proteins, lipids, nucleic acids, and carbohydrates.

Question 6

Describe the antigen recognition between B-cells & T-cells.

Answer 6

B-cells:
Antigen binds to the BCR which activates the B-cells. Those start proliferating and differentiate into one of the following:
- Plasma cells to produce antibodies.
- Memory B-cells.
- IgG expressing B cells to promote isotype switching.

T-cells:
Recognize antigens bound to a specific self MHC protein expressed on the APC, this then activates T-cell which then causes clonal expansion and differentiation of T-cell into 1 of the following:
- Effector CD4+ cells
- Memory CD4+ cells (likewise CD8+ same exact thing).

Question 7

Difference between MHC-I & MHC-II (including their structures)?

Answer 7

MHC-I:
Expressed by all nucleated cells (so not RBCs). MHC-I are highly expressed in APCs. MHC-I are for CD8+ cells.
8*1

MHC-II:
Expressed by APCs only like:
- Dendritic cells
- Macrophages
- B cells

Their structures are different:
MHC-1 has 1 alpha chain which is divided into 3 subunits (a1, a2, & a3). It also has a B2-microglobulin. So in total it has 2 polypeptide chains.

MHC-II has 2 polypeptide chains: 1 alpha & 1 beta.

Question 8

Which MHC do CD4 & CD8 T-cells recognize?

Answer 8

CD4 T-cells recognize MHC-II

CD8 T-cells recognize MHC-I

42 = 8
81= 8
(That’s how u can remember it, both equal 8)

Question 9

What does MHC restriction mean?

Answer 9

MHC restriction means that a T-cell can interact with a self MHC molecule and a foreign antigen bound to it, BUT will only respond to the antigen when it is bound to a particular MHC molecule. self MHC must be correct.

Question 10

How is the MHC-II and antigen expressed on the surface of the APCs?

Answer 10

Let’s imagine we have a macrophage in the tissue & it just consumed a bacteria/virus & put it inside a phagosome. This phagosome fuses with lysosome and bacteria/virus will be killed and broken down into smaller pieces including small peptide fragments that can eventually be presented to T-cells for activation.
MHC class II will be synthesized in the cytosol of that macrophage but a molecule called the invariant chain will be placed on its surface in the ER which will block anything inside the cell from getting into the binding groove of MHC-II. This MHC-II then merges into the phagolysosome & the invariant chain is destroyed once inside & then the MHC-II can bind to some of these broken down proteins & can then go to the surface thus we have an APC with an MHC-II AND a peptide on its surface!

Question 11

What does primary & secondary lymphoid organ mean & do?

Answer 11

Primary lymphoid organs are the bone marrow & thymus. This is where the lymphocytes are made.

Secondary lymphoid organs are spleen, Peyer’s patches, lymph nodes, and mucosal tissue. This where the lymphocytes attack the pathogens.

Question 12

What are the main APCs?

Answer 12

Dendritic cells.

Question 13

What are the professional Antigen Presenting cells? What do they express?

Answer 13

• Dendritic cells are the main one.
• Macrophages.
• B-cells also act as APCs but for antibody class switching.

MHC-II are only expressed on APCs but MHC-I is expressed on both: nucleated cells including APCs.

ONLY ANTIGENS WHICH ARE PEPTIDES CAN BE PUT ON TOP OF TCR & RECOGNIZED.

Question 14

What is HLA gene?

Answer 14

HLA are a group of genes which govern the production of MHCs. HLA genes are located on the short arm of chromosome 6.

Genes coding for MHC-I:
HLA-A, HLA-B, & HLA-C.

Genes coding for MHC-II:
HLA-DP, HLA-DQ, & HLA-DR

Question 15

What are the genes coding for MHC-I & MHC-II?

Answer 15

Genes coding for MHC-I:
HLA-A, HLA-B, & HLA-C.

Genes coding for MHC-II:
HLA-DP, HLA-DQ, & HLA-DR

Question 16

What is the function of MHC-1 (i.e give a fact file profile of MHC-1)?

Answer 16

MHC-1 is expressed on all nucleated cells (So not on RBCs) and even APCs express them since they are nucleated. They express on their surface antigens from intracellular compartment. They present these antigens to CD8+ cytotoxic T-cell.
Genes coding for it are: HLA-A, HLA-B, & HLA-C.

Question 17

What is the function of MHC-II (i.e give a fact file profile of MHC-II)?

Answer 17

MHC-II are only expressed on professional APCs so like: dendritic cells, macrophages, & B-cells.
They process extracellular antigens so from vesicular compartment. They present them to CD4+ helper T-cells.
Genes coding for this: HLA-DR, HLA-DP, & HLA-DQ.

**HLA DM is intracellular only.

Question 18

How are antigens presented via MHC-II?

Answer 18

1- Extracellular antigen is taken up by the macrophage into a phagosome.

2- Phagosome fuses with lysosome to form a phagolysosome.

3- MHC-II is already being synthesized in the cytosol of the macrophage so it fuses with the phagolysosome.

4- Within this phagolysosome, the pathogen would’ve been broken into smaller pieces including peptides so once the MHC-II fuses her it will express peptide on its surface & go to the surface of macrophage to present this peptide antigen.

Question 19

What is HLA-DM?

Answer 19

Those are intracellular only - not found on cell surface.

When the MHC-II is being synthesized in the cytosol of the macrophage, an invariant chain forms a complex with this MHC-II to block the binding of peptides.

Function of HLA-DM:
Catalyze removal of CLIP & binding of peptides to MHC-II. It catalyzes the removal of unstably bound peptides via repetitive binding & rebinding to MHC-II this is called peptide binding.

Question 20

How does MHC-I express their antigens?

Answer 20

Intracellular antigen passes through proteasome which degrades unneeded or damaged proteins by proteolysis, then the peptides are transported to the ER where MHC-I is found then the peptide & MHC-I bind.

Question 21

How does MHC-I & MHC-II express their antigens?

Answer 21

Question 22

Talk about the immature dendritic cells.

Answer 22

Immature DC reach the tissue based on the chemokine gradient. Immature DC reside in the tissue & express PRRs where the PAMPs can bind to it and once they do: phagocytosis.