(I) Lecture 6: T cell Immunity Part I

Question 1

Where do T cells develop?

Answer 1

T cells start to develop in the bone marrow and finish developing in the Thymus

Question 2

Types of T-cells

Answer 2

Cytotoxic T lymphocyte (CTL, CD8+ cells)
- kill infected “target cells” and activate macrophages
- respond to MHC Class I

T helper lymphocyte (Th1, CD4+ cells)`
- activate macrophages, B cells and other cells, and increase response
- respond to MHC Class II

Question 3

APC

Answer 3

Antigen Presenting Cell
- ex. dendritic cells, macrophages and B cells

Question 4

T-cell differentiation

Answer 4

1. Antigen recognition (using APC cells)
2. Activation (of naive CD4+/CD8+ cells)
3. Clonal expansion (cytokines generate expansion)
4. Differentiation

Differentiate into effector CD4+ cells or memory CD4+ cells which differentiate into effectors
- same process for CD8+ cells

Question 5

T cell receptor

Answer 5

has an antigen binding site

each T-cell expresses a TCR with a variable region specific for ONE unique peptide (multiple receptors but all same specificity)

T-cells can only recognize/bind antigens of PROTEIN origin

Question 6

Antigen vs epitope

Answer 6

Antigen: protein
Epitope: peptide (smaller, exposed)

Question 7

T-cell antigen recognition

Answer 7

Epitopes recognized by TCRs are often buried

1. Antigen must first be broken down into peptide fragments
2. Epitope peptide binds to an MHC molecule
3. TCR binds to a complex of MHC and epitope peptide (must be perfect fit to antigen and MHC)`

Question 8

MHC Class I

Answer 8

• peptide comes from ENDOGENOUS sources (both self and not self)
• present to CD8+ T cells
• peptides are shorter than class II
• made up of one large glycoprotein heavy chain and a small protein light chain (ONLY ONE TRANSMEMBRANE DOMAIN)

Question 9

MHC Class II

Answer 9

• peptide comes from EXOGENOUS sources
• present to CD4+ T cells
• peptides are longer
• made up of two nonidentical membrane-bound glycoprotein chains (TWO TRANSMEMBRANE DOMAINS)

Question 10

MHC

Answer 10

Major Histocompatibility Complex

Question 11

MHC-TCR interactions

Answer 11

• antigenic epitopes MUST be associated w/ MHC molecules to be recognized by T cells
• need right peptide and right MHC to be recognized

Question 12

Co-receptors of T-cells

Answer 12

Mature CD4+ expresses co-receptor CD4
Mature CD8+ expresses co-receptor CD8

Co-receptors interact w/ MHC on the SIDE (NOT in the pocket)

Question 13

Superantigens

Answer 13

• bind w/ high affinity to MHC class II on APC (small amount of superantigen = intense T-cell signalling)
• cross-link to beta T-cell receptors
• crosslinking activates both T cell and APC (constant)
• since stimulation is not specific (will work even if peptide is the wrong fit), NO adaptive immunity
• causes excessive production of cytokines (CD4)

Question 14

Effect of superantigens on host

Answer 14

• systemic toxicity
• suppression of adaptive immune response

Question 15

Double Positive stage in T-cell development

Answer 15

The benefit of expressing both is that it can offer T cell options as T cells will not know whether its TCR will bind MHC I and MHC II. Once the T cell finds out which MHC it can bind to, it will keep only one (CD4 or CD8) on its surface.

Question 16

B and T cell development

Answer 16

In the bone marrow, they undergo random gene recombination to acquire a single specificity on the receptors in each B and T cell

Then, they will travel to secondary lymphatic tissues to detect pathogens.

Question 17

Example of superantigen

Answer 17

Toxic Shock Syndrome toxin-I from Staphylococcus aureus

Question 18

Menstrual Toxic Shock Syndrome

Answer 18

• vaginal culture will be positive for abundant S. aureus
• treated w/ IV fluids, anti-staphylococcal antibiotics, and IVIG (intravenous immunoglobulin)

Question 19

Targets of T-cells

Answer 19

main role is against INTRACELLULAR pathogens
- intracellular viruses
- intracellular bacteria (escape phagolysosome)

Question 20

T-cells and cytosolic pathogens

Answer 20

• degraded in cytosol
• peptides bind to MHC class I
• presented to CD8 T cells (cytotoxic)
• causes cell death

Question 21

T-cells and intravesicular pathogens

Answer 21

• degraded in endocytic vesicles (low pH)
• peptides bind to MHC class II
• presented to CD4 T cells (helper cells)
• cause activation of macrophages to kill intravesicular bacteria and parasites

Question 22

How do MHCs work?

Answer 22

• endogenous antigens are degraded by the proteasome into smaller peptides (MHC class I)
• exogenous antigens are engulfed into endocytic compartments and degraded by endosomal and lysosomal enzymes (MHC class II)
• antigenic peptides associate w/ MHC class I or II
• MHC-peptide complexes are then transported to the cell membrane

Question 23

Where is MHC class I expressed?

Answer 23

Expression is found THROUGHOUT the body
- allows ongoing surveillance of internal happenings of the cell

Question 24

Where is MHC class II expressed?

Answer 24

Expression is primarily restricted to antigen-presenting cells

• ONLY specialized leukocytes have this ability

Question 25

What cells express MHC I?

Answer 25

- All nucleated cells express MHC I (dendritic and somatic) - Many unique peptides are presented at same time - not only foreign antigens are loaded, also self-peptides

Question 26

MHC Class I action on cytosolic pathogens

Answer 26

1. Virus infects cell 2. Viral proteins synthesized in cytosol 3. Peptide fragments of viral proteins bound by MHC class I in ER 4. Bound peptides transported by MHC class I to cell surface

Question 27

MHC Class II action on intravesicular pathogens

Answer 27

ONLY APCs can engulf extracellular pathogens and load their antigenic epitopes on MHC class II - since they are nucleated cells, APCs can present antigens that come from intracellular locations on MHC class I as well

Question 28

Memory T cells

Answer 28

Bulk of surviving pathogen-specific cells are memory cells Most effector T cells have short half-lives (only 5-10% remain after pathogen is cleared) % of circulating T cells that are memory cells increase as a person ages - b/c they have been exposed to more pathogens and thymus shrinks, making less T cells

Question 29

True or False Antigenic epitopes recognized by T cells must be associated with MHC molecules to be recognized

Answer 29

True

Question 30

True or False All nucleated cells express MHC molecules

Answer 30

False ONLY APC cells express MHC II

Question 31

True or False A single T cell can express multiple TCRs on its surface. All of these TCRs have different specificities

Answer 31

False A single T cell can express multiple TCRs on its surface. All of these TCRs have the same specificity