Adaptive immune system - T cells Flashcards
1
Q
What cells do the myeloid and lymphoid progenitor give rise to?
A
2
Q
Describe the lymphoid progenitor cell.
A
- It gives rise to lymphocytes.
- It comprise of 20-30% of the peripheral WBCs.
- They are 6-10um in diameter with a large nucleus and a small halo of cytoplasm.
- Upon activation by antigens, they become effector cells or memory cells.
- There are two main types: T-cells and B-cells (T-lymphocytes and B-lymphocytes).
- In the early developmental stage, cells can either pass to the thymus (and become T-cells) or stay in the bone marrow (and become B-cells).
3
Q
Describe the role of the thymus in T-cell development.
A
- T-cells mature in the thymus.
- Immature T-cells develop in the bone marrow then migrate to the thymus to encounter self-antigens.
- During this process, many T-cells die by apoptosis, leaving just those that can generate a useful response to infection.
- The thymus enlarges during childhood, then atrophies (decreases in size) at puberty.
4
Q
List and describe the four T-cell subsets.
A
- αβ T-cells (helper T-cells) (express CD4 and CD3):
- Activated to secrete cytokines to help immune responses, or become memory cells.
- 2 main subgroups: TH1 and TH2 (also Th17).
- Cytotoxic T-cells (express CD8 and CD3):
- Activated to kill infected targets, or to become memory cells.
- Usually cytotoxic in nature and kill via the release of the toxic contents of granules, or induction of apoptosis.
- Regulatory T-cells:
- Mainly CD4+ (some CD8+) cells able to affect immune responses by either suppressing them or activating them through direct cell contact or by the secretion of soluble factors (cytokines).
- 2 types: natural or inducible.
- γδ T-cells:
* T-cell receptor (TCR) formed of the γδ chain recognise lipid antigens.
5
Q
Describe the T-cell receptor (TCR).
A
- It is a dimeric molecule made up of either αβ or γδ chains linked by disulphide links (S-S).
- Each chain has a variable and a constant Ig like domain.
- The variable region has hypervariable regions which are antigen binding sites.
- It’s associated with the signalling complex CD3 (CD3 is the identifier of the T-cell).
6
Q
Alpha beta VS gamma delta
A
7
Q
Describe the Major Histocompatibility Complex (MHC).
A
- It’s present on T-cells; it’s a surface-expressed molecule which binds peptides derived from antigens.
- MHC encodes for human leukocyte antigens (HLA).
- There are two types of MHCs:
- MHC Class I (HLA-A,B and C), expressed on all nucleated cells.
- MHC Class II (HLA-D), expressed on ‘professional’ antigen-presenting cells (dendritic cells and macrophages).
- MHC I is made of an α chain and β2-microglobulin; it is recognised by CD8+ T cells.
- MHC II is made of an α chain and β chain; it is recognised by CD4+ T cells .
8
Q
What are the steps for antigen processing and presentation to CD4 cells?
A
- There is uptake of the pathogens antigen into a vesicle of an antigen presenting cell. The vesicle fuses with a lysosome.
- Within the vesicle the protein is broken down into small peptides.
- At the same time a MHC molecue is generated in the ER.
- A chaperon is a moolecule that makes sure something gets to the right place.
- In order to stop the MHC molecule from binding a peptide in the wroing place, it binds a particular molecule called invariant chain (li) into the binding cleft if the molecule. (So nothing can bind to the molecule if the invariant chain is bound to it).
- The invariant chain bound class II molecule then forms a exoctyic vesicle which fuses with a lysosome and will allow the peptide to bind to the MHC class II molecule.
- To do this a molecule called HLA - DM takes away the CLIP (class II associated invariant peptide) part of the invariant chain.
- This allows a peptide to bind to the MHC class II molecule.
- The peptide-MHC complex is presented on the surface of the cell allowing a CD4+ helper T cell to recognise it.
9
Q
What are the steps for antigen processing and presentation to CD8 cells?
A
- If there is a virus in the cytoplasm the cell will coat the virus in protein called ubiquitin.
- This targets it to be degraded by a proteasome, which chops up the viral protein into peptides which enter into the cytosol.
- The peptides get transported into the ER and get chopped up to even smaller pieces, where they fit the shape of the groove in the MHC I molecule.
- The MHC I – viral peptide molecule is then transported to the membrane and presented on the surface where it can be recognized by CD8+ T cells.
10
Q
List some antigen-presenting cells.
A
- dendritic cells
- tissue specific dendritic cells
- macrophages
- B-cells
- endothelial cells under some conditions
11
Q
What happens to T-cells in the thymus?
A
- T-cells in the thymus enter as thymocytes, not expressing either CD4 nor CD8 (double negative), go through a stage of expressing both (double positive), followed by a decision to be either CD4+ or CD8+.
- They are positively selected to bind to molecules called MHC, and negatively selected if they bind self-peptides (‘education’).
12
Q
Describe CD4 T cells.
A
- They recognise a peptide in the binding groove of MHCII.
- T helped cells: produce a cytokine profile which directs the immune response to a certain outcome.
- T-regulatory cells: responsible for ending an immune response.
13
Q
Describe CD4+ Th1 cells.
A
- They express the co-receptor CD4.
- They help to activate the cellular immune response (it activates macrophages and cytotoxic T-cells).
- It produces the γ-interferon.
- Th1 responses are effective against intracellular infections, bacterial, protozoal and viral.
- Th1 and Th2 are mutually antagonistic.
14
Q
Describe CD4+ Th2 cells.
A
- They express the co-receptor CD4.
- They help to activate the humoural immune response.
- They produce interleukin 4, 5 and 13.
- They activate B-cells to produce antibodies.
- Th2 responses are effective against extracellular cellular infections, bacterial, protozoal and viral.
- They’re effective in IgE production against helminth (worm) infections.
- Th1 and Th2 are mutually antagonistic.
15
Q
Describe CD4+ Th17 cells.
A
- It expresses the co-receptor CD4.
- They help to protect gut mucosa.
- They produce interleukin 17 and 22.
- It recruits neutrophils to sites of infection.
- Th17 responses are effective against extracellular bacteria and fungi.
- It’s effective in promoting neutrophil-mediated inflammation and helping Th1 cells to induce phagocytosis and subsequent killing of pathogens.
