Adaptive Immune System (T Cells) Flashcards
Describe the lymphoid progenitor cell.
It gives rise to lymphocytes.
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).
Describe the role of the thymus in T-cell development.
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 at puberty.
List and describe the four T-cell subsets.
- αβ T-cells (helper T-cells) (express CD4 and CD3):
• activated to secrete cytokines to help immune responses, or become memory cells
• two 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)
• two types: natural or inducible - γδ T-cells:
• T-cell receptor (TCR) formed of the γδ chain recognise lipid antigens
Describe the T-cell receptor (TCR).
It is a dimeric molecule made up of either αβ or γδ chains linked by disulphide links.
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).
Describe the Major Histocompatibility Complex (MHC).
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 .
What are the steps for antigen processing and presentation to CD4 cells?
There is first uptake of the pathogen into a phagosome, which fuses with a lysosome to form a phagolyososome. The proteins are chopped up and peptides generated from the bacteria These vesicles containing the bacterial peptides travelaround until they meet vesicles containing MHC molecules. The
MHC is generated in the ER (alpha and beta chains) and then assembled, MHC II always needs to contain some peptide or the chains come apart. In the ER there is a protein called the invariant chain which sits in the groove between the chain and stabilises it.
MHC II is transported in exocytic vesicles to the membrane, if the cell contains bacterial peptides in vesicles, the two will usually meet and if the peptide fits well into MHC II, then the pathogen peptide displaces the invariant chain and sits in the groove.
This peptide-MHC complex is then presented on the cell surface.
What are the steps for antigen processing and presentation to CD8 cells?
This cell doesn’t need to be an antigen-presenting cell, but it does have to have a nucleus. If virus enters the cell, it will be free in the cytosol. The virus will start to replicate their viral proteins, so these viral proteins will be in the cytosol. The viral proteins undergo ubiquination/gets ubiquinated (get tagged with a polymer of 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.
List some antigen-presenting cells.
- dendritic cells
- tissue specific dendritic cells
- macrophages
- B-cells
- endothelial cells under some conditions
What happens to T-cells in the thymus?
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’).
Describe CD4 T cells.
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
Describe CD4+ Th1 cells.
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.
Describe CD4+ Th2 cells.
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.
Describe CD4+ Th17 cells.
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.
Describe CD4+ Treg cells.
They express the co-receptor CD4, CD25 and FoxP3.
They maintain immune tolerance and suppress immune responses. They produce anti-inflammatory cytokines IL10 and TGFβ. They also have a contact-dependant immunosuppressive effect.
Tregs inhibit the effector functions of CD4+ and CD8+ T-cells. Also, they inhibit the antigen presentation function of B-cells and other antigen-presenting cells.
Describe CD8+ cytotoxic T-cells (CTL).
They express the co-receptor CD8. They eliminate intracellular functions. They produce IL2, TNFα and γIFN. They also have a role in anti-tumour immunity and rejection of transplants.
They kill infected cells in an antigen-specific and cell-contact dependent manner.
