Initiation of Acquired Immune Response - T cells Flashcards
What type of antigens to T cells recognise?
Peptide antigens
What do T cells express?
Single antigen receptor - T cell receptor (TCR)
How do T cells have specificity?
There is a hypervariable tip of the TCR which is involved in binding to a specific antigen
How do T cells recognise peptide antigens?
The antigen needs to be processed and presented to the TCR with Major Histocompatibility Complex (MHC) molecules
What is another name for MHC?
Human Leucocyte Antigens (HLA)
What is the role of MHC?
To display peptide antigens to T cells
What are the features of Class I MHC?
Expressed on all nucleated cells and present antigens to CD8+ T cells
What are the features of Class II MHC?
Only expressed on professional Antigen Presenting Cells (APC) - dendritic cells, macrophages and B cells. Present peptide antigen to CD4+ T cells
What is the role of dendritic cells?
The bridge between the innate and acquired immune system - main function is to process and present antigens on the cell surface to T cells (APCs). Also phagocytic cells
How do dendritic cells fight infection and inflammation?
- Particles and antigens derived from pathogens are released by phagocytes
- Dendritic cells phagocytose pathogen-derived particles and antigens
- Pro-inflammatory TNFa stimulates immature tissue-resident DC to increase expression of co-stimulatory molecules
- DCs digest ingested proteins and display small peptides derived from these on their cell surface = complex for MHC
What is a naive T cell?
A T cell that has never seen an antigen
What is the intermediate between naive T cells and effector T helper cells?
T helper 0
What are 4 main type of effector T cells?
Th1, Th2, Tfh and regulatory T cells (fh=follicular helper)
What do antigen-activated CD4+ T cells secrete?
A T cell growth factor, Interleukin 2 (IL-2) for autocrine-mediated cell proliferation
What is the role of Th0?
Induce autocrina-/paracrine mediated proliferation of CD4+ and CD8+ cells as they produce lots of IL-2
What is IL-2 used by?
Antigen activated CD4+ T cells and CD8+ T cells to allow them to proliferate and differentiate
What happens when Th1 cells migrate out of the lymph nodes and enter sites of inflammation/infection?
Re-activated by the infected, tissue-resident macrophages (antigen specific) - infected macrophages express bacterial peptide antigens on their cell surface (with MHC II). The Th1 cells secrete pro-inflammatory cytokines, which enhances macrophage-mediated killing of internal pathogens = production of reactive oxygen species
How can some pathogens evade phagolysomal killing by macrophages?
Infect and propagate in macrophages by escaping the phagosome.
How do macrophages prevent pathogenic evasion?
Macrophages that respond to Th1 signals become super killers (like neutrophils)
Where are effector Tfh cells re-stimulated by B cells?
In the B cell zone of the lymph node (antigen specific)
What does the re-stimulated effector Tfh cell do?
Stimulate B cells to clonal proliferate and differentiate into a) long-lived plasma cells which secrete high affinity antigen-specific antibodies - IgM to IgG (in Germinal Centre reaction) OR b) long-lived memory B cells (Bm cells)
How are cytotoxic T lymphocytes (CTLs) produced?
Antigen-activated CD8+ cells proliferate and differentiate
What do CTLs do?
Migrate out of the lymph node and enter sites of infection to kill virally infected host cells
How do CD8+ proliferate and differentiate into CTLs?
CD4+ cells differentiate in different Th cells that provide IL-2 to promote the proliferation and differentiation
How do CTLs kill infected host cells?
- CTL recognises and binds to virally infected cell
- CTL programs target death inducing DNA fragmentation
- CTL migrates to new target
- Target cell dies by apoptosis
How do CTLs recognise virally infected cells?
As all nucleated cells express MHC-I on their surface when the cell becomes infected, it presents viral-peptides