T Cell Activation & Generation of Effector T Cells Flashcards
(46 cards)
The life stages of T lymphocytes
Generated in bone marrow => undergo maturation in thymus
Mature naïve T cells released from thymus into the blood
Recirculate between blood and peripheral lymphoid organs (lymph nodes, spleen, MALT)
If they encounter antigens that they recognise => lymphocyte activation, proliferation & differentiation into effector/memory cells
Effector T cells => specialised functions
Memory T cells => memory responses (faster, ⇧efficient)
T cell role
Designed to fight intracellular microbes:
- intracellular bacteria in phagosomes of phagocytes
- viruses: free in cytoplasm of cells (phagocytes or non-phagocytes e.g. epithelial cells)
- cancer cells (mutated proteins from cancer cells)
When do T cells recognise antigens
T cells: do not recognise antigens directly
T cells: recognise antigens only after processing and presentation
Most T cells (αβ TCR T cells) recognise what
=> T cells recognise cell-bound Ags (peptides)
=> peptides from foreign Ags only when bound to major histocompatibility complex (MHC) molecules
Other subsets of T cells recognise what
Other subsets of T cells (γδ T cells recognise antigens that are not peptides
Describe structure of T cell receptor
=> 2 chains: α and β (most common TCR type)
γ and δ (TCR in γδ T cells)
- each chain: 1 variable (V) domain + 1 constant (C) domain
Antigen binding site formed by: Vα + Vβ
- V and C domains of TCR and BCR are homologous
MHC molecules display peptides from processed Ag - compare types
MHC I: presentation of peptides to CD8+ T cells
composed of α chain + β2-microglobulin
MHC II: presentation of peptides to CD4+ T cells
composed of α chain + β chain
γδ T cells recognise antigens that are what
γδ T cells recognise antigens that are not displayed by MHC I and MHC II (are not MHC restricted)
Expression of MHC molecules - compare types
MHC I: all nucleated cells
MHC II: antigen presenting cells: dendritic cells
macrophages
Human MHC molecules = HLA (human leucocyte Ags) - list all with MHC I/II
MHC I: e.g. HLA-A, HLA-B, HLA-C
MHC II: e.g. HLA-DP, HLA-DQ, HLA-DR
Antigen presenting cells (APC) - define
Cells that specialise in the capture and presentation of antigens (Ag) to CD4+ T cells
Professional APCs - give examples and describe roles
Dendritic cells => the only APCs capable to present to naïve T cells
Macrophages => present to previously activated effector T cells
CD8+ T cells - function
CD8+ T cells recognise Ags displayed by nucleated cells (not just APC but also cells that are not APCs)
Dendritic cells - distribution + function
skin, mucosa, tissues
capture microbes
transport microbes from tissues (e.g. epithelia) to draining lymph nodes
process microbes =>Ags
present Ags to naïve T cells
activate naïve T cells
Critical in the initiation (priming) of T cell responses
Naïve T cells need what for activation
Naïve T cells need signals in addition to Ag to get activated
Explain importance for combination of signals 1 and 2
Signal 1: recognition of Ag (peptide:MHC complex) on APC
=> not sufficient to induce T cell activation
=> without signal 2 => no response or anergy of T cell
Signal 2: co-stimulation - describe
=> binding of co-stimulatory molecules (B7 family, e.g. CD80/CD86) on APC by co-stimulatory receptor (CD28) on T cell
=> together with signal 1 => activation of naïve T cells
Signal 2: co-stimulation - effect on APCs
=> APCs exposed to infection increase the expression of co-stimulatory molecules (B7) and of MHC
Infection increases the antigen presenting function of APCs
Signal 3: cytokines produced by APCs (after infection) - functions
=> regulate the differentiation of activated T cells into different types of effector T cells
e. g. IL-12 and IFN-γ from APC => differentiation into Th1
e. g. IL-4 from APC => differentiation into Th2
=> ensure the right type of effector T cell is generated
e.g. effector T cell type that is most suited to respond to the infection that triggered the response
Th1 <=> macrophage co-operation
Th2 <=> B cell and eosinophils / mast cell co-operation
Macrophages - functions
Macrophages
=> phagocytose microbes (e.g. Mycobacteria tuberculosis)
=> Ag presentation to effector CD4+ T cells (Th1)
=> activation of Th1 cells (see later slides)
=> Th1 cells activate macrophage to kill ingested microbes
Antigen presentation to CD8+ T cells - which cells can do this
All nucleated cells can present peptides derived from proteins from antigens present in the cytosol to CD8+ T cells
Nucleated cells can be affected by what
=> all nucleated cells can get infected by viruses
=> all nucleated cells can get cancer-causing mutations
=> CD8+ T cells (cytotoxic T cells, CTLs) specialised to:
- recognise viral antigens and mutated proteins
- eliminate cells infected by viruses/malignant cells
Exogenous Ags - describe processing
Exogenous Ags (e.g. bacteria) taken up in cells, processed and presented by MHC II to CD4+ T cells
Exogenous pathogens (bacteria that grow outside cells)
=> taken up by phagocytes
=> eliminated via killing in phagocytes
=> eliminated by antibodies (via neutralisation, opsonisation and complement activation)
