T Cell Activation & Generation of Effector T Cells Flashcards
What are the two types of adaptive immune responses?
There are two types of adaptive immune responses.
The first is mediated by B lymphocytes which produce antibodies. They are part of humoral immunity and deal with extracellular microbes.
The second is mediated by T lymphocytes (of which there are multiple types). They are part of cellular immunity and deal with intracellular microbes.
Describe the life stages of T lymphocytes.
- they’re generated in bone marrow and undergo maturation in thymus
- mature naïve T cells are released from the thymus into the blood
- they recirculate between the blood and peripheral lymphoid organs (lymph nodes, spleen, MALT)
- if they encounter antigens that they recognise, leads to lymphocyte activation, proliferation & differentiation into effector/memory cells
Effector T cells: specialised functions
Memory T cells: memory responses (faster, more efficient)
What types of intracellular microbes, etc. do T cells respond to?
T cells are 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)
What do TCRs recognise?
T cells do not recognise antigens directly, they only recognise them after processing and presentation.
Most T cells (αβ TCR T cells) recognise peptides.
=> T cells recognise cell-bound Ags (peptides)
=> peptides from foreign Ags only when bound to major histocompatibility complex (MHC) molecules
Describe the structure of the TCR.
T cells recognise antigens via their T cell receptor (TCR).
- it has a similar structure to B cell antigen receptor (BCR)
- it’s made up of 2 chains: α and β (most common TCR type) - the other is γ and δ (the TCR in γδ T cells)
- each chain has 1 variable (V) domain and 1 constant (C) domain (the antigen binding site formed by the two variable domains Vα + Vβ)
- the V and C domains of TCRs and BCRs are homologous
Describe MHCs.
MHC (major histocompatibility complex) molecules display peptides from processed Ag. There are two types: MHC I and MHC II.
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
MHC I presents on all nucleated cells, and MHC II presents on APCs.
Describe APCs.
APCs are antigen presenting cells.
They are cells that specialise in the capture, processing and presentation of antigens (Ag) to CD4+ T cells.
Professional APCs:
- dendritic cells => the only APCs capable to present to naïve T cells
- macrophages => present to previously activated effector T cells
Describe how and to whom the dendritic cells and macrophages present antigens to.
Dendritic cells will uptake the antigen, process and present it to naïve T cells. This activates them and induces them to become effector T cells.
Macrophages uptake the antigen (via phagocytosis) and present them to previously activated T effector cells to warrant an increased immune response.
Describe dendritic cells.
They are located in nearly all tissues that we have. Together, they form a mesh or network so that they can scan for pathogens, detect the, take them up, process them and present them to T cells to activate them (if needed).
Dendritic cells in the skin are called Langerhans cells.
Describe the three signals needed for naïve T cell activation.
The first signal is TCR recognition of the antigen presented by the MHC. However, this alone is not enough to activate a naïve T cell.
It needs a second signal called co-stimulation, which is delivered by the ligation of C28 with the co-stimulatory molecules on the APC, CD80/CD86.
The third signal is by the cytokines produced by the dendritic cells. These cytokines will specifically determine which type of helper cell the T cell differentiated into, based on the type of antigen.
Describe Signal 1 in T cell activation.
Naïve T cells need signals in addition to Ag to get activated
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
Describe Signal 2 in T cell activation.
SIGNAL 2: co-stimulation:
- it is the binding of co-stimulatory molecules (B7 family, e.g. CD80/CD86) on APC by co-stimulatory receptor (CD28) on the T cell
- together with signal 1, it leads to activation of naïve T cells
- this is more important for naïve T cells than for restimulation of previously activated effector or memory T cells
- APCs exposed to infection increase the expression of co-stimulatory molecules (B7) and of MHC
Describe Signal 3 in T cell activation.
SIGNAL 3: cytokines produced by APCs (after infection):
=> 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
List some functions of macrophages.
=> they phagocytose microbes (e.g. Mycobacteria tuberculosis)
=> they are involved in Ag presentation to effector CD4+ T cells (Th1)
=> they induce the activation of Th1 cells (see later slides)
=> Th1 cells activate macrophage to kill ingested microbes
What are CD8+ T cells specialised to do?
All nucleated cells can present peptides derived from proteins from antigens present in the cytosol to CD8+ T cells.
- all nucleated cells can get infected by viruses
- all nucleated cells can get cancer-causing mutations
Thus, CD8+ cells are specialised to:
- recognise viral antigens and mutated proteins
- eliminate cells infected by viruses/malignant cells
