T cell activation and generation of effector T cells Flashcards
What is humoral immunity mediated by?
Mediated by B lymphocytes and the antibodies they produce
What does humoral immunity target and why?
Target extracellular microbes because they’re located on the surface of the cell
What is cellular immunity mediated by?
Mediated by T lymphocytes
What does cellular immunity target?
Target intracellular microbes/pathogens which have found their way in
What do B and T lymphocyte circulate between once they mature and to find what?
Once B and T lymphocyte mature, they circulate between peripheral lymphoid organs and blood to find their antigens
Life stages of T lymphocytes
- T lymphocytes are generated in the bone marrow and undergo maturation in thymus
- Mature naïve T cells are released from thymus into blood
- Recirculate between blood and lymphoid organs
- If they encounter antigens that they recognise it leads to lymphocyte activation, proliferation and differentiation into effector and memory cells
What is the main purpose of T cells and what does this include?
• Main purpose is to defend against intracellular microbes including:
○ Intracellular bacteria in phagosomes of phagocytes
○ Viruses free in cytoplasm of cells
○ Mutated proteins from cancer cells
When do T cells only recognise antigens after?
•T cells only recognise antigens after processing and presentation
What do most T cells have?
Most T cells have alpha-beta TCR
What do T cells only recognise and when bound to what?
• T cells only recognise peptides from foreign antigens when bound to MHC molecules
What does TCR consist of and what does each one have?
• TCR consists of 2 chains, each one has 1 variable domain and 1 constant domain
What is antigen binding to TCR formed by?
Antigen binding is formed by the combination of the variable domain from each chain
What do MHC molecules bind and display from what and for recognition by what?
• MHC molecules bind and display peptides from antigens for recognition by TCR
How many types of MHC are their and what are they?
○ MHC I
○ MHC II
What do MHC I present on what and what are they composed of?
MHC I presents peptides on CD8 T cells which are composed of alpha and beta2 microglobulin
What are MHC I expressed on?
• MHC I expressed on all nucleated cells
What do MHC II present peptides to and what are they composed of?
• MHC II presents peptides to CD4 T cells which are composed of alpha and beta chain
What are MHC II expressed on?
• MHC II expressed on APCs, mainly macrophages and dendritic cells
What are antigen presenting cells?
• Are cells that specialise in the capture and presentation of antigen to CD4 T cells
What do professional APCs include?
- Dendritic cells
- Macrophages
What are dendritic cells the only type of APCs to activate?
○ Dendritic cells are the only APCs that can activate naïve T cells
What do macrophages present to?
○ Macrophages present to previously activated effector T cells
Where are dendritic cells found?
Dendritic cells are found in the skin, mucosa and tissues
What are langerhan cells?
Langerhans cells are dendritic cells in the skin
What do dendritic cells capture and how does it process?
• They capture microbes process them into antigens and transport them to draining lymph nodes where they present to and activate naïve T cells
What must dendritic cells undergo and what are they?
• Dendritic cells must undergo three stages to result in T cell activation:
1. Antigen recognition
i. T cell activation
2. Co stimulation
i. T cell activation
3. Cytokines
i. Type of effector T cell
What happens if there’s no co-stimulation to T cells?
• Without co-stimulation, it will result in the lack of T cell response or anergy of T cell
What is co-stimulation more critical for?
• Co-stimulation is more critical for naïve T cells than previously activated effector/memory T cells
What do APCs exposed to infection increase expression of?
APCs exposed to infection, increase the expression of co-stimulatory molecules and MHC which increases the antigen presenting functions of APCs
What do cytokines regulate the differentiation of?
Cytokines regulate the differentiation of activated T cells into the right type of effector T cells
What do macrophages do?
• Phagocytose microbes
What do macrophages present and to what?
• Present antigens to effector CD4 T cells
What do macrophages activate?
Activate effector Th1 which in turn activate mechanisms within the macrophage to kill ingested microbes
What can all nucleated cells get infected with and what do they present to CD8 T cells?
All nucleated cells can get infected by viruses and present peptides from their cytosol, to CD8 T cells
What do CD8 T cells specialise in?
• CD8 T cells specialise in:
○ Recognising viral antigens and mutated proteins
○ Eliminating cells infected by viruses/malignant cells
Steps involved in antigen processing and presentation to CD8+ T cells
○ Virus can infect any cell and produce cytosolic antigen proteins within the cells
§ This causes cells to develop proteasomes
○ Proteasomes takes up viral protein and breaks it down into peptides
○ Peptides are recruited to lumen of ER by TAP
○ In the ER, there is also the generation of MHC-I with a free peptide groove which binds to a peptide that fits in its groove
○ MHC-I/peptide complex travels to the Golgi where it is transported out using an exocytic vesicle which fuses with plasma membrane and is presented
○ Recognised by CD8 T cells
What do CD4 T cell effectors help macrophages and B cells with?
• CD4 T cell effectors help macrophages and B cells eliminate extracellular bacteria
Steps involved in antigen processing pathway to CD4+ T cells
○ Bacteria taken up into endosome which fuse with lysosome to produce endo-lysosome where it is cleaved into peptides
○ At same time, MHC-II is synthesised in ER and MHC-II unstable if there is a lack of
peptide in its groove. This will cause degradation so needs to be conjugated with
invariable chain so it fills the groove to prevent breakdown
○ MHC-II/invariable chain complex leaves ER, travels to Golgi and is transported out
using an exocytic vesicle
○ Whilst exocytic vesicle is travelling to the membrane, it encounters and fuses with
the endo-lysosome
○ Lysozymes in the endo-lysosome cause the pH to be low and invariable chain is broken down and only small fragment remains = CLIP
○ This compartment also expresses HLA-DM (another MHC-II molecule) = not involved in antigen presentation but has a high affinity for CLIP
○ CLIP can now be removed from the MHC-II and it can bind to a peptide from the
endo-phagosome, that fits in its groove
○ MHC-II is now stabilised and leaves in a vesicle, fuses with plasma membrane and is
presented and can be recognised by CD4 T cells
Different type of effector T cells
- T helper cells
- Cytotoxic T lymphocytes
- Cytotoxic T lymphocytes
- Regulatory T cells
What induces differentiation into Th1?
○ IL-12 and IFN-gamma are released by APCs to induce differentiation into Th1
What does Th1 help?
○ Help phagocytes to kill ingested microbes which causes increased destruction of intracellular pathogens
What does Th1 stimulate?
Also stimulates the production of IgG antibodies which increases phagocytosis of microbes and activate complement
What induces differentiation into Th2?
○ IL-4, IL-25, IL-33 released by APCs/cells infected with helminths to induce
differentiation into Th2
What cytokines does Th2 produce?
○ Th2 then produce the cytokines IL-4, IL-5 and IL-13
What do Th2 work with to produce and what does this play a role in?
○ Work with B cells to produce IgE which plays a role in allergic reactions/asthma and activating eosinophils/mast cells to kill parasites
What does Th17 play a role in?
○ Role in defence against bacteria and fungi
What does Tfh help B cells undergo?
○ Help B cells undergo class switching and affinity maturation
What do cytotoxic T lymphocytes kill?
Kill cells infected by microbes that grow free in the cytosol
What do effector CD8 T cells leave via and migrate to in order to perform their effector functions?
• Effector CD8 T cells leave PLO via blood and migrate to site of antigen entry to
perform their effector functions and eliminate antigen
