Adaptive immunity T cells Flashcards
LO
- Distinguish CD8 and CD4 T cell subsets based on their receptors and functions
- Explain how T cells identify infected cells, pathogens and foreign cells
- Describe how a T cells eliminate viruses and tumour cells
- Distinguish between a CD4 and CD8 T cell response
- Explain how self-reactive T cells are eliminated
Compare innate V adaptive immunity
- response?
- Targets?
- Diversity?
- Memory?
Tell me the steps to how the immune system works?
- You have to identify the pathogen
The immune system uses many receptors to do this
- A decision needs to be made to attack
The attack is planned from tissues like the spleen and the lymph node
- You need a coordinated approach
Cells need to communicate with each other
- You need an army or soldiers to launch the attack
What type of immunity do T cells have?
They have cell-mediated immunity
Tell me about T cells, what do they kill and what do they provide?
- Kill cells infected with pathogens, eg viruses or bacteria
- Provide ‘help’ to B cells
- kill tumour cells
Where do T cells arise and mature?
They arise in the bone marrow but mature in the thymus
Do they produce antibodies? Tell me about this
They do not produce antibody moleucles, but they have surface receptors called T cells receptors (TCR)
What do T cells recognise and how do they do this?
T cells recognize infected and malignant cells through MHC molecules on antigen presenting cells (APCs)
T cells can identify viruses “hiding” in cells, tell me how they do this
Healthy cells have ‘self-antigens’ on the surface of their membranes. They let T-cells know that they are not intruders. If a cell is infected with a virus, it has pieces of virus antigens on its surface. This is a signal for the Killer T-cell that lets it know this is a cell that must be destroyed.
Tell me the most abundant to the least abundant immune cells in the blood (periphery)
When a naive T cells is exposed to antigens, what can it then differentiate into?
Tell me the properties of CD4+ and CD8+ T cells…
Surface molecules?
Secreted molecules?
Functions?
Perforin and granzyme are the killing molecules in CD8+
How do T cells recognise an infected cell?
- The TCR allows T cells to recognise infected cells
- Heterodimer composed of α, β chains
- Each chain has two domains,one variable and one constant domain
Tell me what the TCR is composed of and its associations
- Heterodimer composed of α, β, chains
- The TCR associates with CD3 molecules
- CD3 allows a signal to be fed into the cell
Tell me about the structure of the TCR
- Complementarity Determining Regions (CDRs) - Where the TCR contacts the antigen
- There are three CDRs in the TCR variable domain
Why do T cell receptors need to be very diverse?
because theres such a diversity of pathogens
How do T cells generate diversity to recogise many pathogens?
- Answer lies in VDJ recombination
- There are many genes that make up the TCR locus
- These genes rearrange to make many receptors
VDJ recombination at the alpha locus
VDJ recombination at the beta locus, tell me about this
- Recombination takes place at: Recombination Signal Sequences (RSS)
- Catalyzed by enzymes known as collectively as VDJ recombinase
- The most important are RAG1 and RAG2
- These genes are expressed specifically in lymphocytes
Tell me how VDJ recombination generate diversity in different ways?
Combinational diversity:
From the different combinations of gene segments
Junctional diversity:
From the addition of nucleotides when recombination occurs
Tell me how VDJ recombination occurs at signal sequences?
The most variable region is where the D and J gene segments join, tell me why this is the case?
- This is due to junctional diversity – where extra nucleotides are added when the DNA segments join
- This segment corresponds to the CDR3 loop of the TCR
The body can produce T cell receptors specific for millions of patterns
What does the TCR interact with to detect pathogens?
MHC molecules
MHC molecules present antigenic peptides to T cells
Tell me about the length of peptides that bind in the MHC cleft?
Where do MHC molecules come from?
The peptides presented by MHC class I and class II molecules can be from:
- Self-proteins
- Viral or bacterial proteins
MHC genes are highly polymorphic, tell me about this
- A gene is said to be polymorphic if more than one allele occupies that gene’s locus within a population
- The genes that code for MHC molecules have a lot of genetic diversity within a population
- Many different pathogenic peptides will be bound by MHC molecules
Example of APCs
identify the APCs
Why can’t we fight all infections?
They evolve, we evolve
Tell me about how naïve T cells are activated against a pathogen
What two responses are T helper cells important for?
both humoral and cell mediated responses
T cells require co-stimulation, tell me the 2 signal needed for this two-signal model
- MHC and TCR
- 7.1/B7.2 and CD28
Tell me clonal expansion?
Produces many T cells with T cell receptors specific for a specific MHC/peptide complex
Tell me the T cell weapons and how each of them kills pathogenic cells
Where does T cell development occur in?
The thymus
As T cells develop in the thymus, they progress through different stages. explain these stages and what type of T cells are present in each
Thymic selection
Why are some T cells able to survive both positive and negative T cell selection?
The specificity and avidity of positive and negative selection are different
This allows some T cells to survive both processes
