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
Tell me about MHC?
- MHC = Major Histocompatibility Complex
- MHC molecules bind to proteins from viruses and bacteria and present them to T cells
- They also bind to self-peptides from the cell
- This is called Antigen Presentation
- The TCR interacts with MHC molecules to detect pathogens
MHC molecules present antigenic peptides to T cells
How many classes of MHC are there?
Class I and class II
Tell me about Class I MHC
Class I MHC
- Found on most nucleated cells
- Present endogenous antigens (intracellular, internal)
- Display self-proteins, virus proteins, intracellular pathogens
- Present antigen to cytotoxic T cells (CD8)
Tell me about Class II MHC
Class II MHC
- Found primarily on Antigen presenting cells (APCs)- they are much more specific
- Present exogenous antigens (extracellular, external)
- Phagocytosis, receptor mediate endocytosis
- Present antigen to helper T cells (CD4)
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
What is linked recognition of antigen?
a. the ability of two different antibodies to bind to the same antigen
b. where a B cell can only be activated by helper T cells that response to the same antigen
c. a type of thymus independent B cell activation
d. the ability of an MHC class I moelcules and MHC class II moelucles to bind to the same peptide
b
Where do B cells acquire antigen specificity
a. in the periphery
b. in the germinal centres
c. in the bone marrow
d. in the lymph node
e. all of the above
b
Based on your knowledge of somatic hypermutation would you expect to produce the same antibodies during primary and secondary infection?
a. yes
b. no
b
State the three types of ‘professional’ APCs that express both MHC-I and MHC-II
- Dendritic cells
- Activated macrophages
- Activated B cells
Cells other than APCs that express MHC-I are known as what?
Give examples
‘target’ cells
Target can be virus infected, malignant and aging cells, or cells from a graft
Example of APCs
identify the APCs
Why can’t we fight all infections?
They evolve, we evolve
What is the role of T cells in the immune system?
- An immune response depends on the activation of immune cells
- CD4+ T cells and CD8+ T cells will be activated due to viruses, bacteria and parasites
What can T cells also be activated in response to?
- tumour cells
- Cells from foreign grafts
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
Tell me three Th cell cytokines
IL-2
IL-4
IFNy
Viruses, bacteria and parasites are dealth with differently by the immune system
What are bacteria targeted by?
Bacteria are targeted by CD4+ T cells and CD4 T cells are not killers
As CD4 T cells are not killes, what do they release and what does this stimulate?
They release cytokines
That stimulate…
- Macrophages
- CD8 T cells
- B cells
What are virally infected cells killed by?
CD8+ T cells
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
An effective immune response relies on what?
An effective immune response relies on clonal expansion of activated cells
Tell me clonal expansion?
Produces many T cells with T cell receptors specific for a specific MHC/peptide complex
Tell me how the CD8+ T killing cell works?
- CD8 T cells interact with APCs and detect pathogen peptides on MHC molecules
- These T cells then become activated
Differentiate into cytotoxic T cells
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
State the types of T cell selection in the thymus?
Positive selection
Negative selection
Tell me about positive T cell selection in the thymus
Positive selection = T cells must have a TCR that can recognise MHC and self-peptide, these cells are selected for survival
Tell me about negative T cell selection in the thymus
Negative selection = T cells that recognise MHC and self-peptide too well are deleted (don’t receive any growth signals to keep proliferating or undergo apoptosis)
What does T cell selection in the thymus allow?
Allows recognition of MHC/peptide, without autoimmunity
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
Summary part I and II
Summary part I
- T cells detect antigen through their T cell receptor (TCR)
- Your body can generate many different TCRs through VDJ recombination
- Gives T cells specificity and diversity
- The TCR interacts with MHC molecules to detect peptides from pathogens
- T cells can be divided into CD8+ and CD4+ cells
- CD4 T cells interact with MHC class II molecules on APCs
- CD8 T cells interact with MHC class I molecules on virally infected cells
Summary part II
- Activated CD4+ T cells become Helper T cells
- produce cytokines to assist CD8 T cells, B cells and macrophages
- Activated CD8+ T cells become cytotoxic killer T cells
- Kill virally infected cells and tumour cells
- Activated T cells undergo clonal expansion to form memory cells and effector cells
