T and B cells Flashcards
Where are T cells derived from?
Bone marrow stem cells
Describe where T cell precursors are and what happens to them
- They arrive at the thymus and spend 7-21 days undergoing differentiation and proliferation
- They are mature but antigen naive
What percentage of T cells leave the thymus as mature T cells?
2-4%
How many cells are made in the thymus every day?
Approx. 5x10^7
What percentage of T cells die in the thymus?
95%
What are CD4- positive T cells?
Helper T cells
What are CD8- positive T cells?
Cytotoxic cells
What are CDRs?
- Complimentary Determining regions
* They interact with an MHC peptide complex to activate the lymphocytes
What is meant by CD?
- Cluster of Differentiation
- Cell surface molecules are different on each T cell and can therefore be used to differentiate between the different T cells (and can be recognised by different monoclonal antibodies)
What is the Major Histocompatibility Complex?
- Located on chromosome 6 and consists of approx. 140 genes
- Can be divided into 3 groups: class I, class II and class III
- Class 1: Molecules are present on the surface of virtually every cell. They present antigen fragments to the T cells and bind to the CD8 receptors on cytotoxic T cells
- Class 2: Molecules are found mainly on macrophages and B cells and present antigen to helper T cells, binding to the CD4 receptor
- Class 3: Genes encode for other immune components such as complement of cytokines such as TNF
Briefly describe T cell education
- Small double positive thymocytes (CD4 and CD8) initially express low levels of the receptor they use to recognise the antigen, the TcR
- Most of the TcRs won’t recognise your own MHC molecules so the T cells die do to lack of positive selection
- The cells that do, go on to mature and express high levels of TcR. They then go on to lose CD8 or CD4 to become a single positive cell
- T cells that have a very high affinity for the MHC undergo negative selection to climate T cells which could become auto-reactive T cells
Which cells mediate positive selection of T cells?
Cortical epithelial cells
Which cells mediate negative selection of T cells?
Dendritic cells
Describe the structure of a T cell receptor
- 2 polypeptide chains that are membrane bound with a V and a C domain
- Alpha chain and a beta chain
- There is a transmembrane region and a cytoplasmic tail
How are the TcR and antibody similar?
- Evolutionary related and both members of the immunoglobin superfamily
- Both undergo chromosomal rearrangement
How are the TcR and antibodies different?
The TcR only recognises an antigen when it is bound by an MHC molecule whereas antibodies bind to the antigen they were raised against by themselves
Describe MHC class 1
- Two chains: a heavy chain and a small B2 micro globulin
- upper surface forms a groove into which small 8-10 amino acid peptides sit
- Expressed on almost every cell on your body
- a1, a2,a3 B2
Describe MHC class 2
- Two chains: alpha and beta, both membrane bound
- Upper surface forms a groove into which longer peptides, over 200 amino acids sit
- Expression in more limited to specialised antigen presenting cells and immune cells
- a1, a2, B1, B2
What recognises MHC class 1?
CD8 T cells
What recognises MHC class 2?
CD4 T cells
Describe the peptides picked up by MHC class 1
- Mainly meets peptides in the endoplasmic reticulum
* The peptides are mostly derived from the internal contents of your cells e.g. cytoplasm and nucleus
Describe the peptides picked up by MHC class 2
- Picks up peptides from external sources i.e. outside cells
- They pick the peptides up/meet them in endosomes
Describe the process of MHC class 2 being presented at the cell surface
- Extracellular antigen is taken up by and endocytic vesicle
- The MHC molecule moves from the Endoplasmic reticulum to the Golgi and is then packaged to a vesicle
- The antigen is then broken down in the phagolysosome into peptides
- The two vesicles fuse and the MHC molecule binds to the peptide
- The MHC class 2 molecule presents at the cell surface membrane
Describe the process of MHC class 1 molecule being presented at the cell surface
- The intracellular antigen is transported to the ER
- In the ER, the peptide binds to the MHC molecule
- The MHC molecule then moves to the Golgi and is then packaged into a vesicle
- The MHC class 1 molecule presents at the cell surface
What determines which peptides the MHC molecule presents?
Polymorphisms located in the peptide-binding groove
Where are the areas of polymorphisms in each MHC molecule?
- In the Class 1 molecule, there are two areas of variability on the alpha 1 and 2 subunits
- in the Class 2 molecule, there is one area of variability
What is the major factor in graft rejection with transplants?
MHC disparity: even if a full match is obtained, you have enough different peptides (minor transplant antigens) to trigger slow graft rejection so immunosuppression is required
What are superantigens?
Some bacteria and some viruses produce proteins that interfere with the interaction of TcR and MHC, stimulating large numbers of T cells
e.g. Staphylococcal enterotoxin (SEB) and TSST-1: toxic shock syndrome
What is DiGeorge’s Syndrome?
Failure to develop thymus epithelia, few T cells are produced
What is Severe Combined Immunodeficiency?
SCID: Loss of the T cell compartment which leads to the loss of the ability to produce cell mediated and antibody responses
