9. T and B cell development Flashcards
What role do the B and T cells play in recognition of the foreign antigen?
- elimination of foreign agents by the adaptive immune resides in the functional activity of T + B cells
- ability to recognise foreign antigen resides in the T-cell receptor (TCR) and the BCR (Ig) for B-cells
- each B and T cell that are produced express a unique antigenic receptor therefore the adaptive IS has the ability to interact with any pathogen
- production and diversity repertoire of T and B cells that occurs during their development
How is diversity generated within the antibodies structure?
- number of variable and J gene segments
- One V and one J makes a whole variable domain
- diversity is achieved because you can generate the variable domain by using a different combination of the V+J gene segments
How is variability of the K chain achieved?
40 V and 5J joining gene segments
1V and 1J makes a whole variable domain therefore recombinational diversity = 40 x 5 = 200
How is variability of the variable domain of the T cell receptor 𝛂 chain?
70 V and 61J gene segments
1V and 1J makes a whole variable domain therefore recombinational diversity = 70x61 = 4270
How many genes encode for the human immunoglobulin variable domain?
Recombinational diversity - H chain: 51x27x6 = 8262 - K chain: 40x5 =200 - I chain: 30x4 = 120 Combinational diversity HxK 8262x200 = 1.7x10^6 + HxI: 8262 x 120 = 1x10^6 = 2.7x10^6
How many genes encode for the human immunoglobulin variable domain?
Recombinational diversity - TCR 𝛂 chain: 70x61 = 4270 - TCR 𝛃 chain: 52x2x13 = 1352 Combinational diversity - TCR 𝛂x𝛃: 4270x1352 = 5.7x10^6
How do antigens drive diversity?
Somatic mutation
- mechanism for introducing mutations into v regions of activated B cells (antigen driven), increases antigen affinity
- occurs in germinal centres
Cross switching
- main purpose is that each cross displays a different biological function
How do T cell receptors achieve diversity?
Same as immunoglobulin except with no somatic mutation - no class switching
- Diversity even more focused on CDR3
- More N region diversification
What does a stem cell need in order to become a lymphocyte?
To become a T cell need to express a receptor, therefore it is important for the stem cell to undergo gene rearrangement
To become a B cell need to express an antigen receptor, therefore it is important for the stem cell to undergo gene rearrangement
Why is receptor gene arrangement an important step?
Distruption of receptor gene rearrangement leads to absence of T and B cells
- Equine SCID (severe combined immunodeficiency), inherited as an autosomal recessive trait in 2-3% of arabian horses
- absence of T and B cells, due to deficiency in DNA-dependant protein kinase
- developing lymphocytes cannot undergo VDJ recombination
What are stromal cells (micro-environment)?
Facilitate development of B cells by providing the appropriate factors (soluble) and cell-cell interactions
What 3 ways are T cells developed in the thymus?
- Linage commitment
- Repertoire selection (education)
- Functional maturation
What is the function of the thymus?
Primary site for the development of T cells
Upon entry to the thymus, stem cells receive necessary signals to become functional mature T cells
- these instructions are provided uniquely by the thymus microenvironment in particular thymic epithelial cells
– involves cell-cell contact and production of soluble factors
Thymus is critical for development of mature and competent T cells, since in the absence of enzymes there is a lack of peripheral t cells which leads to the host being immunocompromised
When does the adaptive immune system develop?
Newborn reliant on passive immunity
Adaptive immunity still developing in the newborn
Innate immunity essential for protection
