L15: T Cell Development In The Thymus Flashcards
What are the main lymphocytes within the adaptive immune system
T lymphocytes
B lymphocytes
Where are T lymphocytes derived from
From the thymus
Where are B lymphocytes derived from
B cells in the bone marrow
How do we get T lymphocytes from the thymus
T lymphocyte progenitors are made in the bone marrow then migrate to the thymus to mature into T cells.
How do B cells recognise antigens
Can recognise the antigen directly or by immunoglobulin
What is immunoglobulin also called
Antibodies
What are immunoglobulin/antibodies
Receptors of B cells
What are the chains of immunoglobulin
Heavy and light chains
What are the 2 types of light chains
Kappa and lambda
What do T cell receptors recognise
MHC
What are the forms of T cell receptors
TCR beta and TCR alpha
TCR gamma and TCR delta
Are T cell receptors specific i.e recognise different antigens
Yes
What are the gene regions of T cell receptors
V
D
J
C
What are the specific gene regions of TCR beta and gamma and immunoglobulin heavy chain
V
D
J
C
What are the specific gene regions of TCR alpha, delta and immunoglobulin light chain
V
J
C
What happens to these gene regions to create diversity of the receptors
Become rearranged
How are gene segments of the regions rearranged
1) randomly gene segments from each region are chosen
2) gene segments therefore get rearranged to form a protein of a receptor
If we have random receptor cells being generated due to gene rearrangement how do avoid lymphocytes recognises our own body tissue i.e autoimmune disease
By:
Negative selection
Positive selection
Death by neglect
What is negative selection
When lymphocytes target self antigens and therefore undergo apoptosis
What is positive selection
When lymphocytes recognise the antigens so they survive
What is death by neglect
When lymphocytes don’t recognise foreign or self antigens so they are left alone i.e death by neglect
Where does selection occur for B cells
In the bone marrow
How does negative and positive selection occur in the bone marrow for B cells
1) B cell receptors on an immature B cells binds to self antigen on bone marrow stromal cell
2) if there is no recognition of the self antigen by the receptors the immature B cells survives and matures on for positive selection
3) if however there is recognition of self antigen of bone marrow cells, immature B cells apoptosis and this is negative selection
What is MHC present by to the T cell receptors
Antigen present cells
Where does negative selection and positive selection occur for T cells
In the Thymus
What are the 2 layers of the thymus
Cortex
Medulla
What are the T cell types
CD4+
CD8+
What type of MHC does CD4+ T cell bind to
MHC class 2
What type of MHC class does CD8+ T cell bind to
Class 1
Which type of selection does the cortex of the thymus drive
Positive selection
Which type of selection does the medulla of the thymus drive
Negative selection
Name an example of a antigens presenting cell
Dendritic cells
What happens in the thymus cortex for positive selection
1) if T cells binds to MHC they undergo positive selection and move into the medulla
2) if developing T cells cannot bind to MHC it undergoes death by neglect
What happens in the Thymus medulla for negative selection
1) if T cells bind strongly to MHC they undergone Negative selection
2) if T cells do not bind strongly to MHC they survive and mature further
What are the 2 types of T cell tolerance
Central tolerance
Peripheral tolerance
What is central tolerance of T cells
This is the positive and negative selection that occurs in the thymus
What is peripheral tolerance for
A backup mechanism for T cells that escape negative selection
What is peripheral tolerance
Ignorance
Anergy
Cell death
Regulatory T cell
What is anergy
Switching off the T cell but not killing it
What is regulatory T cells for
Regulating and controlling auto reactive reactions
What are regulatory T cells produced
Thymus
What is the role of regulatory T cells
Suppress auto reactive lymphocytes that escape negative selection
What are the subset of T regulatory cells
CD4+
CD25+
Which factor expressions allow to give T regulatory cells
FOXP3
How to T regulatory cells suppress cells
Secrete cytokine that dampen down T cell responses
Compete for T cell growth factors such as IL2
Contact dependent
What does AIRE stand for
Autoimmune regulator
What is AIRE
A transcription factor
What is AIRE expressed by
Medullary Thymic epithelial cells
What does the AIRE transcription factor allow
Regulates promiscuous gene expression
What is promiscuous gene expression
The Expression of lots of different gene expression in the thymus
What does the promiscuous gene expression allow
Thymus to screen for self reactivity more effectively
Give an example of promiscuous gene expression with AIRE
AIRE allows insulin gene to be expressed in the thymus so that T cells developing recognise insulin and undergo negative selection
What does AIRE protect against in terms of insulin
Diabetes because we are destroying the cells that will kill beta cells in the pancreas
How can FOXP3 deficiency occur
Due to mutation of IPEX
If there is FOXP3 what does this lead to
No development of T regulatory cells and therefore autoimmunity
How does AIRE deficiency occur
Mutation of APECED
What does AIRE deficiency lead to
Prevention of promiscuous gene expression from occurring
What are FOXP3 and AIRE deficiency called
Monoallelic autoimmune diseases
What is Thymus aplasia
Thymus atrophy (shrinkage)
What are the main category causes of thymus aplasia
Genetic
Natural
What are the genetic causes of thymus aplasia
FOXN1 defiency
Complete di George syndrome
What is complete di George syndrome
Children have no thymus
What is FOX1N deficiency
Absence of thymus
What are the natural causes of thymus aplasia
Age related thymus atrophy
What happens to the thymus as we age
Declines in function
What happens to the T cells in age related thymus atrophy
T cells decrease
What is the treatment for di George syndrome
Thymus transplant
