Development of lymphocytes Flashcards
What can B cells deficiency cause?
- Congenital agammaglobulinemia
- Lose immunoglobulins - Common variable immunodeficiency
- Novel biologics
What can T cell deficiency cause?
- Severe combined immunodeficiency which effects younger children
- DiGeorge syndrome where thymus is not functioning properly
- Acquired-HIV/chemotherapy/novel biologics
What is the role of the lymphocyte?
Role is a cornerstone of adaptive immunity
What is the morphology of lymphocytes?
- White cell
- Small
- Large nucleus
What is the lineage of lymphocytes?
T and B cells
What are the 3 functions of lymphocytes?
- Helper
- Cytotoxic
- Regulatory
What are the 2 key features of adaptive immunity?
- Specificity
2. Memory
What is basis of adaptive immunity?
Basis of adaptive immunity is clonal selection
What does each B cell have one type of on its surface?
For B cells, each cell has one Ig -Can switch class but always the same basic Ig on surface
What does each T cell have one type of on its surface?
or T cells, each cell has one T cell receptor
What happens once an antigen matches TCR?
Once antigen that matches TCR is encountered, we amplify that clone and there’s selection and expansion of that clone
What effect is there once the antigen matches the TCR?
Have an effector function where the infection is cleared out
What is the memory function of T cell once they bind with the antigen?
Also have a memory function which is more rapid and specific to secondary responses
Why is the top part of the TCR highly variable?
Top part of TCR is highly variable as genes shuffle around to generate a large number of combinations
Specificity in B cells
B cells with a variable region on top and a constant region at the bottom
What are the 4 basic approaches in predicting pathogens?
- Generic recognisable features
- Associated with damage
- Memory
- Non-self recognition
What are generic recognisable features on pathogens and what are they recognised by?
PAMPs found on pathogen are recognised by PRRs
What is the danger hypothesis and what recognises damage?
a) The danger hypothesis is that as well as the presence of the pathogen, damage must also occur to trigger the immune response
b) DAMP recognise damage
What is non-self recognition?
Recognising that pathogens are different from our own cells
What happens if non-self recognition is wrong?
If this is wrong, it can lead to autoimmunity
- These responses mean that there is a delay in the response
- Might start recognising itself
What is the main purpose of MHC-1 peptide binding to TCR on CD8 T cells?
Main purpose is to protect against viral infection as cell will then present viral peptides instead of own peptides
What are MHC-II?
They are antigen presenting cells
What do MHC-II do and what is their main purpose?
- These are macrophages which engulf pathogens and present on cell surface
- Main purpose is to protect against bacterial infection
What are the steps in thymic selection?
Cells first arrive at thymus and are programmed there
- T cells must be able to bind to MHC
- If not then they die through neglect
- This is known as positive selection
- If not then they die through neglect
Cells in the thymic medulla express tissue specific antigens
- If T cells recognise and bind to those self-peptides the cell dies
- This is known as negative selection
What must T cell recognise and not recognise?
Must recognise self but not bind to it, must not recognise everything as danger and should not be recognising nothing
What have naïve T cells not encountered?
not encountered an antigen yet
What is positive selection of B cells?
Identifies immature B cells with completed antigen receptor gene arrangement
Functional membrane Ig molecules(BCR) provide survival signals
What happens if theirs high avidity self-recognition?
If high avidity self-recognition, receptor editing changes BCR specificity
What does reactivation of RAG gene produce?
Reactivation of RAG genes produces new Ig light chain
What is negative selection of B cells?
If still auto-reactive, immature B cells with high affinity self-recognition die by apoptosis in bone marrow or spleen
What does antigen recognition lead to once transition is made to the IGM+IGD+ mature B cell stage?
Once transition is made to the IGM+ IgD+ mature B cell stage, antigen recognition leads to proliferation and differentiation
What do antibody B cells transform into and what do they produce?
Activated B cells transform into plasma cells which turn into antibody factories
Activated B cells also produce CD27+ memory B cells
What happens to naïve T cells after they leave thymus?
Naïve T cells recirculate primarily from blood to lymph nodes
What do we do to label lymphocytes in vivo?
Labelling lymphocytes in vivo with deuterium labelled glucose
What is deuterium?
Deuterium is a non-radioactive isotope of hydrogen
When do T cells incorporate hydrogen into their molecule?
T cells are extracted and if they were dividing when the labelled glucose was added, then they have incorporated hydrogen into their molecule
Why do Naïve cells have very little labelling by deuterium?
Naïve cells have very little labelling as they have not been dividing
What are TEM?
are effector memory cells
TEM
- Short lived population
- Continually replenished
- Doubling time about 15 days
What are TCM?
Are central memory cells
TCM
Turnover at significant rate
Doubling time about 48 days
Regulatory CD4+ T cells
- Short lived population
- Need continual replenishment
- Some originate from CD25 memory T cells
What do population of cells which have met the pathogen before continue to do?
Population of cells which have met the pathogen before continue to proliferate
How long does short term immunological memory last for?
A month
How long do clones/progeny survive in immunological memory?
Clones/progeny survive a long time
Where are lymphocytes organised mainly?
Organised mainly into lymph nodes
What is the structure of the lymphatic system optimised to facilitate?
Structure of the lymphatic system is optimised to facilitate cellular function
What is the spleen important in ?
Spleen is important in antibody generation
What does a splenectomy increase the risk of?
A splenectomy increases risk of infection
-Especially pneumococcal infection
What are tissue resident T cells usually and what marker does it have and whys it important?
Tissue resident T cells are usually antigen specific cells and have the CD69+ marker which is important in delivering quick responses
What happens to lymphocyte function with age?
Lymphocyte function deteriorate with age
What cells accumulate in immune senescence?
Accumulation of CD57+ cells
What is a key driver of immune senescence?
CMV infection is a key driver of immune senescence
