Development of Lymphocytes Flashcards
What 8 cell types make up the innate immune system?
β neutrophils β macrophages β monocytes β NK β dendritic cells β eosinophils β basophils
What 3 cell types make up the adaptive immune system?
β B cells
β T cells
β plasma cells
What are 2 conditions and 1 drug that can affect B cells?
β Congenital agammaglobulinaemia
β common variable immunodeficiency (CVID)
β rituximab
What are 2 conditions and 3 acquired reasons that can affect T cells?
β SCID
β DiGeorge syndrome
β HIV/chemotherapy/novel biologics
What are the 8 ways that a lymphocyte can be classified?
β Morphology β lineage β function β phenotype β specificity β type of receptor β differentiation β their products
What are the two key features of adaptive immunity?
β Specificity and memory
Describe the basic tenet of adaptive immunity?
β one cell has one specificity β one B cell has one Ig β one T cell has one TCR β selection and expansion of the clone β retention in memory of clonal progeny
How much time does the primary response take to peak?
β A couple of weeks
What is the difference between the primary and secondary response?
β it is quicker and peaks at a higher level
What precursor do B and T cells come from?
β Common lymphoid precursor
What happens to T cells after they are made from the lymphoid precursor?
β They are programmed in the thymus
β They are distributed among lymphoid organs
What is the defining feature of a lymphocyte?
β The receptor
Describe the receptor on an alpha beta T cell?
β alpha chain and a beta chain
β the top region is highly variable
What adds to the diversity of the lymphocyte receptors?
β genetic reshuffling
What are the 4 ways the immune system recognises pathogens?
β It looks like a pathogen
β their presence is associated with damage
β the pathogens have been seen before
β it is not βselfβ
What are DAMPs?
β damage associated molecular patterns
How does the immune system set up a system to recognise things it has not seen before?
β It has so many different combinations that one of them has to be the right one
What is the issue with having such a vast array of possible receptors for detecting pathogens?
β The precursor frequency of the right cell will be low
β you can start recognising βselfβ by chance
Which MHC binds to CD8 T cells?
β MHC I
Which MHC binds to CD4 T cells?
β MHC II
What does every cell in the body express?
β MHC-I
What is the function of MHC-I ?
β peptides that the cell is producing are presented on MHC-I to show T cells that the proteins produced are normal and not viral
What do viruses do to MHC-I and how is this overcome by the immune system?
β They downregulate MHC-I
β CD8 cells recognise the lack of MHC and kill the cells
What are the three issues with the massive possibility approach?
β You can recognise self by accident
β you can recognise everything as being foreign
β you can be underactive
What types of selection occur in the thymus?
β positive and negative
What is positive selection (T cells)?
β In order to work it has to bind to MHC
β if it doesnβt bind at all the cells die by neglect
How does negative selection of T cells occur ?
β There are cells in the thymic medulla that express tissue specific antigen e.g colonic antigen, thyroid antigen
β if those are recognised the cell is killed by negative selection
What is the end result of the selection process in the thymus?
β You end up with cells that can recognise MHC but wonβt recognise thyroid cells, joint cells etc.
β these produce naive cells because they havenβt recognised antigens yet
How is positive selection of B cells done?
β Identifies immature B cells with completed antigen receptor gene rearrangement
β functional membrane Ig molecules (BCR) provide survival signals
How does receptor editing occur in B cells?
β If high avidity self-recognition the receptor editing changes BCR specificity
β reactivation of RAG genes produces new Ig light chain
β if still reactive it rearranges Ξ» light chains
How does negative selection occur in B cells?
β If they are still auto-reactive the immature B cells with high-affinity self-recognition die by apoptosis in the bone marrow or the spleen
What do B cells need to express when they mature?
β IgM and IgD
How do you test for naive T cell levels in the blood?
β Give people labelled glucose with deuterium in it
β remove the T cells
β if they have been dividing during the period where the label has been given they will have the label
β naive cells do not pick up the label and flat lines occur
What is the doubling time of TEM (effector memory) and what does this mean about their lifespan?
β 15 days
β short lived
What is the doubling time of TCM (central memory) and what is their turnover like?
β 48 days
β turnover at a significant rate
What is the lifespan of Treg cells like?
β short lived population
β need continual replenishment
What do activated B cells become?
β Plasma cells
What organ has a key role in antibody generation?
β the spleen
What happens if the spleen is removed?
β increases the risk of infection
What is a key marker of tissue resident memory cells?
β CD69+
What is a key driver of immune senescence?
β CMV infection
What happens during immune senescence?
β telomere shortening
β change in functional attributes
β accumulation of CD57+ cells
