Development of Lymphocytes Flashcards
What are the cells of the innate immune system?
Macrophages, Neutrophils, Monocytes, Eosinophils, Basophils, Natural Killer Cells, Dendritic Cells
What are the cells of the adaptive immune system?
- B-cells
- T-cells
- Plasma cells
Why do we need lymphocytes?
- We need lymphocytes for immunological memory
- A secondary infection with a previously infected pathogen will result in a immune response of greater speed and magnitude
- When we dont have lymphocytes for example low CD4+ in HIV infection we can allow other pathogens to cause opportunistic infections
- A secondary infection with a previously infected pathogen will result in a immune response of greater speed and magnitude
What are some examples of lymphocytes deficiency/ defect syndromes (B-cells)?
- Congenital agammaglobulinaemia = blocks growth of normal and mature B-cells body will make little Igs
- Common variable immunodeficiency (CVID)
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Novel biologics (Rituximab)
- Treats non-hodgkins lymphoma will bind to CD20 molecules on abnormal B-cells
Examples of lymphocytes deficiency/ defect syndromes (T-cells)?
- Severe Combined Immunodeficiency (SCID)
- DiGeorge Syndrome
- Acquired à HIV/ Chemotherapy/ Novel Biologics
How can we define a lymphocyte?
Many ways we can classify them based on their
- Morphology → White cell, small, large nucleus
- Lineage → T and B cells
- Function → Helper, Cytotoxic, Regulatory
- Specificity → What Ab they produce or epitope they recogise (TCR)
- Type of receptor → Ig class for B cells/ αβ vs γd for T-cells
- What they produce → TH1 (IL-2, IFN- γ); TH2 (IL-4, IL-5, IL-6, IL-10)
What are the two features of adaptive immunity?
- Specificity
- Memory
Describe the specificity of the adaptive immune system?
- For B cells = one cell, one Ig
- May class switch but also same basic Ig
- May undergo affinity maturation
- For T cells = one cell, one T cell receptor (TCR)
- Selection (when antigen is recognised for Ab) and expansion of that clone
- You will have an expanded number of T cells and B cells which are ready for next round of infection
- These cells will be retained in ‘memory’ of clonal progeny
- Continued production of antibody
- More rapid secondary response
- Selection (when antigen is recognised for Ab) and expansion of that clone
What is the difference between the B and T cell lineage?
- Both B and T cells will come from the same common lymphoid progenitor
- B-cells = Will come from bone marrow and end up in the lymph nodes and circualte in bloood
- T-cells = Programmed in the thymus
What is the T cell receptor made up of?
Consists of an alpha and beta chain
How do variable regions of the receptors get their random specificity?
- The genes will shuffle around so you will have the abillity to produce many different combinations
- This is because millions of pathogens you may meet the genetic system cant have a code for every possible pathogen. The immune system will cope with this by having a gene which will splice all the different bits in
How do lymphocytes recognise their enemy?
- There are generic recognisable features e.g. TLR à PAMP
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Their presence is associated with damage
- E.g. tissue damage will produce an inflammatory response, DAMPs will recognise damage and act accordingly
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Basis of memory of the adaptive system
- This allows the body to recognise previously encountered pathogens, however pathogens are constantly trying to evolve and disguise themselves in ways where they can avoid being killed by the immune system and ‘make them look like the good guys.
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Its not me, It shouldn’t be there (Autoimmunity)
- This is non-self-recognition; however, this can sometimes go wrong which results in autoimmune diseases
How does the immune system set up a system to recognise unknown pathogens?
The immune system will recognise pathogens and antigens that it has not previously encountered NOT by GENETIC PRE-ENCODING but sets up a ‘massive array of possibilities approach’
- This essentially means the huge diversity of T cell receptors and B cell receptors (immunoglobulin molecules) and the theory that at least one of these is likely to match the antigen in the body
What may be a problem with setting up this massive array of possibilities approach?
- There is a low precursor frequency in the primary response (response isn’t very fast)
- We may mot set up the array broadly enough
- We may start recognising self-antigens
What is the problem with the immune system recognising cancer cells?
- They are still ‘self’ they still express MHC
- Instead the immune cells will need to look for the expression of cancer specific immune targets
Describe the posotive and negative selection of T-cells
- In the thymus there will programming
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Posotive selection
- T cell receptor must bind MHC, if it doesnt bind it will die
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Negative selection
- Cells in the thymic medulla will express tissue specific antigens
- E.g oesophageal antigen/ thyroid antigen
- If the T-cells recognise these will die as they must not bind self peptides (can be at risk of causing autoimmune diseases)
- Cells in the thymic medulla will express tissue specific antigens
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Posotive selection
Describe the function of CD4+ T regulatory cells
- These are short-lived in the population
- Need continual replenishment
- Some originate from CD25 = memory T cells
- Treg cells will ensure that the immune response doesnt go overboard. They are produced in the same activation and amplification cascade that produces the effector cells
Where are lymphocytes mainly organised?
- Mainly organised into lymph modes
- Lymph nodes are a meeting place for T cells, B cells and APCs
- The APC’s will come out of the lymphatics bearing pathogens , naive T-cells will see if they can recognise the antigens on their surface
