Development of Lymphocytes Flashcards
Name cells of the two immune systems.
INNATE:
- Neutrophils
- Macrophages
- NK Cells
- Dendritic cells
- Monocytes
- Eosinophils
- Basophils
ADAPTIVE:
- B Cells
- T Cells
- Plasma Cells
Why do we have lymphocytes?
Without them, we wouldn’t be able to get memory of pathogens, so we won’t get a bigger and faster secondary response.
Give some example of lymphocyte deficiency/ defect syndromes.
B Cells:
- Congenital agammaglobulinaemia (lose immunoglobulins)
- Common variable immunodeficiency (CVID)
- Novel biologics – Rituximab
T Cells:
- Severe Combined Immunodeficiency (SCID)
- DiGeorge syndrome (thymus doesn’t work properly)
- Acquired – HIV/ Chemotherapy/ Novel biologics
What dimensions can we use to define a lymphocyte?
Morphology:
- White cell; small, large nucleus
Lineage:
- e.g. T and B cells
Function: what they do
- e.g. Helper/ Cytotoxic/ Regulatory
Phenotype: what surface markers they express
- usually functional receptors – not just there for our convenience!
Specificity:
- What target – What Ab they produce or epitope they recognise (TCR)
Type of receptor: - Ig class for B cell/ αβ vs γδ for T cells
Differentiation:
- immature/ mature/ senescent
What they produce:
- TH1 (IL-2, IFN-γ); TH2 (IL-4, IL-5, IlL-6, IL-10)
What are the two key features of adaptive immunity?
Specificity – picks up on what you’ve seen before
Memory – has a quicker and bigger secondary response
Describe the specificity of the adaptive immune system.
For B cells – one cell, one Ig
- may class switch but always 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
- retention in ‘memory’ of clonal progeny (continues production of antibody (B cells) and has a more rapid specific secondary response (B and T cells).
How do the variable regions of the receptors get their random specificity?
The antigen-binding site is highly variable. The genes can shuffle round, so you have this ability to produce many combinations.
Your genome cannot code for absolutely every single combination, so instead it has a gene that splices the different bits in. After shuffling, it locks the gene (to allow for the specificity).
How do immune cells recognise the ‘bad guys’?
There are four basic approaches:
1) – it looks like a ‘bad guy’
- generic recognisable features – e.g. TLR, PAMPs, etc.
2) – their presence is associated with damage
- The Danger Hypothesis (not only presence of pathogen, but also damage needed for action to take place)
- Damage-associated molecular pattern molecules (DAMP)
3) – I’ve seen this before, and last time it was a ‘bad guy’
- Basis of the adaptive immune system (memory)
4) – it’s not me, so it shouldn’t be there:
- autoimmunity
How does the immune system set up a system to recognise things it has not seen yet?
It uses the ‘massive array of possibilities’ approach: tt generates this huge diversity of T and B cell receptors, and one of these should be able to catch the foreign body.
What problems might the ‘massive array of possibilities’ approach generate?
- over-assidiuous recognition
- under-assiduous recognition
- self-recognition
Assiduous: to be careful, methodical and very persistant.
How is recognising cancer cells a problem?
They are still “self”; they still express MHC, etc.
Instead, the immune cells must look for the expression of cancer-specific immune targets.
Describe the significance of MHC Class I and II.
Every normal cell will express MHC I. In it’s peptide groove, it puts components on the cell to show what it going on inside the cell.
If a virus invades the cell, it will start presenting viral peptides. A CD8 T cell will come along, recognise the foreign peptide, and kill the cell.
APCs express MHC II. When it engulfs something, it will express those peptides on its MHC II surface, and CD4 cells will come by to confirm if it is foreign or not.
Some viruses overcome this MHC II mechanism by downregulating the amount of MHC II made. However, the way that the body combats this is by NK cells, which will kill a cell if it recognises that there is ‘loss-of-self’ i.e. no MHC present.
Describe the positive and negative selection of T cells.
T cells will go to the thymus and go through positive selection. In order to work, they have to bind to MHC. If it doesn’t it dies by neglect. If it does, it goes through negative selection. There are cells in the thymic medulla that express tissue-specific antigens. If they bind to those, they are killed off. If not, they survive.
What we end up with (theoretically) are T cells that are sufficiently good at binding to MHC to recognise organisms, but they don’t recognise self-MHC, so will not cause an autoimmune disease.
From these cell, you set up an array called naïve cells (those that haven’t chosen to be CD4 or CD8 yet)
Describe the B cell repertoire selection process.
POSITIVE SELECTION:
The body dentifies immature B cells with completed antigen receptor gene rearrangement.
Functional membrane Ig molecules (BCR) provide survival signals, which aid in the selection of the cell.
RECEPTOR EDITING:
Immature B cells that recognize self antigens with high avidity are often induced to change their specificities by a process called receptor editing. This induces the reactivation of RAG genes and the rearrangement and production of a new Ig light chain, allowing the cell to express a different (edited) B cell receptor that is not self-reactive.
If it is still self-reactive, we rearrange its λ light chains.
NEGATIVE SELECTION:
If they are still auto-reactive, immature B cells with high-affinity self-recognition die by apoptosis in the bone marrow or spleen.
Once the transition is made to the IgM+ IgD+ mature B cell stage, antigen recognition leads to their proliferation and differentiation.
Describe the two types of memory cells.
TEM: Effector Memory Cells:
- short-lived population
- continually replenished
- doubling time about 15 days
- circulate between lymphoid organs and tissues
- has low CCR7 and CD62L
- can rapidly make effector cytokines providing rapid protection (such as IFN-gamma, IL-4, IL-5)
TCM: Central Memory Cells:
- turnover at a significant rate
- doubling time is about 48 days
- have CCR7 (chemokine receptor 7, which is responsible for the lymphocyte recruitment to secondary lymphoid tissues) and CD62L (for L-selectin, which acts as a ‘honing’ receptor for lymphoctes to enter secondary lymphoid tissue)
- they enter lymph nodes and recirculate (they are protective against systemic infection)
