Immunology: Development of Lymphocytes Flashcards
1
Q
Name the immune system cells that are part of the innate immune system
A
- Neutrophils
- Macrophages
- NK Cells
- Dendritic cells
- Monocytes
- Eosinophils
- Basophils
2
Q
Name the immune system cells that are part of the adaptive immune system
A
- B cells
- T cells
- Plasma cells
3
Q
Why do we have lymphocytes?
A
- Without them, we wouldn’t be able to get memory of pathogens, so we won’t get a bigger and faster secondary response if we get re-infected
4
Q
What are some examples of causes of lymphocyte deficiencies/defect syndromes?
A
-
B cells
- Congenital agammaglobulinaemia - loss of gamma globulin
- Common variable disease (CVID)
- Novel biologics - Rituximab
-
T cells
- Severe combined immunodeficiency
- DiGeorge syndrome
- Acquired - HIV/Chemotherapy/Novel biologics
5
Q
What dimensions can we use to define a lymphocyte?
A
- Morphology: White cell; small, large nucleus
- Lineage: E.g. T cells and B cells
- Function: E.g. Helper / Cytotoxic / Regulatory
- Phenotype (what surface markers they express): Usually functional receptors
- Specificity: What they target - what antibody do they produce or epitope they recognise
- Type of receptor: - Ig class for B cell/ αβ vs γδ for T cells
- Differentiation: Immature / mature / senescent
- What they produce: E.g. TH1 (IL-2, IFN-γ); TH2 (IL-4, IL-5, IlL-6, IL-10)
6
Q
What are the 2 key features of adaptive immunity?
A
- Specificity - Targeted response
- Memory - Allows for quicker and bigger response if exposed to same antigen again
7
Q
Explain the specificity of the adaptive immune system
A
- Explained by clonal selection theory - one cell has one specificity
-
B cells - one cell, produces one Ig
- May class switch (IgM -> IgG) but always same basic Ig
- May undergo affinity maturation
- T cells - one cell, one type of T-cell receptor (TCR)
- When specific antigen recognised by T cell or B cell (selection) that clone is amplified (expansion)
- There’s also retention in ‘memory’ of clonal progeny of lymphocytes which means:
- Continued production of antibody (B cells)
- More rapid specific secondary response (B and T cells)
8
Q
How is specificity achieved by a lymphocyte?
A
- T-cells - Each T-cell has one type of TCR
- B-cells - Each B-cell has one Ig (B-cell receptor)
- Antigen-binding site of TCR and Ig highly variable
- This is because genes that code for TCR or Ig able to shuflle around to produce different combos
- Genome can’t code for every single code so it has a gene that splices the different bits in
- After shuffling, it locks the gene - can’t make another receptor type once gene’s locked
9
Q
How do immune system cells recognise pathogens?
A
-
Looks like a pathogen
- Has general recognisable features e.g. PAMPs
-
Their presence is associated with damage
- Danger hypothesis (not only presence of pathogen, but also damage needed for action to take place)
- DAMPs (Damage-associated molecular pattern molecules)
-
Immune system cell recognises antigen and “remembers” that it’s associated with damage/disease
- Basis of adpative immune system (memory)
-
Non-self recognition
- Can lead to autoimmunity
10
Q
How does the immune system recognise things it hasn’t seen yet?
A
- Massive array of possibilties approach
- Immune system generates huge diversity of T-cell receptors and Immunglobulins (B-cell receptors) so that one of them is able to identify the foreign body
11
Q
What are the problems with the “massive array of possibilities approach” to identifying unknown pathogens?
A
- Causes a delay in primary immune response to particular pathogen - although massive no. of B and T cells produced only small no. able to recognise each type of pathogen so will take time to recognise it
- Over-assidiuous recognition - set up reponse to something that doesn’t cause harm
- Under-assiduous recognition - might miss something/not set up a correct response
- Self-recognition - recognising self as enemy - autoimmune disease
12
Q
Why is recognition of tumour cells by immune system cells difficult?
A
- Tumour cells are still classed as “self” - still express MHC, etc
- Instead, the immune cells must look for the expression of cancer-specific immune targets
13
Q
What type of peptide do MHC class I and II present? What receptor and cell type do they bind to?
A
- MHC class I - Presents intracellular peptides, including viral peptides, binds to TCR on CD8 T-cells
- MHC class II - Presents
14
Q
What is the significance of MHC class I and II?
A
- MHC class I
- All normal cells express MHC class I
- In peptide binding cleft of MHC class I cell will put components of the cell to show what it going on inside the cell
- If a virus infects a cell then infected cell will place viral peptides on peptide binding cleft of MHC class I
- This allows cytotoxic T-cell (CD8+ T-cell) to recognise viral peptides and kill infected cell
- MHC class II
- Antigen presenting cells (APCs) express MHC class II
- When they phagocytose something they’ll express the peptides from that thing on MHC class II
- CD4+ T-cells recognise those peptides as either “self” or “foreign”
15
Q
Describe the process of thymic selection
A
- Immature T-cells go to the thymus and first undergo positive selection
- Positive selection involves these immature T-cells binding to MHC
- If they don’t bind to MHC then they die by neglect
- If they successfully bind to MHC the immature T-cells then go through negative selection
- During negative selection cells in thymic medulla express tissue-specific antigens
- If the immature T-cels recognise these antigens they are killed and if they don’t they survive
- By the end of thymic selection you should end up with T-cells sufficiently capable at binding to MHC to recognise organisms, but not capable of recognising self-MHC, so will not cause autoimmune disease
19
Q
How can you test for presence of Naïve T cells in the blood?
A
- Deuterium labelled glucose taken by patient
- T cells are then extracted
- Naïve t cells will have little labelling as they are dividing very slowly
21
Q
What cell types can a Naïve T cell differentiate into?
A
- Effector memory cells (TEM)
- Central memory cell (TCM)
- T regulatory cells
26
Q
Where are lymphocytes mainly found?
A
-
Lymphatic system
- Organised mainly into Lymph Nodes
- Architecture optimised to facilitate cellular interaction
-
Spleen
- Key role is antibody production
- Tissues
