Development of Lymphocytes (Overview of the Adaptive Immune System) Flashcards
Name cells of the innate immune system
- Neutrophils
- Monocytes
- NK
- Macrophages
- Eosinophils
- Basophils
- Dendritic cells
Name cells involved in adaptive immunity
- T cells
- B cells
- Plasma Cells
What other somatic cells are involved in the immune response?
Tissue cells (e.g. endothelial cells) and Platelets
Describe the significance of Lymphocytes
- Very powerful + Diverse
- Actively dividing homeostatic populations
- Key to protection against infection and cancer
What is the function of lymphocytes?
Lineage:
- T and B cells
Function:
- e.g. helper / cytotoxic / regulatory
Produce:
- Th1: IL-2, IFN-ɣ Th2: IL-4, 5, 6, and 10
What are the 2 key features of adaptive immunity?
- Specificity: targeted
- Memory: rapid response
Describe the specificity of B cells
For B cells - one cell, one Ig
- May class switch (IgM → IgG) but always the same basic Ig receptor
- May undergo affinity maturation
Describe T cell specificity
For T cells - one cell, one TCR
Selection and expansion of that clone
Retention in ‘memory’ of clonal progeny
- Continues production of antibody (B cells)
- More rapid specific secondary responses (B and T cells)
Give examples of B cell defect syndromes
Congenital agammaglobulinemia
Common variable immunodeficiency
Novel biologics - Rituximab
Name some T cell defects
Severe combined immunodeficiency (SCID)
DiGeorge Syndrome
Acquired - HIV / Chemotherapy / Novel biologics
Where do T/ B lymphocytes originate?
Both produced from same lymphoid precursor in bone marrow and end up in lymph nodes from where they circulate the body
Where do T cells mature?
T cells mature in thymus and recirculate as Th cells (CD4+) and are distributed among lymphoid organs
What is the variable region of TCRs?
The variable region of the TCR is the antigen binding site that provides specificity
How are specific lymphocyte receptors formed?
Generation of diversity via gene reassortment is a key process
What are the 4 basic approaches of predicting pathogens?
- Generic recognisable features e.g. TLR, PAMPs
- Presence associated with damage e.g. DAMPs
- Recurrent pathogens - adaptive immune response
- Autoimmunity - non-self recognition
What are the problems with lymphocytes predicting unknown pathogens?
- Delayed response due to a low precursor frequency during primary response
- May miss pathogen due to lack of specificity
- Over- or under-assiduous recognition
- Self recognition
How do lymphocytes recognise tumour cells?
Still “self”
Express cancer-specific immune targets that are recognisable
Outline the peptide-MHC complexes that form on T cells
MHC-I plus peptide binds to TCR on CD8 T cells
MHC-II plus peptide binds to TCR on CD4 T cells
What is the effect of T cell positive selection in thymus?
Positive selection: Lymphocytes must bind MHC or they die
What is the result of negative T cell selection in the thymus?
Must not bind self peptides
Cells in thymic medulla express tissue specific antigens (colonal, endothelial etc.) if bound to these antigens the cell dies
⇒ Naive T cells
Describe B cell positive selection
Identifies immature B cells with completed antigen receptor gene rearrangement
Functional membrane Ig molecules (BCR) provide survival signals
How does B cell receptor editing occur?
If high avidity self-recognition - receptor editing changes BCR specificity
Reactivation of RAG genes produces new Ig light chain
If still reactive, rearranges λ light chains
When do B cells undergo negative selection?
If still auto-reactive, immature B cells with high-affinity self-recognition die by apoptosis in bone marrow or spleen
What is the effect of mature B lymphocyte presence?
Once the transition is made to the IgM+ IgD+ mature B cell stage, antigen recognition leads to proliferation and differentiation
Where do T cells go after maturation in thymus?
Naïve cells recirculate primarily from blood to lymph nodes
Outline the T cell memory heterogeneity
- Central memory: TCM
- Effector memory: ECM
- Regulatory T cells: Treg
Describe the central memory of T cells
Central memory (Tcm)
- CCR7+ and CD62L+
- Enter Lymph Nodes and recirculate
Describe the effector memory of T cells
Effector memory (Tem) - CCR7- and CD62L- - Migrate into tissues - Rapid effector activity - Cytolytic, cytokines (IFg, IL-4, IL-5)
Which memory T cells have a higher turnover?
Effector memory CD4 T cells have faster turnover than central memory T cells: Tem > Tcm
Describe the lifespan of effector memory T cells
TEM effector memory cells:
- Short Lived population
- Continually replenished
- Doubling time ~15 days
Outline the lifespan of central memory T cells
TCM: central memory cells:
- Turnover at significant rate
- Doubling time ~48 days
Describe the longevity of CD4+ regulatory cells
> short lived population
Need continual replenishment
Some originate from CD25- memory T cells
How are Treg cells produced?
Produced in same lymphocyte activation cascade and are also antigen specific
Why are there more memory cells than naive T cells?
Memory populations > “naive” pools - population of cells that have previously met pathogen continue to proliferate: makes memory cells a flexible population (continuously changing)
Describe the concepts of immunological memory
- Accrued cumulatively over time
- ‘Stored’ for future use
- Readily available when required
- Dynamic process
Describe B cell development
Activated B cells transform into Plasma cells
“Antibody factories”
also produce CD27+ memory B cells
How does immune senescence occur?
Lymphocyte function deteriorates with age
- Both age of the cell and age of the individual
- Telomere shortening
- Change in functional attributes
- Accumulation of CD57+ cells
- CMV infection a key driver of immune senescence
