T1 L4 Adaptive immunity 1 Flashcards
Describe the innate response
Rapid response
Pattern-recognition receptors
Increased cytokines and costimulatory molecules
Direct response for host defence - phagocytosis, antimicrobial activity
Describe the adaptive response
Slow response
Recognition - initially low affinity receptors
Gene rearrangement and clonal expansion
Memory
How many B cells circulate in the body?
10 billion
How many B cells are made everyday?
10 million
What is the lifespan of an immature B cell?
5 days
Where do B cells develop?
Bone marrow
Where do T cells develop?
Thymus
Describe T cell production in adults
Thymus has atrophied
Thymus has some residual corticomedullary tissue with myocytes
New T-cells are generated in extrathymic sites
Long-lived peripheral T-cell pool
Describe the involvement of stromal cells in the development of T cells
Development is compartmentalised
Distinct types of stroll cells
Describe the involvement of stromal cells in the development of B cells
Stromal cells are in the bone marrow
Describe the pathway of T lymphocyte development from the lymphoid stem cell
1) Lymphoid stem cell
2) Pro-T lymphocyte
3) Early thymocyte
4) Common thymocyte
5) Th lymphocyte, Tc/s lymphocyte
Describe the pathway of B lymphocyte development from the lymphoid stem cell
1) Lymphoid stem cell
2) Pro-B lymphocyte
3) Pre-B lymphocyte
4) Early B lymphocyte
5) Activated B lymphocyte, plasma cell
What are the 3 stages of B cell development?
Phase 1: generation of antigen receptor
Phase 2: refinement of antigen receptor repertoire
Phase 3: stimulation by foreign antigens
Describe the 1st phase of B-cell development
Generation of antigen receptor
- V(D)J gene rearrangement –> antigen receptor
Describe the 2nd phase of B-cell development
Refinement of antigen receptor repertoire
- antigen receptor is tested for antigen recognition
- positive selection for antigen receptor that recognises ‘‘self’’ antigens weakly
- negative selection for antigen receptor that binds strongly to ‘‘self’’ antigens. Cells eliminated via apoptosis
Describe the 3rd phase of B-cell development
Stimulation by foreign antigens
- clonal selection of lymphocytes
- generation of effector and memory lymphocytes
Describe thymus dependent antigens
Dependent upon helper T-cells to induce antibody production
Recognises proteins
Describe thymus independent antigens
Doesn’t need helper T cells to induce antibody production
Recognises polysaccharides and lipids
Describe the 2 signal model for B-cell antigens
Engagement of antigen receptor (signal 1) isn’t sufficient to activate B-cell
Need co-stimulatory signal (signal 2), CD40/CD40L
Describe the 2 signal model for T independent antigens
Polymeric complexes of B cell receptors on surface of cell bind together to cross link antigens they are binding. Amplifies signal B cell receives. Autoactivation of B cell
Describe the 2 signal model for T dependent antigens
More common
Only a few receptors on surface can recognise the antigen, they don’t polymerise but lead to internalisation of that antigen
Describe the T-cell independent response
Simple, repetitive antigens - often carbohydrates
Mostly IgM
Modest affinity
No memory
B cells activated by direct B-cell receptor cross linking and aggregation
B cells can also be activated via Toll-like receptors
Describe the B cell development (antigen dependent)
T-cell / B-cell collaboration
- required for antibody response to complex antigens
- requires direct, physical B-T interaction
- involves multiple cell surface receptors on T and B cells
- Both B & T cells must recognise antigen
- Both B & T cells need signal 1 and signal 2
Class switch recombination
Describe the steps of the T-cell dependent B-cell response
1) Antigen binding to B cell receptor provides ‘‘signal 1’’ to B cell
2) Antigen is internalised & processed. Antigenic peptides displayed on MHC for T-cell recognition
3) Th (helper T-cell) recognises antigen MHC complexes via T-cell antigen receptor & provides ‘‘signal 1’’ to T-cell
4) CD80 / CD86 on B-cell bind to CD28 on T cell to provide ‘‘signal 2’’ on T cell
5) T-cell activation leads to up regulation of CD40L which binds to CD40 providing ‘‘signal 2’’ on T-cell
6) Cytokine production by activated T cells also help activate B cell
7) B cell proliferates and differentiates into antibody-secreting B cell (plasma cell)
What is the signalling complex for B cells?
Ig-alpha
Ig-beta
What is the signalling complex for T cells?
CD3 complex
What is the initial lag of the primary antibody response?
5-10 days
What is the initial lag of the secondary antibody response?
1-3 days
What is the peak response of the antibody responses?
Primary response: smaller
Secondary response: larger
What is the antibody isotype in the primary antibody response?
Usually IgM > IgG
What is the antibody isotype in the secondary immune response?
Relative increases in IgG & under certain situations in IgA or IgE
