4. Adaptive immunity 1 Flashcards
Innate immunity
Rapid response
Recognise patterns e.g. via PRRs e.g. MBL, scavenger receptors
increases cytokines, costimulatory molecules to allow for adaptive response
direct response for host defence - phagocytosis, antimicrobial activity
Adaptive response
Slow response, recognition intially low affinity receptors
Response - T and B cells with receptors encoded by fully rearranged genes
Memory
Comparison of B-cell add T-cell development
both develop in specialised microenvironments - bone marrow for B cells, thymus for T cells
B cells made in BM for life, T cells in thymus, decrease at puberty, also generated in other sites, long-lived peripheral T-cell pool
both have diverse Ag receptor repertoire via gene rearrangement
What guides B and T cell development?
Stromal cells
compartmentalised distinct stromal cells for T cells
stromal cells in bone marrow for B cells
both involve cell death via apoptosis
Changes in lymphoid cell antigens as they mature
As lymphocytes mature from a common lymphoid progenitor, they bifurcate at B cell/T cell stage and then express different antigens on their surface. These cluster as the cell matures.
B cell development
Common lymphoid progenitor, Pro-B, large Pre-B, small Pre-B, immature
Want to develop memory B cells and plasma cells
Plasma cells
Produce antibodies
Connector between innate and immune response
Phases of development
1st phase: Generation of antigen receptor by V(D)J rearrangement
2nd phase: refinement of Ag receptor repertoire. Antigen receptor is tested for antigen recognition. Positive selection: for Ag receptor that recognises self Ag weakly
Negative selection: for Ag receptor binds strongly to self Ags - these are eliminiated via apoptosis
3rd phase: stimulation by foreign Ag
- clonal selection of lymphocytes
- generation of effector and memory lymphocytes
Where do the diffferent phases of lymphocyte development take place?
1st phase (generation of antigen receptor) and 2nd phase (refining antigen receptor repertoire) in primary lymphoid organs
3rd phase - stimulation by foreign antigen - secondary lymphoid organs
What are the two types of B-cell antigens?
thymus dependent and thymus independent antigens
Thymus dependent antigens
Dependent upon helper T cells to induce antibody production. Proteins.
Thymus independent antigens
does not need helper T cells to induce antibody production.
Polysaccharides, lipids.
What kind of signalling is needed to engage an antigen receptor?
2 signal model: engagement of antigen receptor (BCR, “signal 1”) is not sufficient to activate B cell. Also need co-stimulatory signal (“signal 2”).
In T-cell independent and dependent B-cells
Features of a T-cell independent response
- Simple, repetitive antigens (often carbohydrates)
- Mostly IgM
- Modest affinity
- No memory
- B cells activated by direct BCR crosslinking
- B cells can also be activated via Toll-like receptors (TLRs)
How do T-independent antigens activate B-cells?
T-independent antigens activate B-cells by direct BCR aggregation
Stages of antigen dependent B-cell development
Organisation of lymphoid organs
T-independent B cell activation
T-cell / B-cell collaboration
Class switch recombination
T-cell/B-cell collaboration
- Required for antibody response to complex antigens– proteins, lipids
- Requires direct, physical B-T interaction
- Involves multiple cell surface receptors on T and B cells
- Both B and T cell must recognise antigen (but not necessarily the same epitope)
- Both B and T cells need signal 1 (through antigen receptor) and signal 2 (co-stimulation)
T-cell dependent B-cell response
Sequence of events:
Antigen binding to BCR provides “Signal 1” to B-cell.
Antigen is internalised, processed and antigenic peptides are displayed on MHC for T-cell recognition.
TH (helper T-cell) recognizes antigen-MHC complex via the T-cell antigen receptor (TCR): provides “Signal 1” to T-cell.
CD80/CD86 on B-cell binding to CD28 on T-cell provides “Signal 2” to T-cell.
T-cell activation leads to up-regulation of CD40L which bind to CD40 providing “Signal 2” to B-cell.
Cytokine production by activated T-cell also help to activate B-cell.
B-cell proliferates and differentiates into antibody secreting B cell (plasma cell).
Antigen recognition by B-cells vs T-cells
Both form their antigen receptors by V(D)J recombination
B-cell receptor (BCR) consists of 2 HC and 2 LC (membrane and secreted Ig).
T-cell receptor (TCR) consists of ab heterodimer (membrane form only).
Both signal by associating with signaling complex in membrane:
Ig-alpha and Ig-beta for B-cells, CD3 complex for T-cells.
B-cells can bind intact protein antigen in solution.
T-cells bind peptides displayed on the surface of another cell : an “antigen presenting cell” (dendritic cell, macrophage, or B-cell).
Primary antibody response
After first infection, B cells are activated and antibody secreting cells in peripheral lymphoid tissues, then low-level antibody production
5-10 day lag, smaller peak response, more IgM than IgG, lower average affinity and more variable
Secondary antibody response
Happens upon repeat infection
usually 1-3 days, larger peak response, relative increase in IgG and under certain situations IgA or IgE (heavy class switching) higher average affinity (affinity maturation)
