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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


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)