6.8, 6.9 - Antibodies, B cells and T cells

Antigens and specific recognition

An adaptive immune response targets particular molecular features rather than treating every foreign particle in the same way.

Many pathogen antigens are proteins or polysaccharides on their surfaces. A single bacterium can carry several different antigens. Antigens can also be soluble molecules, such as a bacterial toxin. The body's own cells carry self antigens; a normally functioning immune system is tolerant of the body's own tissues. The term antigen does not mean that a molecule must itself cause disease.

An antibody therefore recognises a molecular region, rather than an entire bacterium as one object. Antibodies are also called immunoglobulins. Some antibody molecules are cell-surface receptors; others are secreted into body fluids.

Lymphocytes are white blood cells that include B cells and T cells. Before a particular infection, the body already has many different lymphocytes with different antigen receptors. Recognition selects cells with a suitable receptor; the pathogen does not instruct every lymphocyte to manufacture a new matching receptor.

B cells have membrane-bound antibody molecules that act as antigen receptors. An antigen can bind directly to a B-cell receptor if its binding site is complementary to that antigen's recognised region. A B cell with a different binding site is not selected by that antigen. This specificity depends on the three-dimensional structure of the binding site, which follows from the antibody's amino acid sequence.

T cells also have specific receptors, but they recognise antigen fragments presented on another cell's surface, rather than binding free intact antigen in the way B-cell receptors do. Recognition is the first step; appropriate additional activation signals are also needed for a full response.

Antigen presentation and helper T cells

Phagocytosis can both remove a pathogen and provide information that helps start a specific response.

A macrophage is a large phagocytic white blood cell. It engulfs a pathogen into a vesicle; fusion with lysosomes supplies enzymes that digest the pathogen. Some protein fragments derived from the pathogen are displayed at the macrophage's cell surface, held by membrane proteins called MHC proteins. The fragment is exposed for recognition; it is not an intact pathogen being released from the cell.

Macrophages therefore link the non-specific phagocytic response to the specific adaptive response. Dendritic cells are also important antigen-presenting cells, particularly in starting responses by T cells that have not encountered their antigen before. B cells can present fragments of antigen they have taken up. An antigen-presenting cell is a role, not a separate name for every white blood cell.

A T helper cell with a suitable receptor recognises a presented antigen fragment. Helper T cells recognise fragments displayed on MHC class II, found on professional antigen-presenting cells such as macrophages, dendritic cells and B cells. With the additional activation signals, the selected helper cell becomes activated. It divides by mitosis, producing a clone of cells with the same antigen specificity. This multiplication is clonal expansion.

Activated helper T cells release cytokines, signalling proteins that change the activity of other immune cells. They help antigen-selected B cells proliferate and differentiate, support the activation and expansion of killer T cells, and can activate macrophages to destroy ingested pathogens more effectively. Helper T cells coordinate these responses; they do not secrete antibodies or perform the killer T cell's direct attack on an infected body cell.

Much lymphocyte activation and proliferation occurs in lymphoid tissues, such as lymph nodes, where antigen-presenting cells and suitable lymphocytes can meet. Cells and their products can then act at sites of infection.

B-cell clones and plasma cells

The B-cell response converts recognition of an antigen into production of large quantities of a matching antibody.

Consider a response to a pathogen's protein antigen. A B cell binds that antigen using its surface receptor, takes it up, processes it and presents a fragment on MHC class II. An already activated helper T cell that recognises the appropriate presented fragment can interact with the B cell. Contact signals and cytokines from the helper cell support B-cell activation. B-cell binding and T-cell help therefore connect recognition to a controlled response. This describes the helper-dependent response to protein antigens; it is not a claim that every possible B-cell response requires identical signals.

The selected B cell divides by mitosis to form a clone. Clonal selection is the selection of the cells that recognise the antigen; clonal expansion is their subsequent multiplication. The clone's descendants differentiate into cells with different jobs:

• B effector cells become antibody-secreting plasma cells. Plasma cells release large quantities of antibodies with the relevant specificity into tissue fluid, lymph and blood plasma. Their abundant rough endoplasmic reticulum and Golgi apparatus support protein synthesis and secretion.
• B memory cells retain the antigen specificity and persist after the initial response, ready for a later encounter. They are not simply a reserve supply of antibodies.

Plasma cells are cells; blood plasma is the fluid component of blood. They are different meanings of the word plasma. Likewise, a cytokine from a helper T cell is a signal to a B cell, not an antibody and not material that turns the helper cell into a B cell.

Reasoning from a controlled comparison

The table is an original, simplified prediction for a helper-dependent response to protein antigen X. Each culture starts with equal numbers of living B cells whose receptors recognise X. All other culture conditions are the same; no antibody is supplied at the start. “Helper signals present” means the required compatible contact and cytokine signals are provided.

Comparing A with B isolates the contribution of helper signals while keeping antigen X present. Comparing A with C isolates antigen recognition while keeping helper signals present. Together, the predictions show why helper signals alone do not make every B cell secrete antibodies. A positive antibody measurement is evidence of an antibody-secreting output; it does not by itself measure the number of memory cells formed. These are illustrative predictions, not reported experimental results or proof that all immune responses follow the same conditions.