| THE REACTION WITH, THE RESPONSE TO, AND THE ELIMINATION OF, ANTIGENS
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| On binding to the antigen, the cell divides and then differentiates into progeny with an effector function or a memory function
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| On successful antigen binding, accompanied with a requisite number of so-called costimulatory signals, the cell is activated to enter the cell cycle leading to repeated division or proliferation. This results in multiple daughter cells or a clone. This is followed by differentiation which alters the functional capabilities of the cell, and it may be accompanied by a change in the cell's appearance. Differentiation can either lead to the development of an effector function or the generation of memory. The aim is to create clones of cells that have precisely the same specificity for antigen and the process is termed the clonal selection. Antigen therefore determines the specific lymphocyte that will undergo activation. This outcome is assisted by the structural organization of the lymphoid tissues, together with the lymphoid traffic between them. This ensures that antigen is inspected by many lymphocytes and can select for proliferation and differentiation the cell that bears a specific and reciprocal antigen receptor.
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| Clonal selection (Fig. 36.5) ensures not only an adequate number of effector cells to deal with the threat at the time of initial stimulation, but also a suitable number of part-primed memory cells that will be able to complete their activation more rapidly on subsequent exposure.
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| Memory is one of the components that distinguish the specific immune response from the nonspecific response
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| How memory is generated is still the subject of continuing research: it has been suggested that the partial triggering of lymphocytes is an important mechanism. The partially triggered cells fail to undergo complete differentiation to the effector cell state and appear to return to a resting state. On subsequent exposure to the same antigen that partially triggered them previously, the time to complete proliferation and activation is significantly shortened, thus leading to a quicker and more effective response.
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| Specific immune response is responsible for the elimination of antigens that are intracellular or integral to the cell surface
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| Figure 36.5 Clonal selection in B cells. Antigen-specific (Ag-specific) secretory immunoglobulin (sIg) on the B-cell membrane has a shape reciprocal to the antigen. Antigen-immunoglobulin binding leads to activation and proliferation to produce a clone of antigen-specific B cells. Each member of the specifically activated clone then undergoes differentiation into a plasma cell, which produces large quantities of a single homogeneous immunoglobulin with identical specificity to the sIg that triggered the response in the first instance. |
| As indicated above, specific immune response is mediated by cellular and humoral elements. The specific immune response has been classically described as having cellular and humoral arms, T cells being considered responsible for cellular immunity and B cells for humoral immunity. It is now established that the role of cellular, or T-cell mediated, immunity is dealing
with chronic intracellular infections, mediating the immune response to tumors, the rejection of transplanted tissue and contact hypersensitivity. Chronic intracellular infections may be bacterial (e.g. tuberculosis), viral, fungal or parasitic,
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| T cells are responsible for the regulation of the activities of the other arms of the immune response
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These functions include:
- increasing the numbers of cells capable of responding to the particular antigen;
- preventing the antigen gaining access to so far unaffected cells;
- limiting damage, i.e. assisting already altered cells to rid themselves of antigens by enhancing the capacity the affected cells have for self-cure and destroying those cells that do not have such capacity;
- making sure that any antigenic material released will be mopped up by other elements of the immune response, (both specific and nonspecific), clearing the damage and generating memory of the process.
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| Figure 36.6 The integrated cellular immune response. T-helper cells (Th cells) are involved in many aspects of the cellular immune response. Cytokine and direct Th cell-mediated activation of B cells leads to differentiation to plasma cells, which secrete antibody. AG:AB, antigen-antibody; APC, antigen presenting cell; Tc, cytotoxic T cell; Th, T helper cell. |
| All of these other functions can be achieved either by direct cell-cell contact or by the secretion of soluble mediators that interact with the relevant cells, be they other T cells, B cells, NK cells, cells involved in the nonspecific immune response, or cells of other tissues. The responsibilities for providing all these functions, with the exception of killing cells, resides in a subpopulation of T cells. Not surprisingly, as they have the role of assisting the rest of the immune response and host response, these cells have been termed T-helper cells (Fig. 36.6).
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| This population of T cells achieves its goals for the elimination of intracellular antigen by the secretion of cytokines and direct interaction with the B cells responsible for antibody-mediated immunity, other T cells, and macrophages
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| These cells can be identified phenotypically by its expression of CD4, together with its nonexpression of CD8. The term CD4 T cell is synonymous with T-helper cell.
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| T-helper cells can also differentiate into those that drive a proinflammatory response and those that drive an anti-inflammatory response
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| It is now recognized that T-helper cells can be further divided into helper cells that drive the immune response towards a proinflammatory or antibody-based response and helper cells that drive the response towards an antagonistic anti-inflammatory or cell-orientated response. This differentiation is made on the basis of the profiles of secreted cytokines.
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The lymphocyte-derived cytokines perform the following actions:
- augment further the nonspecific immune response;
- determine the form of the specific immune response to be used;
- assist the relevant cellular components in mediating it.
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| Other cells are cytotoxic and kill cells that carry a 'recognizable' antigen, i.e. the antigen for which the killer cells carry a receptor
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| The other major T cell subpopulation are the cytotoxic T cells (Tc) specifically responsible for killing those cells that express on their surface the antigen for which the Tc carries the appropriate TCR. Like T-helper cells, cytotoxic T cells can be identified phenotypically and are CD8+, CD4-. These cells employ a mechanism of killing that is similar to that used by the complement system (see earlier) but requires direct cellular interaction between the Tc and the target cell. A polymeric macromolecule termed perforin is inserted into the target cell wall, breaching its integrity. Unlike the complement system, reliance is not placed on this alone and enzymes (granzymes) from the Tc cell are introduced into the target cell, to hasten cell death.
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