Electrode Materials

Cell type Function

Macrophage/monocyte Phagocytose foreign material Polymorphonuclear cells or

granulocytes

Phagocytose foreign material

Lymphocytes

T Cell-mediated cytotoxicity—major histocompatibility complex restricted (MHCr)

TH or TS Helper or suppressor

B Antibody production

Natural killer (NK) Cell-mediated cytotoxicity (non-MHCr)

Mechanisms of sensitisation and allergy

The immune system defends the body against invading organisms, exogenous antigens, and host cells that have become neoplastic. In addition, the immune system is an active participant in autoimmune disease, hypersensitivity reactions and transplant tissue rejections.

Most of the blood cells, first described in the previous section on the haematopoietic system, have immunological functions. The most significant of these are the lymphocytes, which are involved in the two main phases of the immune response—the induction phase and the sensitisation phase. This second phase then consists of two components—an antibody-mediated component and a cell-mediated component.

The lymphocytes are divided into two main groups:

■ B cells, which are involved in the production of antibodies.

■ T cells, which are important in the induction phase of the immune response and are responsible for cell-mediated reactions. There are helper/inducer, suppressor and cytotoxic T cells.

Specific immunological response

The specific immunological response increases the efficiency of the organism’s defence response. The response is both more efficient, and can be specific to an individual pathogen or toxicant.

The antigen

The initial step in the immune response is recognition by the organism that something is present which is foreign. This is called the antigen. The antigen may be:

■ a bacteria or microorganism

■ products of organisms, such as excreta of dust mites or bacterial proteins

■ a large chemical molecule

■ a small chemical molecule called a hapten (these are chemicals that are too small to be recognised as antigens in their own right, and must bind to proteins to evoke a response)

■ proteins

■ some drugs.

T cell-antigen-B cell complex

The principal cells in antigen recognition are the T and B lymphocytes; more specifically, the T helper cells and B cells. These bind cooperatively or simultaneously to the antigen at different sites, and a T helper cell-antigen-B cell complex forms. The T helper cell also releases soluble factors that stimulate the proliferation of B cells. These cloned B cells mature into antibody-producing cells, the plasma cells.

The antibody

The antibody is a Y-shaped protein structure called gammaglobulin or immunoglobulin (Ig), with the arms of the Y being specific recognition sites for specific antigens. There are a range of different categories of antibody, which differ from each other in certain structural respects. These are IgG, IgM, IgE, IgA and IgD.

Antibodies improve the organism’s capacity to respond to toxic insult. Apart from their ability to interact directly with pathogens or toxins, they can also multiply many times, making the defence reaction specific and effective.

Systemic responses in inflammatory reactions

In addition to the local changes in an area where an inflammatory response is occurring, there are sometimes various general responses which may affect the whole organism. For example:

■ rise in temperature, due to increased biological activity

■ increase in blood cell populations, such as leukocytes (leukocytosis), neutrophils (neutrophilia) or monocytes

■ increase in concentration of circulating proteins, enzymes and mediators (such as fibrinogen, α2-macroglobulin and components of complement)

■ change in immune function.

All of these reactions are based on and are dependent of the scope and intensity of the inflammatory response.

Unwanted inflammatory and immune responses

The inflammatory and immune responses outlined above are complex and elaborate.

They are also not without problems. The immune response to an antigen is potentially a

‘double-edged sword’ that can either protect or harm the host. Of course, the paramount biological effects of the immune response are the humoral (B cell) and cellular (T cell) recognition and elimination of infectious agents and other foreign antigens. Nevertheless, re-exposure of some previously sensitised individuals to the same antigen may bring about an exaggerated (‘hyper-sensitive’) or misdirected immune response that results in local tissue injury or in systemic manifestations, including shock or death. Immune responses that result in tissue injury or other pathophysiological changes are called hypersensitivity (allergic/immunopathological) reactions.

The ensuing tissue injury may involve:

■ release of vasoactive substances (primary and secondary mediators)

■ phagocytosis or lysis of cells

■ activation of the inflammatory and cytolytic components of the complement system

■ release from recruited inflammatory cells of proteolytic enzymes, cytokines, and other mediators of tissue injury and inflammation.

The antibody-induced inflammatory response can, in certain circumstances, be inappropriately triggered, or triggered to induce exaggerated reactions. Unwanted immune responses are termed allergic or hypersensitivity reactions, and have been classified into four types: Type I (anaphylactic), Type II (antibody-dependent/cytotoxic), Type III (immune complex) and Type IV (cell-mediated/delayed) hypersensitivity (see Table 3.9) (Gallin 1993).

Type I Immediate or anaphylactic hypersensitivity

This occurs when the antigenic material, which is not of itself noxious, evokes the production of IgE-type antibodies. Antigens which can cause this reaction include grass

pollen, house-dust mite products, some foods, chemicals and drugs. IgE antibodies bind to mast cells and on subsequent exposure cause the release of histamine, platelet-activating factors, eicosanoids and cytokines. Effects may be localised to the nose (hay fever), skin (urticaria), bronchus (asthma) or gastrointestinal system. In some cases, the reaction is more generalised and can produce anaphylactic shock which can be immediately life-threatening. This process is basically an inappropriate deployment of antibody-mast cell interactions.

Type II Antibody-dependent cytotoxic hypersensitivity

All cells within an organism have properties which allow the immune system to recognise that they belong to the host organism (‘self’), and should not be targeted for an immune reaction. If the immune system fails to recognise cells as being part of the host organism, it will initiate an immune response. This Type II response can arise spontaneously in autoimmune conditions (where antibody is directed against host antigen or ‘self’) or can occur, for example, after incompatible blood transfusions or alteration of cell properties to remove ‘host identity’ by drugs or chemicals. The basic mechanism is an initiation of the complement sequence by the antigen-antibody reaction.

Table 3.9 Immunological mechanisms of