ALL INJURIES, INCLUDING BURNS, ARE IMMUNOSUPPRESSIVE.

The ability of injured patients to survive often depends on an adequate immune mechanism to combat the constant threat of sepsis. We therefore need to understand the immune response and its potential for manipulation.

HISTORICAL NOTES.  Early investigations were closely tied to the immune response in surgery and trauma. In 1966 it was reported that the Phytohemagglutinin (PHA) response of human lymphocytes following surgical operations was impaired. Within a few years, in burned patients and animals, it had been observed that tuberculin reactions were abolished in severe burns, the inflammatory reaction behaved differently, and immunoglobulins leaked from the circulation thereby prejudicing opsonization and phagocytosis. Interest in the field expanded rapidly when it was noted that the observed changes could be quantitatively correlated with patient survival. Since that time, research has moved along with progress in molecular biology and immunogenetics, in the hope that interventions could be formulated for the benefit of patients.

FUNDAMENTALS AND DEFINITIONS

The Immune Response basically depends on the interaction of a series of cells and a large number of soluble products of these and other cells, including interleukins, chemokines, cytokines, complement proteins, and peptides. We will first discuss the most important cells together with their receptors - which makes the cells respond- then the products of the cells with their function.

CENTRAL CELLS OF THE IMMUNE RESPONSE

THE LYMPHOCYTE

The principal master-cell of the immune system. The lymphocyte has surface receptors which allow it to interact with the environment. This is followed by differentiation, activation, transcription, and the manufacture of several soluble products with biological function which are then extruded into the environment.

PRINCIPAL TYPES OF LYMPHOCYTES

Lymphocytes can differentiate into “thymic-dependent” or T-cells, and “bursa-dependent” or B-cells. This nomenclature has nothing to do with function: it is historical nomenclature going back to original theories derived from animal research which has persisted through the years. T-cells are further divided into helper T-cells (Th or T4) and cytotoxic/suppressor (Ts or T8) cells depending on their receptor expression. Another class of cell, the NK or natural-killer cell also fits into this family. B cells mature into plasma cells which make immunoglobulins. In addition, T4 cells have been subdivided according to whether they produce proinflammatory cytokines, principally TNF, IL-1 and IL-6, (Th-1 cells) or antiinflammatory cytokines such as IL-4, IL-8 and IL-10 (Th-2 cells).

The next series of schematics illustrates some of the more important receptors by which these cells may be recognized.

The receptors illustrated in the above drawings induce the cell to engage in important immunological functions. The receptor may be identical to the product  the cell will secrete when induced. For example, when a stimulant activates the IL-2R receptor of T-cells, those cells will begin secreting IL-2, which then recruits other, dormant T-cells to become activated.