14.6 The Immune System

193

Table 14.3 Stages of cancer and some genetic correlates

Stage

Macrodescription

Microdescription

A

Dedifferentiated tissue (atavism)

Inherited mutations

B

Benign epithelial cancer

Acquired mutations: increased

exposure to carcinogens from the

environment

C

Adenocarcinoma

p53 gene involved

D

Metastasis

Many mutations

and more abnormal aneuploidy. Given that aneuploidy implies extra copies of some

chromosomes and damage to or deletion of others, the resulting cell is likely to

show phenotypically deviant behaviour, including the ability to hyperproliferate and

rapidly evolve drug resistance.

14.6

The Immune System

The higher metazoans have developed a sophisticated mechanism for neutralizing

external attack at the micrometre and nanometre scales, at which the dangers are

bacteria and other microbes, viruses, and dust particles. This mechanism is called

the immune system and is divided into innate and adaptive parts. The primary (ini-

tial) response is innate and consists in the ingestion of foreign microbodies and

nanobodies by phagocytes. The adaptive immune system, which is only found in the

highest organisms, involves T-cells (matured in the thymus) that have thousands of

copies of the so-called T-cell receptor (TCR) on their surfaces. In principle, each

T-cell has a different TCR, and each one can bind to (i.e., is a receptor for) a par-

ticular oligopeptide–MHC complex, ³⁸ provided that the peptide is not from one of

the organism’s proteins. As a result of the binding, these “helper” T-cells release

cytokines, which themselves trigger the proliferation and recruitment of cytotoxic or

killer T-cells, which release perforin, a protein that perforates the target cell mem-

brane when it binds to it. At the same time, B-cells (matured in the bone marrow)

produce antibodies able to bind to portions (“antigens”) of the foreign objects. Each

B-cell produces a unique antibody. ³⁹ The binding of a B-cell to “its” antigen leads to

clonal expansion of that B-cell and concomitant expansion of antibody production.

The antibodies binding to the antigens of the foreign objects form molecular com-

38 The MHC (major histocompatibility complex) is a system of proteins residing on the surface of

a cell that complexes with certain oligopeptides derived from a sample of the internal proteins of

the cell.

39 The antibody is a protein made by several different polypeptide chains. Part of the molecule is

the same for all antibodies and part is unique. Tonegawa (1983) demonstrated that the diversity

of antibodies was due to somatic generation of genetic diversity among the genes coding for the

variable (unique) part.