Principles of Immunology
There are two features which distinguished immune responses from the non-specific defence mechanisms such as
inflammation. The first is the specificity of the reaction, which is easiest to appreciate in terms of antibody
responses but it is also true of the cellular immune responses; an essential part of this specificity is the remarkable
ability to distinguish between self and non-self. The second is memory by which a second challenge with a
stimulus provokes a more rapid and more vigorous immune response. These concepts began to be formulated by
Jenner and were developed by Pasteur, Erlich, Landsteiner, Medawar, Burnet, and many others. In the last 30
years, the cellular and molecular basis of these two characteristics has become much clearer.
Immune reactions play important roles in most disease processes. Much of what is observed at the bedside
involves immune responses, although the visible, palpable, or audible end-result can be quite distant from the
primary event. End-immune reactions can be divided into two: those dependent on antibody (humoral responses)
and those on T lymphocytes (cell-mediated immune responses, CMI). Antibody reactions themselves are normally
quite silent in vivo (e.g. neutralizing virus infectivity), but sometimes antibodies may trigger various secondary
events that become literally visible (e.g. anaphylaxis) or revealed on investigation (e.g. haemolysis). Cell-mediated
immune responses may also be silent (e.g. clearing of some virus infections by T cells lysing infected cells or
releasing interferon) or visible (e.g. delayed hypersensitivity reactions in the skin) or revealed by investigation
(e.g. kidney graft rejection).
These two different types of immune response are indicative of the basic division of lymphocytes into two types,
B and T cells. They interact with each other and with a third important cell, the antigen presenting cell. The
following sections explain how these cells work, as far as possible at a molecular level.
Antigens
Both B and T lymphocytes make the fundamental distinction between self and non-self. This is quite remarkable;
for example each species will make antibody to cytochrome c of other species but not self, even though they are
closely related proteins differing in very few amino acids. Similarly, T cells respond to all HLA (transplantation)
antigens of other members of the species but not self. The mechanisms that underlie this self tolerance are
complex and will be explained later. First, the nature of antigens recognized by B and T cells need to be examined,
because there are important differences.
Antigens recognized by B cells
B lymphocytes recognize antigen through their surface antibody receptors. In chemical terms, the recognition is
identical to that by secreted antibody. The antibody reacts with the native proteins. The availability of large
amounts of purified antibodies, particularly monoclonal antibodies secreted by hybridomas, has facilitated detailed
