Just as resistance to disease can be innate
(inborn) or acquired, the mechanisms
mediating it can be correspondingly divided into innate (left) and adaptive
(right), each composed of both cellular (lower half) and humoral elements
(i.e. free in serum or body fluids; upper half). Adaptive mechanisms, more
recently evolved, perform many of their functions by interacting with the older
innate ones.
Innate immunity is activated when
cells use specialized sets of receptors (see Fig. 5) to recognize different
types of microorganisms (bacteria, viruses, etc.) that have managed to penetrate
the host. Binding to these receptors activates a limited number of basic microbial
disposal mechanisms, such as phagocytosis of bacteria by macro- phages and
neutrophils, or the release of antiviral interferons. Many of the mechanisms
involved in innate immunity are largely the same as those responsible for
non-specifically reacting to tissue damage, with the production of inflammation
(cover up the right-hand part of the figure to appreciate this). However,
as the nature of the innate immune response depends on the type of infection,
the term ‘non-specific’, although often used as a synonym for ‘innate’, is not completely
accurate.
Adaptive immunity is based on the
special properties of lymphocytes (T and B, lower right), which can
respond selectively to thousands of different non-self materials, or ‘antigens’,
leading to specific memory and a permanently altered pattern of response – an adaptation
to the animal’s own surroundings. Adaptive mechanisms can function on their
own against certain antigens (cover up the left-hand part of the figure), but
the majority of their effects are exerted by means of the interaction of
antibody with complement and the phagocytic cells of innate immunity, and of T
cells with macro- phages (broken lines). Through their activation of these
innate mechanisms, adaptive responses frequently provoke inflammation,
either acute or chronic; when it becomes a nuisance this is called hypersensitivity.
The individual elements of this
highly simplified scheme are illus-trated in more detail in the remainder of
this book.
Interferons A family of proteins produced rapidly by many
cells in response to virus infection, which block the replication of virus in
the infected cell and its neighbours. Interferons also have an important role
in communication between immune cells (see Figs 23 and 24).
Defensins Antimicrobial peptides, particularly important
in the early protection of the lungs and digestive tract against bacteria.
Lysozyme (muramidase) An enzyme secreted by macrophages
that attacks the cell wall of some bacteria.
Complement A group of proteins present in serum which when
activated produce widespread inflammatory effects, as well as lysis of
bacteria, etc. Some bacteria activate complement directly, while others only do
so with the help of antibody (see Fig. 6).
Lysis Irreversible leakage of cell contents following
membrane damage. In the case of a bacterium this would be fatal to the microbe.
Mast cell A large tissue cell that releases inflammatory
mediators when damaged, and also under the influence of antibody. By increasing
vascular permeability, inflammation allows complement and cells to enter the
tissues from the blood (for further details of this process see Fig. 7).
PMN Polymorphonuclear leucocyte (80% of white cells
in human blood), a short-lived ‘scavenger’ blood cell whose granules contain
powerful bactericidal enzymes. The name derives from the peculiar shapes of the
nuclei.
MAC Macrophage, a large tissue cell responsible for
removing damaged tissue, cells, bacteria, etc. Both PMNs and macrophages come
from the bone marrow, and are therefore classed as myeloid cells.
DC Dendritic cells present antigen to T cells, and
thus initiate all T-cell-dependent immune responses. Not to be confused with
follicular dendritic cells, which store antigen for B cells (see Fig. 19).
Phagocytosis (‘cell eating’) Engulfment of a particle by a
cell. Macrophages and PMNs (which used to be called ‘microphages’) are the most
important phagocytic cells. The great majority of foreign materials entering
the tissues are ultimately disposed of by this mechanism.
Cytotoxicity Macrophages can kill some targets (perhaps
including tumour cells) without phagocytosing them, and there are a variety of
other cells with cytotoxic abilities.
NK (natural killer) cell A lymphocyte-like cell capable of killing some
targets, notably virus-infected cells and tumour cells, but without the
receptor or the fine specificity characteristic of true lymphocytes.
Antigen Strictly speaking, a substance that stimulates
the production of antibody. However, the term is applied to substances
that stimulate any type of adaptive immune response. Typically, antigens are
foreign (‘non-self’) and either
particulate (e.g. cells, bacteria) or large protein or polysaccharide molecules. Under special
conditions small molecules and even ‘self’ components can become antigenic (see
Figs 18–21).
Specific; specificity Terms used to denote the production of an
immune response more or less selective for the stimulus, such as a lymphocyte
that responds to, or an antibody that ‘fits’ a particular antigen. For example,
antibody against measles virus will not bind to mumps virus: it is ‘specific’
for measles.
Lymphocyte A small cell found in blood, from which it recirculates
through the tissues and back via the lymph, ‘policing’ the body for non-self
material. Its ability to recognize individual antigens through its specialized
surface receptors and to divide into numerous cells of identical specificity
and long lifespan makes it the ideal cell for adaptive responses. Two major
populations of lymphocytes are recognized: T and B (see also Fig. 15). B lymphocytes secrete antibody, the humoral
element of adaptive immunity.
Antibody is a major fraction of serum proteins, often
called immunoglobulin. It is made up of a collection of very similar proteins
each able to bind specifically to different antigens, and resulting in a very
large repertoire of antigen-binding molecules. Antibodies can bind to and
neutralize bacterial toxins and some viruses directly but they also act by opsonization
and by activating complement on the surface of invading pathogens
(see below).
T (‘thymus-derived’) lymphocytes are
further divided into subpopulations that ‘help’ B lymphocytes, kill
virus-infected cells, activate macrophages and drive inflammation (see Fig.
21).
Interactions between innate and
adaptive immunity
Opsonization A phenomenon whereby antibodies bind to the
surface of bacteria, viruses or other parasites, and increase their adherence
and phagocytosis. Antibody also activates complement on the surface of invading
pathogens. Adaptive immunity thus harnesses innate immunity to destroy many
microorganisms.
Complement As mentioned above, complement is often
activated by antibody bound to microbial surfaces. However, binding of complement
to antigen can also greatly increase its ability to activate a strong and
lasting B-cell response – an example of ‘reverse interaction’ between adaptive
and innate immune mechanisms.
Presentation of antigens to T and B cells by dendritic cells
is necessary for most adaptive responses; presentation by dendritic cells
usually requires activation of these cells by contact with microbial components
(e.g. bacterial cell walls), another example of ‘reverse interaction’ between
adaptive and innate immune mechanisms.
Help by T cells is required for many branches of
both adaptive and innate immunity. T-cell help is required for the secretion of
most antibodies by B cells, for activating macrophages to kill intracellular
pathogens and for an effective cytotoxic
T-cell response.
