Recognition And Receptors: The Keys To Immunity
Before any immune mechanism can go into action,
there must be a recognition that
something exists for it to act against. Normally this means foreign material
such as a virus, bacterium or other infectious organism. This recognition is
carried out by a series of recognition molecules or receptors. Some of
these (upper part of figure) circulate freely in blood or body fluids, others
are fixed to the membranes of various cells or reside inside the cell cytoplasm
(lower part). In every case, some constituent of the foreign material must
interact with the recognition molecule like a key fitting into the right lock.
This initial act of recognition opens the door that leads eventually to a full immune
response.
These receptors are quite different
in the innate and the adaptive immune system. The innate system (left)
possesses a limited number, known as pattern-recognition receptors (PRRs),
which have been selected during evolution to recognize structures common to
groups of disease-causing organisms
(pathogen-associated
molecular patterns, PAMPs); one
example is the lipopolysaccharide (LPS) in some. bacterial cell walls (for more details see Fig.
5). These PRRs act as the ‘early warning’ system of immunity, triggering a
rapid inflammatory response (see Fig. 2) which precedes and is essential for a
subsequent adaptive response. In contrast, the adaptive system has thousands of
millions of different receptors on its B and T lymphocytes (right), each one
exquisitely sensitive to one individual molecular structure. The responses
triggered by these receptors offer more effective protection against infection,
but are usually much slower to develop (see Figs 18–21).
Linking the two systems are the
families of major histocompatibility complex (MHC) molecules (centre),
specialized for ‘serving up’ foreign molecules to T lymphocytes. Another set of
‘linking’ receptors are those by which molecules such as antibody and complement become
bound to cells,
where they can
themselves act as receptors.
Complement A complex set of serum proteins, some of which
can be triggered by contact with bacterial surfaces (for details see Fig. 6).
Once activated, complement can damage some cells and initiate inflammation.
Some cells possess receptors for complement, which can assist the process of
phagocytosis (see Fig. 9).
Mannose-binding lectin (MBL) binds the surface of bacteria and fungi, and
can activate complement or act directly to assist phagocytosis.
Acute phase proteins Another complex set of serum proteins. Unlike
complement, these proteins are mostly present at very low levels in serum, but
are rapidly produced in high amounts by the liver following infection, where
they contribute to inflammation and immune recognition. Several acute phase
proteins also function as PRRs.
PRR Pattern-recognition receptors have now been
described for every type of pathogen, and more are being discovered all the
time. They can broadly be divided in terms of cellular localization, e.g. cell
membrane, endosome/phagosome and cytoplasm. Although they are represented by a
bewildering variety of types of molecules, their common functional feature is
they regulate the innate immune response to infection. Note that not all PRRs
are found on all types of cell, the majority being restricted to macrophages
and dendritic cells (MAC, DC in figure). Further details of PRR types are given
in Fig. 5.
Receptors feature in a number of
other biological processes, many of them outside the scope of this book. Here
are a few that are relevant to immunity.
Virus receptors To enter a cell, a virus has to ‘dock’ with
some cell- surface molecule; examples are CD4 for HIV (see Fig. 28) and the
acetylcholine receptor for rabies.
Cytokine receptors Communication between immune cells is largely
mediated by ‘messenger’ molecules known as cytokines (see Figs 23 and 24). To
respond to a cytokine, a cell needs to possess a receptor for it.
Hormone receptors In the same way as cytokines, hormones (e.g.
insulin, steroids) will
only act on
cells carrying the
appropriate receptor.
Adaptive immune system
Antibody Antibody molecules (for details see Figs 13,
14, 19 and 20) can act as both soluble and cell-bound receptors.
1
On the B
lymphocyte, antibody molecules synthesized in the cell are exported to the
surface membrane where they recognize small components of protein,
carbohydrates or other biological macromolecules (‘antigens’) and are taken
into the cell to start the triggering process. Each B lymphocyte is programmed
to make antibody of one single recognition type out of a possible hundreds of
millions.
2
When the B
lymphocyte is triggered, large amounts of its antibody are secreted to act as
soluble recognition elements in the blood and tissue fluids; this is referred
to as the ‘antibody response’. Antibody in serum is often referred to as
immunoglobulin (Ig).
3
Some cells
possess ‘Fc receptors’ (FcR in figure) that allow them to take up antibody,
insert it in their membrane, and thus become able to recognize a wide range of
antigens. This can greatly improve phago- cytosis, but can also be responsible
for allergies (see Fig. 35).
T-cell receptor (TcR in figure) T lymphocytes carry receptors
that have a similar basic structure to antibody on B lymphocytes (for further
details see Figs 12 and 18) but with important differences:
1
They are
specialized to recognize only small peptides (pieces of proteins) bound to MHC
molecules (see below);
2
They are
not exported, but act only at the T-cell surface.
MHC molecules These come in two types. MHC class I molecules
are expressed on all nucleated cells while class II MHC molecules are normally
found only on B lymphocytes, macrophages and dendritic cells. Their role is to
‘present’ small antigenic peptides to the T-cell receptor. The class of MHC and
the type of T cell determine the characteristics of the resulting immune response
(see Figs 11 and 18). Their name comes from their important role in stimulating
transplant rejection (see Fig. 39).
NK cell receptors Natural killer cells share features of both
lymphocytes and innate immune cells. They are specialized for killing virus-infected
cells and some tumours, and they possess receptors of two opposing kinds.
1
Activating
receptors are analogous to PRRs, recognizing changes associated with stress and
virus infection.
2
Inhibitory
receptors recognize MHC class I molecules, preventing NK cells killing normal
cells. The final result thus depends on the balance between activation and
inhibition (for further details see Figs 10, 15 and 42).
