This thesis is concerned with immunohistological studies of adult human connective tissues and
with connective tissues in the adult and embryonic
rat.The concept that the constitution of connective
tissues represents a response by synthesising
cells to their environment, provides a basis for
conjecture concerning the processes involved in
ageing and rheumatoid disease.The concept that a mutual interplay between a
cell and its environment is involved in the maintenance
of the integrity of connective tissues has,
it is suggested, relevance to rheumatoid disease.
Alterations in the representation of any one constituent
of connective tissue, whether attributable
to abnormal genetic endowment or somatic mutation
in the relevant synthesizing cell, are likely to
initiate changes in the environment, and therefore
the function of cells synthesizing related constituents
of connective tissue. Although this concept
takes into account the view that rheumatoid disease
involves a restricted number of somatic mutations,
responsible perhaps for the formation of a tissue
constituent which is abnormally susceptible to
damage by trauma or infection, a major difficulty
arises. The present concept appears to require
that to the rheumatoid factors be ascribed a role
in the metabolism, or in the control of the synthesis
of one or other of the constituents of adult
connective tissue. This view is hardly tenable,
It may be, however, that the rheumatoid factors
reflect the activity of a gene- enzyme system which
is responsible for the synthesis of a constituent
of connective tissue peculiarly susceptible to
degradation by trauma or micro -organisms. It is
not necessary, however, to deny immune mechanisms
as a role in the production of rheumatoid factors.
The view that rheumatoid factors reflect intense
immunological activity in rheumatoid disease is
not necessarily irreconcilable with the proposition
that one of the initiating events in rheumatoid
disease may be the synthesis of a constituent of
connective tissue which is abnormally susceptible
to degradation by the action of micro -organisms
or trauma.In connection with ageing, the possibility is
considered that subtle changes in the structure of
the collagen molecule may contribute to the age
associated alterations in the rheological properties of collagen. This is not to deny the proposition
that the increased structural stability of
aged collagen is to be attributed to an increase
in the number and strength of cross links between
and within collagen macromolecules, but merely to
suggest that the nature of the intra- and inter-molecular cross links, the rate at which they can
form, and the ease with which cross linking agents
can react with adjacent collagen macromolecules,
are governed by the subtle structure of the collagen
molecule. The proposition that ageing is associated
with changes in the subtle structure of the
collagen molecule may be open to investigation by
means of a study of the patterns of immunological
reactivity manifested by neutral salt-soluble,
acetic acid-soluble and insoluble collagen obtained
from subjects of different ages
