Immunodeficiencies due to insufficiency and weakening of the function of proteins of the complement system.
Insufficiency of complement is no more than 2% of
all primary immunodeficiencies. Most primary defects of one or more components
of the complement system are inherited by an autosomal recessive trait and are
manifested by a violation of opsonization, phagocytosis, and destruction of microorganisms.
It is accompanied by severe infections, up to
sepsis. Insufficiency of complement is often observed in autoimmune diseases,
for example, SLE (systemic lupus erythematosus).
Individuals with a C2 defect component are
susceptible to diseases caused by encapsulated bacteria (eg S. pneumoniae).
Persons with a defect in the C3 component are
predisposed to infections caused by pyogenic bacteria that activate the
complement system through a lectin-mediated and alternative pathway
(encapsulated bacteria, S. aureus, etc.), and also due to the opsonization of
the phagocytosis object.
Persons with deficiency of the final components of
complement activation (C5-C9) and also components of the alternative pathway -
factor D and properdin are susceptible to infections caused by two species of
Neisseria - N. gonorrhoeae and N. meningitidis. Persons with this pathology are
very susceptible to inflammation of the meningitis caused by N. meningitidis.
This also indicates that the presence of a membrane-attack complex is extremely
important for protection against bacteria that are outside the target cells.
This is confirmed by the fact of a 10 000-fold increase in the incidence of
meningitis in persons who have genetic defects in the membrane-attack complex.
Since the early components of the complement
system (C1q, C1r and C1s, C4 or C2) normally participate in the elimination of
immune complexes and cells undergoing apoptotic death, their defect may lead to
the development of autoimmune diseases, manifested, for example, in lupus-like
syndrome.
The most severe clinical manifestations have a
violation of complement functions associated with a deficiency of C1 inhibitor,
which leads to hereditary angioedema. The disease is transmitted as an
autosomal dominant trait. The inhibitor C1 blocks not only the classical
pathway of complement activation, but also inhibits the activity of the
elements of the kinin and plasmin system associated with it, as well as the
blood coagulation system. The development of angioedema is caused by the
accumulation of peptides C5a and C3a, which have a strong vasotropic effect and
contribute to an increase in the permeability of capillaries. Accumulation of
large fragments participating in the cascade of complement reactions is
neutralized due to the active work of the complement control system.
It should be noted that the defect of a number of
complement components does not lead to clinical manifestations, as it is
overlapped by other components of this system. For example, the defect of
components C1 and C4 does not lead to an increase in susceptibility to
bacterial infections, since the complement system can also be activated by
alternative and lectin-mediated pathways.
Thus, defects in the components of the complement
system are accompanied by a decrease in resistance to certain infections (in
particular, neisserial) and immunocomplex pathology with lupus syndrome. There
is a certain selectivity in the relationship between the breakdown of genes of
specific groups of factors and types of disturbances. For example:
1) a decrease in resistance to infection by
Neisseria is characteristic for defects in the factors of the alternative
complement pathway, as well as late components;
2) immunocomplex lesion is inherent in defects of
early factors of the classical pathway;
3) in case of NW deficit all characteristic types
of lesions are combined, which reflects the key position of this factor in the
complement system.
Attention is drawn to the insignificance of the
consequences of the disturbance of the lytic phase of complement activation
(resistance only to Neisserias decreases, and genetic defects of factor C9 do
not appear clinically at all), which obviously reflects the "modest"
significance of the corresponding mechanism in immune defense.
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