A great number of field
studies have demonstrated that the relationship between infection and
malnutrition is bidirectional (figures 3) [Brown, K. H. 1994], [Brown, K. H 2003]. The site of
interaction as well as the type of pathogen can largely determine which type of
immune response will proceed, and weather it will be an optimal response.
Initiation of both innate and adaptive immune responses involves the activation
and proliferation of immune cells and the synthesis of an array of molecules;
the associated DNA replication, RNA expression, protein synthesis and protein
secretion consumes
additional anabolic energy. Consequently, the nutritional status
of the host critically determines the out come of infection [Schiables U. E.;
and Keuftman, S. H. E. 2007].
Malnourished children suffer in greater proportion from
bacterial gastrointestinal and respiratory infections [De Onis, M.; et al.,
1993]. The first line of defense against these types of infection is
innate immune response, particularly epithelia barriers and the muscoca immune
response [Janeway, C. A., JR., and; Medzhitov, R . 2002]. PCM significantly
compromises mucosal epithelial barriers in the gastro intesternal, respiratory
and urogenital tracks. For example, vitamin A deficiencies include the loss of
mucus-producing cell. This loss of productive muscus blanket increases
susceptibility to infection by pathogens that would ordinarily be trapped in
the muscus and swept away, by cleansing flow of mucus out the body. Barrier
defects of mucous membranes are critical in the pathogenesis of respiratory and
gastrointestinal tract infection [Cunnigham-Rundies, S.; et al.,
2005].
In particular,
muicosal barrier immunity is impaired in the malnourished, host in the
gastrointinal track due to the altered architecture and composition of the
intestinal mucosal tissues which includes
flattened hypotrophic microvili, reduced
lymphocyte counts in peyer’s patches or reduced IgA secretion (De Onis, et
al., 1993]. Secretory IgA is an
important component of the mucosal immune response that protects the upper
respiratory and gastrointestinal tract against infection with pathogenic
organisms.
Previously, it
has been reported that total IgA concentration is reduced in intestinal mucosa
of protein-malnourished mice[McGee,DV,; and McMurray,D.N. 1998],[Nikawa, T.; et al., 1999]. The authors suggest that
protein malnutrition may decrease IgA content by suppressing the proliferation
and or maturation suppresses the expression of the epithelial IgA-transporting
protein, which decreases the total IgA concentration in the intestinal lumen [Sulliven P. B.; et al., 1990]. Thus, PCM appears to impair IgA dependent mucosal
cimmune defenses, including the production of IgA by plasma cell and its
secretion into the lumen of the intestine [Nikawa, T.; et al., 1999].
In protein malnourished mice, significantly decreased level
of 1L-4 were reported in small intestinal mucosa interestingly, these findings
correlated with reduced secretory IgA production [Nikawa, T.; et al., 1999]. Malnourished mice, which
are more susceptible to infection, exhibit altered innate immune responses and
decreased nitric oxide production from resident peritoneal macrophages compared
to control mice (Anstead, G. M.; et
al., . 2001].
The level and features of the App response are dependent on
host nutritional state and infection severity [Fleck, A. 1989]. Severe malnutrition affects the App
response by reducing the availability of precursors for App synthesis or by
reducing the synthesis of modulating proinflammatory cytokines such as IL-1 and
IL-6. proinflammation cytokines
responses during the acute phase of infection are affected by malnutrition
specifically, serum IL-1 concentration are markedly lower in infected,
malnourished children compared to infected, well-nourished children (Reid,
M.; et
al., 2002]. It has been reported the
severely malnourished children mount only partial App response to the
infection, particularly; Children with edematous malnutrition had higher plasma
concentrations of C reactive protein -1- antirysin and
heptogbolin [Sauerwein, R. W.; et al.,
1997].
Complement, another element of the innate immune response,
is also altered during malnutrition. Specifically, serum levels of C3 tend to
be decreased in severely malnourished children compared to normal children
[Neyestani, T. R.; and Woodward, B. 2005].
As the initial event in phagocytosis and microbial killing are largely
complement dependent, this deficiency resulted in significant impairment in
leukocyte microbial capacity early in infection, which was particularly evident
from grain-negative organisms. [Keusch, G. T. 2003].
Additionally, serum level of leukotrienes, which enhance
leukocyte accumulation and phagocyte capacity, have been reported to be marked
diminished in children with PCM. For example, decreased leukotriene levels were
associated with reduced microbial ingestion killing by phagocytic cells
(Peters-Golden, M.; et al., 2005]. Moreover, it has been reported that
experimental malnutrition impairs leukocyte exudation into local inflammatory
sites by reducing production of the chemokine macrophage inflammatory protein
(Ikeda, S.; et al., 2001]. In
additional to decreased chemokine production, there is a decreased in the
functionality of the chemokine that is produced; combined, these factors can result
in an inadequate inflammatory response.
The changes in mucosed immune function presumably account
for the increased mortality seen in malnourished children. Therefore, PCM may
increase susceptibility to gastrointestinal and respiratory infections possibly
as a result of impaired muosal immune response and/or systemic alteration of
immune response.
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