striated epith at both ends of GI tract provides a greater barrier to infection than the single layered columnar epith
stomach, small and large intest have layer of unstirred mucus that is continuous over the epith which provides additional barrier by enveloping organisms preventing their entry into the columnar epith
if barrier breaks down anywhere, vulnerable to invasion by microorganisms
The gastric hydrochloric acid
kills most bacteria that reach the stomach, thus providing an important barrier to intestinal pathogens and maintaining the normally low bacterial counts of the stomach and upper small intestine
gastric juice is inhibitory to bacteria – gastric acid is the determinant of inhibition
increased likelihood of infections (eg Salmonella, Shigella, Vibrio cholerae, ETEC, Giardia lamblia) if gastric acid secretion is decreased – lower infecting dose, higher prevalence of infections, small intestinal bacterial overgrowth
Motor activity
is important in clearing organisms at various sites in the GI tract
diminished salivary secretion and/or inability to swallow increases the likelihood of oral infections (eg candidiasis)
Treatment with agents that impair propulsive activity may Ý the duration and severity of invasive bacterial diseases
The normal enteric microbiota
provides additional barrier to implantation and spread of invading pathogens
Normal flora occupy "niches" or compete for attachment sites in GI tract making sites unavailable for pathogens
Metabolites
(eg short chain fatty acids, hydrogen sulfide) or polypeptide antibiotics (bacteriocidins) elaborated by bacteria may contribute to the antagonism
Normal flora may establish pH and redox conditions that are adverse to pathogens
Shigella can establish in germ free guinea pigs, but not in E. Coli infected guinea pigs (suppresses pathogens)
Pre-treatment with streptomycin markedly reduces the infection dose of Salmonella in mice Þ kills off normal flora
Normal flora decreases pathogen establishment Þ Antibiotic therapy may lead to increased colonization of Clostridium difficle leading to antibiotic-assoc colitis
Defense against Enteramoeba hystolytica
via mucin degrading bacteria which produce glycosidases (degrades glycoside of E. hystolytica)
Normal flora prevents bacterial translocations
Other mechanisms
Lysozyme
(present in saliva and GI secretions) – is a glycosidase which degrades mural peptides in bacterial cell wall
Defensins (cryptidins)
– The Paneth cells of intestinal crypts secrete an antibacterial peptide similar to the defensin of PMNs with a broad range of activity against enteric bacteria
Bile salts
– present in the upper small intestine in concentrations that are inhibitory to several bacteria
Intestinal Phospholipase
– An intestinal phospholipase A2 from mice Paneth cells has bactericidal properties against E. Coli and Listeria monocytogenes. Rats and mice have a similar enzyme in Paneth enzyme secretions
Iron containing compounds
(lactoferrin, lactoperoxidase) – present in secretions, active against several bacteria. Their effects against some bacteria are enhanced by IgA in a nonspecific manner
Host immune response
– may provide protection in a nonspecific manner. Natural antibodies, opsonins and complement may be inhibitory (but to a lesser extent). Natural killer cells and phagocytes are active in the mucosa
Breast feeding
– confers immunity to infection by multiple mechanisms
Lymphatic and portal clearance and reticuloendothelial function
– in liver, further reduce spread or infection
Specific (Immune) Resistance Mechanisms
Help control primary infection and prevent reinfection
The major effector component of mucosal immune response is immunoglobulin A (IgA) secretion – the IgA antibody response alone can be protective
The mechanism of IgA mediated resistance is mainly by immune exclusion – secretory IgA prevents colonization by pathogens by agglutination or by blocking adherence to specific receptors in the mucosal lining or mucus layer
IgA may bind to toxins or products of organisms thus preventing their actions on the host
IgA antibodies may enhance secondary immune responses by enhancing absorption of pathogens thru the M cells thus providing a stronger antigenic rechallenge
Other "hypothesized" mechanisms for IgA mediated resistance include direct killing, enzyme inactivation of bacteria, antibody dependent cellular cytotoxicity, and opsonic and phagocytic toxicity
Host immunity to reinfection with a pathogen that gains entry thru the GI tract is superior following the natural infection or immunization with the whole organism than after administration of purified antigen from the same pathogen
For infections acquired thru the GI tract, immunization thru the oral route is more desirable – both oral polio vaccines and parenteral inactivated polio vaccines protect from paralytic poliomyelitis similarly, the latter fails to prevent subsequent mucosal infection with the poliovirus