Immunology And Germfree Life

In general, the major difference between germ-free and conventional animals is on a quantitative rather than a qualitative level. This seems to hold true for innate as well as for acquired immunity.

Serum from germ-free animals contains complement in similar amounts as in conventional animals, whereas the levels of specific antibodies are reduced. On a cellular level, polymorphonuclear neutrophiles (PMNs) from germ-free animals are equal to their conventional counterparts with regard to phagocytic capacity (49) and chemotaxis (50), and an apparent reduction in phagocytosis is due to humoral factors, i.e., reduced antibodies (52).

The most striking difference between germ-free and conventional animals is found with regard to the lymphoid immune system. In most—if not all—conventional

Table 2 A Consequence Analysis of One Microbiota Associated Characteristic

Statement: SCFAs are normally produced in high amounts by the intestinal microbiota; they are partly absorbed, and partly excreted in feces Mechanism behind possible consequences

Biochemical: SCFAs are involved in several metabolic pathways Immunological: Uncertain consequences Place Locally

In the intestinal lumen At the mucosa surface Within the mucosa cells Distant

In the liver, pancreas, brain etc. Form Direct Locally

Main anions in intestinal content Growth promotion of some microbes Growth suppression of others Growth regulation of mucosa cells Distant

Energy supply to the general metabolism Indirect Locally

"Promoted" microbes produce suppressive bacteriocins Direct suppression provides niches for other microbes to grow Distant

Metabolic alternations act on production of insulin, etc. Consequence Physiological

Locally the SCFAs are parts of direct/indirect regulatory

Mechanisms for water and electrolyte absorption; the net effect is antidiarrheic, involved in regulation of carbohydrate metabolism, etc. Pathophysiological

Involved in hepatic coma. Probably involved in colonic cancer, ulcerative, and pseudomembraneous colitis, etc.

Abbreviation: SCFA, short chain fatty acid.

mammalian species, there are more lymphoid cells associated with the GI tract than with the spleen, peripheral lymph nodes, and blood taken together, and gut-associated B cells account for more than 80% of all B cells in the human body (52). The total daily output of dimeric IgA is 0.8 g per m of intestine, an amount equivalent to the output of a lactating mammary gland (52).

The gut-associated lymphoid tissue (GALT) has to be considered both from the perspective of its composition and spatial complexity, and an extensive evaluation is beyond the scope of this review. Interested readers may search in Medline for names such as Bengt Bjorksten, Per Brandtzaeg, John Cebra, and Agnes Wold, among others. In the future, it is reasonable to assume that germ-free animals will be used in several settings, as (1) germ-free inbred animals, with and without genetic manipulation of defined components of their immune systems or their epithelium, (2) isogenic strains of a given bacterial species expressing defined endogenous or foreign epitopes, and (3) prior or simultaneous administration of other competing organisms. In all these future experiments, it might be wise to keep in mind that it is a constant "trialogue" of interactions between intestinal microbes, epithelium, and GALT. As pointed out elsewhere (6) these interactions are probably dynamic, reciprocal, and combinatorial, making it difficult to separate out a single tune in this cacophony of noise. Utilization of gnotobiotic animals might represent a suitable reductionistic "noise filter," allowing us to study host-microbe cross-talks in greater details. For more information on the role of the intestinal microbiota on the immune system, see the chapter by Moreau elsewhere in this book.

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