Self and non self - The immune system may be regarded as a guardian of
our self. The outer world, or the non-self, presents itself to our organism
as antigens whose images are stored in the immune system memory, and manifested
as receptors or antibodies. Antigens are sampled by a special sensory organ,
the mucosa-associated lymphoid tissue, or MALT. Since our body is covered by
an impermeable horny layer that prevents antigen intrusion, antigens are sampled
only by mucosae, particularly by the gut-associated lymphoid tissue, or GALT.
The gastro-intestinal mucosa is covered by two types of epithelia: enterocytes
responsible for absorption and secretion, and M-cells, which sample antigens.
M-cells are located above lymphoid follicles, or Peyer's patches (1).
Figure 1 depicts the relationship between
the different cells. Enterocytes cover crypts and villi, and M-cells occur in
dome areas above the lymphoid follicles.
The relationship between enterocytes and M-cells is depicted in
Figure 2. The two cell types are glued together by tight junctions, (zonula
occludens), and form the mucosal barrier. Small molecules, e.g., haptens, amino
acids, sugar units and lipids are absorbed by enterocytes. Larger particles,
e.g., bacteria, viruses, lectins, and yeast, are taken in by M-cells. After
crossing the M-cell, they are ingested by macrophages, and presented by them
to local lymphocytes which continue to the nearest lymphoid follicle. From there
they reach the entire lymphatic system. The epi-follicular dome and its covering
epithelium is the gut antigenic sense organ. Similar sense organs exist in the
bronchus-associated lymphoid tissue, BALT, in the nasal cavity, tonsils, and
salivary gland excretory ducts.
Bacterial translocation - M-cells actively ingest all particular matter
in their vicinity, e.g., bacteria, viruses, yeast, or endotoxin. The occurrence
of live bacteria beyond the mucosal barrier is known as bacterial translocation.
This a physiological process that does not lead to disease: "portal vein endotoxinemia
of gut origin in minute amounts is a normal physiological phenomenon", and "the
mesenteric lymph node is the most reliable site to culture for the purposes
of monitoring bacterial translocation" (2). Translocated
bacteria, even pathogens, continue living in our organism for a while without
causing overt harm. Their pathogenicity depends, among other things, upon the
host-pathogen balance. A compromised host, on one hand and a vigorous pathogen,
on the other, tip the balance in favor of the invader, which is manifested by
clinical infection. Some pathogens may damage the mucosal barrier, and cross
it directly, causing clinical infections, e.g., enteritis. Compared with the
ongoing bacterial translocation, this occurs relatively rarely. Bacterial translocation
may also be influenced by the gut eco-system. Anaerobes that adhere to the mucosa
probably control the entry of enterobacteria (2) (3).
Immunological memory - Immunological memory is carried
by memory lymphocytes. Since they are relatively short-lived, the immune system
may lose its memory when they are gone. They might transfer their memory to
their progeny; however, the memory response to non replicating protein antigens
decays rapidly. By 30-40 days after transfer of lymphocytes to adoptive recipient
mice, the relative memory response dropped to 10%. Immunological memory might
be refreshed by persisting antigens. Some postulate that "memory cells do not
really exist; what we call memory cells are just cells that are maintained in
a state of activation (4). Apparently, bacterial
translocation provides the necessary antigenic stimulus for memory persistence.
Translocated bacteria may be vital to our health.
The intestinal eco-system - Microbes are everywhere,
and inhabit our skin and intestine. The newborn baby receives its microbial
flora, which already infects it at birth, from its mother. The development of
our personal microbial community, known as primary succession, involves an ordered
sequential change in the microbial populations of the community. Succession
ends when the community consists of up to 400 different species, and attains
homeostasis. It is stable, resists any change in its content, and repels unwelcome
microbes like the hospital strain (3). Eco-system evolution is a complex process
that repeats itself in every growing child. By infecting the baby, its mother
transmits to it the best microbial populations that she has gathered. This is
a vertical inheritance of a protecting eco-system that is adapted later to the
needs of the adult. The child also inherits the translocated bacteria that mold
its immunological memory.
Eco-system and translocated bacteria may be manipulated by diet. This fascinating
facet of nutrition is still a mystery. It forms a rationale for alternative
medical treatments, e.g., herbal medicine, juice therapy, and various diets.
Imagine "immunizing" a population against pathogens by a suitable diet.
Latent viruses might boost immunological memory - Bacterial translocation
should turn our attention to the possibility of viral translocation. Viruses
may also maintain immunological memory. Take, for instance, the herpes virus
that is incorporated into the host DNA. Its products might activate lymphocytes
to keep recognizing herpes viruses. Only when the host becomes compromised,
do they gain strength and produce blisters. Even retroviruses may play a similar
role, and protect us against retrovirus-induced cancer.
Gershom Zajicek
1. Gebert A, Rothkotter HJ, Pabst R. M cells in Peyer's
patches of the intestine. Internat Rev Cytol 157, 91-149, 1996.
2. Van Leeuwen PAM, Boermeester MA, Houdijk APJ et
al. Clinical significance of translocation. Gut suppl 1 S28-S34, 1994.
3. Zajicek G. Antibiotic resistance and the intestinal
flora. The Cancer J 9, 214, 1996.
4. Gray D. Immunological memory: a function of antigen
persistence.Trends in Microbiol. 1, 39-41, 1993.
