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ScienceWeek
IMMUNOLOGY: ON THE IMMUNE RESPONSE OF DROSOPHILA
The following points are made by Jules A. Hoffmann (Nature 2003 426:33):
1) Metazoans have developed efficient mechanisms to oppose microbial invaders. Innate immunity is common to all metazoans and serves as a first-line defence. Its hallmarks are the recognition of microorganisms by germline-encoded, non-rearranging receptors, and rapid effector mechanisms that involve phagocytosis, activation of proteolytic cascades and synthesis of potent antimicrobial peptides(1,2).
2) Adaptive immunity appeared in the ancestors of cartilaginous fish and is restricted today to some 45,000 vertebrate species, where it coexists with innate immune defenses. Adaptive immunity depends on the generation of a complex repertoire of immune receptors in lymphocytes through somatic gene rearrangement, and on the clonal expansion of activated lymphocytes. In contrast to innate immunity, adaptive immunity is endowed with memory.
3) Being devoid of adaptive immune reactions, the fruit fly Drosophila host defence seems to be a model system for the study of pristine innate immune defenses. The antimicrobial response in this species, as in other metazoans, comprises both cellular and humoral reactions. The cellular defence is best illustrated by the strong phagocytic activities of the predominant blood cells, the plasmatocytes(3,4). The hallmark of the humoral reactions is the induction by microbial challenge of antimicrobial peptide genes in the fat body (equivalent of the mammalian liver), followed by the secretion of these peptides into the hemolymph (blood)(5). Other humoral reactions -- for example, melanization -- also contribute to the Drosophila host defence(4). Furthermore, as in other animal phyla, epithelial immune reactions, which involve the local synthesis of antimicrobial peptides, are activated in response to infection.
4) Seven distinct Drosophila inducible antimicrobial peptides (or peptide families) have now been identified. They are structurally diverse and, as their mammalian counterparts, are mostly small in size (5 kDa), cationic, and predominantly membrane active. Their activity spectra are directed either against fungi (Drosomycins, Metchnikowin), or against Gram-positive (Defensin) and Gram-negative (Attacins, Cecropins, Drosocin, Diptericins) bacteria. It is assumed that their combined activities largely contribute to blocking the growth of invading microorganisms in the hemolymph.
5) In summary: Drosophila mounts a potent host defence when challenged by various microorganisms. Analysis of this defence by molecular genetics has now provided a global picture of the mechanisms by which this insect senses infection, discriminates between various classes of microorganisms, and induces the production of effector molecules, among which antimicrobial peptides are prominent. An unexpected result of these studies was the discovery that most of the genes involved in the Drosophila host defence are homologous or very similar to genes implicated in mammalian innate immune defenses. Recent progress in research on Drosophila immune defence provides evidence for similarities and differences between Drosophila immune responses and mammalian innate immunity.
References (abridged):
1. Medzhitov, R. & Janeway, C. Jr Innate immunity. N. Engl. J. Med. 343, 338-344 (2000)
2. Janeway, C. A. Jr & Medzhitov, R. Innate immune recognition. Annu. Rev. Immunol. 20, 197-216 (2002)
3. Rizki, R. M. & Rizki, T. M. Selective destruction of a host blood cell type by a parasitoid wasp. Proc. Natl Acad. Sci. USA 81, 6154-6158 (1984)
4. Braun, A., Hoffmann, J. A. & Meister, M. Analysis of the Drosophila host defense in domino mutant larvae, which are devoid of hemocytes. Proc. Natl Acad. Sci. USA 95, 14337-14342 (1998)
5. Hoffmann, J. A. & Reichhart, J. M. Drosophila innate immunity: an evolutionary perspective. Nature Immunol. 3, 121-126 (2002)
Nature http://www.nature.com/nature
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ON INNATE IMMUNITY
The following points are made by Peter Parham (Nature 2003 423:20):
1) Immunology ostensibly began with ancient Greek physicians, who marvelled at their observation that patients who had survived a bout of plague were resistant to the disease when it came around again. From this germ was born the idea of vaccination -- a small controlled infection, like a sort of immunological rehearsal, designed to confer future resistance to full-blown infection while causing only mere discomfort, rather than disease. What those Greeks also initiated was the tendency for immunologists to tackle their subject in a backward manner. They had become captivated by immunological memory, a late-acting feature of the immune response that only becomes useful if and when the first battle between person and pathogen -- the primary infection --has been won by other means.
2) Memory is the end point for adaptive immunity, the part of defence that is mediated by white blood cells called B cells and T cells. Although fascinating to immunologists for their strength and specificity, these soldiers are not speedy. Typically found in a state of suspended animation, B and T cells only become fit to fight about a week after combat begins. During this first week of a primary infection, defence is in the hands of innate immunity. One of several paths can be followed: the infection can gain the upper hand, leading to death or chronic debilitating disease; alternatively, an acute infection can cause a temporary state of disease, which ends when innate immunity calls up reinforcements in the guise of adaptive immunity. Patients who experience either of these outcomes have been carefully studied by physicians ever since the time of the ancient Greeks.
3) A third possibility is that the infection will be terminated quickly by innate immune mechanisms without the involvement of adaptive immunity and with no major symptom of disease. In this happy circumstance, in which health is maintained or only mildly perturbed, neither ancient Greeks nor their modern counterparts would be likely to consult a physician. Consequently, this most desirable of outcomes, in which the war is won with little collateral damage, remains understudied and poorly appreciated.
Nature http://www.nature.com/nature
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Notes:
All biological organisms are subject to invasive attack by microbial pathogens, and the survivability of biological organisms depends on the activation of various protective mechanisms (immune responses) when a microbial invasion occurs.
In biology, the "immunity" of organisms to infection by various pathogens is functionally characterized into 2 types: The term "innate immunity" refers to non-specific antimicrobial systems of response (e.g., phagocytosis: engulfment and digestion of microbes by "killer" cells) that are innate and not intrinsically affected by prior contact with the infectious agent; the term "adaptive immunity" refers to immune responses which involve an enhanced ability to respond to specific molecular *antigens presented by the invading pathogenic entity, the enhancement dependent on prior contact with the same pathogen. In addition, the concept of innate immunity generally refers to the first-line host defense that serves to limit infection in the early hours after exposure to microorganisms.
Recent data have highlighted similarities between pathogen recognition, signaling pathways, and effector mechanisms of innate immunity in both the fruit fly Drosophila and in mammals, pointing to a common ancestry of these defenses. In addition to its role in the early phase of defense, innate immunity in mammals appears to play a key role in stimulating the subsequent clonal response of adaptive immunity.
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