So what evidence is there to support this broad hypothesis?
This is a list of support and further reading that might help to establish the value of some of the ideas.
Where the article is behind a paywall there are a few ways still to be able to obtain the article. Look at the PubMed entry [PMED] and see if it is available in the repository. (You can also go directly to this repository to search for the paper.) If not available, searh for the article in Google Scholar . The authors' web repositories can sometimes be found. Finally, seach in any general search engine – I prefer Google as advertising sites do not obscure the wanted results too much. In desperation, consider approaching the authors.
- Holmes B. "Fanning the flames." New Scientist 2004, May 22, Pages 40-43
- A BBC Radio 4 programme on "Inflammation".
- Hensen PM. "Dampening inflammation." Nature Immunology 6 (December) 2005, Pages 1179-1181 (plus other articles in this edition).
- McGonagle M.& McDermott MF. "A Proposed Classification of the Immunological Diseases." PLoS Med 2006 3(8):1242-1248. These authors discuss the idea of "auto-inflammatory diseases".
- Barton GM. "A calculated response: control of inflammation by the innate immune system." J. Clin. Invest. 2008:118:413-420 . A great review of many of the issues.
- Medzhitov R. "Origin and physiological roles of inflammation." Nature. 2008 Jul 24;454(7203):428-35. (Note this Nature insight articles is part of a group of papers.)
- Medzhitov R. "Inflammation 2010: new adventures of an old flame." Cell. 2010 Mar 19;140(6):771-6. (Note, this whole of this issue of Cell contains many relevant articles.)
- Ramos GC. "Inflammation as an Animal Development Phenomenon." Clin Dev Immunol. 2012;2012:983203. doi: 10.1155/2012/983203 . (This is a good historical/philosophical/logical look at the role of inflammation in form homeostasis.)
- Dobson GP, Biros E, Letson HL & Morris JL. "Living in a Hostile World: Inflammation, New Drug Development, and Coronavirus." Front Immunol 2021 Jan 22;11:61013 Here is an "inflammocentric" view of the immune system that I (generally) concur with. They make the interesting point that Metchnikoff and inflammation have been largely overlooked in 20th century immunology. Cunliffe and morphostasis remain "invisible". Perhaps they have not come across my contributions.
- Niec RE, Alexander Y. Rudensky AY, and Fuchs E. Inflammatory adaptation in barrier tissues Cell 2021; 184:3361-3375 Pubmed number not yet available These authors present a paper outlining a tissue homeostatic response revolving around prior inflammatory encounters. Quote: "It is now clear that within tissues, diverse cell types ranging from cells of the adaptive and innate immune system to tissue stem cells are subject to inflammation-induced modulation of their numbers and cell-intrinsic characteristics. These cells, along with other long-lived cells within barrier tissues, including fibroblasts, endothelial cells, and neurons, enable collective retention of inflammatory memory." Cunliffe and morphostasis remain "invisible". Perhaps they have not come across my contributions.
- Comptes Rendus Biologies, whole issue June 2004 (327:509-607)
- Hedrick SM. "The Acquired Immune System: A Vantage from Beneath." Immunity 2004, 21: 607-615.
- Reis ES. Barbuto JAM. Isaaca L. "Complement components, regulators and receptors are produced by human monocyte-derived dendritic cells" Immunobiology 2007, 212 (3) 151-157. This makes it more probable that all phagocytes manufacture many complement factors and release them in their vicinity. The liver probably acts as a phagocyte populated factory for producing circulating complement factors.
- Brines M & Cerami, A. "The Receptor That Tames the Innate Immune Response." Mol Med. 2012; 18(1): 486-496. doi: 10.2119/molmed.2011.00414. This is an interesting discussion of a "scorched earth" function of innate immunity.
- Pembroke TPL, Gallimore AM & Godkin A. "Rapid innate control of antigen abrogates adaptive immunity." Immunology 2013 138:293-297. An indication that the immune system may, indeed, work in a sequence of barrages (shells) that progressively fail. (See my published article, A Proliferation of Pathogens etc" in the published section.)
- Tauber AI. "Metchnikoff and the phagocytosis theory." Nat Rev Mol Cell Biol. 2003 Nov;4(11):897-901. (Available here also: http://blogs.bu.edu/ait/files/2012/08/Tauber-Metchnikoff-Phagocytosis.pdf ) This is a good summary of Metchnikoffs perspicacity. . It can also be found here
- Mills CD. "Anatomy of a discovery: M1 and M2 macrophages." Front Immunol. 2015, 6:212. . Charlie Mills has been studying macrophages for many years; he is the originator of the M1/M2 macrophage idea. The next two articles are also from his department.
- Mills CD, Ley K, Buchmann K, Canton J. "Sequential Immune Responses: The Weapons of Immunity." J Innate Immun. 2015 Apr 2. [Epub ahead of print]
- Mills CD, Lenz LL, Ley K. "Macrophages at the fork in the road to health or disease." Front Immunol. 2015, 6:59.
Evolution and comparative immunology
- Rinkevich B. "Primitive immune systems: are your ways my ways." Immunological Rev 2004, 198:25-35
- Gura T. "Roots of immunity" New Scientist 19th Feb 2000 page 24. This is a very useful comparison of animal and plant defence. It is worth mentioning, here, the usefulness of aspirin in the management of human infections/inflammation. In both plants and animals, aspirin lowers the threshold at which individual cells opt for apoptosis. This emphasises the centrality of "elective suicide" as a core defence mechanism and points towards it being one of the earliest shells to be added in metazoans.
- Danivlova N. "The evolution of immune mechanisms." J Exp Zoolog B Mol Dev Evol 2006, 306(6):496-520. This is a useful discussion though I would not have put this much emphasis on self non-self discrimination and pathogen elimination. There is subtle support for: the shell structure of the successive refinements of defence mechanisms; a role for the immune system in tissue homeostasis; a number of other subtle shifts in emphasis that move (to my view) a considerable way along the trend towards the morphostasis viewpoint.
- Miller DJ, Hemmrich G, Ball EE et al. "The innate immune repertoire in Cnidaria – ancestral complexity and stochastic gene loss." Genome Biol. 2007 Apr 16;8(4):R59 [Epub ahead of print]. Clear indication that C3, perforin/MAC and TLR genes present in these "basal" animals.
- Jones JGD. Dangl JL. "The plant immune system." Nature 2006; 444:323-29. Comparative immunology really but this article gives insight into the probable core strategies of the mammalian immune system.
- Anderson MK., Rast, JP. "Universal rules of immunity." Immunol Cell Biol 2009 Epub ahead of print. (Evolution of adaptive immunity.)
- Boller T. He SY. "Innate immunity in plants: an arms race between pattern recognition receptors in plants and effectors in microbial pathogens." Science 2009 May 8;324(5928):742-4.
- Sokolova IM. "Apoptosis in molluscan immune defense." Invertebrate Survival Journal 2009 6:49-58
- Cooper EL. "Evolution of immune systems from self/not self to danger to artificial immune systems (AIS)" Phys Life Rev. 2010 Mar;7(1):55-78
- Lackie AM. "Transplantation immunity in arthropods: is immunorecognition merely wound healing?" Chapter 10 in "Immunity in invertebrates" Ed Brehelin, M., Springer-Verlag Berlin Heidelberg 1986
- Augustin R. Fraunea S. & Bosch TCG. "How Hydra senses and destroys microbes." Semin Immunol, 2010 (Feb) 22(1): 54-58 (also visible here). TLR and NOD at the evolutionary base of metazoan tissue homeostasis.
- Chen G Zhuchenko O Kuspa A. "Immune-like phagocyte activity in the social amoeba." Science. 2007 Aug 3;317(5838):678-81 doi:10.1126/science.1143991 (Toll goes back a LONG way).
- Moreno-García M, Recio-Tótoro B, Claudio-Piedras F, Lanz-Mendoza H. "Injury and immune response: applying the danger theory to mosquitoes." Frontiers in Plant Science. 2014. Here the authors discuss the relevance of the interaction of PAMPs (MAMPs) and damage signals in mosquitos; non-damaging microbes, although identified by MAMPs, may be tolerated. They highlight (and reference) a book by G. Salt in which (45 years ago, 1970) he proposed the idea that insects can recognize and react against danger/damage molecules . In his seminal paper, he anticipated that micro-organisms damage host tissues of insects directly or indirectly by ". . . releasing abnormal if not toxic substances. An insect has need, then, for protection against foreign or abnormal particles of molecular size." He mentioned that the defense is not only related to recognition of self or non-self, but also to damage: "Since the cells of each kind of insect react to most infections, but not to all, those cells must be able to distinguish the organisms to which they react from others which they do not molest" and called attention to the fact that the . . . "defence reaction must lie principally in its effect on alien parasites, and particularly on those that endanger the life of their host." (The italicised text is – more or less – taken straight from their paper.)
- Heil M, Land WG, Tör M. "Editorial: Wound Recognition across the Tree of Life." Front Plant Sci. 2016 Sep 1;7:1319 [There is no mention of either Cunliffe or morphostasis.]
- Sanabria NM, Huang JC, Dubery IA. "Self/nonself perception in plants in innate immunity and defense." Self/Nonself 2010 Jan;1(1):40-54.
- Sanabria N, Goring D, Nürnberger T, Dubery I."Self/nonself perception and recognition mechanisms in plants: a comparison of self-incompatibility and innate immunity." New Phytol. 2008;178(3):503-14.
- Huene al, Sanders SM, Ma Z, et al. "A family of unusual immunoglobulin superfamily genes in an invertebrate histocompatibility complex" Proc Nat Acad Sci 2022 119:40 (so far only epub data found) This appears to be confirmation that the IgSF superfamily arose in colonial cnidarians. That emphasises the probability that peptide binding in the MHC complex likely acts to take advantage of allorecognition genes originating from mechanisms of colonial competition.
Immune surveillance for cancer (and other cancer articles)
- Pardoll D. "Does the immune system see tumors as foreign or self?" Ann Rev Immunology 2003, 21: 807-839 (Look in Google scholar for full text.)
- Fidler IJ. Schroit AJ. "Recognition and destruction of neoplastic cells by activated macrophages: discrimination of altered self." BBA Rev Cancer 1998, 948:151-173
- de Visser KE. Eichten A. Coussens LM. "Paradoxical roles of the immune system during cancer development." Nature Reviews Cancer (Jan) 2006, 6:24-37
- Bhardwaj N. "Harnessing the immune system to treat cancer." J. Clin. Invest. 2007 117: 1130-1136. This, and the next four articles, are part of a special review series published in this edition of the JCI.
- Swann JB. & Smyth MJ. "Immune surveillance of tumors." J. Clin. Invest. 2007 117: 1137-1146.
- Sica A. Bronte V. "Altered macrophage differentiation and immune dysfunction in tumor development." J. Clin. Invest. 2T.J.007 117: 1155-1166
- Curiel TJ. "Tregs and rethinking cancer immunotherapy." J. Clin. Invest. 2007 117: 1167-1174
- Lin W-W., Karin M. "A cytokine-mediated link between innate immunity, inflammation, and cancer." J. Clin. Invest. 2007 117: 1175-1183
- Ruggiero RA, Bustuoabad OD. "The biological sense of cancer: a hypothesis." Theor Biol Med Model. 2006 Dec 15;3:43.
- Atsumi T Singh R Sabharwal L et al. "Inflammation amplifier, a new paradigm in cancer biology." Cancer Res 2013 [online first] doi:10.1158/0008-5472.CAN-13-2322
- Prendergast GC. "A perspective on cancer as an abortive autoimmune response to altered-self." Cancer Res. 2015 Jan 1;75(1):3-4. doi: 10.1158/0008-5472.CAN-14-3532
- Antonio N, Bønnelykke-Behrndtz ML, Ward LC, Collin J, Christensen IJ, Steiniche T, Schmidt H, Feng Y & Martin P. "The wound inflammatory response exacerbates growth of pre-neoplastic cells and progression to cancer." EMBO J. 2015 Jul 1. pii: e201490147. [Epub ahead of print]
- Martincorena I, Roshan A, Gerstung M, Ellis P, Van Loo P, McLaren S, Wedge DC, Fullam A, Alexandrov LB, Tubio JM, Stebbings L, Menzies A, Widaa S, Stratton MR, Jones PH & Campbell PJ. "Tumor evolution. High burden and pervasive positive selection of somatic mutations in normal human skin." Science. 2015 May 22;348(6237):880-6. doi: 10.1126/science.aaa6806
Gap junctions and immune function
- Oviedo-Orta, E., Evans, W.H. "Gap junctions and connexin-mediated communication in the immune system." Biochim Biophys Acta 2004, 1662:102-112
- Oviedo-Orta, E. This researcher seems to be a major source of research into GJs and the immune system. This site lists his papers
- Alves, L.A., Campos de Carvalho, A.C, Savino, W. "Gap junctions: a novel route for direct cell-cell communication in the immune system?" Immunology Today, 1998 Jun;19(6):269-75
- Neijssen, J., Herberts, C., Drijfhout, J.W., Reits, E., Janssen, L. and Neefjes, J. "Cross-presentation by intercellular peptide transfer through gap junctions" Nature 2005, 434:83-88 (also a News and views comment same issue).
- Matsue H, Yao J, Matsue K, Nagasaka A, Sugiyama H, Aoki R, Kitamura M, Shimada S. "Gap junction-mediated intercellular communication between dendritic cells (DCs) is required for effective activation of DCs." J Immunol. 2006 Jan 1;176(1):181-90.
- Neijssen, J., Pang, B., Neefjes, J. "Gap junction-mediated intercellular communication in the immune system." Prog Biophys Mol Biol. 2007;94(1-2):207-18. Great overview article. Particularly note "cordon sanitaire".
- Todd, K.L., Kristan, W.B., French, K.A. "Gap junction expression is required for normal chemical synapse formation." J Neurosci. 2010 Nov 10;30(45):15277-85. Describes how preliminary GJ formation leads to neuronal synapse. May have ramifications for immune synapse.
- Mendoza-Naranjo A, et al. "Functional gap junctions accumulate at the immunological synapse and contribute to T cell activation". J Immunol. 2011 187(6):3121-32.
- Rustom A. "The missing link: does tunnelling nanotube-based supercellularity provide a new understanding of chronic and lifestyle diseases?" Open Biol. 2016 Jun;6(6). pii: 160057
Tissue homeostasis (including apoptosis as part of this)
- Grimsley, C., Ravichandram, K.S. "Cues for apoptotic cell engulfment: eat-me, don't eat-me and come-get-me signals." Trends Cell Biol 2003, 13:648-656
- Maderna, P., Godson, C. "Phagocytosis of apoptotic cells and the resolution of inflammation." Biochim Biophys Acta 2003, 1639:141-151
- Gordon, S. "Pathogen recognition or homeostasis? APC receptor functions in innate immunity." C.R.Biologies 2004, 327:603-607 (Comptes Rendus Biologies)
- See the de Visser article in section "Immune surveillance for cancer" above.
- Cvetanovic M, Mitchell JE, Patel V. et al. "Specific recognition of apoptotic cells reveals a ubiquitous and unconventional innate immunity." J Biol Chem 2006, 281: 20055-20067
- Perryman, S.V., Sylvester, K.G. "Repair and regeneration: opportunities for carcinogenesis from tissue stem cells." J Cell Mol Med 2006 Apr-Jun;10(2):292-308
- Erwig, L.P., Henson, P.M. "Immunological Consequences of Apoptotic Cell Phagocytosis." Am J Pathol. 2007 May 18; [Epub ahead of print]. PubMed ref.
- Köhl J. "The role of complement in danger sensing and transmission." Immunol Res. 2006;34(2):157-76.
- Köhl J. "Self, non-self, and danger: a complelementary view." Adv Exp Med Biol 2006, 586:71-94
- Neumann H, Kotter MR, Franklin RJ. "Debris clearance by microglia: an essential link between degeneration and regeneration." Brain. 2009 Feb;132(Pt 2):288-95.
- Silverman GJ, Grönwall C, Vas J, Chen Y. "Natural autoantibodies to apoptotic cell membranes regulate fundamental innate immune functions and suppress inflammation." Discov Med 2009, 8(42):151-6. (Available through www.discoverymedicine.com ). Suggests that the role of B-cells/free antibodies has its roots in (targeted) tissue debris clearance.
- Bukovsky A. "Immune maintenance of self in morphostasis of distinct tissues, tumour growth and regenerative medicine." Scand J Immunol 2011 73:159-189.
- Tegla CA, Cudrici C, Patel S, Trippe R, Rus V, Niculescu F, and Rus H. "Membrane attack by complement: the assembly and biology of terminal complement complexes." Immunol Res. 2011 Oct;51(1):45-60.
- Senovilla L, Galluzzi L, Zitvogel L, Kroemer G. "Immunosurveillance as a regulator of tissue homeostasis." Trends Immunol. 2013 Oct;34(10):471-81. [ doi: 10.1016/j.it.2013.06.005 ] (Note, once again, there is no acknowledgement of the existence of my Morphostasis articles. They are clearly relevant to this article. Perhaps this is appropriate; but this continuing erasure from acknowledgement has, historically, dramatically slowed the "uptake" of the ideas.)
- Seminars in Immunology, Volume 26, Issue 4, Pages 275-354 (August 2014). "Evolution of immune pathways in regeneration and repair: recent concepts and translational perspectives." Here is a clear shift in emphasis (in the origin and purpose, particulalry of the innate immune sytem) away from a bug hunting, chasing and killing system towards a tissue homeostatic mechanism.
- Marques RE, Marques PE, Guabiraba R, Teixeira MM. "Exploring the Homeostatic and Sensory Roles of the Immune System." Front Immunol. 2016 Mar 31;7:125 The authors broaden the perceived rôle and purpose of the immune system and, also, its relationship to the nervous system.
- Henson PM, Bratton DL. "Antiinflammatory effects of apoptotic cells." J Clin Invest. 2013 Jul;123(7):2773-4 The authors discuss the evolving relationship among apoptosis, phagocytosis, and inflammation.
- Cosovanu C, Neumann C. "The Many Functions of Foxp3+ Regulatory T Cells in the Intestine" Frontiers in Immunology, 2020 11:2710 This emphasises the emergent role of Regulatory T Cells in tissue homeostatis, regeneration and repair.
- Meizlish ML, Ruth A, Franklin RA, Zhou X & Medzhitov R. "Tissue Homeostasis and Inflammation" Annu Rev Immunol, 2021. 39:557-581
- Bukovsky A. "Immunology of tissue homeostasis, ovarian cancer growth and regression, and long lasting cancer immune prophylaxis – review of literature." Histol Histopathol. 2021 Jan;36(1):31-46
- Muñoz-Rojas AR, Mathis D. "Tissue regulatory T cells: regulatory chameleons." Nat Rev Immunol (2021).
- Joishy S K and Balasegaram M. "Tissue Healing and Regeneration" Folia traumatologica Geigy (GY284 Sept 1980). I was clearing out my loft of numercous photocopies etc (20220308) and found this Geigy monograph. This could well have influenced my approach to the immune system, though the date on which I acquired this is not clear. I cannot find reference to this monograph on any search engine. I have a vague recollection that someone sent me this having read "my ideas so far". I have a copy should anyone want to see it.
- Mass E, Nimmerjahn F, Kierdorf K & Schlitzer A. "Tissue-specific macrophages: how they develop and choreograph tissue biology." Nature Rev Immunol, 2023 published online This is an excellent analysis of macrophages and tissue management. I like it.
- Poletaev A. The Natural Autoimmunity: Self-Recognition, Self-Interaction, and Self-Maintenance. 2014, Autoimmun Res 1(1): 1001.
- Nicholson A, Schumm SN and Beachy SH (Rapporteurs). "Understanding the Role of the Immune System in Improving Tissue Regeneration: Proceedings of a Workshop." 2022 (I think). This masquerades an interesting revelation on Kuhn's "invisibility of revolutions". There is an earlier summary on the same workshop.
Autoimmunity (this is arguably a subset of tissue homeostasis)
- Land WL. "Role of DAMPs and cell death in autoimmune diseases: the example of multiple sclerosis." Genes Immun, 2023 Apr;24(2):57-70. This is an interesting discussion paper that questions the idea that auto-immunity is caused by a faulty immune system (this idea is more a less a "given" for those who believe in the discrimination of self from non-self epitopes). He refers to Polly Matzinger's article (reference 4 – cited immediately below) that proposes a similar perspective. You need to decide if either of these articles propose something substantively different to the basic ideas covered in my (formally) published articles and here at my Morphostasis web site. I will shortly create an "Other Thoughts"" section on DAMPs. Walter Land either doees not know of my contributions, does not wish to acknowledge them or does not feel they are of any relevance.
- Matzinger PC. "Autoimmunity: Are we asking the right question?." Front Immunol 2022 Nov 3;13:864633. As with the Walter Land reference above, Polly does not acknowledge my contributions. However, I know that she is fully aware of them.
Autophagy and Apoptosis
- Deretic V. "Autophagy as an immune defense mechanism." Curr Opin Immunol 2006;18:375-382.
- Patel, S., Caplan, J., Dinesh-Kumar, SP. "Autophagy in the control of programmed cell death." Curr Opin Plant Biol. 2006 9(4):391-6. Evidence for its role in plant defence too.
- Amano, A., Nakagawa, I., Yoshimori T. "Autophagy in Innate Immunity against Intracellular Bacteria." J Biochem (Tokyo). 2006 140(2):161-6.
- Swanson, M.S. "Autophagy: eating for good health." J Immunol 2006, 177(8):4945-51.
- Delgado, MA, Deretic V. "Toll-like receptors in control of immunological autophagy." Cell Death Differ 2009 Jul;16(7):976-83.
- Behar SM, Martin CJ, Booty MG, Nishimura T, Zhao X, Gan HX, Divangahi M, Remold HG. "Apoptosis is an innate defense function of macrophages against Mycobacterium tuberculosis." Mucosal Immunol. 2011 May;4(3):279-87
- Ashida H, Mimuro H, Ogawa M, Kobayashi T, Sanada T, Kim M, Sasakawa C. "Cell death and infection: A double-edged sword for host and pathogen survival." J Cell Biol 2011 [epub]
Models and hypothesis and the philosophy of immunity
- Vaz, N.M., Pordeus, V. "Visiting immunology." Arq Bras Cardiol. 2005 Nov;85(5):350-62.
- Pradeu T, Cooper EL. "The danger theory: 20 years later." Front Immunol. 2012 Sep 17;3:287.
- Manjili M.H. "The adaptation model of immunity." Immunotherapy 2014, 6(1), 59-70. This article does not appear to have been influenced by my published papers.
- Eberl, G. "A new vision of immunity: homeostasis of the superorganism." Mucosal Immunology, 2010 3:450-460 [doi:10.1038/mi.2010.20]. This article does not appear to have been influenced by my published papers.
- Golub, E.S. "Is the Function of the Immune System only to Protect?" NATO ASI Series 1992 66:15-26. Here is a prescient piece. I don't think I have seen this before and, even now, I can only see the "free" bits (the teaser). However, it is philosophically interesting and, interestingly,makes the point that, "From [the immune system's] beginnings as a means of conferring protection by vaccination, it has become perceived as responsible for protection on its own, that is, without artificial immunization. The evolutionary pressures on a system that has evolved to protect by itself are quite different than those on a system that can be manipulated to protect."
- Grignolio A, Mishto M, Faria AMC, Garagnani P, Franceschi C and Tieri P. "Towards a Liquid Self: How Time, Geography, and Life Experiences Reshape the Biological Identity." Front. Immunol. (Inflammation)
- Land WG. "How Evolution Tells Us To Induce Allotolerance." Exp Clin Transplant 2015 Suppl 1: 46-54. . This article is on pages 46-54 of the supplement (which is what this www link leads to – the DOI link is not yet recognised, perhaps because it is too new). Note that Walter Gotleib Land has published a number of articles around a damage model of innate and adaptive immune activation. These appear to be contemporaneous with Polly Matzinger's danger theory. They are worth searching out. This particular article paints a perspective that I find little fault with.
- Tauber AI. "The immunological self: a centenary perspective." Perspect Biol Med. 1991 Autumn;35(1):74-86 . Here is a 1991 article on Metchnikoff's views that makes my contributions look naïve. I have only recently come across this article (June 2015).
- Golub E.S. "Is the function of the immune system only to protect?" In "Theoretical and Experimental Insights into Immunology." (Proceedings of the NATO Advanced Research Workshop on Theoretical Immunology, Sep 27 – Oct 1, 1991). Edited by Perelson A.S and Weisbuch G. Springer-Verlag, Berlin, Heidelberg, New York, London, Paris, Tokyo, Hong Kong, Barcelona, Budapest, published 1992. ISBN-13:978-3-642-76979-5 . This is an interesting discussion noting the general and perhaps erroneous assumption that the role of the IS is primarily protection from infection. He makes the point (and I agree) that the immune system is most effective against non-pathogenic organisms.
- Veiga-Fernandes H, Freitas AA. "The S(c)ensory Immune System Theory." Trends Immunol. 2017 Oct;38(10):777-788 . The authors have either not come across my articles or have decided not to mention or reference them.
- Eberl G, Pradeu T. "Towards a General Theory of Immunity?" Trends Immunol. 2017 Dec 8. pii: S1471-4906(17)30226-0 . Again, the authors have either not come across my articles or have decided not to mention or reference them.
- Zach M, Greslehner GP "Towards an extended view of immunity: A philosophical perspective." Anaesth Crit Care Pain Med, 2022 41(6):101156 An interesting summation but another instance where Cunliffe and homeostasis do not exist.
- Matzinger P. "Tolerance, danger, and the extended family." Annu Rev Immunol. 1994;12:991-1045. . I am not aware that Polly has ever cited me or bought my contributions to the attention of other people in the field. She has met and knows me. I'd be interested to hear if anyone believes that they have been introduced to my writing through her. There must be some strategic reason why my contributions have remained eclipsed. Walter Land, who is an occasional co-author with her, does not appear (to me) to have acknowledged my work either; but I am sure that we have not met.
- Zach M, Greslehner GP. "Understanding immunity: an alternative framework beyond defense and strength" Biology & Philosophy (2023) 38:7 This article does not acknowledge the existence of my publications.
PAMPs or MAMPs (pathogen or microbe associated molecular patterns) and pathogens
- Strober, W., "Epithelial cells pay a Toll for protection." Nature Medicine 10(9):898-900
- Casadevall, A., Pirofski, L-A. "Host pathogen interactions: redefining the basic concepts of virulence and pathogenicity." Infection & Immunity 1999, 678):3703-3713
- Seong SY, Matzinger P., "Hydrophobicity: an ancient damage-associated molecular pattern that initiates innate immune responses." Nat Rev Immunol. 2004 Jun;4(6):469-78. (Also relevant to tissue homeostasis.)
- Ingle, R.A., Carstens, M., Denby, K.J. "PAMP recognition and the plant-pathogen arms race." BioEssays 2006 ,28(9):880-9. Interesting parallels with animals. Subtle "recognition" that they are "microbe associated" rather than "pathogen associated" molecular patterns.
- Vance RE, Isberg RR, Portnoy DA. "Patterns of pathogenesis: discrimination of pathogenic and nonpathogenic microbes by the innate immune system." Cell Host Microbe. 2009 Jul 23;6(1):10-21. (I found this an excellent read – provocative thinking.)
- Casadevall, A., Pirofski, L-A. "Virulence factors and their mechanisms of action: the view from a damage-response framework." J Water Health. 2009, 7(S1):s2-s18 (DOI:10.2166/wh.2009.036 – PubMed citation not yet available).
- Hardt, W-D. "Infected Cell in Trouble: Bystander Cells Ring the Bell." Immunity 2010 33:5 652-654.
- Lazzaro BP, Rolff J. "Immunology. Danger, microbes, and homeostasis." Science. 2011 Apr 1;332(6025):43-4 (also here)
- Tang AH. "Are you my friends or are you my enemies?" Self Nonself. 2011 Jul;2(3):142-146
- Zhou F, Emonet A, Dénervaud Tendon V, et al. "Co-incidence of Damage and Microbial Patterns Controls Localized Immune Responses in Roots." Cell. 2020;180(3):440-453.e18. This emphasises the need for coincident damage in promoting a response to MAMPs.
- Park JH et al (from Gerard Eberl's department) "Innate immune recognition of a bacterial MAMP leads to conditional activation of pro- or anti-inflammatory responses." A bioRxiv preprint – no journal attribution yet
- Katz DH, Skidmore BJ. "Self-recognition as a means of cell communication in biologic systems: the immune system is not an exception to the general rule." Birth Defects Original Article Series 1978, 14(2):327-341
- More to follow ....
- Casadevall A., Pirofski L-A. "Host-Pathogen Interactions: Redefining the Basic Concepts of Virulence and Pathogenicity." Infect. Immun. 1999 67: 3703-3713
- Rohmer L, Hocquet D, Miller SI. "Are pathogenic bacteria just looking for food? Metabolism and microbial pathogenesis.." Trends Microbiol. 2011 Jul;19(7):341-8
- Bethune MT and Khosla C. "Parallels between Pathogens and Gluten Peptides in Celiac Sprue." PLoS Pathog. Feb 2008; 4(2): e34.
- Casadevall A., Pirofski L-A. Ditch the term pathogen. Nature. 2014 Dec 11;516(7530):165-6 Here, the authors exolore the use of the term "pathogen".
- Ramon-Luing LA, Palacios Y, Ruiz A, Téllez-Navarrete NA and Chavez-Galan L. Virulence Factors of Mycobacterium tuberculosis as Modulators of Cell Death Mechanisms. Pathogens 2023, 12(6), 839 No yet in PubMed. This is a detailed discussion (list) of the influence of MycoTB on different aspects of cell death. It read a bit like a list to me but it's useful. It does not explore the possible strategy that MycoTB deliberately induces an adjuvant provoked autoaggressive immune attack on self tissues and the consequent focal immune suppression to avert piecemeal self destruction – but it lays the groundwork to launch that.
- The Blind Men and the Elephant
- Lagendijk, A. "Pushing for power." Nature v438:p429 (24th Nov) 2005
- Woese, C.R. "A New Biology for a New Century" Microbiol Mol Biol Rev. 2004 Jun;68(2):173-86 in which he muses on reductionism, "bigger pictures" and "a guiding vision".]
- Coutinho, A., "On Doing Science" (a speech by; visible here).
- Garfield, E., "The metaphor-science connection." Essays of an Information Scientist 1986:9;316-323
- Shneider, AM. "Four stages of a scientific discipline; four types of scientist." Trends Biochem Sci. 2009 May;34(5):217-23
- Barber B. "Resistance by scientists to scientific discovery." Science 1961 134:569-602 (also visible here). A "must read" article for those who wonder why new ideas are (r)ejected.
- Raup, D.M., "New Ideas Are 'Guilty Until Proved Innocent'." The Scientist 1986, 1(1):18. An interesting appraisal of conceptual upheavals.
- Fleck, Ludwig. An article about this philosopher on science in the Stanford Encyclopedia of Philosophy. Earlier than Thomas Kuhn. Many of the same themes and an emphasis on communal beliefs.
- Pradeu T. "The Limits of the Self: Immunology and Biological Identity." Oxford University Press. 2012 ISBN 978-0199775286. Chapter 2 is a good historical/philosophical analysis.
- Arroyo-Santos A and Olson ME. "Metaphors as surrogate variables. The case of adaptive radiation." PhilSci Archive 2011. The general discussion is particularly interesting.
- Huang S. – see Innovation section below
- Swiatczak B. "Immune balance: the development of the idea and its application." J Hist Biol 2014, 47:411-442. Good historico-philosophical review of immune theories.
- Taylor C, Dewsbury BM. "On the Problem and Promise of Metaphor Use in Science and Science Communication". J Microbiol Biol Educ 2018 19(1):1-5 I found this to be a great commentry on metaphor in science.
- Shallit J. "Science, pseudoscience, and the three stages of truth." 2005 Department of Computer Science. University of Waterloo. (How new ideas are first greeted, through to how they are finally regarded – before recycling!.)
- Fleisher W, Šešelja D. "Responsibility for Collective Epistemic Harms." Philos. Sci. 2023, 90(1) 1-20 An interesting discussion of a corporate duty of responsibility that ought to avert any harmful suppression of investigation and/or research.
History of immunology
- Moulin The immune system: a key concept for the history of immunology Hist Philos Life Sci 1989;11(2):221-36 This is a good 1969 summary of thought around immunology. Is has faint echos of where the discipline will be heading in 2023 and beyond.
- Durand PM, Ramsey G. The concepts and origins of cell mortality. Hist Philos Life Sci, 2023 Jun 8;45(2):23. This is a useful summary of the historical emergence of the idea or stategised cell death.
Beating back the tide of entropy – life as a manifestation of entropy dissipation
- James J Kay has an extensive site dedicated to this subject, these articles in particular.
- Life as a manifestation of the 2nd law of thermodynamics
- Order from Disorder: The Thermodynamics of Complexity in Biology
- Moore, A., "Life defined." (Editorial) BioEssays 2012, 34:253-254. In my opinion, an excellent assessment of "What is life?" The point that I would like to emphasise is that life, as we know it (ranging from viruses to mammals), probably became evolutionarily inevitable once the reproductive "method" of ensuring the persistence (nurture/reproduction) of order changed from an analogue catalysis to a digitally managed catalysis (RNA, DNA).
- A bit related and very informative, this film highlights the process of decay and recycling. "After Life:The Strange Science of Decay", BBC 4, BBC iplayer. This will probably disappear from the iplayer site before too long. Search the net for snippets.
- Chaisson, E. "The natural science underlying big history." ScientificWorldJournal, 2014:384912
- Ball P, "How life (and death) spring from disorder" ; this fascinating article appeared in Quanta magazine in late January 2017. This is the PDF of the article (this does not include the "Readers Comments"). There are a few points that I may wish to add (probably in the comments added to my "Intentional pathogen killing – or denial of substrate?" article – see Published. I strongly agree with most of the expressed, broad principles. Two points are worth making here; life probably started with the stearic concentration of particular isomers (left or right handed molecules) long before this concentration principle "discovered" the utility of digitally initiated concentration methods (T- R- and D-NA). Before then it was (to my mind) probably based on analogue catalysis; and this would be long before more pure forms of reproduction (vs simple catalysis) emerged.
- "Exclusion Of Diversity And Creativity Impedes Scientific Innovation." Fred M Cowan 1995
- Huang S. "When peers are not peers and don't know it: The Dunning-Kruger effect and self-fulfilling prophecy in peer-review." Bioessays. 2013 May;35(5):414-6.
- Rennie D, "Innovation and peer review" Chapter 5 in "Peer review in health sciences" Ed Godlee F and Jefferson T. 1999 and newer edition 2003 BMJ Books. ISBN 0727916858
- Romano M, Cifelli RL. "100 yeas of continental drift Science 2015, Nov 20;350(6263):915-6 This is an excellent decription of a true, major paradigm shift.
- In this section I will highlight articles that emphasise the anti-inflammatory properties of tolerance and the growing realisation that regulatory T-cell recruitment can lead to immune tolerance. The (absolute) historical view has been that clonal deletion is responsible for tolerance within the foetal thymus. We only have to find a smattering of regulatory T-cell commitment within the foetal thysmus to bring this historical view into question. Then we have to ask "how much" and "for what purpose" does clonal deletion contribute to thymic tolerance.
- Dikiy S, Rudensky AY. "Principles of regulatory T cell function." Immunity . 2023 Feb 14;56(2):240-255
- Thierry Mora T, Walczak AM. "Towards a quantitative theory of tolerance." Trends Immunol 2023, Jul;44(7):512-518 This article seems to call into question the assumption that self reactive T-Cells are deleted in the thymus – "the elimination of self-reactive T cells is at best incomplete".
Other interesting references
- Obhrai, J. & Goldstein, D.R. "The role of Toll-like receptors in solid organ transplantation". Transplantation 2006, 81(4):497-502
- Khan, W.I. & Collins, S.M. "Gut motor function: immunological control in enteric infection and inflammation." Clin Exp Immunol 2006, 143:389-387
- Rios-Barrera, V.A et al. "Macrophage and T-lymphocyte apoptosis during experimental pulmonary tuberculosis: their relationship to mycobacterial virulence." Eur J Immunol 2006, 36:345-353
- Niederkorn, J.Y. "See no evil, hear no evil, do no evil: the lessons of immune privilege." Nature Immunol 2006, 7:345-359
- Blaser, M.J. "Who are we? Indigenous microbes and the ecology of human diseases." Embo Reports 2006, 7:956-960 (currently freely available – 03/10/06 – at this site). Pathogenic organisms evolve with us.
- Galon, J., Costes, A., Sanchez-Cabo, F., et al. "Type, density, and location of immune cells within human colorectal tumors predict clinical outcome." Science 2006, Sep 29;313(5795):1960-4. Firm indication of cancer immunosurveillance.
- RNA interference – 2006 Nobel award release – two good explanations. Press release and Advanced information.
- Burch, P.R.J. R., Burwell, G. "Self and Not-Self a Clonal Induction Approach to Immunology." Q Rev Biol 1965, 40:3;252-279. I don't remember having read this before but, perhaps I did and don't recall it. Burch and Burwell (morphostasis) were well known to me in the early" days. Whatever, it just goes to show, "Originality is nothing but judicious imitation": Voltaire.
- Aller, M-A., Arias, J-L., Sánchez-Patán,F., Arias, J. "The inflammatory response: An efficient way of life." Med Sci Monit 2006; 12(10): RA225-234
- Lawrence T, Gilroy DW. "Chronic inflammation: a failure of resolution?" Int J Exp Pathol. 2007 Apr;88(2):85-94.
- Markiewski MM, Nilsson B, Ekdahl KN, Mollnes TE, Lambris JD. "Complement and coagulation: strangers or partners in crime?" Trends Immunol. 2007 Apr;28(4):184-92.
- Cortes-Jorges H. "Bubble algae: selected descriptions, controls and comments". Reefkeeping (online magazine) 2002:Feb http://reefkeeping.com/issues/2002-02/hcj/feature/index.php . A revealing article that discusses the denial of resources in coral tank ecosystems.
- Garber, E.D. "The host as a growth medium." Ann N Y Acad Sci. 1960 Nov 21;88:1187-94. I have not managed to obtain the full article but it looks as though Garber may have suggested that the host protects itself by sequestering nutrient material. There is an earlier 1956 article too: "The Role of Nutrition in the Host-Parasite Relationship." Proc Natl Acad Sci U S A. 1954 Dec;40(12):1112-8.
- Youngsteadt E. "Dying Generously" Am Sci 2011, 99(3):208 "Altruistic" elective suicide in single celled organisms.
- Lathrop SK, Bloom SM, Rao SM, Nutsch K, Lio CW, Santacruz N, Peterson DA, Stappenbeck TS, Hsieh CS. "Peripheral education of the immune system by colonic commensal microbiota." Nature. 2011 Sep 21. Evidence that tolerant immune responses are invoked to co-operators.
- Naviaux, Robert K. "Metabolic Features of the Cell Danger Response." Mitochondrion (2013) Epub ahead of publication
- Legoux FP, Lim JB et al "CD4+ T Cell Tolerance to Tissue-Restricted Self Antigens Is Mediated by Antigen-Specific Regulatory T Cells Rather Than Deletion" Immunity, 2015 17;43(5):896-908
- Davis MM "Not-So-Negative Selection" Immunity, 2015 Nov 17;43(5):833-5 (Editorial comment on the Legoux et al paper above.)
- Burch PRJ, "The biology of cancer a new approach" 1976, MTP Press, ISBN 0852000898 . This is interesting. I have just bought this book (Jan 2017) because it was "resurrected" on the web just recently and I have long been aware of Burch's work. I suspect that this book may well have come into the Middlesbrough Gen Hosp library back in 1976 – when I my interest in Behcet's syndrome began. This – particularly Chapter 2 – could well have set my thoughts moving in a very productive direction.
- Katz DH, Skidmore BJ. "Self-recognition as a means of cell communication in biologic systems: the immune system is not an exception to the general rule."Birth Defects Orig Artic Ser. 1978;14(2):327-41
And now there is an increasing flurry or articles wanting to challenge conventional views
- Muraille E. "Redefining the Immune System as a Social Interface for Cooperative Processes." Plos Pathog 2013 9(3)
- Malyshkin AP. "Adaptive immunity: the concept of linked functions." Immunol Innov 2013, 1:1-7
- Pradeu T. "Immunity and the emergence of individuality." Just at his web site as far as I can see.
- Malyshev I.Y., Manukhina E.B. and Malyshev Y.I. "Physiological organization of immune response based on The homeostatic mechanism of matrix reprogramming: Implication in tumor and biotechnology." Medical Hypotheses (2014)
- Land W. G. "Damage-Associated Molecular Patterns in Human Diseases" Volume 1: Injury-Induced Innate Immune Responses
Computing – maintaining integrity – an emerging view that uses analogies with biology
- Burbeck, S. "Multicellular computing." (start with this page then explore the rest . Don't miss the original paper ).
- Article about Uwe Aickelin's work in New scientist
- Cohen, I.R., "Immune System Computation and the Immunological Homunculus." 2006 (visible here ).
- Twycross, J., Aickelin, U. "Biological Inspiration for Artificial Immune Systems". This is an excellent article, in my opinion, and immunologists would all be enlightened by reading it.