The objective of this introduction is to outline certain historical and theoretical frames of modern immunology. Immunology as a discipline that has been shaped relatively recently attempts to explain all kinds of phenomena safeguarding the integrity of an organism. An organism is understood as a complex multi-system structure developed in the course of evolution. In the case of such a broad sense concept of immunity a penetrating discussion is required. Thus, biology philosophers as well as scientists – immunologists, for nearly 50. years have been analysing the basic definitions, which led them to interesting conclusions

Jacek S. Podgórski

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AVANT Volume III, Number 1/2012 www.avant.edu.pl/en  19    Who is on guard for harmony? On harmony, phagocytes and immunological identity Jacek S. Podgórski1 Department of Philosophy of Science Nicolaus Copernicus University Torun, Poland translation: Anna Węgrzyn  Abstract The objective of this introduction is to outline certain historical and theoretical frames of modern immunology. Immunology as a discipline that has been shaped relatively recently attempts to explain all kinds of phenomena safeguarding the integrity of an organism. An organism is understood as a complex multi-system structure developed in the course of evolution. In the case of such a broad sense concept of immunity a penetrating discussion is required. Thus, biology philoso-phers as well as scientists – immunologists, for nearly 50. years have been analys-ing the basic definitions, which led them to interesting conclusions. Keywords:  immunological  self,  immunological  selfhood,  phagocytosis,  immu-nological tolerance theory, Jerne’s network theory  Introduction In a standard way immunology is presented as a discipline looking into how living organisms defend themselves against infections, hazardous substances and foreign tissues. A classical paradigm assumes that an organism is capable of defending itself due  to being equipped with highly  specialised mechanisms classifying the encountered objects into ‘self’ and ‘non-self’ ones. The issue of organism peculiar-ity was also tackled by philosophers of biology. Together with immunologists they tried to provide answers to two kinds of questions. The first kind is of an ontologi-cal character and concerns the nature of immunological self: What are the limits to                                                            1 Special thanks to Łukasz Afeltowicz.  Immune System, Immune Self  20what may be seen as self?; How to define what is self?; How does the immunological self of an organism change in time?, etc. (Schaffner 1993: 8-19; Sarkar 1991: 125-138). The other kind of issues was related to the explanation procedures applied in immunology: Do the terms and models used with regard to immunology explain the researched phenomena in a satisfactory manner?; Is the reductionist description of immunological  phenomena  expressed  in  molecular  structure  categories  sufficient? (Schaffner 1993: 64-89; Sarkar 1991: 138-163). The  perception  of  immunological  phenomena  in  the  self/non-self  categories  has prevailed since the 1950s. However, today this paradigm is more and more often contested. This results from the fact that modern research reveals the behaviours of immunological system that cannot be expressed in the category of mechanisms distinguishing the self and non-self objects (Janeway and others 2001). In the following introductory text I am going to outline the basics of a standard immunological paradigm with its historical background, as well as point to its limi-tations and possible alternative conceptualisations. However, before I do that I would like to introduce certain basic categories from the field of immunology.  Immune system Immune system is a set of cells (including a gene-programmed network of lympho-cytes), tissues and organism mechanisms, defending an organism against diseases through an identification and liquidation of pathogens and cancerous cells. These elements constantly seek various pathogenic conditions, and, by doing so, discern the healthy cells and tissues of an organism. Such activities aim at maintaining the biological balance – immunological homeostasis (Clark 2007: 3-14; Klein 1990). In  the  course  of  evolution  of  species  the  mechanisms  of  pathogen  detection evolved to such a degree that the defensive cells are now able to ‘learn’ and react adequately to the surroundings. As an example, each simple single-celled organism (e.g. bacteria) has a specified enzyme system protecting it from viral infections. Human immune system is composed of multiple protein types (e.g. cytokine), cells (e.g. lymphocytes T and B), tissues (e.g. mucous membrane tissues, nasopharynx) and organs (e.g. thymus, spleen) that interact in a complex and dynamic way, cre-ating a complex system of structural interlocking (Janeway and others 2001; Howes 2008). The organs of immune system may be divided into central (primary) and peripheral (secondary) ones. The immune system of mammals consists of two interrelated subsystems: innate and acquired immunity (Clark 2007: 3-7). Innate immunity is a system of primitive mechanisms and physical barriers – a sort of a first-line defence. Those barriers are constituted, among other things, by various tissue types that prevent pathogens from having access to an organism. If a pathogen manages to break through the AVANT Volume III, Number 1/2012 www.avant.edu.pl/en  21said barriers, innate immune system will recognize it and remove it; however, it is not capable of remembering the pathogen pattern, nor prepare itself for a similar infection in the future. In other words, innate system is deprived of immunological memory.  In the situation when an ‘intruder’ manages to successfully avoid the response of non-specific  (innate)  immunity,  mammals  may  make  use  of  another  protective barrier, i.e. an acquired or adaptive immune system. Such a subsystem is able to remember subsequent infections and improve its response to them in the future by recognising a previously eliminated pathogen. When an ‘intruder’ is destroyed, the subsystem ‘learns’ its response. This allows it to faster recognise and destroy this type of threats in the future (Clark 2007: 43-60). As we may see on the example of the above description, immunology is dominated by  the  metaphor  of  a  military  conflict,  where  ‘enemy  forces’  are  clearly  distin-guishable from an organism’s ‘own army’ as if they were uniformed soldiers and marked vehicles. However, the problem rests in the fact that such a metaphor is more and more frequently subject to questioning. It is difficult to point to an object that could be an equivalent of a clear and always recognisable marking (Howes 2008:  280-284).  An  example  is  the  host-friendly  intestinal  bacteria  that  are  not fought by the immune system, although in their structure they remind of patho-gens. Immune system ‘leaves’ its own cells ‘alone’, however starts to treat them as ‘hostile’ as soon as they die or become damaged. An interesting example is organ transplantation.  Before  the  surgery  doctors  check  the  number  of  the  so-called compatible tissue markers between the donor and the recipient, while chemically supressing the immune system of the recipient. Still, at times the markers fail – a seemingly  compatible  organ  may  be  rejected  by  the  recipient’s  organism.  This happens supposedly due to the fact that at the moment of operation the organism is ‘in distress’, which results in a strong immunological reaction (Wood 2006). An-other  mystery  is  found  in  numerous  immunological  diseases  which  –  generally speaking – consist in the immune system’s attacking and destroying the cells of its own organism. Because of the above doubts, immune system is now commonly perceived as a network, a cognitive system or even an interlocutor maintaining a dialogue with the organism (Cohen 2001). Let us now proceed to a historical reconstruction of the self/non-self paradigm de-velopment as well as modern attempts to move beyond its limitations.  The self/non-self paradigm and beyond it The  historical  background  of  the  paradigm  should  begin  with  works  of  Claude Bernard (1813-1878), a French doctor and physiologist (Silverstein 1989).  It was him that posed the following question: How do we define particular metabolic limi-tations necessary for a regular functioning of living organisms? In his depiction, the Immune System, Immune Self  22body was composed of clearly divided modules, where the autonomy of the whole depended  on  the  balance  of  ‘internal  elements’.  This  form  of  physical  atomism radically changed the perception of the functions of an organism relying on an internal architecture of a limited environment (Tauber 1994: 51-53). Another of Bernard’s innovations consisted in the introduction of a military metaphor when considering immunity. According to Bernard, in order to reach the state of homeo-stasis an organism uses its ‘military forces’ to attack and destroy the ‘enemy’ that is disturbing its balance. Another important phase was the research carried out by Élie Metchnikoff (1845-1916) on phagocytes’ behaviour and significance for the immunity. This is how he described  immunity:  for  an  organism  to  function  properly  it  is  required  to  be equipped with a regulatory system, i.e. a system providing an order to ‘everything’; the ‘harmony’ of an organism is disturbed by foreign factors, and what is responsi-ble for its restoration are specialized individuals shaped in the course of natural selection  (Tauber  2003:  897).  Such  an  individual  was  seen  in  a  phagocyte  re-searched by Metchnikoff, whose function rested in the absorption, and at the same time,  neutralization  of  ‘non-self’  or  damaged  cells  (Tauber  2003:  898-901).  The phagocyte played the role of a ‘guard’ distinguishing and separating what was self (friendly, functional) from what was ‘non-self’ (toxic, damaged) (Tauber, Chernyak 1991: 135-175). In the first half of the 20th c. immunology focused on an attempt to determine the chemical base of immunological reactions. After World War II the main research objects were transplantology and autoimmune reactions, as well as widely under-stood genetics. Also at that time, in one of his numerous publications, Sir Frank Macfarlane Burnet (1899-1985) introduced the term of ‘immunological self’. This category, derived from psychology, gave rise to the theory of immunological toler-ance (Burnet 1957: 67-69). Burnet described immunological reaction process in the following way: an organism has a certain biological identity acquired as early as in the prenatal period; such an identity has a genetic base. Each cell characterised by a proper pattern will be tolerated by immune system as friendly, whereas other objects, which do not have the said pattern, will trigger off an immunological reac-tion. In that period immunology concentrated on the examination of lymphocyte struc-ture and function. Burnet proposed a hypothesis according to which these cells were related to the mechanism of acquired immunity (Burnet 1959). This hypothe-sis was developed and tested by other researchers. Burnet spoke about immunity in the categories of immunological memory of cells that remember the intruder in order to be able to recognise it sooner in the future. Such a perception, in a way extending the previous concepts, became known as a clonal selection paradigm (Silverstein 2002: 793-796). It was to explain, among other things, the phenomenon of autoimmunization underlying autoimmune diseases. AVANT Volume III, Number 1/2012 www.avant.edu.pl/en  23A  different  approach  was  proposed  by  Niels  Kaj  Jerne  (1911-1994).  The  central category of his explanatory model was an immunological network, i.e. a set of in-terrelated cells belonging to immune system, whose task was not to protect an or-ganism against the non-self but rather to regulate – inhibit or strengthen – its own reactions (Jerne 1974: 373-389). We may say that Metchnikoff and Burnet focused on single cells, whereas Jerne pointed to interrelations between specialized agents. For instance, he pointed to the activity of antibodies (their production, formulation and adjustment). Following his idea, an antibody not only recognises a foreign an-tigen, but it is also capable of recognising particular antigens characteristic for its own structures. This means that depending on the situation, a ‘recognising’ ele-ment may at times prove to be the ‘recognised’ one. In simpler words, recognition of the self/non-self depends on the elements involved in the ‘discussion’ subject to particular ‘grammatical’ rules of constantly transforming immunological biology (Jerne 1984: 5-24).    Conclusions It is necessary to point to three key moments in the history of immunology (Sarkar 1996: 125-170). First, Metchnikoff stated that immune system fulfils two functions: it defines an organism’s identity and maintains its integrity – wholeness. The sec-ond important moment was formulating by Burnet the mechanism of differentia-tion of the self/non-self. The third moment was the description of the phenomenon of immunity by Jerne as ‘flexible’ and ‘discursive’ (Varela 1994: 31-40). In his pro-posal, the way of describing immunological phenomena may not be limited to the stiff logic of distinguishing the self/non-self. According to him, it should illustrate the system’s cognitive capabilities that are subject to changes in a given biological environment (Jerne 1985: 439-451; Cohen 1992: 490-494).  Bibliography Burnet, F.M. 1957. A modification of Jerne’s theory of antibody production using the concept of clonal selection. Australian Journal of Science, 20: 67-69. Burnet, F.M. 1959. The Clonal Selection Theory of Acquired Immunity. Vanderbilt University Pres: Nashville. Clark,  W.R.  2007.  In  Defense  of  Self,  How  the  Immune  System  Really  Works  in  Managing Health and Disease, Oxford University Press, New York. Cohen, I.R. 1992. The cognitive paradigm and the immunological homunculus. Immunology Today, 13: 490-494. Cohn, M. 1998. The self-nonself discrimination in the context of function. Theoretical Medi-cine and Bioethics, 19 :475-484. Crist E., Tauber A.I. 1999. Selfhood, Immunity, and the Biological Imagination: The Thought of Frank Macfarlane Burnet. Biology and Philosophy, 15 :509-533. Immune System, Immune Self  24Howes, M. 2008. Self and Nonself, red. S. Sarkar, A. Plutynski, A Companion to the Philoso-phy of Biology. Blackwell Publishing, Oxford. Janeway, Ch.A.,Jr, Travers, P., Walport, M., Shlomchik, M. J., red. 2001. Immunobiology. The Immune System in Health and Disease. 5th edition. Garland Science, New York. Jerne, N.K. 1974. Towards a network theory of the immune system. Annals of Institute Pas-teur/Immunology (Paris), 125C: 373-389. Jerne, N.K. 1984. Idiotypic Networks and Other Preconceived Ideas. Immunological Reviews, 79: 5-24. Jerne, N.K. 1985. The generative grammar of the immune system. Bioscience Reports, 5: 439-451. Sarkar, S. 1996. Biological information: A skeptical look at some central dogmas of molecu-lar biology. red. S. Sarkar, The Philosophy and History of Molecular Biology: New Perspec-tives. Kluwer Academic Publishers Group, Dordrecht. Schaffner, F.K. 1993. 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