Extensive work has suggested that a number of endogenous molecules such as heat shock proteins (hsp) may be potent activators of the innate immune system capable of inducing proinflammatory cytokine production by the monocyte-macrophage system and the activation and maturation of dendritic cells. The cytokine-like effects of these endogenous molecules are mediated via the Toll-like receptor (TLR) signal-transduction pathways in a manner similar to lipopolysaccharide (LPS; via TLR4) and bacterial lipoproteins (via TLR2). However, recent evidence suggests that the reported cytokine effects of hsp may be a result of the contaminating LPS and LPS-associated molecules. The reasons for previous failure to recognize the contaminant(s) being responsible for the putative TLR ligands of hsp include failure to use highly purified hsp free of LPS contamination; failure to recognize the heat sensitivity of LPS; and failure to consider contaminant(s) other than LPS. Whether other reported putative endogenous ligands of TLR2 and TLR4 are a result of contamination of pathogen-associated molecular patterns is not clear. It is essential that efforts should be directed to conclusively determine whether the reported putative endogenous ligands of TLRs are a result of the endogenous molecules or of contaminant(s), before exploring further the implication and therapeutic potential of these putative TLR ligands.

https://jlb.onlinelibrary.wiley.com/doi/pdf/10.1189/jlb.0304127

Endogenous ligands of Toll-like receptors

Every organisation from the scale of whole countries down to small companies has a list of system developments which have ended in various forms of disaster. The nature of the failures varies but typical examples are: cost overruns; timescale overruns and sometimes, loss of life. The post-mortems to these systems reveal a wide range of reasons all the way from hardware failures, through software errors right to major system level mistakes. More importantly a large number of these systems share one attribute: complexity. This paper presents a fresh look at the nature of complexity in the building of computer based systems.

http://ieeexplore.ieee.org/iel3/4458/12639/00581896.pdf

Complex systems

The Self and Its Brain.

The immune system is a complex system of cells and molecules that can provide us with a basic defense against pathogenic organisms. Like the nervous system, the immune system performs pattern recognition tasks, learns, and retains a memory of the antigens that it has fought. The immune system contains more than 10{sup 7} different clones of cells that communicate via cell-cell contact and the secretion of molecules. Performing complex tasks such as learning and memory involves cooperation among large numbers of components of the immune system and hence there is interest in using methods and concepts from statistical physics. Furthermore, the immune response develops in time and the description of its time evolution is an interesting problem in dynamical systems. In this paper, the authors provide a brief introduction to the biology of the immune system and discuss a number of immunological problems in which the use of physical concepts and mathematical methods has increased our understanding. {copyright} {ital 1997} {ital The American Physical Society}

/pdf/immunology-for-physicists-514mx7dzf7.pdf

Immunology for physicists

Heat-shock proteins as activators of the innate immune system

To effect the molecular integrity of the individual, the immune system has to gather antigenic information and respond in a meaningful way. Immunologists traditionally have focused their research on analyzing the component parts of the system. The achievements of immunology in its analytical enterprise have now made it possible to begin the task of synthesis. In this paper, we shall consider how the immune system combines germline and somatic information using a chemical language to establish the functional meaning of antigens.

/pdf/immune-information-self-organization-and-meaning-fn8738udnp.pdf

Immune information, self-organization and meaning.

T cell proliferative responses of type 1 diabetes patients and healthy individuals to human hsp60 and its peptides.

The cellular computer DNA: Program or data

to Immune Networks.- I.- Natural Id-Anti-Id Networks and the Immunological Homunculus.- Self-Nonself Immunological Tolerance and Idiotype Networks.- II.- Extensive Percolation in Reasonable Idiotypic Networks.- The Concept of Idiotypic Network: Deficient or Premature?.- Dynamical Behavior of Discrete Models of Jerne's Network.- Some Reflections on Memory in Shape Space.- III.- Regulation of the Immune Response: A Discrete Mapping Approach.- Simulation of the Immune Cellular Response by Small Neural Networks.- Discrete Time Versus Continuous Time Approach to the Autoimmune Response.- Optimizing the Immune Control of Parasitic Invasion.- Index of Contributors.

Theories of immune networks

Random boolean networks are defined and used as models of systems composed of many interacting components. Computer simulations showing the organization of these networks in subnets, as well as a temporal organization in limit cycles are reported. The influence of the different boolean laws on this organization is investigated and results concerning the stability of the organization against “surgery” and external noise are presented.

Henri Atlan

Papers

Immune information, self-organization and meaning.

T cell proliferative responses of type 1 diabetes patients and healthy individuals to human hsp60 and its peptides.

The cellular computer DNA: Program or data

Theories of immune networks

Random Boolean Networks