Platelets as autonomous drones for hemostatic and immune surveillance

Platelets participate in many important physiological processes, including hemostasis and immunity. However, despite their broad participation in these evolutionarily critical roles, the anucleate platelet is uniquely mammalian. In contrast with the large nucleated equivalents in lower vertebrates, we find that the design template for the evolutionary specialization of platelets shares remarkable similarities with human-engineered unmanned aerial vehicles in terms of overall autonomy, maneuverability, and expendability. Here, we review evidence illustrating how platelets are uniquely suited for surveillance and the manner in which they consequently provide various types of support to other cell types.J.L. Li is supported by Agency for Science, Technology and Research funding. A. Zarbock is supported by Deutsche Forschungsgemeinschaft (ZA428/13-1 and INST211/604-2 A05). A. Hidalgo is supported by Plan Estatal de Investigación Científica y Técnica y de Innovación 2013–2016 (SAF2015-65607-R and PCIN-2014-103), Programa Estatal de I+D+i Orientada a los Retos de la Sociedad Retos Investigación I+D+i from MECI, and cofunding from Fondo Europeo de Desarrollo Regional. Centro Nacional de Investigaciones Cardiovasculares Carlos III is supported by the MECI and the Pro CNIC Foundation and is a Severo Ochoa Center of Excellence (MECI award SEV-2015-0505).S

Antigenic Complementarity in the Origins of Autoimmunity: A General Theory Illustrated With a Case Study of Idiopathic Thrombocytopenia Purpura

We describe a novel, testable theory of autoimmunity, outline novel predictions made by the theory, and illustrate its application to unravelling the possible causes of idiopathic thrombocytopenia purpura (ITP). Pairs of stereochemically complementary antigens induce complementary immune responses (antibody or T-cell) that create loss of regulation and civil war within the immune system itself. Antibodies attack antibodies creating circulating immune complexes; T-cells attack T-cells creating perivascular cuffing. This immunological civil war abrogates the self-nonself distinction. If at least one of the complementary antigens mimics a self antigen, then this unregulated immune response will target host tissues as well. Data demonstrating that complementary antigens are found in some animal models of autoimmunity and may be present in various human diseases, especially ITP, are reviewed. Specific mechanisms for preventing autoimmunity or suppressing existing autoimmunity are derived from the theory, and critical tests proposed. Finally, we argue that Koch's postulates are inadequate for establishing disease causation for multiple-antigen diseases and discuss the possibility that current research has failed to elucidate the causes of human autoimmune diseases because we are using the wrong criteria

Reduced transforming growth factor-beta1 production by mononuclear cells from patients with active chronic idiopathic thrombocytopenic purpura.

Chronic idiopathic thrombocytopenic purpura (ITP) is an autoimmune disorder in which activated T-helper (Th) cells and different Th-cell cytokines might play an important role. We have recently reported that chronic ITP patients in remission had elevated plasma levels of the Th3 cytokine transforming growth factor-beta1 (TGF-beta1), possibly as a part of a bystander immune suppression. In the present study we found that, in ITP patients with active disease [platelet count (plc) 150 x 10(9)/l (1894 +/- 244 pg/ml; n =12;