Immunologic Signatures of Rejection

This book collects salient observational data, derived predominantly from human studies, regarding the mechanism(s) of rejection in various pathologic conditions; the premise is that immune rejection, better defined as "immune-mediated, tissue-specific destruction" (TSD), comprises a broad range of phenomena ranging from tumor regression, to clearance of pathogen through destruction of infected cells, autoimmunity, allograft rejection by the host and host versus graft reactions. Like different hands can turn on or off a switch, distinct mechanisms can trigger TSD; however, a convergent pathway is ultimately observed when TSD occurs consisting of a dramatic switch from chronic to acute inflammation leading to the activation of a restricted number of genes that we comprise in the immunologic constant of rejection (ICR) model. Although the ICR model does not address "why" rejection occurs but rather "how", and it may not contribute an explanation for the determinism of rejection, it provides, if correct, a simplified road map about the convergent pathways leading to TSD. This offers the opportunity to identify a common target for immune manipulation with therapeutic purposes since ICR-related pathways are restricted in expression to the tissues in which TSD occurs while are shut off in the rest of a normal organism. The book includes chapters from outstanding basic and/or observational scientists that have contributed to this area either by defining mechanisms relevant to the understanding of the inflammatory switch or by describing how this occurs in human tissues under different pathological conditions. We would like to entice our reader(s) to test with us, through, the readings, whether our hypothesis is correct; we predict that common themes will emerge particularly if attention will be paid to the general phenomenon of TSD rather than the peculiarities of individual pathologies. With the hope of having contributed with this book something novel andimportant and we wish our reader a pleasant journey in the wondrous land of immune-mediated, tissue-specific destruction.

Résumé
This book discusses the mechanisms leading to immune-mediated tissue rejection following the hypothesis that independent of the disease process the final effector mechanism is shared by most (but not all) pathologies and it is relatively simple. The book covers evidence gathered to support the thesis by studies performed in humans during rejection or in experimental models and will focus particularly (but not exclusively) on the analysis of the rejected tissue rather than the systemic circulation. Several disease processes are discussed including example of chronic inflammatory process without resolution of the pathologic process and acute one with resolution of the pathologic process (clearance of pathogen, rejection of tumor) or unwanted tissue destruction (allograft rejection, autoimmunity).

Contenu
Part One - From delayed allergy reaction to the immunologic constant or rejection 1. Ena Wang and Francesco M Marincola Part Two - The immune biology of rejection; basic principles 2. Experimental models of rejection Anil Shanker A 3. Cancer and Inflammation Alberto Mantovani 4. The immunologic switch Giorgio Trinchieri 5. The angiogenic switch Douglas Noonan 6. Chemokines and cytotoxic effector molecules in rejection Alan Krensky 7. Immune cell activation: the clinical perspective David F Stroncek Part Three - Circulating patterns associated with chronic and acute immune pathology 8. Immune signatures detectable in peripheral lymphocytes: a modular view Damien Chaussabel 9. Immune signatures associated with unresolving compared to resolving infections: the HCV model Robert E Lanford 10. Immune signatures associated with unresolving infections: the HIV model Luigi Buonaguro 11. Immune signatures associated with the cancer-bearing status Peter P Lee Part Four - Tissue-specific patterns associated with chronic inflammatory processes 12. Signatures associated with destructive autoimmune pathologies Steve Jacobson 13. Predictors of favorable outcome in cancer Zoltan Pos 14. Other predictors of outcome - George Coukos 15. Transcriptional profiling of melanoma as a potential predictive biomarker for response to immunotherapy Thomas F. Gajewski 16. Predictors of allograft rejection - Sarwal Minnie Part Five - Signatures associated with acute rejection 17. Graft vs Host Fran Hakim 18. Tumor rejection Ena Wang 19. Allograft rejection Davide Bedognetti