Preface

There has been tremendous progress in the field of immunology in recent years, which could be attributed to the recent adoption of high-throughput technological approaches for genomics, transcriptomics, and proteomics. New techniques have revolutionized biomedical science in terms of innovative platforms for diagnostics, therapeutics, and prophylactics. These technological advances and their role in accelerating basic and clinical research sparked the idea for this book, which brings together relevant research of the methodology and applications for gaining better insight into human diseases.

Cells sense and respond to a variety of signals in terms of the physiological functions of living organisms. In the context of immune cells, signalling events are crucial drivers in recruiting the cells to the site of infection and interaction with other cells (cell-cell interaction) that leads to the release of soluble factors such as cytokines. These soluble factors travel through the bloodstream and mediate their effects on neighbouring or distant cells, which eventually determines the outcome of disease via a series of complex cellular interactions. Cellular interactions involved in the recognition of pathogens and their molecules begins the cell signalling cascade by ligation of cell surface receptors, activation of transcription factors and downstream components that drives the outcome of infection. Overall, signal transduction cassettes include the membrane receptors, effector signalling and regulatory proteins that coordinate to detect, amplify, and orchestrate the external signals of cellular responses. During infection, the main immunological players, innate and adaptive immune cells, are key in combatting the infection. As per the conventional cell signalling process, binding of the antigen generates an intracellular signalling cascade, however, there are a diversity of antigenic receptors that trigger many signals for orchestrating immunological outcomes.

We have focussed on understanding the innate and adaptive arms of immunity that recognize foreign protein segments based on a programmed series of immune cell synapses between T cells and antigen-presenting cells (APCs). These interactions are crucial for immediate and long-term responsiveness of T cells to major histocompatibility complex (MHC)–peptide complexes depending on the thresholds that are tuned at the cell synapses and determine immune responses. The fine-tuning of these thresholds remains vital for the host, as an overreaction to self-proteins can be the cause of autoimmune dysfunctions, whereas underreaction to pathogens can equally be detrimental in terms of the development of susceptibilities to a variety of infections and tumours. Apart from immunological synapses, the importance of cytoskeleton dynamics, cell asymmetry, and membrane patterning for the setting threshold for immune cell activation also play an important role in immune cell signalling and regulation of immune response.

Currently, much attention has been paid to understanding the role of molecular events in immunological processes. Our current understanding is based on an array of model systems and with the advent of recent technological platforms, it is likely that many surprises will be revealed.

Keeping these facts in mind and expanding our knowledge about immune cell signalling and its role in disease management, this book has been organized into two sections. It begins with the tools and recent use of model systems for understanding disease pathology, which will eventually help in designing strategies for disease management, which has been covered in the second section. Briefly, the chapter outlines are as follows:

Chapter 1 reviews the flow cytometric approach for primary immunodeficiency diseases. It examines different techniques for immunophenotyping molecules for better understanding of immunological interactions. Chapter 2 briefly discusses the use of organoid models for cell-cell interactions and their benefits for regenerative medicine and designing personalized therapies. Chapter 3 discusses recent innovative models for studying lung diseases. It includes a comprehensive outlook on organ-on-chip and organoids for a better understanding of lung pathologies and designing strategies for the management of lung fibrosis. Chapter 4 examines nanoparticle-based immunotherapy for managing cancer. Chapter 5 comprehensively reviews immunological signalling for the development of allergies. The chapter briefly covers eosinophils, basophils, immunoglobulins, Th2 responses, and histamines as the crucial determinants for the development of allergies. Chapter 6 provides up-to-date information on the molecular understanding of SARS-CoV2 and other coronavirus ancestors. The chapter gives an outlook about the molecular tools for dissecting the virus and that help in targeting specific molecular structures for designing vaccines and managing the epidemic outbreak. Chapter 7 provides a comprehensive outlook on the molecular dynamics of vector and malarial parasite interactions, with the aim to provide insight into host-parasite cellular interactions to abrogate disease transmission. Chapter 8 reviews and summarizes the recent advances in understanding dendritic cells for pathogenic infections. It covers different aspects of immunological interactions orchestrated via dendritic cells for regulating immunological outcomes. Chapter 9 covers recent information and gaps in the understanding of modulation in innate immune responses against Zika virus infection during pregnancy. It provides a brief discussion on recent technological advances that can overcome current knowledge gaps. Finally, Chapter 10 addresses the role of toll-like receptors (TLRs) in cancer progression and how these receptors can be targeted for the management of a disease.

The two sections of this volume include the study of different molecular phenomena that eventually drive infection outcomes as well as manipulation of this phenomena for effective treatment of disease symptoms. Different signalling mediators drive the production of messenger molecules that mediate their action, leading to the elicitation/ suppression of immune responses. The book presents a balanced approach in line with the previous edition, which also explained various molecular and immunological tools for better understanding of cellular interactions. I hope this edition provides students and researchers comprehensive information on cellular interactions in terms of disease management aspects and their utility in bench side as well as bedside applications.

#### **Bhawana Singh**

Department of Medicine, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India Section 1
