Computational Immunology

Basics

Shyamasree Ghosh

• Publisher: CRC Press
• Year: 2019
• ISBN:
  9781351025522
• Edition: 1
• Topic: Medicine
• Subtopic: Biotechnology in Medicine

The immune system is highly complex system with large number of macromolecules, signaling pathways, protein-protein interactions, and gene expressions. Studies from genomics, transcriptomics, metabolomics are generating huge high throughput data that needs to be analyzed for understanding the Immune system in Health and Disease. Computational approaches arehelping in understanding the study of complex biology of immunology and thereby enabling design of therapeutic strategies in diseases like infectious diseases, immunodeficiency, allergic, hypersensitive, autoimmune disorders and diseases like Cancer, HIV etc.

Computational Immunology: Basics highlights the basics of the immune system and function in health and disease.

This book offers comprehensive coverage of the most essential topics, including

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• Overview of Immunology and computational Immunology

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• Immune organs and cells, antigen, antibody, B, cell, T cell

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• Antigen Processing and presentation

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• Diseases due to abnormalities of the immune system

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• Cancer Biology

Shyamasree Ghosh (MSc, PhD, PGDHE, PGDBI), is currently working in the School of Biological Sciences, National Institute of Science Education and Research (NISER), Bhubaneswar, DAE, Govt of India, graduated from the prestigious Presidency College Kolkata in 1998. She was awarded the prestigious National Scholarship from the Government of India. She has worked and published extensively in glycobiology, sialic acids, immunology, stem cells and nanotechnology. She has authored several publications that include books and encyclopedia chapters in reputed journals and books.

1	Overview of Immunology and Computational Immunology

1.1 INTRODUCTION

The immune system acts as the defence system of our body. Through its hallmark property of recognition and response, it aims at conferring protection to our body from foreign pathogens, preventing diseases and thus enables us to have a healthy life. Our body is challenged by a host of pathogens ranging from infectious agents such as viruses, bacteria, fungi, protozoans, and worms. The immune system is highly complex in its function and structure; it involves a network of cells and organs and molecules such as cytokines, chemokines, histocompatibility complexes, antibodies, anti-histamines; the complement system; signalling pathways; and antimicrobials and other molecules that function in an intricate manner to combat infection and disease and therefore confer immunity upon us. The immune system plays major roles in defence against infections and tumour and recognises and responds to tissue grafts during transplantation. However, an aberration in the function of our normal immune system may lead to a disease state. Abnormal immune responses can result in infections, allergies, and autoimmune, inflammatory and immunodeficiency disorders. Therefore, understanding these complicated interactions would help us in deciphering and diagnosing the aberrations seen in disease states and designing appropriate remedies.

1.2 HISTORY OF THE SCIENCE OF IMMUNOLOGY

Perhaps the earliest of developments in the field of immunology lies in the initial visualisation of live cells under the microscope (Figure 1.1), but the concept of immunity from disease originated in the fifth century BC in Greece. Thucydides observed that individuals who had already contracted plague and recovered became ‘immune’ or ‘exempt’ from subsequent plague infection.

The earliest recognised attempt to intentionally induce immunity took place in the tenth century BC in China. This early attempt involved immunity to smallpox and the process of variolation, wherein healthy people were exposed to liquid from smallpox lesions. Variolation found popularity in eighteenth century England when Lady Mary Wortley Montague survived smallpox infection and, in 1718, her five-year-old son was variolated. However, despite its knowledge and earlier use, Edward Jenner is known as the discoverer of the smallpox vaccine. In 1774, Benjamin Jesty, a farmer, inoculated his wife with the vaccinia virus.

In 1875, Robert Koch, a country physician, injected a rabbit’s ear with anthrax-infected animal blood and the rabbit died. He found that lymphocytes had transfected bacteria to the rabbit. Through studies on chickens infected with the cholera bacillus, Louis Pasteur discovered the concept of attenuation, or reduced virulence, of a virulent strain of the chicken cholera bacillus and he developed the concept called vaccination. Koch postulated the germ theory of disease (Figure 1.2).

Metchnikoff, the Russian zoologist (Figure 1.3), was a pioneer scientist in the field of cellular immunology [1] and is known as the father of natural immunity [2,3,4,5]. He recognised the phenomenon of phagocytosis that occurs during immunity to infection and found that components of the serum were involved in phagocytosis. The Nobel Prize was awarded to Elie Metchnikoff in 1908, together with German Physician Paul Ehrlich (Figure 1.4), as pioneers of cellular and humoral immunology, respectively, and for their work on immunity [2,3]. von Behring and Kitasato found antibodies, and von Behring was awarded the Nobel Prize in Physiology or Medicine in 1901.

FIGURE 1.1 Thucydides: 460–400 BC. (Adapted from Wikipedia, https://commons.wikimedia.org/wiki/File:Thucydides_pushkin02.webp.)

FIGURE 1.2 Robert Koch: 1843–1910. (Adapted from https://en.wikipedia.org/wiki/Robert_Koch#/media/File:RobertKoch_cropped.webp.)

The concept of the humoral branch of immunity flourished between 1900 and 1942, and the important roles of antibody and complement in humoral immunity (HI) were established by the eminent scientists von Behring and Roux and Bordet, respectively. During this time, the immunopathology of the Arthus reaction, anaphylaxis, serum sickness, and haemolytic anaemia and the role of antibodies in diseases were described. The term immunochemistry was coined by the eminent scientist Arrhenius. The study of antigen–antibody reactions and quantitative precipitin reactions by scientists Michael Heidelberger and Elvin Kabat added to the growing understanding of the immunoglobulin (Ig) molecule, and in 1950s, the structure of antibodies was elucidated by scientist Rodney Porter and Gerard Edelman. The origin of delayed-type hypersensitivity was first recognised by Koch in 1883, and allograft rejection was studied by Medawar in 1944. The study of the cellular branch of the immune system has its origin in the works of Landsteiner and Chase, in 1942. Prior to the 1950s, the generation of antibody diversity was not known, and in 1956, Burnet wrote that antigen directs, rather than selects, antibody formation. Jerne, Talmage, and Burnet were eminent scientists working independently who developed the clonal selection theory. In 1955, Jerne published a paper titled ‘The Natural-Selection Theory of Antibody Formation’ [8] in which he described the concept of the ‘selective’ hypothesis. According to Burnet, the clonal selection theory states that animals contain numerous cells called lymphocytes, and that each lymphocyte reacts to an antig...