A Treasury of 60 years of Fascinating Research in Molecular Immunity by Kendall A. Smith

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A Treasury of 60 years of Fascinating Research in Molecular Immunity by Kendall A. Smith

Molecular Immunity: A Chronology of 60 Years of Discovery is a publication that brings together the amazing progress made in the field of immunology over the past 60 years.  Through this publication, Kendall A Smith explores the importance of molecules, which are the key factors that therapeutically intervene in the immune system enhancing or suppressing immune reactivity in the human body. The immune system cannot be considered as a passive system that only functions by responding to stimuli from the external environment. Similar to all other bodily systems, the immune system is regulated by endogenous hormone-like molecules via specific hormone-like receptors.

Through this publication, Dr. Smith strings together the breakthrough researches which developed immunology as a rapidly expanding area of biology, making major contributions to the 21st century medicine. This publication is also a reference to the present generation of scientists who wants to acquire knowledge about the immune system. Though the molecular revolution started around 1980’s, Dr. Smith brings out the background and history of researches and observations starting from 1957, which formed the basis of further fascinating explorations in this field.

Dr. Smith introduces the short seminal hypothesis paper, “The Clonal Selection Theory”, from Sir MacFarlane Burnet (dated 1957), which set the stage and paved the way for next 60 years of experimentation in immunology.  In 1960, Peter Nowell made the breakthrough finding of lymphocyte blastic transformation and findings on mitosis and cytokinesis. The researches in 1962 by Gowens demonstrated that lymphocytes proliferated in vivo after antigenic simulation, and later in 1963 and 1964, Kurt Hirschhorn Fritz Bach extended the experiments on specific antigen in vitro. These findings made the prediction from Burnet that antigen selected lymphocytes could undergo proliferative clonal expansion, a reality. Furthermore, extensive research studies were conducted by many researchers such as Neils Jerne, Jacques Miller, and Max Cooper in the 1960’s. By 1965, adaptive antigen-specific immunity was established to derive from small lymphocytes that originated in the thymus. The first reports of antigen-non-specific mitogenic activities produced by alloantigen-stimulated leukocytes were also released in 1965.

Consequent studies were carried out on immune response genes and cellular cooperation.

The study then extends to “interleukins”, which are classes of glycoproteins produced by leucocytes for regulating immune responses. The later chapters of this publication talk about molecular mechanisms of T-Cell Cytolysis with specific experiments of mechanisms of cell-mediated cytolysis and also about T Cell “Help”.

Dr. Smith brings about the elucidation of the structures of MHC genes and their products. From the research studies, it is concluded that T Cell-mediated functions of cytotoxicity and help are not mutually exclusive T Cell-functions predictable by MHC restriction. MHC restriction is mediated by the T cell exclusive expression of two co-receptor modules, CD4 and CD8. Processing and presentation of peptides via MHC Class I or Class II occur through distinct metabolic pathways.

Dr. Smith then explores the studies on molecules of macrophages, which act as phagocytic immune cells responsible for engulfing pathogens and destroying them. Macrophages can be activated by cytokines such as interferon-gamma (IFN-gamma) and bacterial endotoxins, such as lipopolysaccharide (LPS). Activated macrophages undergo changes and kill invading bacteria or infected cells.

There are also in-depth studies on additional T cell signals and regulatory T Cells. CTLA4 or CTLA-4 (cytotoxic T-lymphocyte-associated protein 4), also known as CD152 (cluster of differentiation 152), is a protein receptor that functions as an immune checkpoint and downregulates immune responses. The studies on CTLA4 as a negative regulator of T-cell activation are provided in detail in this publication.

Dr. Smith also brings about the research explorations starting from the discoveries of lymphotoxin (LT) and tumor necrosis factor (TNF) to the present day age of cytokine inhibitors as therapeutics.

The publication concludes with a chapter dedicated to immunotherapy. Immunotherapy, also called biologic therapy, is a type of cancer treatment that boosts the body’s natural defenses to fight cancer.

The publication walks us through the initial major researches in immunology, in the early 1960s, to the researches and studies by a new generation of immunologists on cloned genes, antibodies, cytokines, and reagents that has transformed the new science of molecular immunology. 

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