Immunity is the ability of an individual to recognize the self molecules that make up ones own body and to distinguish them from such nonself molecules as those found in infectious microorganisms and toxins. This process has a prominent genetic component. Knowledge of the genetic and molecular basis of the mammalian immune system has increased in parallel with the explosive advances made in somatic cell and molecular genetics.

There are two major components of the immune system, both originating from the same precursor stem cells. The bursa component provides B lymphocytes, a class of white blood cells that, when appropriately stimulated, differentiate into plasma cells. These latter cells produce circulating soluble proteins called antibodies or immunoglobulins. Antibodies are produced in response to substances called antigens, most of which are foreign proteins or polysaccharides. An antibody molecule can recognize a specific antigen, combine with it, and initiate its destruction. This so-called humoral immunity is accomplished through a complicated series of interactions with other molecules and cells; some of these interactions are mediated by another group of lymphocytes, the T lymphocytes, which are derived from the thymus gland. Once a B lymphocyte has been exposed to a specific antigen, it remembers the contact so that future exposure will cause an accelerated and magnified immune reaction. This is a manifestation of what has been called immunological memory.

The thymus component of the immune system centres on the thymus-derived T lymphocytes. In addition to regulating the B cells in producing humoral immunity, the T cells also directly attack cells that display foreign antigens. This process, called cellular immunity, is of great importance in protecting the body against a variety of viruses as well as cancer cells. Cellular immunity is also the chief cause of the rejection of organ transplants. The T lymphocytes provide a complex network consisting of a series of helper cells (which are antigen-specific), amplifier cells, suppressor cells, and cytotoxic (killer) cells, all of which are important in immune regulation.

One of the central problems in understanding the genetics of the immune system has been in explaining the genetic regulation of antibody production. Immunobiologists have demonstrated that the system can produce well over one million specific antibodies, each corresponding to a particular antigen. It would be difficult to envisage that each antibody is encoded by a separate gene; such an arrangement would require a disproportionate share of the entire human genome. Recombinant DNA analysis has illuminated the mechanisms by which a limited number of immunoglobulin genes can encode this vast number of antibodies.

Each antibody molecule consists of several different polypeptide chainsthe light chains (L) and the longer heavy chains (H). The latter determine to which of five different classes (IgM, IgG, IgA, IgD, or IgE) an immunoglobulin belongs. Both the L and H chains are unique among proteins in that they contain constant and variable parts. The constant parts have relatively identical amino acid sequences in any given antibody. The variable parts, on the other hand, have different amino acid sequences in each antibody molecule. It is the variable parts, then, that determine the specificity of the antibody.

Recombinant DNA studies of immunoglobulin genes in mice have revealed that the light-chain genes are encoded in four separate parts in germ-line DNA: a leader segment (L), a variable segment (V), a joining segment (J), and a constant segment (C). These segments are widely separated in the DNA of an embryonic cell, but in a mature B lymphocyte they are found in relative proximity (albeit separated by introns). The mouse has more than 200 light-chain variable region genes, only one of which will be incorporated into the proximal sequence that codes for the antibody production in a given B lymphocyte. Antibody diversity is greatly enhanced by this system, as the V and J segments rearrange and assort randomly in each B-lymphocyte precursor cell. The mechanisms by which this DNA rearrangement takes place are not clear, but transposons are undoubtedly involved. Similar combinatorial processes take place in the genes that code for the heavy chains; furthermore, both the light-chain and heavy-chain genes can undergo somatic mutations to create new antibody-coding sequences. The net effect of these combinatorial and mutational processes enables the coding of millions of specific antibody molecules from a limited number of genes. It should be stressed, however, that each B lymphocyte can produce only one antibody. It is the B lymphocyte population as a whole that produces the tremendous variety of antibodies in humans and other mammals.

Plasma cell tumours (myelomas) have made it possible to study individual antibodies, since these tumours, which are descendants of a single plasma cell, produce one antibody in abundance. Another method of obtaining large amounts of a specific antibody is by fusing a B lymphocyte with a rapidly growing cancer cell. The resultant hybrid cell, known as a hybridoma, multiplies rapidly in culture. Since the antibodies obtained from hybridomas are produced by clones derived from a single lymphocyte, they are called monoclonal antibodies.

As has been stated, cellular immunity is mediated by T lymphocytes that can recognize infected body cells, cancer cells, and the cells of a foreign transplant. The control of cellular immune reactions is provided by a linked group of genes, known as the major histocompatibility complex (MHC). These genes code for the major histocompatibility antigens, which are found on the surface of almost all nucleated somatic cells. The major histocompatibility antigens were first discovered on the leukocytes (white blood cells) and are therefore usually referred to as the HLA (human leukocyte group A) antigens.

The advent of the transplantation of human organs in the 1950s made the question of tissue compatibility between donor and recipient of vital importance, and it was in this context that the HLA antigens and the MHC were elucidated. Investigators found that the MHC resides on the short arm of chromosome 6, on four closely associated sites designated HLA-A, HLA-B, HLA-C, and HLA-D. Each locus is highly polymorphic; i.e., each is represented by a great many alleles within the human gene pool. These alleles, like those of the ABO blood group system, are expressed in codominant fashion. Because of the large number of alleles at each HLA locus, there is an extremely low probability of any two individuals (other than siblings) having identical HLA genotypes. (Since a person inherits one chromosome 6 from each parent, siblings have a 25 percent probability of having received the same paternal and maternal chromosomes 6 and thus of being HLA matched.)

Although HLA antigens are largely responsible for the rejection of organ transplants, it is obvious that the MHC did not evolve to prevent the transfer of organs from one person to another. Indeed, information obtained from the histocompatibility complex in the mouse (which is very similar in its genetic organization to that of the human) suggests that a primary function of the HLA antigens is to regulate the number of specific cytotoxic T killer cells, which have the ability to destroy virus-infected cells and cancer cells.

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Human genetics - Immunogenetics | Britannica

2014 book by Nicholas Wade

A Troublesome Inheritance: Genes, Race and Human History is a 2014 book by Nicholas Wade, a British writer, journalist, and former science and health editor for The New York Times.[1][2][3][4] In the book, Wade argues that human evolution has been "recent, copious and regional"[5][6][7] and that this has important implications for social sciences.[8] The book has been widely denounced by the scientific community for misrepresenting research into human population genetics.[9][10][11]

Wade writes about racial differences in economic success between Whites, Blacks, and East Asians, and offers the argument that racial differences come from genetic differences amplified by culture. In the first part of the book, Wade provides an account of human genetics research. In the second part of his book, Wade proposes that regional differences in evolution of social behavior explain many differences among different human societies around the world.[12]

The book has been widely denounced by scientists, including many of those upon whose work the book was based.[9][10][11][13] On 8 August 2014, The New York Times Book Review published an open letter signed by 139 faculty members in population genetics and evolutionary biology[9][10] which read:[13]

Wade juxtaposes an incomplete and inaccurate account of our research on human genetic differences with speculation that recent natural selection has led to worldwide differences in I.Q. test results, political institutions and economic development. We reject Wade's implication that our findings substantiate his guesswork. They do not.

We are in full agreement that there is no support from the field of population genetics for Wade's conjectures.[13]

After publication, the letter was signed by four more faculty members.[11] In reply, Wade wrote, "This letter is driven by politics, not science. I am confident that most of the signatories have not read my book and are responding to a slanted summary devised by the organizers."[9][14] Wade added that he had asked the letter's main authors, Graham Coop and Michael Eisen, for a list of errors so that he could correct future editions of the book.[10][14]

Evolutionary geneticist Mark Jobling, one of the signatories to the letter, wrote an opinion piece in the peer-reviewed journal Investigative Genetics explaining that the unprecedented letter was necessary due to both the fallacious nature of Wade's argument and its political ramifications, stating that "Its enthusiastic proponents already include some high profile white supremacists and a former Grand Wizard of the Ku Klux Klan."[15] Biologist Marcus Feldman, another of the signatories to the letter, further criticized Wade's book, arguing that "By invoking Richard Lynn on racial variation in IQ and wealth, Wade departs from his 'speculative arena,' leaving us to infer not only that he is a devout hereditarian, but also that he is comfortable with Lynn's racist worldview."[16]

The book was further criticized in a series of five reviews by Agustn Fuentes, Jonathan M. Marks, Jennifer Raff, Charles C. Roseman and Laura R. Stein, which were published together in the scientific journal Human Biology.[17] Marks, for instance, described the book as "entirely derivative, an argument made from selective citations, misrepresentations, and speculative pseudoscience."[18] The publishers made all the reviews accessible on open access in order to facilitate discussions on the subject.[19]

Anthropologist Greg Laden writes that anthropologists were mostly critical of the book, while psychologists and economists generally received it more warmly.[7] Laden concludes that "A Troublesome Inheritance is itself troubling, not for its politics but for its science. Its arguments are only mildly amended versions of arguments discarded decades ago by those who methodically and systematically study human behavioral variation across cultures."[7]

Evolutionary biologist H. Allen Orr wrote in The New York Review of Books that "Wade's survey of human population genomics is lively and generally serviceable. It is not, however, without error. He exaggerates, for example, the percentage of the human genome that shows evidence of recent natural selection."[12] Orr comments that, in its second part, "the book resembles a heavily biological version of Francis Fukuyama's claims about the effect of social institutions on the fates of states in his The Origins of Political Order (2011)."[12] Orr criticizes Wade for failing to provide sufficient evidence for his claims, though according to Orr, Wade concedes that evidence for his thesis is "nearly nonexistent."[12] Orr further comments:

Wade also thinks that "evolutionary differences between societies on the various continents may underlie major and otherwise imperfectly explained turning points in history such as the rise of the West and the decline of the Islamic world and China." Here, and especially in his treatment of why the industrial revolution flourished in England, his book leans heavily on Gregory Clark's A Farewell to Alms (2007).[12]

Political scientist Charles Murray wrote a positive review in The Wall Street Journal,[20] calling the book "historic"[4] and stating that opposition to the book among academics would be motivated by "political correctness".[21] Economist Walter E. Block criticized parts of the book, but concluded Wade's "moral and intellectual courage cannot be denied".[22] Statistician Andrew Gelman writes, "As a statistician and political scientist, I see naivete in Wade's quickness to assume a genetic association for any change in social behavior."[23]

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A Troublesome Inheritance - Wikipedia