Peter Parham > Quotes

“Unlike some other immune-system gene families, whose genes are all clustered together on one chromosome, the 10 human TLR genes are distributed between five chromosomes. This reflects the ancient, invertebrate origin of the Toll-like receptors, which were present before the two genome-wide duplications that occurred during the early evolution of the vertebrates around 500 million years ago. On the basis of sequence similarities, the Toll-like receptors form four evolutionary lineages (I, II, III, and IV) that are descendants of the four Toll-like receptor loci formed by these two ancient genome duplications.”
― Peter Parham, The Immune System

“The total number of different specific antibodies that can be made by an individual is known as the antibody repertoire and it might be as high as 10^16. In practice, the number of B cells limits the actual repertoire to closer to 10^9.”
― Peter Parham, The Immune System, Fourth Edition

“When vaccination programs are successful to the point where the disease is unfamiliar to physicians and public alike, then concerns can arise with real or perceived side effects of a vaccine that affect a very small minority of those vaccinated. Such concerns lead to fewer children being vaccinated and to increasing occurrence of the disease.”
― Peter Parham, The Immune System, Fourth Edition

“The majority of genes in the [MHC (Mean Histocompatibility Complex)] class I region are not involved in the immune system; neither do the class I genes form as a compact cluster as the class II genes. Whereas genes encoding class II molecules are only present in the class II region of the HLA [(Human Leukocyte Antigen) complex], genes encoding class I molecules and related class I-like molecules are found on several different chromosomes. A further difference is that HLA class II molecules are dedicated components of adaptive immunity that serve only to present antigen to T cells, whereas HLA class I and class I-like molecules encompass a broader range of functions, including uptake of IgG in the gut, regulation of iron metabolism, and regulation of NK [(Natural Killer)]-cell function in the innate immune response. Together, these genetic and functional differences show that MCH class I is the older form of MHC molecule and that MHC class II evolved more recently from MHC class I. Consistent with this proposition, MHC class II is not always essential for a vertebrate immune system, unlike class I. The Atlantic cod manages very well with only MHC class I genes.”
― Peter Parham

“In the absence of infection, more than 100 million NK cells are circulating at speed throughout the human body, fully loaded with poisons whose sole function is to kill human cells. This dangerous state of affairs necessitates strict regulation of the activation and implementation of NK-cell cytotoxicity.”
― Peter Parham, The Immune System, Fourth Edition

“The RAG [(Recombination-Activating Gene)] genes [which assist in the facilitation of V(D)J recombination] lack the introns that characterize eukaryotic genes. In this unusual feature they resemble the transposase gene of a transposon, a type of genetic element that can make and move copies of itself to different chromosomal locations. The essential components of a transposon are a transposase—an enzyme that cuts double-stranded DNA—and regions of repetitive DNA, called the terminal repeat sequences, that are recognized by the transposase. These two features allow the transposon to be excised from one location and inserted into another. The similarity of the RAG recombinase to a transposase has led to the hypothesis that the mechanism now used to rearrange immunoglobulin and T-cell receptor gene segments originated in a vertebrate ancestor with the insertion of a transposon into a gene encoding a receptor of innate immunity. The inserted transposase genes evolved to encode RAG proteins, and the terminal repeat sequences evolved to become the recombination signal sequences for the first rearranging gene segments. During this evolution, the transposase gene and the long terminal repeats of the transposon were separated and became components of different genes, both expressed specifically in lymphocytes. Today, the human RAG genes are on chromosome 11[,] and on four other chromosomes are the much-expanded sets of rearranging antigen-receptor genes.”
― Peter Parham, The Immune System, Fourth Edition

“Somatic hypermutation gives rise to B cells bearing mutant immunoglobulin molecules on their surface. Some of these mutant immunoglobulins have substitutions in the antigen-binding site that increase its affinity for the antigen. B cells bearing these mutant high-affinity immunoglobulin receptors compete most effectively for binding to antigen and are preferentially selected to mature into antibody-secreting plasma cells. The mutant antibodies that emerge from the selection do not have a random distribution of amino-acid substitutions. The changes are concentrated at positions in the heavy-chain and light-chain CDR loops that form the antigen-binding site and directly contact antigen. As the adaptive immune response to infection proceeds, antibodies of progressively higher affinity for the infecting pathogen are produced – a phenomenon called affinity maturation. Affinity maturation is a process of evolution in which variant immunoglobulins generated in a random manner are subjected to selection for improved binding to a pathogen. It achieves in a few days what would require thousands, if not millions, of years of classical Darwinian evolution in a conventional gene. This capacity for extraordinarily rapid evolution in pathogen-binding immunoglobulins is a major factor in allowing the human immune system to keep up with the generally faster-evolving pathogens.”
― Peter Parham, The Immune System, Fourth Edition