Malaria-Specific Antibody Diversification via Interchromosomal Insertion of a Non-Immunoglobulin Gene Sequence

Identifying broadly neutralizing antibodies against infectious agents such as influenza A viruses, HIV, and Plasmodium falciparum that display impressive degrees of antigenic variation is a major focus of investigators developing therapeutics and vaccines for pathogens of importance in public health (Corti and Lanzavecchia, 2013).  In a previous post, I discussed one study (Klein et al., 2013) illustrating the sorts of unanticipated types of mutations found for broadly neutralizing antibodies against HIV.  Lanzavecchia and colleagues have now identified antibodies reactive with antigens encoded by different isolates of Plasmodium falciparum and expressed on infected erythrocytes (Nature, 2015).  They find an unexpected source for the heavy chain variable domain amino acid sequences that confer the broad anti-malarial reactivity against proteins in the RIFIN family. (more…)

Nietzsche Undone: An Infection that Doesn’t Kill You Can Make You Weaker

The German philosopher, Friedrich Nietzsche, is known for a number of ideas among which a particularly oft-quoted one is, “That which does not kill us makes us stronger” (https://www.goodreads.com/quotes/30-that-which-does-not-kill-us-makes-us-stronger). A recent report in Cell (Fonseca et al., 2015) offers evidence that in the context of infection and immunity, the above aphorism may not be a reliable guide to reality. (more…)

Fever: how does it work?

A careful reading of the review of fever in “Fever: Friend or Foe?”, reveals the embarrassing deficiency in medical science’s understanding of how fever, much less anorexia, functions in infection. Since fever (as well as anorexia and other components of the acute-phase response) is induced by our own cytokines, it is virtually axiomatic that fever has been more beneficial than harmful on an evolutionary scale (since otherwise the response would have been deleted). As a “fan” of fever, I’ve compiled a list of six potential benefits of fever, each of which is found in the literature and has a reasonable experimental or theoretical basis (and each likely has some degree of correctness). Note that the first four are based on fever being a heat stressor. Have a look and then see my take on it.

Fever may work by:
1) directly harming pathogens,*
2) inducing apoptosis of infected cells (and neoplastic cells),
3) inducing host’s heat shock proteins to protect host cells during infection,
4) inducing heat shock proteins in pathogens—extracellular heat shock proteins activate immune responses as “danger signals”,
5) increasing efficacy of immune responses since they work better at slightly elevated temperatures,*
6) turning down the immune response by causing apoptosis of neutrophils and lymphocytes. (more…)

The Case for Applying Negative Selection to Thoughts on Clonal Selection by Prospect Magazine’s Number One 2013 “World Thinker”

Currently, I am on vacation near the beach in South Carolina.  Consequently, I have opted for a topic that is bit different than the majority of my monthly commentaries in that it focuses not on a recent original report but instead on a conceptual point made in a book over thirty years ago.  Nevertheless, after a somewhat less strictly scientific diversion I will come to the central idea at issue, which is arguably the premier exemplar of the relevance of evolutionary principles to the operation of the immune system on short time scales, by which I refer to the concept of clonal selection.  But first, we make a foray into the world of magazine publishing and the niche within that domain focusing on the arguably more intellectual readers. (more…)