Evolution of the Immune System

The amphibian epidermis presents many barriers that prevent pathogen infection. Much effort has been placed on examining determinants of infectivity and pathogenicity of Batrachochytrium dendrobatidis (Bd) in amphibians. However, no research has examined how trauma to the epidermis can affect susceptibility to and virulence of Bd infections in amphibians. Trauma is a common entry point for secondary infections that would otherwise be immunologically defensible to a host. The objective of our study was to determine if epidermal trauma would impact the outcome of Bd exposure. We predicted that epidermal trauma would make amphibians more susceptible to infection and result in more virulent infections. To test this prediction we compared susceptibility to infection, mortality, and survival time among three groups of Fowler's Toads, Anaxyrus fowleri (Hinckley); trauma and Bd, Bd only, and no Bd. Counter to our predictions we found that, with reference to negative controls, epidermal trauma and Bd together reduced susceptibility to infection, reduced overall mortality, and increased survival time compared to toads exposed to Bd only. Epidermal trauma is commonplace for wild amphibians, and is caused by predation attempts, combat, and unfavorable environmental conditions. We suggest that trauma to the epidermis preceding exposure to Batrachochytrium dendrobatidis elicits an innate immune response not initiated by the pathogen alone. Our data suggest that trauma could temporarily reduce susceptibility to, and virulence of, Batrachochytrium dendrobatidis infections of amphibians.

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The Vigor of Defense Against Non-Self: Potential Superiority of Allorestricted T Cells in Immunotherapy of Cancer?

Burdach

Kolb

2013

Front. Oncol.

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Men and sharks are both jawed vertebrates at the top of the food chain. Sharks are the first extant to develop adaptive immunity preserved to man throughout jawed vertebrates. We hypothesize here, that T cell receptor/major histocompatibility complex (TCR/MHC) interactions developed as the defense mechanism of carnivors against takeover by their victims’ cells derived pathogens. Germline encoded TCR segments have been conserved in evolution, providing the MHC bias of TCR. Ancestor genes of MHC polymorphisms may have first developed as a mating preference system, that later in evolution provided host immune responses destroying infectious non-self, yet maintaining tolerance to self. Pathogens may thus have simultaneously selected for alloimmunity. Allorejection has been observed in sharks and men. Cannibalism is a common ecological interaction in the animal kingdom, especially prevalent in aquatic communities; it favors selection of intraspecies allo responses for defense of self integrity. Alloreactive T cells do not undergo negative selection of strong TCR/MHC interactions; thus, they react stronger than self-MHC recognizing T cells. High levels of genetic diversity at MHC genes play a critical role in protecting populations of vertebrate species from contagious cells displaying stemness and homing features, including cancer cells. Recognition of self-MHC fails especially in diseases, which predominantly arise with age and after the peak of reproduction, e.g., cancer. So far, the treatment of malignant disease with autologous T cells has widely failed. Allorecognition constitutes an extremely powerful mechanism in evolution, which may be employed in immunotherapy of cancer by MHC-disparate, e.g., haploidentical transplantation and consecutive treatment with T cells from the donor parents recognizing tumor selective peptides presented by the non-inherited haplotype on the tumor.

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Evolution of the Immune System

Cited by 3 publications

References 40 publications

Limb Regeneration in Amphibians

Limb Regeneration in Amphibians

Epidermal Trauma Reduces the Impact of Batrachochytrium dendrobatidis in Fowler's Toads (Anaxyrus fowleri)

The Vigor of Defense Against Non-Self: Potential Superiority of Allorestricted T Cells in Immunotherapy of Cancer?

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