Evolution of Adaptive Immunity

Two Trees (creative digital image)

I attended a "Weiser Endowed Lecture in Immunology" featuring Dr Max Cooper of the Emory University School of Medicine, speaking on "Evolution of adaptive immunity" at the University of Washington in 2012.  Dr Cooper's work is foundational in this subject area.

It is interesting that immunity systems follow a phylogenetic pathway much as the phylogeny of species themselves do. The evolutionary pathway of jawless vertebrates (of whom hagfish and lampreys are surviving members), possess differences in comparison to the common evolutionary pathway followed by other vertebrates.

Lampreys and hagfish do not possess a thymus , nor do they possess a spleen.    Lampreys and hagfish do not possess Major Histocompatibility Complex (MHC) 1 or 2, T-cell receptors or recombination activating genes (RAG 1 and 2) which play an active role in the recombination of T-cell and immunoglobulin  receptors. Lampreys and hagfish posses hematopoietic tissue, the former in the intestine and the latter in the portal vein.  With these changes, the lampreys and hagfish diverged off the common immune system evolutionary pathway prior to the development of certain MHC class immunity in other species.  This is an important benchmark due to the major role that the MHC class plays in vertebrates.  It is a vital aspect which makes the concept of a separate phylogenetic pathway earmarked for the immune system so interesting.  If lampreys do not possess a thymus, then what substitutes in its place?

Lampreys and hagfish utilize a system of leucine-rich repeats )(LRR's) to mediate immune system responses using Variable Lymphocyte Receptor (VLRs), (VLRA's, VLRB's and VLRC's).  The interesting aspect of the jawless vertebrate immune system function is comparing its action in structure and function to the immune systems we are familiar with.  VLRB's have structures similar to toll like receptors (proteins that play a key role in the innate immune system), while their functions are similar to those of antibodies,  and they possess humoral characteristics (using macromolecules in extracellular fluids in immunity systems). They act using discrete populations of lymphocytes (types of white blood cells) .

VLRBs act as an adaptive immune system and can differentiate foreign from self in recognizing lymphocytes.

Lampreys posses a diverse variety of leucine-rich repeats which code for germline and mature genes. They possess a specificity for carbohydrate and protein receptors on bacterial and mammalian cells. They bind antigens with high avidity and affinity, describing the binding capacity of multiple versus single interactions of antibodies with antigenic epitopes.

 In "Evolutionary implications of a third lymphocyte lineage in lamprey", the authors find a thymoid source for VLRA and VLRC assembly in the lamprey gill tips, while VLRB assembly occurs in hematopoietic typhosole and kidney tissues.  VLRC appeared more numerous than VLRA, and predominated in the skin.  They conclude that a similar body plan of two T-cell type lymphocytes in a thymoid type structure and one B-cell type lymphocyte in the blood and kidneys shows some similarity in basic structure to the immune system for jawed vertebrate, while achieving adaptive immunity through different means.

Monclonal VLRB antibodies  from immunized lamprey larvae can recognize plasma cells from myeloma patients.  VLR4, a monoclonal VLRB specific for BclA, the bacillus collagen-like protein, has shown to be specific for B. Anthracis spores.  Information on B. Anthracis can be obtained from the US Centers for Disease Control (CDC) CDC - Anthrax and the World Health Organization (WHO) WHO - Anthrax.

Research indicates a number of applications where VLR's can recognize certain immumogens  An immunogen is any antigen that is capable of inducing humoral and/or cell-mediated immune response rather than immunological tolerance.  These applications include diagnosis, research and bioterrorism investigations.