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Alan Young, Bede Morris, Charles Mackay, John Hay, John Reynolds, Waldemar L. Olszewski, Wayne Hein
Does lymph just move as we move around? Yes, it does seem to do so somewhat.
A pioneer in this relatively obscure field of immunology is the Polish researcher, Waldemar L. Olszewski. He and colleagues demonstrated changes in lymph pressure and flow in a healthy human in response to physical movement (Intrinsic contractility of prenodal lymph vesse… [Am J Physiol. 1980]; The lymphatic system in body homeostasis: p… [Lymphat Res Biol. 2003]).
Olszewski and colleagues also showed that concentrations of lymph proteins fluctuate in tandem with physical movements unlike plasma protein levels, which remain relatively stable (Flow and composition of leg lymph in norm… [Acta Physiol Scand. 1977]; Lymph flow and composition of leg lymph in normal male leg immobilized for 24 hours. Olszewski WL, Engeset A, Sokolowski J. Acta Physiol Scand 1977; 10: 169-178; Lymph flow and protein in the normal male leg dur… [Lymphology. 1977]; Twenty-four hour variation in flow and co… [Acta Physiol Scand. 1977]).
I became interested in Olszewski‘s work when I discovered his work on the disease, Filariasis, caused by the parasitic worms such as Wuchereria bancrofti, clever little organisms that appear to have learned the really ingenious trick of hiding in plain sight by figuring out how to live and grow within our lymphatics!
What does our lymph have (to make it move)? Short answer: synergistic actions of valves and smooth muscle contractions.
The lymphatic system is often referred to as our “second circulatory system“. However, our lymphatic network differs from our blood circulation in two important aspects:
1. There is no heart-like central pump to circulate lymph within our body.
2. Lymphatic flow is not even circulation per se but rather a unidirectional flow of lymph collected from tissues and then poured from the thoracic duct and right lymphatic duct into our blood circulation through either the jugular and/or subclavian veins.
Lymph flow starts in the tissues where interstitial fluid, macromolecules and leukocytes enter blind-ended lymphatic capillaries, which are highly permeable with discontinuous basement membranes. In addition, these vessels are highly sensitive to slight changes in interstitial tissue fluid volume, which causes them to open. These qualities allow fluid and cell uptake from tissues. Endothelial cells lining the lymphatic vessels have overlapping cell-cell junctions that act as check-valves to prevent backward flow of lymph (Evidence for a second valve system in lymphatics: en… [FASEB J. 2001]; The role of the lymphatic system in vacci… [Adv Drug Deliv Rev. 2011]). Individual capillaries merge to form larger lymphatic vessels. Lymphatic vessels are segmented into lymphangions. A lymphangion is defined as the segment of a lymphatic vessel between two unidirectional semi-lunar valves that prevent backflow (The lymphatic system in body homeostasis: p… [Lymphat Res Biol. 2003]). Lymphangions have underlying smooth muscle layers, which rhythmically contract and relax under the control of the autonomic nervous system. Synergistic function of the two types of valves and the smooth muscle generates a peristaltic motion, which forces the lymph from one lymphangion to the next (A model for mechanics of primary lymphatic val… [J Biomech Eng. 2003]; Lymphatic smooth muscle: the motor u… [Int J Biochem Cell Biol. 2004]; Contractile physiology of lymphatics.). Olszewski estimates that lymphatic vessels contract spontaneously and rhythmically four to six times a minute (The lymphatic system in body homeostasis: p… [Lymphat Res Biol. 2003]).
Someone who is bedridden is likely to have one or more underlying problem(s) that could adversely influence their immune function so it would be difficult to implicate their poor immune function solely to their being bedridden. On the other hand, Olszewski‘s empirical data suggests that small amounts of exercise are likely to improve lymphatic drainage, and maybe especially so for a sick person. However, this may not improve immune function per se, especially the strength and quality of adaptive immune responses, which depend more on variables such as precursor frequencies of antigen-specific memory lymphocytes, presence of appropriately activated antigen-laden antigen-presenting cells, and tissue-specific factors which regulate and shape the nature of the immune response.
A brief review published in Nature in 2005 (Lymphatic system: unlocking the drains.) suggests that our body’s long-neglected “second circulatory system” is finally coming into its own as a research subject worthy of attention by both high-profile researchers and high-profile research publications (irony intended). This has to do with recent discoveries that found an association of lymphangiogenesis (growth of new lymphatic vessels) with diseases ranging from tumors to asthma.
Finally, I want to emphasize that Olszewski‘s data on human lymphatics is pioneering and important because it fills a lacuna in our knowledge and understanding of immunology, hewn as it is from a mish-mash of different animal models. On the one hand, much of it comes from rodent animal models (primarily mouse, less so rat, guinea pig, ferret). However, being relatively tiny creatures, it is extremely technically challenging to say the least to study their lymphatic system. I should know. In my years at the NIH, a question in one of my research projects required lymphatic drainage, which necessitated draining the thoracic duct of live mice in order to collect the lymph fluid draining the site of injection before it poured into the blood circulation. My supervisor, who performed the thoracic duct cannulation, proudly estimated that she was among perhaps five people in the world capable of performing this surgery! Given this lacuna in our research knowledge on immune function, starting with Bede Morris, an Australian veterinarian, the sheep has become the animal model of choice for studying the lymphatic system. In fact, through the entire existence of the Basel Institute for Immunology, the sheep lymphatic program was a fertile area of research, helping establish the careers of many (sheep) immunologists such as John Hay, Wayne Hein, Charles Mackay, John Reynolds, Alan Young, among others. However, using rodent models for studying the cells of the immune system, and sheep for studying the drains/pipes of the immune system obviously does not make for a happy middle. This not only serves to emphasize the relative scarcity of research in human lymphatics, but also the pioneering nature of much of Waldemar L. Olszewski‘s work, albeit much of it published in relatively obscure, and not high profile, scientific journals.
TK Talk 