In order to adequately defend ourselves against any pathogen that could invade our body, the cells of the immune system must be in constant motion so that they can carry out surveillance even in the most remote places of our body. The cells of non-specific immunity (including granulocytes, macrophages, dendritic cells, NK cells and mast cells) are very dispersed, but the cells of specific immunity are found mainly in the secondary immune organs, where they produce the presentation of the antigen and the stimulation of lymphocytes that can recognize it.
The scattered nature of the immune system raises three interesting unknowns that are very difficult to sort out: how many immune cells we have, exactly how many we have in each organ, and what their total weight is.
An interesting recently published study attempts to answer these questions. Since it is completely impossible to count the cells individually, the authors used a triple strategy.
First, they conducted a comprehensive bibliographic review and collected all available data on the presence of immune cells in tissues. Specifically, they tried to record not only histological data but also the different cell densities, i.e. the number of cells per gram of tissue.
Distribution of immune cells in the human body. Estimates of immune cell populations by cell type and tissue, grouped by primary tissues and systems. GI stands for gastrointestinal tract.PNAS, CC BY-NC-ND
Second, they used multichannel cell imaging, a new technology that allows the simultaneous identification of many biomarkers. This enables the detection of complex tissues and cellular phenotypes.
And third, they used deconvolution based on methylation patterns. Although the name may seem bizarre, cellular unfolding involves using computational techniques to estimate the proportion of cells present in a given tissue. Since each cell has a characteristic methylation pattern, the combination of both techniques allows the identification of the different cell subpopulations present in a sample.
Billions of cells
The use and cross-validation of these three techniques allowed the authors to conclude that a prototypical person – that is, a 20-30 year old man, 176 centimeters tall and weighing 73 kilos – has a total of 1.8 x 10¹² cells. That’s almost two billion (1.8 billion according to Spanish nomenclature) cells. There are many of these, especially when you consider that muscle and fat tissue make up 75% of total body mass, but as very large cells they only make up 0.2% of all cells in our body.
Most immune cells are found in two places: the bone marrow and the lymphatic tissue. The bone marrow contains 40% of this astronomical total number of cells – 80% neutrophils. 39% of the immune cells are located in the lymphatic tissue, with lymphocytes clearly predominating. The skin, lungs, and gastrointestinal tract each contain a modest 3% of the total.
Macrophages, which are poorly represented in many tissues, accumulate in the liver, where they make up 70% of this organ’s immune cells. This is also where 30% of all NK cells are located. It can be deduced that the liver plays an important role in the immune response, especially with regard to the clearance of antigens that have invaded via the digestive tract.
More than a kilo
The study offers some surprising findings. For example, if the immune system were a solid organ, it would weigh 1.2 kilos. In other words, it would have almost the same weight as the liver, which is considered the largest and heaviest organ.
Of these 1.2 kilos, macrophages, which make up only 15% of the total immune cells, would weigh 600 grams. And the even rarer dendritic cells would weigh another 100 grams more. Because? Well, due to the size of these two cell types, which is in contrast to the small lymphocytes, which, despite their high number, would only total less than 200 grams. The most relevant is the mass of immune cells contained in the bone marrow and lymphoid tissue (30% and 27% of the total, respectively).
The biggest surprise, however, concerns the gastrointestinal tract. Contrary to belief, only 3% of the total immune cells are located here, much less than expected. And it is also surprising that around 70% of the total plasma cells that produce antibodies accumulate in the digestive tract.
view in the future
This study is relevant because it combines several approaches to solve problems that do not allow a direct approach and that may be of interest in determining the number of cells belonging to other lineages.
More importantly, by providing us with a global distribution of the immune system’s cells, it can help us better understand its global organization and thus learn how to modulate it to develop innovative therapies.
Ignacio J. Molina Pineda de las Infantas, Professor of Immunology, Biomedical Research Center, University of Granada.
This article was originally published on The Conversation.
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