Cells of the immune system

This chapter has zero relevance to any specific element of Section S  from the 2023 CICM Primary Syllabus.  It is not clear whether trainees are expected to know any of this material, nor is it clear that grown-ass intensivists would find any value in it. Second part exam questions about leukocyte abnormalities and neutropenia can be interpreted as vague movements in this direction, but no question has historically asked about these cells or their functions directly. And rightly so, as critical care staff are not histologists who would ever be relied upon to identify them under the microscope, nor haematologists who would be called upon to interpret their abnormalities, nor immunologists who would be asked to manage their function, nor oncologists who would be expected to control their overpopulation. Intensive care specialists can be, at most, expected to look upon the abnormal number in the blood results, and benumb themselves about the depressing prospects of speaking to the family. Still, from some internal place of professional scientific curiosity there must come some questions, such as "what are these cells, and what do they do, and what happens when they do too much or not enough, and how to stop them, or to make them go harder". 

In summary:

The reader is invited to suggest any alternative peer-reviewed resources that might be listed here as a "one-stop shop" for immune cell information, as presently none compile all of the necessary work into one small digestable bolus. 

Morphology of leukocytes

Leukocytes, "white" cells of the blood which are in actual fact transparent "colourless globules in the buffy coat of the blood", became so-called seemingly to discriminate them from the red corpuscles, but it is not clear who specifically decided to call them white. It is something probably lost in the 194 pages of Essai d'hématologie pathologique by Gabriel Andral (1843), or a reference to the passing turn of phrase "globules blancs du pus" by de Senac in 1749. It is probably entirely by chance that we do not refer to these cells as achromocytes or diaphanocytes. Lost in the dust of library shelves, in the ancient bound copies of the Journal of the Royal Society of Medicine, a conversation between Sir Humphry Rolleston (1934) and the bacteriologist William Bulloch recalls that:

"the word " leucocyte" made its appearance first in 1855 in M. P. Littre and C. Robin's Dictionnaire de medecine (Nysten); it was probably suggested by, and derived from, the word leucocythemie employed in 1851 by Hughes Bennett (1812-75) in a paper read before the Societe de biologie in Paris, to describe "white-cell blood."

Stain-related names like "neutrophil" and "eosinophil" are usually attributed to Max Schulze, but in fact Schulze never actually used those words and was mostly looking at live unstained specimens, and for him the exploration of a heated leukocyte culture was a tedious detour on his way to the study of nerve endings. These cells need to be killed and stained with hematoxylin and eosin to give them the characteristic appearance that was ultimately described and canonised by Paul Ehrlich around 1878.  We are all indebted to the excellent work by Bodzas et al (2023), who took their old Olympus BX51 (a solid workhorse of the cell scientist) and created a high-resolution dataset containing a total of 16027 annotated image of leukocytes, and then shared them on Figshare.  As the result, the reader is again subjected to the author's inexplicable relentless need to put calipers on everything, which has culminated in a diagram that probably adds nothing to the page, except an extra 770kb of loading time:

It is unlikely that the size and structure of leukocytes will ever form the topic of a question, because whereas in red cells the morphology and volume are suspicious for disease, they are less relevant in white cells. 

Distribution of leukocytes

For the graphics and detail in what follows, we are indebted to the excellent paper by Sender et al (2023), which features amazingly lucid use of graphics to present their scientific content. Their images are borrowed here, shamelessly without permission but with full credit and in homage to the original authors. To summarise their findings for the non-visual learner:

• The average human contains about 1.2kg of immune cells, which represents about 1.7% of the total population, similar to the standing armies of Kuwait and Austria.  
• Of these, 
  • About 50% is macrophages, though they are only 10% of the total number (being largest)
  • About 15% is neutrophils, residing mostly in the marrow
  • About 15% is lymphocytes, mostly in the lymph nodes and spleen
  • The rest is mostly mast cells and dendritic cells
• Of the organs, immune cell distribution is:
  • 40% each in the bone marrow and lymphatic system
  • 10% in the liver (6% of the liver by mass)
  • 3-4% in the lungs
  • 3-4% in the gastrointestinal tract
  • 2% in the blood