Introducing the characters of “Cells at Work!”

Blood. It is the stuff of life. It runs along the blood vessels of the human body, delivering oxygen and nutrients to cells while carrying off carbon dioxide and wastes. It is made up of two components: plasma and cells. Plasma, making up 55% of blood, is the liquid component containing proteins, electrolytes, nutrients and wastes suspended in water. The characters of Cells at Work! reside in the cellular component making up the remaining 45%. Nearly all cells in the blood are red blood cells with the remainder residing in a buffy coat composed of platelets and white blood cells.

Red blood cells (aka erythrocytes)

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Red blood cells are biconcave, disc-shaped cells that have neither a nucleus nor organelles, allowing them to pack lots of haemoglobin to carry oxygen around the body. Haemoglobin absorbs all colours except red which is reflected back into human eyes, giving the cells the red appearance. Red blood cells are also flexible, allowing them to fit into vessels of varying widths. They typically live for around 120 days before they are broken down by macrophages in the spleen.

Platelets

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Platelets are fragments of megakaryocytes that live in the bone marrow. They don’t possess a nucleus, but they still contain other organelles such as mitochondria. Platelets heal scrapes and wounds around the body by establishing a plug around broken areas of the endothelium (blood vessel walls) and releasing substances to initiate the clotting process.

White blood cells (leukocytes)

White blood cells are part of the immune system, protecting the body against infection by detecting and eliminating pathogens such as bacteria and viruses. They can be split into two groups. Most white blood cell subsets, including granulocytes (cells that store granules) and phagocytes (cells that phagocytose or engulf and degrade pathogens), belong to the innate immune system. The innate immune system, activated within hours of being exposed to pathogens, elicit a generic response to restrict infection to a small area of the body.

Neutrophils

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Most (60-70%) circulating white blood cells are neutrophils, named due to their weak dye staining. Neutrophils have a multilobed nucleus connected by thin chromatin strands and small granules containing enzymes that kill and break down pathogens. Being the first white blood cells to arrive at the infected site, they phagocytose and degrade pathogens. However, they die very quickly within hours of entering the tissue, either being engulfed by macrophages or appearing in pus oozing from blood clots. Circulating neutrophils also only live for a week max, so it is very unlikely that Red Blood Cell would see the same neutrophil in real-life.

Monocytes and macrophages

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Monocyte

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Macrophage

Monocytes, slightly larger than neutrophils, have a C-shaped nucleus. They circulate in the blood, but when they enter an infected site they transform into macrophages. Macrophages serve a variety of roles, mainly phagocytosing and degrading pathogens, foreign substances, damaged tissue and dead neutrophils. They also release proteins called cytokines to coordinate the activities of other cells and parts of the body and present antigens to maintain adaptive immune responses.

Dendritic cells (DCs)

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Dendritic cells are mononuclear cells best characterised by the numerous dendrites emerging from the centre. Located in many organs around the body such as the gut and lungs, they survey the blood and external environment for pathogens. Should it detect a pathogen, the dendritic cell will digest it and present a piece of the pathogen (an epitope) to a T cell to initiate adaptive immune responses.

Eosinophils

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Eosinophils, named due to the acidic dye eosin identifying these cells, possess a bi-lobed nucleus and a cytoplasm filled with medium-sized granules. Eosinophil granules mostly contain MBP (Major Basic Protein) which immobilise and kill parasites, positioning eosinophils as protectors of parasitic infection. Eosinophil granules also contain histaminase and arylsulfatase that break down histamine and leukotrienes respectively to dampen inflammation and allergy

Basophils

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Basophils, best identified by basic dyes such as haematoxylin (baso- = base-loving), have a bi- or tri-lobed nucleus that is mostly obscured by big granules. Basophils respond to infections, particularly those against large parasites such as ticks and worms. Their granules contain a lot of histamine that when released dilate blood vessels and increase permeability, allowing cells and proteins to move from blood to tissue. Histamine from basophils and mast cells is also involved in the development of allergies.

Mast cells

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Mast cells are similar in appearance to basophils in that their granules may obscure the nucleus. Unlike basophils; however, mast cells reside in tissues, only have a single nucleus and are typically oval-shaped. Their granules contain enzymes that are released during infection to initiate inflammation by damaging tissue. Mast cells also release histamine to dilate blood vessels and increase their permeability, easing access of white blood cells to the infected site.

Lymphocytes

Lymphocytes are white blood cells characterised by a single round nucleus occupying almost all of the cytoplasm. They are part of the adaptive immune system that takes days to mount a strong, specific immune response to completely resolve infection. The adaptive immune system also transforms some lymphocytes into memory cells, allowing the body to “remember” the infection so that it can mount a quicker, stronger immune response should the pathogen reappear. There are various lymphocyte subsets in the blood that are characterised by different receptors detecting assorted parts of the pathogen.

T cells.

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		Killer T cell	Helper T cell	Regulatory T cell

T cells make up 90% of lymphocytes in the blood. They contain a T cell receptor that interacts with peptide fragments of pathogens (epitopes) on DCs to become activated, initiating cell-mediated immune responses. There are three main T cell subsets.

Killer T cells, as the name suggests, kill cells in the body that have been infected (by intracellular bacteria or viruses), transformed (i.e., tumour cells in cancer) or foreign (e.g., cells from blood transfusions or organ transplants of a genetically dissimilar person).

Helper T cells coordinate and strengthen immune responses by secreting a repertoire of cytokines depending on the specific infection or disease. A subset of helper T cells called regulatory T cells limits the strength of immune responses, particularly after the infection is resolved.

B cells

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Plasma cell

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Memory B cell

B cells make up 5% of lymphocytes in the blood. They contain a B cell receptor (basically an antibody stuck on the cell membrane) that interacts with native components of pathogens to initiate humoral-mediated immune responses. This involves antibodies that bind to pathogens, not only neutralising and killing them (via lysis) but also enabling them to be engulfed and degraded by phagocytes. Most activated B cells transform into plasma cells that produce antibodies. Some B cells transform into long-lived memory B cells that are retained in the body. These cells, when exposed to the same pathogen in the future, can proliferate and differentiate very quickly to produce quicker, stronger immune responses.

NK cells

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NK cells are unique in that even though they have a similar morphology to lymphocytes, they function as innate immune cells. Similar to killer T cells, they kill infected or tumour cells caused by different diseases. However, their method of activation is different to those of a killer T cell (how they vary will be explained in a later blog post).

Conclusion

Blood is an important vehicle for transporting materials around the human body. In addition to plasma containing water and other soluble components, the blood also possesses a variety of cells that perform different roles. In particular, the different white blood cell subsets making up the immune system have various ways of defending the body against infection and other diseases both internal and external. These, along with the other cells in the body, are represented by humanised characters in Cells at Work! which offer a simple tool for explaining how your body works and how it defends itself against infection and disease.