Perhaps not only white blood cells participate in inflammation, but, other cells of the body such as tissue mast cells, tissue macrophages, and vascular endothelial cells equally play crucial roles in the inflammatory process. The four most important inflammatory cells are neutrophils, lymphocytes, macrophages and vascular endothelial cells.
Neutrophils, the quick response troops of inflammation
In diapedesis, neutrophils first roll along the endothelial surface before adhering to it. After the adhesion, neutrophils emigrate from blood vessel to extravascular tissue space. Adhesion molecules expressed by both vascular endothelial cells and neutrophils promote the interaction, between neutrophils and vascular endothelial cells, and subsequent emigration of neutrophils. Neutrophils fight bacterial infections mainly and are present mainly in sites of acute inflammation. In the inflamed area, neutrophils phagocytose bacteria and other foreign bodies and release microbicidal enzymes into the phagolysosomes. Among the microbial enzymes present in neutrophil lysosomal granules are cationic proteins, acid hydrolases, elastase, cathepsins, phospholipase A2, lysozyme, alkaline phosphatase, vitamin B12 binding protein, and lactoferrin.
The half-life of neutrophils is rather short; they almost never survive up to two (2) days in blood. However, once they arrive at inflamed tissue, inflammatory cytokines may increase the half-life of neutrophils, making them survive for a couple of days at the inflammation site. Immediately neutrophils arrive at the site of inflammation, their essential function is to phagocytose microbes and small foreign particles. After phagocytosis, neutrophils kill engulfed microbes.
The formation and accumulation of pus strongly indicates the presence of bacteria (bacterial infection). Actually, pus is an collection of dead neutrophils mainly; neutrophils are the most abundant cells that constitute pus. Perhaps not all bacterial infections produce pus in the body; pyogenic bacteria are the pus-producing bacteria.
After few rounds of phagocytosis in the inflamed tissue, neutrophils die by apoptosis in large numbers and part of their lysosomal enzymes spill into surrounding tissue. The lysosomal enzymes cause mild to severe local tissue digestion and damage. Local tissue digestion causes the production of more fluid at the site of inflammation contributing to pus.
Neutrophils recognize microbes by opsonins and other recognition molecules. Examples of opsonins are antibodies, C3b fragment of complement, and C-reactive proteins. Opsonins and recognition molecules bind to microbial cell membrane and enables neutrophils recognize and bind the microbe. Once bound, neutrophils engulf the microbe and kill it.
Neutrophils kill engulfed microbes by two main mechanisms:
- Neutrophils kill engulfed microbe by releasing the content of their lysosomal granules into the phagolysosome containing the microbe
- Neutrophils also kill engulfed microbe by generating toxic oxygen metabolites, which damage microbial cell membrane ultimately killing the microbial cell.
In type-III hypersensitivity (immune complex mediated hypersensitivity), the inappropriate activation of neutrophils causes neutrophils to release proteolytic tissue damaging enzymes and toxic oxygen metabolites which cause damage to host tissues at the site of the reaction.
Neutrophils, also called polymorphonuclear cells or simply polymorphs are the principal cells that play key roles in the earliest events that occur during acute inflammation. Neutrophils get the name ‘polymorphonuclear cells’ because of the morphology of the nuclei of mature neutrophils. Nuclei of mature neutrophils assume a multi-lobed configuration.
What feature can help you recognize neutrophils in tissue preparations?
The multi-lobed configuration of their nuclei makes neutrophils easy to identify.
Neutrophils develop from myeloid stem cells in the bone marrow. Neutrophils are the most numerous white blood cells, accounting for about 60 to 70 per cent of total white blood count. In addition to circulating neutrophils, bone marrow serves as a reservoir that constantly has a large store of neutrophils. In conditions where tissue need for neutrophils exceeds what the vessels can supply, bone marrows of the body respond by releasing neutrophils from the bone marrow neutrophil pool. This condition called neutrophilic leukocytosis is part of the systemic responses acute local tissue inflammation.
Neutrophils are the ‘quick response troops’ of inflammation and are the first group to enter the inflamed area. During inflammation, neutrophils roll along the activated endothelium, adhere to the endothelium before migrating out of the blood vessels finally. As neutrophils migrate out of the blood vessels, they go into tissue spaces. Activated endothelium is an endothelium that expresses cell-adhesion molecules in significant amount.
Chemotaxins released at the site of damage attract neutrophils to the site of reaction. The invading microorganism, damaged local tissue of host, and immune cells all synthesize and release chemotaxins. Examples of chemotaxins are C3a, C5a, LTB4 and chemokines.
Thus, chemotaxins as well as cell-adhesion molecules account for the emigration of neutrophils from blood vessels into extravascular spaces.
When neutrophils arrive at the tissue spaces, they engulf, kill and degrade microbes.
Eosinophils or eosinophilic granulocytes, so named because their cytoplasmic granules stain deeply with eosin dye. Eosinophil literally translates ‘eosin-loving’. Eosinophils are the predominant inflammatory cells associated with parasite-induced inflammation and allergic reactions.
Although eosinophils are phagocytic, their main function in inflammation is to kill parasitic pathogens. The cytoplasmic granules of eosinophils contain varieties of microbicidal agents and inflammatory mediators. Eosinophils particularly fight multicellular parasites in tissues. Eosinophils play major roles in type-1 hypersensitivity reactions (allergy).
Among the more important inflammatory mediators are:
- lysosomal enzymes e.g. major basic proteins
- toxic oxygen metabolites
- inflammatory cytokines
In body tissues (i.e. outside blood vessels), the half-life of eosinophils is slightly longer than that of neutrophils. On average, an eosinophilic granulocyte lives 10 days more than the lifespan of an average neutrophilic granulocyte. Moreover, eosinophils are present abundantly in mucus membranes of the body.
Identifying eosinophils in tissues
Eosinophils are easy to recognize, because of their big, bright abundant cytoplasmic granules.
Basophils occur in blood in very low number and accounts for less than 1% of total white blood count. Like neutrophils and eosinophils, basophils emigrate from blood to tissue spaces at sites of inflammation. Phagocytic ability of basophil is minimal and barely significant.
Lymphocytes have scanty cytoplasm that stains lightly. All lymphocytes have similar morphology, but show functional differences. Based on the functional differences, we have three populations of lymphocytes as follows:
- Natural killer cells
Moreover, B- and T-lymphocyte shave different subtypes.
The presence of significantly large numbers of lymphocytes in a tissue indicates that the inflammation is chronic, and most likely has viral infection as the inciting stimuli.
Plasma cells are differentiated B-cells that produce antibodies. The appearance of plasma cells is quite distinct from that of B-ells. Unlike B-cells, which have scanty cytoplasm, plasma cells have abundant cytoplasm because they actively secrete large amounts of antibodies. Moreover, plasma cells possess eccentrically placed nuclei (i.e. their nuclei do not occupy the center of the cytoplasm) whereas B-cells posses centrally placed nuclei. The presence of numerous plasma cells (not B-cells) in any organ or tissue or lymph node indicates chronic/persistent antigenic stimulation. This happens mostly when some persistent bacteria infect the body.