Heterophils are a type of white blood cell, also known as leukocytes, that play an important role in the immune system. These cells are part of the innate immune response, acting as a first line of defense against invading pathogens. Their primary function involves identifying and neutralizing harmful foreign substances. As such, heterophils are an important component in maintaining the health of many animal species.
What Are Heterophils and Where Are They Found?
Heterophils are defined by their distinct morphological characteristics, which differentiate them from other white blood cells. When stained with Romanowsky stains, these round cells exhibit prominent, often brick-red or orange-red, rod-shaped or spindle-shaped cytoplasmic granules. The nucleus of a mature heterophil typically appears lobed or irregularly shaped.
These granulocytes serve as the primary phagocytic cells in several animal groups, in contrast to mammals. They are commonly found in birds, reptiles, rabbits, guinea pigs, and chinchillas, as well as some fish and amphibians. In these species, heterophils are often the second most numerous circulating white blood cell, though their prevalence can vary depending on the species and age.
How Heterophils Protect the Body
Heterophils are highly effective in protecting the body through their broad spectrum of antimicrobial activity. Their main function is phagocytosis, the process of engulfing and destroying invading pathogens. Upon detecting bacterial molecules, often through specialized receptors, heterophils become activated and migrate rapidly to sites of infection or inflammation. This rapid mobilization allows them to initiate an early immune response.
Once at the site of infection, heterophils release antimicrobial substances stored in their cytoplasmic granules, a process known as degranulation. These granules contain various enzymes and peptides, such as acid phosphatase, lysozyme, β-glucuronidase, and beta-defensins, which are capable of killing a wide range of bacterial pathogens. Heterophils primarily rely on non-oxidative mechanisms for their bactericidal effects. In addition to direct killing, heterophils can also produce heterophil extracellular traps (HETs) to capture and neutralize pathogens.
Heterophils Compared to Neutrophils
Heterophils share functional similarities with mammalian neutrophils, which are the primary phagocytic granulocytes in mammals, but they possess distinct structural and functional differences. Both cell types are polymorphonuclear leukocytes, meaning they have multi-lobed nuclei, and are key components of the innate immune system, serving as first responders to inflammation and infection. A notable difference lies in their cytoplasmic granules and their content.
Unlike mammalian neutrophils, heterophils lack the enzyme myeloperoxidase. This enzyme is important in neutrophils for generating reactive oxygen species, which are a part of their killing mechanism. The absence of myeloperoxidase in heterophils means they rely more on non-oxygen-dependent mechanisms for killing pathogens, such as the release of antimicrobial peptides like beta-defensins and other lysosomal enzymes. Structurally, heterophil granules are typically larger and stain more intensely, appearing deep orange to red, compared to the finer, often inconspicuous granules of mammalian neutrophils. These differences influence how heterophils contribute to inflammatory lesions, often leading to the formation of heterophil granulomas rather than the pus characteristic of neutrophil-mediated inflammation in mammals.
When Heterophil Levels Change
Changes in the number of circulating heterophils are often indicative of an active immune response in the animals that possess them. An increase in heterophil numbers, a condition known as heterophilia, frequently signals the presence of bacterial infections or inflammation. This increase is often accompanied by the presence of immature heterophils, known as a “left shift,” which indicates a heightened demand on the bone marrow to produce these cells in response to the infection.
Veterinary professionals frequently utilize heterophil counts as a diagnostic tool. The ratio of heterophils to lymphocytes (H:L ratio) can provide insights into a patient’s physiological stress and immune status. While a baseline count is helpful for individual animals due to species variations, a significant elevation in heterophils, sometimes with accompanying morphological changes, can guide diagnostic and treatment decisions. Conversely, a decrease in heterophil numbers, or heteropenia, can occur during severe stress or overwhelming infections, suggesting the body’s inability to keep up with the immune demand.