Sheep red blood cells (SRBCs), also known as ovine erythrocytes, are the oxygen-transporting cells found in the blood of sheep. These cells are a foundational reagent in biological and immunological laboratories worldwide, utilized for decades as a standardized biological tool. Their consistent availability and predictable reactions have made them a reliable component for studying complex immune system functions. This utility extends beyond basic research, serving as an important element in both historical and contemporary diagnostic testing procedures.
Unique Biological Properties
The surface of SRBCs carries a unique set of molecules that define their utility in research, particularly a type of antigen known as heterophile antigen. These specific antigens are chemically distinct from those found on human red blood cells, which allows the immune systems of other animals to recognize them as foreign targets. The structural components of the SRBC membrane also differ from human cells, showing variations in protein makeup, such as the relative amounts of Band 3 and Band 4.1 proteins.
Sheep red blood cells are also notably smaller than human erythrocytes. A property contributing to their strong immunogenicity is the presence of ribonucleic acid (RNA) within the cell. This RNA acts as a “danger signal” that actively stimulates an immune response, making SRBCs highly effective at provoking an immune reaction in experimental models. This combination of size, distinct membrane proteins, and potent antigenic properties forms the basis of their value in immunological assays.
Role in Immune System Studies
Sheep red blood cells are frequently used as a model antigen to trigger and measure the immune response in experimental animals, providing a consistent standard for immunologists. When injected into a mouse or rabbit, the SRBCs provoke a strong and measurable antibody response from B-cells, allowing researchers to study the kinetics of antibody production. This standardized method is routinely employed to assess B-cell function and quantify the production of hemolysin, an antibody capable of lysing the SRBCs.
SRBCs are also a long-standing tool in the study of cell-mediated immunity through a technique called the E-rosette formation assay. Human T-lymphocytes possess a surface receptor, CD2, that naturally binds to molecules on the surface of the sheep red blood cell. When mixed together under specific conditions, the T-lymphocytes become surrounded by several SRBCs, forming a distinctive cluster that resembles a flower rosette. This physical clustering allowed researchers to isolate and identify T-cells, distinguishing them from other lymphocyte populations.
The cells serve as an indicator system in classical complement fixation assays (CFT). The SRBCs are coated with anti-sheep antibodies (hemolysin) to create a sensitized cell. If a patient’s serum contains antibodies that fix the complement system in the first step, the complement is consumed and is unavailable to lyse the sensitized SRBCs in the second step, resulting in a positive, non-lysed test. Conversely, if no reaction occurs in the first step, the free complement lyses the SRBCs, turning the solution clear as a negative result.
Applications in Diagnostic Testing
The most historically significant application of SRBCs in human diagnostics is the Paul-Bunnell test, used to confirm the presence of infectious mononucleosis. The disease induces the production of unique heterophile antibodies in the patient’s blood. These specific antibodies have the ability to bind and agglutinate (clump) the heterophile antigens present on the surface of the sheep red blood cells.
A positive result is identified by observing the visible clumping of the SRBCs when mixed with a patient’s serum sample. The test was refined by incorporating differential absorption steps using guinea pig kidney and ox red cells to distinguish the mononucleosis antibodies from other types of naturally occurring heterophile antibodies. Although modern, more specific tests have largely replaced the original Paul-Bunnell method, the underlying principle of using SRBCs to detect these specific antibodies remains a foundational concept in clinical serology.
In veterinary medicine, SRBCs are incorporated into diagnostic tests for animal diseases, such as the complement fixation test for Contagious Bovine Pleuropneumonia (CBPP) in cattle. The cells continue to be used in various other agglutination tests to detect the presence of specific antibodies or antigens in a wide array of animal species. The reliable, visible reaction of the sheep red blood cell surface to specific antibodies makes it a simple yet effective tool for initial disease screening.