List Biological Laboratories’ (List Labs) catalog of products is related to furthering research in human health and preventing disease, most commonly as the starting materials for vaccine research & development or production around the world. Vaccines are mainly identified for their capacity to prevent diseases that the body’s innate defensive mechanisms (the skin and specialized cells in the blood, for example) can’t resist unaided. However, there are many other uses for these purified materials in medical research, and you will likely encounter wording on our website that is not part of everyday vocabulary for non-scientists. This article is intended to provide a basic understanding of some of the more frequently used terms and aid you in selecting the products most essential to your projects.
Toxin vs. Toxoid
For starters, what is the difference between “toxin” and “toxoid”. Broadly defined, anything that can cause harm to an organism is a toxin. However, for List Labs’ products and in biological usage, a toxin refers to a bacterial or viral product that has harmful effects when it enters the body (List Labs’ toxins are in a highly purified form). A toxoid is a chemically altered toxin that has reduced or no toxicity and is used for its remaining antigenic activity, which can stimulate an immune response.
Take, for example, cholera, a disease produced by Vibrio cholerae bacteria, possibly through contact with body fluids from a person ill with cholera or through contaminated water supply. Cholera causes severe diarrhea, and untreated, it can be fatal. However, the purified List Labs’ cholera toxin by chemical modification becomes a toxoid that lacks toxic activity but retains structures that make it useful for immunization of research animals or stimulation of immune cells in vitro.
How do Toxoids Impact the Immune Process?
To understand how some List Labs products work, an overview of the immune process is helpful. During the course of a day, we frequently touch, ingest, or breathe in something that has potential to harm the body. Our cells react to this invader: is this a threat, or not, and if so, how serious is the threat?
What is the Innate Immune Response?
The innate immune response is the first order of defense in the immune process. There are many different cell types in our body. Some of these cells are equipped by their structural and biochemical components to destroy dangerous microbial invaders–pathogens–quickly. The inflammation that we experience from minor infections is often a sign of this process as cells from the blood destroy the pathogen. This happens quickly, within hours.
What is the Adaptive Immune Response?
Another cellular response system requires a longer time to react to the threat. These cells react by changing from an inactive form to one that will start a more complex defensive process: this is the second step, the adaptive immune response. There are two different classes of cells that comprise the adaptive immune response; they differ by the structures that give them their ability to bind antigens– the invading bacteria and viruses. Both these cells are called lymphocytes; individually, they are the B-lymphocytes (B-cells) and T-lymphocytes (T-cells). Both originate from stem cells in the bone marrow; B and T refer to the place in the body where they mature. T-cells mature in the thymus into several subclasses of T-cells that circulate in the blood and lymph. “Killer” T-cells recognize foreign antigens on cell surfaces (e.g. from viral infection or malignancy). “Helper” T-cells induce B-cells to produce antibodies. “Suppressor” T-cells dampen or regulate the immune response to prevent over-reaction. B-cells mature in the bone marrow and migrate to secondary lymphoid tissues (e.g. spleen and lymph nodes). When they encounter foreign antigens and/or helper T-cells, they are stimulated to divide and expand clonally to produce antibodies and differentiate into plasma cells.
What is Immune Memory?
After the B and T-lymphocytes react to an antigen, two results are possible. The first, and desirable result, is that the invader is identified and defeated, leaving behind what might be called its criminal record: immune memory. When the antigen comes creeping back in the future, the adaptive immune system recognizes it and attacks. The second possibility is an over-reaction and lack of cessation of the adaptive immune process that is harmful to the body: an autoimmunecondition.
Antigens, Epitopes and Vaccines
Where do vaccines come into this process? An antigen is a substance that causes the body to mount an immune response against it. Antigens include toxins, bacteria, viruses, or other substances that the body recognizes as foreign or not “self”. Vaccines have structural features similar to structures of the toxin or invading pathogen that can elicit adaptive immunity.
An epitope is a specific molecular region on the surface of an antigen, typically one of many on the antigen, that elicits an immune response and is capable of binding with the specific antibody produced by the response. A toxin has many epitopes that can be recognized by the immune response. The epitopes that are required for toxicity have been altered chemically in toxoids or by specific genetic mutations in inactive mutants; however, many epitopes are retained and can stimulate an adaptive or memory immune response that will be effective against the toxin.
Toxins and Toxoid Products for Research
Below is a list of toxin and toxoid or inactive mutant pairs of products available to support your research.
Toxin and product numbers
Botulinum Neurotoxin Type A from Clostridiumbotulinum – 130A, 130B, 9130A
The world of microbial pathology is often understood as a system of various organisms who are trying to survive by using plants or animals as “hosts”. The dynamics of these systems can described the pathogen as trying to establish a living space for itself, while the “host” does its best to evict these unwelcome tenants. One of the most commonly known pathogens is Staphylococcus, a highly adaptable and ubiquitous opportunistic pathogen. The staphylococcal enterotoxins are small heat-stable proteins used by Staphylococcus strains to help them in their attempt to colonize.
One of the most notable and yet poorly understood properties of Staphylococcal enterotoxin B (SEB) is its potent ability to stimulate immune T-cell proliferation. It doesn’t make sense that a bacterium that is intent on colonization would find it advantageous to promote an immune response. On the other hand, it could have been coincidence or selective adaptation that the mammalian immune system learned to recognize one of its most ubiquitous enemies. After many of years of observation by immunologists that lymphocytes proliferated when enterotoxin was added to whole blood in test tubes, John Kappler dubbed them superantigens (Kappler, 1989).
Nakanjako D., Ssewanyana I., Nabatanzi R., Kiragga A., Kamya M., Cao H., Mayanja-Kizza H., (2013) Impaired T-cell proliferation among HAART-treated adults with suboptimal CD4 recovery in an African cohort. BMC Immunol. 14: 26. PMID: 23786370
Scheible K., Secor-Socha S., Wightman T., Wang H., Mariani TJ., Topham DJ., Pryhuber G., Quataert S., (2012) Stability of T cell phenotype and functional assays following heparinizedumbilical cord blood collection. Cytometry A. 81(11):937-49. PMID: 23027690
Stam J., Abdulahad W., Huitema MG., Roozendaal C., Limburg PC., van Stuijvenberg M,. Schölvinck EH., (2011) Fluorescent cell barcoding as a tool to assess the age-related development of intracellular cytokine production in small amounts of blood from infants. PLoS One 6(10):e25690. PMID: 22043291
Xu Y., Fernandez C., Alcantara S., Bailey M., De Rose R., Kelleher AD., Zaunders J., Kent SJ., (2013) Serial study of lymph node cell subsets using fine needle aspiration in pigtail macaques. J ImmunolMethods 394(1-2):73-83. PMID: 23702165
The significance of T-cell stimulation by SEB has been the topic of much hypothesis and discussion. The site of SEB binding to T-cells has been investigated to a molecular level (Li, 1998; Saline, 2010). SEB and other enterotoxins are used in investigations of innate immunity to bacterial infections, signaling by toll-like receptors, and the modulation of inflammatory responses, especially cytokine stimulation (Kumar, 2010; Ortega, 2010; Vidlak, 2011;Edwards, 2012). The function, origin, and role in adaptation that t-cell stimulation serves will be a topic of ongoing scientific debate. In any case it is clear that SEB and other bacterial superantigens are very good at bypassing the antigen recognition by T-cells (Sundberg, 2002; Kumar, 2013). Some investigation into the biochemical level of SEB recognition by T-cells has indicated that this protein shares antigenic sequences with known self-antigens in mammals (White, 1989). This observation supports the theory that activation of T-cells plays a role in noninfectious diseases like autoimmune responses (Edwards, 1996; Kumar, 1997; Li, 1996; Sundberg, 2002), which might make SEB an appropriate stimulator when studying these mechanisms of disease. List Labs provides for SEB produced in a native Staphylococcus aureus, for research purposes that provides potent stimulation of the immune system and cytokine production.
Edwards CK., Zhou T., Zhang J., Baker TJ., De M., Long RE., Borcherding DR., Bowlin TL., Bluethmann H., Mountz JD., (1996) Inhibition of superantigen-induced proinflammatory cytokine production and inflammatory arthritis in MRL-lpr/lpr mice by a transcriptional inhibitor of TNF-alpha. J Immunol 157(4): 1758-1772. PMID: 8759766
Edwards LA., O’Neill C., Furman MA., Hicks S., Torrente F., Pérez-Machado M., Wellington EM., Phillips AD., Murch SH., (2012) Enterotoxin-producing staphylococci cause intestinal inflammation by a combination of direct epithelial cytopathy and superantigen-mediated T-cell activation. Inflamm Bowel Dis 18(4): 624-640. PMID: 21887731
Kappler J., Kotzin B., Herron L., Gelfand EW., Bigler RD., Boylston A., Carrel S., Posnett DN., Choi Y., Marrack P., (1989) V beta-specific stimulation of human T cells by staphylococcal toxins. Science 244(4906): 811-813. PMID: 2524876
Kumar S., Colpitts SL., Ménoret A., Budelsky AL., Lefrancois L., Vella AT., (2013) Rapid alphabeta T-cell responses orchestrate innate immunity in response to Staphylococcal enterotoxin A. Mucosal Immunol 6(5): 1006-1015. PMID: 23321986
Kumar S., Ménoret A., Ngoi SM., Vella AT., (2010) The systemic and pulmonary immune response to staphylococcal enterotoxins. Toxins (Basel) 2(7): 1898-1912. PMID: 22069664
Kumar V., Aziz F., Sercarz E., Miller A ., (1997) Regulatory T cells specific for the same framework 3 region of the Vbeta8.2 chain are involved in the control of collagen II-induced arthritis and experimental autoimmune encephalomyelitis. J Exp Med 185(10): 1725-1733. PMID: 9151697
Li H., Llera A., Tsuchiya D., Leder L., Ysern X., Schlievert PM., Karjalainen K., Mariuzza RA., (1998) Three-dimensional structure of the complex between a T cell receptor beta chain and the superantigen staphylococcal enterotoxin B. Immunity 9(6): 807-816. PMID: 9881971