One big challenge for physicists working in medical research is learning the language of biology that our clinical colleagues are so well versed in. From adherant junctions to white matter, I’ve made my own glossary of biological terms to help me understand concepts and communicate better. The following definitions are by no means indepth, but are instead at a basic level to help myself and my fellow physicists continue to grow our dialogue with the medical community.
Disclaimer: I cannot confirm the 100% accuracy of the following definitions. They are my attempt to summarize what I’ve read online, in texts and papers, and from talking to people who know much more than me. Please let me know if you see any errors or if there are any terms that should be added to the glossary.
A B C D E F G H I J K L M N O P R S T U V W Y
Adherant junctions: protein complexes that occur at cell-cell junctions. They provide strong mechanical attachments between adjacent cells. Found in mesaxons and paranodes, and many other places.
Antigen: Any of the various substances that, when recognized as non-self by the adaptive immune system, triggers an immune response, stimulating the production of an antibody that specifically reacts with it.
Antigen presenting cell (APC): A cell that facilitates the immune response by holding foreign antigens with major histocompatibility complex (MHC) on its surface and presenting them to lymphocytes. T-cells may recognize these complexes using their T-cell receptors (TCRs). T cells cannot recognise, and therefore cannot respond to, ‘free’ antigens. T cells can only ‘see’ an antigen that has been processed and presented by cells via carrier molecules like MHC and CD1 molecules. Types of APCs include: dendritic cells, macrophages, monocytes, certain B cells
Antibody: An immunoglobulin protein produced by B-lymphocytes of the immune system that binds to a specific antigen molecule
Astrocytes: Also knowns as astroglia or astrocytic glia. They are star-shaped glial cells in the brain and spinal cord and are the most abundant cell in the human brain. Astrocytes are classically identified using histological analysis; many of these cells express the intermediate filament protein glial fibrillary acidic protein (GFAP). They perform many functions, including:
-biochemical support of endothelial cells that form the blood–brain barrier,
-provision of nutrients to the nervous tissue (such as lactate),
-fuel neurons with glycogen
-maintenance of extracellular ion balance (astrocytes express potassium channels at a high density. When neurons are active, they release potassium, increasing the local extracellular concentration. Because astrocytes are highly permeable to potassium, they rapidly clear the excess accumulation in the extracellular space)
-promotion of the myelinating activity of oligodendrocytes (electrical activity in neurons causes them to release ATP, which serves as an important stimulus for myelin to form. However, the ATP does not act directly on oligodendrocytes. Instead, it causes astrocytes to secrete cytokine leukemia inhibitory factor (LIF), a regulatory protein that promotes the myelinating activity of oligodendrocytes. This suggest that astrocytes have an executive-coordinating role in the brain)
-play a role in the repair and scarring process of the brain and spinal cord following injury (upon injury to nerve cells within the central nervous system, astrocytes fill up the space to form a glial scar, repairing the area and replacing the CNS cells that cannot regenerate)
Axon: long, slender projection of a nerve cell, or neuron, that typically conducts electrical impulses away from the neuron’s cell body.
B cell: One of the main types of cells involved in the humoral immune response. A type of white blood cell (called a b-lymphocytes) that is designed to provide immunity in the body by developing antibodies when they are exposed to antigens or foreign bodies that invoke an immune response. B cells develop from stem cells in the bone marrow and are generated continuously (they are the most common type of lymphocyte). The immature B cells are activated when they come into contact with an antigen, which forces them to mature, and are then released into the bloodstream and lymphatic system. They spread throughout the body and concentrate in the spleen and lymph nodes. A mature B cell is then capable of creating antibodies specific to that antigen. This adaptive nature of B cells makes them a critical part of the immune system’s ability to fight off infection. B cells can be distinguished from other lymphocytes, such as T cells and natural killer cells (NK cells), by the presence of a protein on the B cell’s outer surface known as a B cell receptor (BCR). This specialized receptor protein allows a B cell to bind to a specific antigen.
Cajal bands: Cytoplasmic channels that lie beneath the surface of the Schwann cell (PNS) plasma membrane and that are separated from each other by the appositions formed by the protein complexes
CD3: Cluster of differentiation 3. A protein complex that is composed of 4 distinct chains. CD3 is initially expressed in the cytoplasm of pro-thymocytes, the stem cells from which T cells arise in the thymus. The pro-thymocytes differentiate into common thymocytes, and then into medullary thymocytes, and it is at this latter stage that CD3 antigen begins to migrate to the cell membrane. The antigen is found bound to the membranes of all mature T-cells, and in virtually no other cell type. This high specificity, combined with the presence of CD3 at all stages of T-cell development, makes it a useful immunohistochemical marker for T-cells in tissue sections.
CD20: a protein that is expressed on the surface of B cells, starting at the pre-B cell stage and also on mature B cells in the bone marrow and in the periphery. CD20 is generally coexpressed on B cells with CD19, another B cell differentiation marker. CD20 appears to play a role in B cell development, differentiation, and cell-cycle initiation events.
Cerebral malaria: a form of severe malaria that involves encephalopathy specifically related to P. falciparum infection. Individuals with cerebral malaria frequently exhibit neurological symptoms, including abnormal posturing, nystagmus, conjugate gaze palsy (failure of the eyes to turn together in the same direction), seizures, or coma. P. falciparum parasite displays adhesive proteins on the surface of the infected blood cells, causing the blood cells to stick to the walls of small blood vessels, thereby sequestering the parasite from passage through the general circulation and the spleen. Sequestered red blood cells can breach the blood–brain barrier and cause cerebral malaria.
Compact myelin: the regions of the myelin bilayer where the cytoplasmic surfaces condense into a compact myelin sheath and form the major dense line. Comprises the majority of the myelin internode. Compact myelin inhibits ion exchange during nerve conduction by having a low capacitance and high resistance.
Connexin: gap junction protein. Six connexins assemble to form a connexon, or hemichannel, that can be a part of a gap junction channel between the cytoplasm of two adjacent cells.
Cyclic AMP (Cyclic adenosine monophosphate, cAMP): a second messenger important in many biological processes. cAMP is derived from adenosine triphosphate (ATP) and used for intracellular signal transduction in many different organisms.
Cytokine: Any of various regulatory proteins, such as the interleukins and lymphokines, that are released by cells of the immune system and act as intercellular mediators in the generation of an immune response. Cytokines include interferon.
Demyelination: loss of, or damage to, the myelin sheath in the central or peripheral nervous system. CNS demyelination is the pathological hallmark of multiple sclerosis.
Dendritic cell: immunes cells who’s main function is to process antigen material and present it on the surface to other cells of the immune system. Dendritic cells are present in tissues in contact with the external environment, such as the skin (Langerhans cells), and the inner lining of the nose, lungs, stomach and intestines. They can also be found in an immature state in the blood. Once activated, they migrate to the lymph nodes where they interact with T cells and B cells to initiate and shape the adaptive immune response.
Edema: swelling from excessive accumulation of watery fluid in cells, tissues, or serous cavities
Erythrocyte: Also known as red blood cell, red cell or red corpuscle. Hemoglobin-containing blood cells transport oxygen from the lungs to tissues. In the tissues, the red blood cells exchange their oxygen for carbon dioxide, which is brought back to the lungs to be exhaled.
Gap junctions: a specialized intercellular connection. It directly connects the cytoplasm of two cells, which allows various molecules and ions to pass freely between cells. One gap junction channel is composed of two connexons (or hemichannels) which connect across the intercellular space.
Glial cell: Also known as neuroglia or glia. Greek for “glue”. Supportive cell in the CNS. They are non-neuronal cells that maintain homeostasis, form myelin, and provide support and protection for the brain’s neurons. Glial cells are the most abundant cell types in the central nervous system. Historically it was believed that glia outnumber neurons by 10-50 times, but some dispute this and suggest the ratio is closer to 1:1.
There are three types of glial cells:
3. microglia (eg macrophages)
Glia cell junction: gap junctional communication between glial cells. Not limited to either astrocyte-to-astrocyte or oligodendrocyte-to-oligodendrocyte, but it also occurs between both cell types.
Grey matter: tissue of the brain and spinal cord, containing nerve cell bodies, dendrites, synpases, and bare (unmyelinated) axons. The grey matter is the site of coordination between nerves of the central nervous system.
Hemosideran: A protein that stores iron in the body, derived chiefly from the hemoglobin released during hemolysis
Inflammation: a reaction of the body’s immune system to infection or invasion. In addition to demyelination, inflammation is the other pathological hallmark of multiple sclerosis. The T cells recognize myelin as foreign and attack it as if it were an invading virus. This triggers inflammatory processes, stimulating other immune cells and soluble factors like cytokines and antibodies. Further leaks form in the blood–brain barrier, which in turn cause a number of other damaging effects such as swelling, activation of macrophages, and more activation of cytokines and other destructive proteins.
Interleukin: Any of a class of cytokines that act to stimulate, regulate, or modulate lymphocytes such as T cells. Interleukin-1, which has two subtypes, is released by macrophages and certain other cells, and regulates cell-mediated and humoral immunity. It induces the production of interleukin-2 by helper T cells. Interleukin-2 stimulates the proliferation of helper T cells, stimulates B cell growth and differentiation, and has been used experimentally to treat cancer. Interleukin-3 is released by mast cells and helper T cells in response to an antigen and stimulates the growth of blood stem cells and lymphoid cells such as macrophages and mast cells. There are many other interleukins that are part of the immune system.
Internodal myelin: myelin found between nodes of Ranvier. Each myelin internode can be divided into two ultrastructurally and functionally distinct domains: compact myelin and the paranodal loops.
Leukocytes: white blood cells whose chief function is to protect the body against infection. They act as scavengers and to help fight infections when they occur. They are bigger than red blood cells. Leukocytes lack hemoglobin and are therefore colorless.
Lymphocytes: a type of white blood cell, which are an important part of the immune system. Lymphocytes can defend the body against infection because they can distinguish the body’s own cells from foreign ones. Once they recognize foreign material in the body, they produce chemicals to destroy that material. Two types of lymphocyte are produced in the bone marrow before birth: B lymphocytes (B cells) and T lymphocytes (T cells). All lymphocytes are capable of producing chemicals to fight foreign molecules. Any molecule recognized by the body as foreign is called an antigen. A lymphocyte, whether B or T, is specific for only one kind of antigen. Only when the appropriate antigen is encountered does the cell become stimulated. Only mature lymphocytes can carry out immune responses.
Lucifer yellow: a fluorescent dye used in cell biology. The key property of Lucifer yellow is that it can readily visualized in both living and fixed cells using a fluorescence microscope (the specimen is illuminated with light of a specific wavelength (or wavelengths) which is absorbed by the dye particles, causing them to emit light of longer wavelengths (i.e. of a different color than the absorbed light))
Macrophage: Greek for “big eaters”. Macrophages function in both non-specific defense (innate immunity) as well as help initiate specific defense mechanisms (adaptive immunity) of vertebrate animals. Their role is to phagocytose, or engulf and then digest, cellular debris and pathogens, either as stationary or as mobile cells. They also stimulate lymphocytes and other immune cells to respond to pathogens. Macrophages are usually immobile but become actively mobile when stimulated by inflammation. They are produced by the differentiation of monocytes in tissues. Macrophages survive in the body for up to a maximum of several months.
Major Histocompatibility Complex (MHC): a cell surface molecule encoded by a large gene family in all vertebrates. MHC is an area of the genome which codes for a series of proteins expressed on the cells in the body. These proteins serve as flags for the immune system which allow the immune system to distinguish between “self” proteins which belong in the body, and “nonself” proteins which are foreign. The T cells of the immune system interface with the proteins produced by the major histocompatibility complex, using this information to determine whether or not material encountered in the body belongs there. These proteins take the form of antigens. If the immune system recognizes an antigen as harmful, it can take steps to kill the cell it is attached to. This is designed to allow the immune system to kill bacteria and other organisms which make their way into the body, and to allow the immune system to identify cells which have been infected by viruses so that the spread of the virus can be stopped.
Mesaxon: The outer (abaxonal) mesaxon is the connection of the outer cell membrane to the compact myelin sheath. The inner (periaxonal) mesaxon is the connection between the myelin sheath and the inner part of the cell membrane of the Schwann cell / oligodendrocyte which is directly opposite the axolemma, i.e. the cell membrane of the nerve fibre ensheathed by the Schwann cell / oligodendrocyte.
Microelectroporation: a mechanical method used to introduce polar molecules into a host cell through the cell membrane. In this procedure, a large electric pulse temporarily disturbs the phospholipid bilayer, allowing molecules like DNA to pass into the cell
Microglia: a type of glial cell that are the resident macrophages of the brain and spinal cord, and thus act as the first and main form of active immune defense in the central nervous system (CNS). Microglia are found only in the CNS and constitute 20% of the total glial cell population within the brain. Microglia are constantly scavenging the CNS for plaques, damaged neurons, and infectious agents. Microglia must be able to recognize foreign bodies, swallow them, and act as antigen presenting cells, activating T-cells. Microglia are extremely sensitive to even small pathological changes in the CNS; they achieve this sensitivity in part by having unique potassium channels that respond to even small changes in extracellular potassium. In their downregulated form, microglia lack the MHC class I/MHC class II proteins, IFN-γ cytokines, CD45 antigens, and many other surface receptors required to act in the antigen-presenting, phagocytic, and cytotoxic roles that hallmark normal macrophages. Microglia also differ from macrophages in that they are much more tightly regulated spatially and temporally in order to maintain a precise immune response.
Microglial cells are extremely plastic, and undergo a variety of structural changes based on their location and current role. This level of plasticity is required to fulfill the vast variety of immunological functions that microglia perform, as well as maintaining homeostasis within the brain. If microglia were not capable of this they would need to be replaced on a regular basis like macrophages, and would not be available to the CNS immune defense on extremely short notice without causing immunological imbalance under normal conditions. There are various types of microglia, including:
(1) Ameboid (found mainly within the perinatal white matter areas in the corpus callosum. This shape allows the microglial free movement throughout the neural tissue, which allows it to fulfill its role as a scavenger cell. Amoeboid microglia are able to phagocytose debris, but do not fulfill the same antigen-presenting and inflammatory roles as activated microglia. Amoeboid microglia are especially prevalent during the development and rewiring of the brain, when there are large amounts of extracellular debris and apoptotic cells to remove.
(2) Ramified (commonly found at strategic locations throughout the entire brain and spinal cord in the absence of foreign material or dying cells. This “resting” form of microglia is composed of long branching processes and a small cellular body. The body of the ramified form remains fairly motionless, while its branches are constantly moving and surveying the surrounding area. The branches are very sensitive to small changes in physiological condition.
(a) Non-phagocytic (this state is actually part of a graded response as microglia move from their ramified form to their fully active phagocytic form. Once activated the cells undergo several key morphological changes including the thickening and retraction of branches. Activated non-phagocytic microglia generally appear as “bushy,” “rods,” or small ameboids depending on how far along the ramified to full phagocytic transformation continuum they are.)
(b) phagocytic (the maximally immune responsive form of microglia. These cells generally take on a large, ameboid shape. Phagocytic microglia travel to the site of the injury, engulf the offending material, and secrete pro-inflammatory factors to promote more cells to proliferate and do the same. Activated phagocytic microglia also interact with astrocytes and neural cells to fight off the infection as quickly as possible with minimal damage to the healthy brain cells.
Monocyte: a type of white blood cell and part of the innate immune system of vertebrates. Monocytes play multiple roles in immune function including replenishing resident macrophages and dendritic cells under normal states, and in response to inflammation signals, moving quickly (approx. 8–12 hours) to sites of infection in the tissues and divide/differentiating into macrophages and dendritic cells to elicit an immune response. Monocytes are attracted to a damaged site by chemical substances through chemotaxis, triggered by a range of stimuli including damaged cells, pathogens and cytokines released by macrophages already at the site. Half of all monocytes are stored in the spleen.
Myelin: A white fatty material composed chiefly of alternating layers of lipids and lipoproteins that encloses the axons of myelinated nerve fibers. It is an electrical insulator that serves to speed the conduction of nerve impulses in these nerve fibers.
Natural killer (NK) cells: a type of cytotoxic lymphocyte critical to the innate immune system. NK cells provide rapid responses to virally infected cells and respond to tumor formation, acting at around 3 days after infection. Typically immune cells detect major histocompatibility complex (MHC) presented on infected cell surfaces, triggering cytokine release causing lysis or apoptosis. NK cells are unique as they have the ability to recognize stressed cells in the absence of antibodies and MHC, allowing for a much faster immune reaction. They were named “natural killers” because of the initial notion that they do not require activation in order to kill cells that are missing “self” markers of MHC. NK cells make up ~5-15% of the total circulated lymphocyte population
Neurolemma: Also known as neurilemma. The outermost nucleated cytoplasmic layer of Schwann cells that surrounds the axon of the neuron (ie, the outermost layer of the nerve fiber in the peripheral nervous system). In the CNS, axons are myelinated by oligodendrocytes and lack neurolemma. The myelin sheaths of oligodendrocytes do not have neurolemma because excess cytoplasm is directed centrally toward the oligodendrocyte cell body.
Neurofilament: a cytoplasmic filament approximately 10nm in diameter occurring in the neurons. They are a major component of the neuronal cytoskeleton, and are believed to function primarily to provide structural support for the axon and to regulate axon diameter. They may be involved in the intracellular transport of metabolites.
Neuron: nerve cell; any of the conducting cells of the nervous system, consisting of a cell body, containing the nucleus and its surrounding cytoplasm, and the axon and dendrites. The average number of neurons in the brain is 100 billion.
Node of Ranvier: A short interval in the myelin sheath of a nerve fiber, occurring between every two successive segments of the myelin sheath. In this region the axon is not covered by myelin.
Non-compact myelin: provides cytoplasmic continuity between myelin forming cells and various regions of the myelin internode. Noncompact myelin surrounds the exterior of the CNS internode.
Oligodendrocyte: (from Greek, meaning cells with a few branches), or oligodendroglia (Greek, few tree glue): a type of brain cell (glial cell). Their main function is the insulation of axons in the CNS. A single oligodendrocyte can extend its processes to 50 axons, wrapping around approximately 1 μm of myelin sheath around each axon
Paranodal myelin areas: demarcate the longitudinal ends of each internode, facilitate ion exchange at the Node of Ranvier, a small ‘‘bare patch’’ of axon that separates each successive internode. As compact myelin approaches the node, the major dense line ‘‘opens up’’ to accommodate cytoplasm. The paranodal loops are roughly regular and symmetric on each side of the node. Each paranodal loop makes contact with the axon.
Periaxonal space: the inner surface of myelin internodes, where myelin attached to axons
Schmidt-Lantermann Clefts (SLC’s): structures where the cytoplasmic surfaces of the myelin sheath have not compacted to form the major dense line and, instead, contain Schwann or glial cell cytoplasm. These funnel-shaped interruptions in the regular structure of the myelin sheath of nerve fibres were formerly interpreted as actual breaks in the sheath but are now shown by electron microscopy to correspond each to a strand of cytoplasm locally separating the two otherwise fused oligodendroglial (or, in peripheral nerves, Schwann cell) membranes composing the myelin sheath. The function of the SLC’s isn’t fully understood – one function appears to be that they act as a beneficial ‘‘shortcut’’ for communication between the outer and inner aspects of the myelin internode. Incisure-like structures have been identified in electron micrographs of larger CNS myelin internodes. Radial diffusion of small ions through incisures has been documented. However, diffusion does not occur through the cytoplasm of the funnel-shaped incisures but by gap junction-mediated diffusion through incisure membranes.
Schwann cell (neurolemmocytes): the principal glia of the PNS. Myelinating Schwann cells wrap around axons of motor and sensory neurons to form the myelin sheath. Individual myelinating Schwann cells cover about 100 micrometres of an axon. Unlike oligodendrocytes, each myelinating Schwann cell provides insulation to only one axon. 10,000 Schwann cells are needed to cover a 1m long axon.
T cell: Also known as T lymphocyte. A principal type of white blood cell that completes maturation in the thymus (a gland found in the chest) and that has various roles in the immune system, including the identification of specific foreign antigens in the body and the activation and deactivation of other immune cells. There are several types of T lymphocytes and each plays a separate role in the immune system:
(1) Helper T cells: assist other white blood cells in immunologic processes, including maturation of B cells into plasma cells and memory B cells, and activation of cytotoxic T cells and macrophages. These cells are also known as CD4+ T cells because they express the CD4 protein on their surface. Helper T cells become activated when they are presented with peptide antigens by MHC class II molecules, expressed on the surface of antigen presenting cells. Once activated, they divide rapidly and secrete small proteins called cytokines that regulate or assist in the active immune response.
(2) Cytotoxic T cells search the body for cells infected by antigens. When a killer T cell recognizes an antigen (presented by MHC class 1) attached to a cell of the body, it attaches itself to the surface of the infected cell. It then secretes toxic chemicals into the cell, killing both the antigen and the infected cell. These cells are also known as CD8+ T cells since they express the CD8 glycoprotein at their surface.
(3) Memory T cells: a subset of antigen-specific T cells that persist long-term after an infection has resolved. They quickly expand to large numbers of effector T cells upon re-exposure to their cognate antigen, thus providing the immune system with “memory” against past infections. Memory T cells have become “experienced” by having encountered antigen during a prior infection, encounter with cancer, or previous vaccination. At a second encounter with the invader, memory T cells can reproduce to mount a faster and stronger immune response than the first time the immune system responded to the invader. Memory cells may be either CD4+ or CD8+.
(4) Regulatory T cells (Treg cells): formerly known as suppressor T cells, are crucial for the maintenance of immunological tolerance. Their major role is to shut down T cell-mediated immunity toward the end of an immune reaction.
(5) Natural killer T cells: recognize glycolipid antigen presented by a molecule called CD1d. Once activated, these cells can perform functions ascribed to both T-helper and T-cytotoxic cells.
Tight junctions: the closely associated areas of two cells whose membranes join together forming a virtually impermeable barrier to fluid. They restrict the movement of lipids and proteins from specific membrane domains. Tight junctions in the paranodal loops prevent large molecules from entering the potential space between the layers of the myelin sheath.
Transferrin: A protein in blood plasma that carries iron derived from food intake to the liver, spleen, and bone marrow.
Vacuoles: A small cavity in the cytoplasm of a cell, bound by a single membrane and containing water, food, or metabolic waste.
Wallerian degeneration: The degeneration of a nerve fiber that has been separated from its nutritive center by injury or disease, characterized by segmentation of the myelin and resulting in atrophy and destruction of the axon.
White matter: Whitish nerve tissue in the brain and spinal cord, chiefly composed of myelinated nerve fibers and containing few or no neuronal cell bodies or dendrites.