Acquired – resulting from external and environmental factors, rather than inherited. In humans, most immunity is acquired, not innate, relying on the presence of antigens (foreign substances) in order to develop immunity against them.
Adenoviruses – a group of viruses causing respiratory diseases (including the common cold) and conjunctivitis.
Adherence, adhesion – see cytoadherence.
Allele – one of several variations of a gene. Different alleles produce different inherited characteristics, e.g. hair colour.
Amino acids – the building blocks of proteins. Most human proteins are synthesised from a range of 20 different amino acids.
Animal model – a laboratory animal used to imitate disease or understand gene function. Usually, in these animals a gene has been modified or removed from its genome. In medical research mouse models are often used. (also see knock-in and knockout mice).
Antibody – a type of protein molecule produced by cells of the immune system, in response to the presence of a foreign substance, known as an antigen. Antibodies bind to antigens in a precise physico/chemical manner and thus neutralise their activity. Over a lifetime, the body will produce thousands of different antibodies to the range of antigens it encounters. Antibody molecules consist of two “light” and two “heavy” protein chains, only part of which actually come into contact with the antigen. The area of the antibody known as the variable region is different and specific for each type of antibody.
Antigen – a substance or organism recognised by the body as being foreign, and which stimulates an immune response. It also refers to certain endogenous, or naturally present, classes of molecules located on the surface of many cells and which are genetically different between individuals.
Antigen processing and presentation – a function of some types of cells in the immune system, namely macrophages, dendritic cells, and B cells, involving the processing, or degradation, of an antigen into small protein fragments. These fragments, usually 8-20 amino acids in length, are then bound to “antigen-binding grooves” in MHC molecules on the cell surface. Circulating T cells are able to recognise an antigen presented in this way, and can become activated to mount a specific immune response against the antigen.
Antigenic determinant – see epitope.
Antisense strand – in double-stranded DNA, the strand opposite, and complementary to, the “sense” or gene strand. The antisense strand is the template for producing mRNA. Synthetically produced antisense (cDNA) fragments can be used to bind specifically to genes of experimental interest, and are therefore useful tools in controlling gene expression.
Apoptosis – the death of a cell in a programmed sequence, involving reduction and absorption of the cell contents. It is the normal, and preferred, method used by the body to dispose of its damaged, diseased or unwanted cells, minimising both the spread of infection and the risk of autoimmunity.
Arboviruses – arthropod-borne viruses – a large group of viruses spread mainly by blood-sucking insects (such as mosquitoes) between a variety of hosts such as birds, domestic and native animals, and man. The elimination of arboviral diseases worldwide, particularly those in epidemic proportions such as malaria and dengue fever, requires substantial effort in reducing the numbers of mosquitoes able to carry the virus, and is a focus of research at QIMR.
Ataxia-telangiectasia (A-T) – a genetically inherited disease. Sufferers of A-T have neurological and immune system impairment, and increased susceptibility to various kinds of cancers. This condition is associated with several mutations in the ATM gene.
ATM gene, ATM protein – a gene and its protein product, whose normal function is to repair breaks in cell DNA caused by UV radiation. ATM gene mutations are associated with the disease ataxia-telangiectasia. Cells with ATM mutations are radiation sensitive, and show chromosomal instability due to the lack of DNA repair. A recent discovery at QIMR is that certain ATM gene mutations are linked with a significant percentage of breast cancers.
Autoimmunity – an abnormal condition of the body, where the immune response to an antigen can “crossreact” with and kill normal cells. This can give rise to autoimmune diseases such as rheumatoid arthritis and diabetes.
Autologous – from the same individual, particularly with reference to cells, genes, or molecules.
Autosome – any of the cell’s chromosomes, except X- or Y-chromosomes (sex chromosomes). In humans, there are 22 pairs of autosomes. The pattern of inheritance of genes on these chromosomes is referred to as autosomal inheritance.
B-cell – an immune system cell type, a class of lymphocyte, which secretes antibodies that circulate in the bloodstream.Vaccination induces antibody production by B cells that usually confers lifelong immunity against diseases like polio, measles, mumps etc.
Bacteria – organisms consisting of just one cell, surrounded by a cell wall. Bacteria have nuclei containing DNA, and replicate by mitosis. Many bacteria are pathogenic (disease-causing), for example streptococcus and chlamydia, while others are harmless and some are even beneficial to humans, such as the bacteria in yoghurt.
Base pair – in double-stranded DNA, a pair of bases on different strands that are linked, or bonded, to each other. Adenine(A) bases on one strand always complement a thymine (T) base on the other strand, forming the base pair A-T. Cytosine (C) and guanine (G) form the other base pair (C-G).
Candidate gene – a gene whose function suggests that it may be involved in the genetic variation observed for a particular trait. For example, a regulatory gene, whose protein product controls the activity of other genes, may be involved in the development of cancer.
cDNA – complementary DNA – single-stranded DNA, synthesized in the lab from mRNA templates using the enzyme reversetranscriptase. cDNAs are free of introns, promoters or other control sequences, and so mostly represent DNA that codes forprotein. cDNAs can be used in situ to identify and locate genes on their chromosomes. They are also used in microarray studies.
CD antigens – (Cluster of Differentiation, or Cluster Designation) – cell surface markers, or receptors, for various subsets of the lymphocyte population. CD4 antigens identify helper T cells. CD8 antigens mark CTLs (cytotoxic T cells) and suppressor T cells.
CD4 cells – see helper T cells.
CDR – complementarity-determining region – in an antibody, the region that makes contact with the antigen; in a T cell, part of the T cell receptor (TCR) that makes contact with the antigen. The amino acid sequences of these regions are highly variable, but specific for each antigen.
Cell differentiation – the process by which a cell changes from a stem (undifferentiated) cell to an adult cell, becoming modified and specialized for the performance of a specific function, e.g. liver cell, skin cell. Differentiation involves the controlled activation and de-activation of genes.
Centrifuge – a machine used to separate cells, cell fragments, or fluids of different densities by rotating them in tubes at high speed. Denser material tends to move to the bottom of the tube, displacing lighter particles to the top.
Chemokine – a type of cytokine (a chemical messenger) with chemoattractant properties, involved in the migration ofmacrophages, neutrophils and lymphocytes, and their activation in the immune response.
Chromosome – a strand of DNA containing thousands of genes. Chromosomes are found in the cell nucleus, and are tightly coiled around protective proteins called histones. Most human cells contain 23 pairs of chromosomes, comprising 22 pairs ofautosomes and one pair of sex chromosomes.
Clinical trial – a procedure to test a drug or therapy on human volunteers. Normally, a clinical trial is preceded by extensive laboratory research, including in vitro and animal model studies, which give a prior indication of its potential success. Approval to conduct clinical trials is usually a function of an ethics committee associated with the institution conducting the trial, and/or government regulatory bodies. Trials are generally conducted in three stages. A phase I trial represents the first stage of testing of the product, usually on healthy subjects, to determine issues such as absorption pathways, side effects, and safety. In phase II, the therapy is trialled on patients, often using a randomised, double-blind protocol. This means that patients are treated with either the product or a placebo, by random selection, neither researchers nor patients knowing who is receiving which treatment. Phase III is an extension of phase II, where dosages, routes of administration, appropriate patient categories, and other factors are optimised by large scale testing, following which the therapy may be commercially viable. At QIMR Berghofer, several cancer therapies are being trialled, one being dendritic cell therapy for prostate cancer and melanoma.
Clone – a population of cells all carrying the same DNA profile (genotype), for example, a colony of bacteria cultured from a single parent. Also, an organism with an identical DNA profile to another, as in identical twins. In immunology, a clone is a cultured T cell population made up of cells of identical T cell receptors (TCR).
Codon – a triplet of RNA or DNA bases that represents the code for a single amino acid. For example, C-G-C (cytosine-guanine-cytosine) codes for the amino acid arginine, U-G-A for tryptophan. Other codons such as the start codon, A-U-G, and the stop codons, U-A-A or U-A-G indicate the initiation and termination of translation on an mRNA strand. Many inherited diseases are due to a mutation in just one base in a codon, generating mistakes in the composition, and therefore the functionality, of the protein they code for.
Complement – in genetic terms, a DNA strand which binds, or hybridises, exactly to another, to form a double strand. In immunology, complement is a protein involved in the immune response, binding to antigen–antibody complexes and assisting in their breakdown.
Complementary – in double-stranded DNA, describing strands able to bind to each other. In base sequence, an adenine on one strand is complementary to, or matched by, a thymine on the other. Similarly with guanine and cytosine.
Complementary DNA – see cDNA.
Confocal microscopy – state-of-the-art microscopy using fluorescent-dyed cellular material and laser, rather than visible, light as the light source. This enables very high resolution of fine detail within cells, and consequently is of enormous use in investigating cellular changes such as maturation or infection.
Cohort – in a population or epidemiological study, a subgroup of individuals sharing a certain characteristic, e.g. age, smoking habits, diabetes.
CTLs – cytotoxic T lymphocytes – a group of lymphocytes, extremely potent and specific in action, that rapidly kill virus-,bacteria-, or parasite-infected cells, by destroying the cell membrane and inducing apoptosis.
Cytoadherence – the ability of a cell to adhere to a surface or another cell. This property may be dramatically changed in disease. In malaria, infected red blood cells become “sticky” and adhere to the walls of blood vessels, where they replicate large numbers of the malaria parasite. Tumour cells have different cytoadherent properties to normal cells, adhering to other tumour cells but not to normal cells.
Cytokines – extracellular hormones or messengers, secreted mainly by macrophages and T cells, that interact with the immune, nervous, and endocrine systems. Cytokines regulate the intensity and duration of immune responses, and can be stimulatory or suppressive. Interleukins, interferons, and some growth factors are examples of cytokines.
Cytotoxic T-cells – see CTLs.
Dendritic cells – DC’s – a large immune system cell type, characterised by its branched appearance, and found in the skin and mucosal membranes. They are typically the first to arrive at the site of infection or injury, and are able to engulf (phagocytose) or bind antigens and transport them to the lymph nodes, where they present the antigen to other immune cells and initiate CTL production. See immunotherapy.
Deoxyribonucleic acid – see DNA.
Derepression – the process of “turning on” the expression of a gene or set of genes by displacement of a repressor protein from an area known as the promoter region. When attached to the promoter region, the repressor protein prevents transcription.
Determinants – see epitopes.
Diploid – in human cells, having two sets of chromosomes, one of paternal origin, the other maternal.
Diploid number – the total number of chromosomes in a normal (diploid) cell. In most human cells it is 46 (23 pairs).
DNA – deoxyribonucleic acid – helical chains consisting of adenine, thymine, cytosine, and guanine bases, arranged intogenes, and further, into chromosomes, that contain the code for life for a particular organism. Located in the nucleus of most cells, DNA is normally double stranded, existing as tight coils condensed around protective proteins called histones.
DNA construct – a segment of DNA, usually a gene, inserted into a vector such as a plasmid, and able to be transferred into a “host” cell that will incorporate the gene into its own genome. Constructs are used in research and biotechnology, such as in the commercial production of antibiotics using bacteria.
DNA hybridisation – a laboratory technique using a DNA probe to identify an identical or nearly identical DNA sequence in a mixed population. The degree of similarity between different single-stranded fragments of DNA is reflected by the extent to which they will bind, or hybridise, with each other. A technique known as FISH (fluorescent in situ hybridisation) uses DNA probes to identify the locations of genes on chromosomes.
DNA methylation – the addition of methyl groups ( -CH 3) to cytosine or adenine bases in DNA. Methylation occurs naturally and is thought to have a role in suppressing gene expression, and also in X-chromosome inactivation.
DNA probe – a radioactive or fluorescent labelled (tagged) segment of single-stranded DNA used in hybridisation and other studies to detect a specific DNA sequence. If the tagged sequence is complementary to any one in the mixture, the two sequences will form a double strand and be difficult to separate
DNA replication – the process in which the DNA double helix unwinds and makes a copy of itself. Complete replication occurs in cell division.
DNA sequencing – determining the order of adenine, guanine, thymine and cytosine bases in a sequence of DNA. The Human Genome Project is responsible for sequencing the full DNA complement, the genome, of the human cell. In 2000, the Draft Genome Sequence, containing about 95% of the code, was published. Currently, the human genome is thought to contain about 30,000 genes.
Domain – a part of a protein having a discrete function or conformation, e.g. as an antigenic determinant or epitope. A domain can be as small as a few amino acid residues, or as large as half of the entire protein.
Dominance – the strength of physical expression of one allele, or variant, of a gene over another. In human genetic inheritance, every gene pair contains a gene from each parent. For example, if a child of a blue-eyed and a brown-eyed parent inherits one gene for each eye colour, he or she will be brown-eyed, because of the dominance of the brown-eyed gene.
Double helix, double stranded – the double-stranded arrangement of DNA, with two complementary strands that intertwine in a helical fashion, the base pairs bonding between the strands like rungs on a ladder.
Downregulation – reduction of the normal level of gene expression.
Duplication – a genetic mutation resulting in more than one copy of a gene or a section of a chromosome (known as partial duplication), or even a whole chromosome. In the case of partial duplication, the copied sections are integrated back into the chromosome.
EBV – Epstein-Barr virus – the widely-occurring virus that causes infectious mononucleosis (IM), also known as glandular fever; some forms of Hodgkin’s disease; post-transplant lymphomas (PTLD); some types of nasopharyngeal carcinoma; and Burkitt’s lymphoma. About 90% of adults are EBV positive. EBV infects B cells, and establishes a latent, or background, infection, which is kept in check by the immune system, and is lifelong. Exposure to EBV during childhood results in protection from infectious mononucleosis in later years.
Effector cells – in the immune system, normally referring to CTLs, but also an alternate name for plasma cells (antibodysecreting cells), and a group name for CTLs, helper T cells and suppressor T cells.
Effector molecule – a molecule that influences the behaviour of a regulatory molecule such as a repressor protein, thereby influencing gene expression. Bmx protein is an effector molecule, abnormal forms of which are found in leukemia.
Electroporation – an electrical treatment of cells, useful as a method of introducing plasmids. It produces transient pores in the cell membrane, through which DNA or RNA can enter the cell. The pores subsequently close off, ensuring that the DNA or RNA stays inside the cell.
Electrophoresis – a process often used in the lab where samples of DNA, RNA, or protein can be separated on a gel by applying an electric current across it. PAGE (polyacrylamide gel electrophoresis) is a common research tool to separate proteins and also in DNA sequencing.
Endometriosis – a painful and often debilitating medical condition in which uterine lining tissue is present in areas of the abdominal cavity outside of the uterus. These segments respond to the hormonal cycle, shedding at each menstruation and resulting in blood loss into the pelvic cavity. Endometriosis can significantly affect fertility and is a subject of research at QIMR.
Enzyme – a type of protein made by the cell in order to encourage or regulate particular biochemical reactions, usually to increase the rate at which the reaction would occur naturally. Enzyme names usually have the suffix -ase. One example is ferric reductase, which reduces iron in the intestinal contents (ferric iron, Fe+3) to ferrous iron (Fe+2), to make it more soluble and so more easily absorbed by cells of the intestinal lining.
Epidemiological study – the study of the path of a disease, or aspect of health, within a community, taking into account causative factors, lifestyle and environmental influences, medical intervention, etc. A recent such survey undertaken by QIMR is the 5-year Nambour Skin Cancer Study, which demonstrated the effectiveness of daily sunscreen application in reducing the incidence of certain types of skin cancer.
Epitope – the part of an antigen evoking a response by, and which binds to, an antibody or a T cell. Large antigens may contain many different epitopes, each capable of stimulating production of a different specific antibody or CTL. Epitopes may only be a few amino acids long.
Epstein-Barr virus – see EBV.
Expression – see gene expression.
Flow cytometry – a flow-through, computer-driven system, employing laser and fluorescence technology to recognise and count cells based on physical attributes such as size, status of division of DNA (i.e. stage in the cell cycle), organelle type etc. Cell sorting, more commonly known as FACS (fluorescence-activated cell sorting), is an extension of this technology, whereby cells of particular interest can be individually removed from the cell mix by electrostatically charging them. FACS has many applications, for example, in analysis of the cell cycle, measurement of apoptosis, and cell function studies, in health and disease states.
Fluorescence – emission of visible light from an object irradiated with a different, usually UV, light; also, a laboratory technique whereby a molecule, DNA strand, etc of interest is “tagged” with a marker that fluoresces under microscopic examination, allowing the location and the quantity of the marker of interest to be displayed.
Gene – the “unit of heredity” – DNA that contains the code for a protein, or part of a protein. There are thousands of genes on each human chromosome. Since the completion of the Human Genome Project in 2001, the total number of genes in the human genome is now found to be about 30,000. Structurally, a gene consists of a promoter region, which allows for control over the activity, or expression, of the gene, and one or more exons (areas that code for the gene’s protein product). If two or more exons are present, they are separated by introns (non-coding regions). Genes comprise about 2% of the total DNA in a cell. The remaining DNA is of largely unknown function.
Gene expression – the process of gene transcription and translation, i.e. the reading of the DNA sequence to produce anmRNA, and the decoding of the mRNA on the ribosomes of the cell, to produce its protein product. In any adult cell, only genes required for the current function of the cell type are “switched on” or expressed. The expression of genes can change with cancer or disease. One example is the suppression of an enzyme called testisin in cancer of the prostate.
Gene expression profiling – see expression profiling.
Gene mapping – determination of the physical location of genes on a chromosome, and the relative distance between them. Distances along a chromosome are measured in numbers of bases e.g.10kb (10,000 bases) or in angstroms. Gene mapping provides information about inheritance patterns and clustering of gene groups.
Gene therapy – the treatment of inherited diseases by introducing into the cells of affected individuals a normal copy of the defective gene causing the disorder. Embryonic cells can be treated, referred to as germline or heritable gene therapy, resulting in all cells in the organism, and future progeny, all containing the introduced gene. The use of other cells, such as adult organ cells, is called somatic cell or non-inheritable gene therapy.
Genomics – the branch of science/technology which specializes in the systematic study of genomes and the production of their gene products (proteins), their role in health and disease, and the effects of manipulation of these systems by agents such as pharmaceuticals and radiation. Proteomics is a closely allied field.
Genomic imprinting – a pattern of gene expression that is determined by the parent of origin for the gene. In a normal cell, which contains genes from both parents for any characteristic, this means that only one (i.e. either the maternal, or the paternal) allele is expressed, contrary to most genes, where both alleles are expressed.
Germline – originating from a sperm or ovum cell, or a zygote (when a sperm cell fertilises an egg), or from the cells which give rise to these. Mutations in germline cells are carried between generations. See gene therapy.
Granulocyte – a type of leucocyte including neutrophils, basophils, and eosinophils, that have enzyme-filled granules in the cell cytoplasm. The contents of these granules are discharged from the cell in the presence of infected cells, tumour cells, etc.
Growth factors – molecules, particularly proteins, that have a variety of roles in the stimulation of new cell growth and cell maintenance, by binding to receptors on the cell surface. Human Growth Hormone (HGH) is one example.
Haematopoeisis – the production of red blood cells (erythrocytes) and white blood cells (leucocytes) in the bone marrow. These cells, originating as bone marrow stem cells, leave the bone marrow and enter the bloodstream, where maturation, and transport to the tissues, can occur. Blood cells have a limited life compared with most body cells, partially due to the mechanical stresses of being pumped around the body under pressure, especially through small capillaries less than one cell in diameter. Leucocytes are produced at the rate of about 1 billion per day.
Haemochromatosis – a genetic disorder of iron metabolism, which results in the deposition of iron in the major organs, primarily in the liver, pancreas and heart. Untreated, the disorder results in organ damage and associated cirrhosis, diabetes and heart failure.
HCMV – human cytomegalovirus – a group of herpesviruses, present in up to 85% of the population. Usually, HCMV is only mildly infectious, except in babies, where congenital HCMV infection can result in deafness, vision impairment and mental retardation; also in organ transplant recipients, and people who work with children. Much research is being done to produce avaccine for HCMV.
Helper T-cells – also known as CD4 cells, T4 cells, or CD4 lymphocytes – a type of T cell carrying the CD4 receptor, and responsible for cytokine-mediated stimulation of other cells of the immune system, namely B cells and T cells.
Heterozygosity – possessing differing alleles for a particular gene, each inherited from a different parent.
HLAs – Human Leucocyte Antigens – “self” antigens found on the surface of all human cells. In organ transplantation, HLAs have to be matched by tissue typing, in the same principle as blood typing for a transfusion, so that the immune system will not reject the new organ
Homeostasis – the maintenance of normal cell, organ or body function, especially following an event such as an immune response to infection. During an immune response, large numbers of cells are produced in response to an infection, resulting in increased white cell numbers in the blood and tissues. After elimination of the infectious agent most of these cells die, allowing the body to return to normal.
Immortalised cell line – cells that are transformed, or changed, by a virus or a genetic mutation into a cell line or population which can proliferate, or grow, indefinitely. Cancer cells are an example.
Immune response – the reaction of the body to an antigen, such as bacteria, virus, parasite, allergen, or tumour cell. The immune response can be divided into several phases – the “innate” first response, mediated by cells able to destroy and phagocytose (engulf) a large range of foreign organisms; the secondary, “adaptive” response, characterised by the generation of antibodies and T cells that are specific for the antigen; and a third, “suppression” phase, where the production of immune cells reverts to normal (homeostasis), and the information necessary to mount a future immune response to that antigen is retained in bone marrow memory cells.
Immune system – the set of cells, and their activity against antigens, or infectious agents, that comprise the body’s defence system against disease and cancer formation. By numbers, lymphocytes are the major cellular components of the immune system, which also includes dendritic cells, monocytes, granulocytes (eosinophils, basophils, and neutrophils), mast cells, and platelets.
Immunity – the body’s protection against an infection. Achieving immunity is the role of the immune system.
Immunocompetence – the state of the immune system of being functionally adequate. Immunocompetence can be altered – “compromised” – by immunosuppressive drugs, infectious agents such as HIV or EBV, and cancers such as leukaemia.
Immunocompromised – a state where the immune response of the body is lowered, by drugs (as with organ transplant recipients), radiation, cancer, viral infection (such as EBV or HIV), or even malnutrition.
Immunological tolerance – or immunotolerance – recognition of “self”, the phenomenon by which the immune systemnormally suppresses immunological responses to cells of the body, i.e. self-antigens. In diseases such as rheumatoid arthritis, this mechanism is faulty, and the body is attacked by its own immune system.
Immunosuppression – suppression of the immune response, seen in some diseases and cancers. Artificial immunosuppression is necessary following organ transplants in order to prevent rejection of the new organ.
Immunotherapy – the manipulation of the body’s immune system, often in vitro, to help fight disease. One type of immunotherapy being investigated at QIMR is dendritic cell (DC) therapy, where the patients’s own DC’s are collected, grown in culture with an extract of their own tumour (e.g. from a prostate cancer), and subsequently reintroduced to the body to induce an immune response against the tumour.
Introns – in a gene, regions of DNA situated between exons (DNA coding for protein). Introns can contain repeat sequences, vestigial gene fragments, inverted sequences, etc and some are believed to have a role in regulating transcription. During transcription, both introns and exons are transcribed, but introns are spliced (cut out) of the final mRNA copy.
Irradiation – treatment with, or exposure to, any form of radiation. Cell cultures are often irradiated in the lab to induce the production of mutations.
“Junk” DNA – an older term for the regions of DNA on the genome that lie between genes, and once thought to have little or no function. Now it is known that these regions may have significant roles in the control of gene expression.
Killer T-cells – see CTLs (cytotoxic T-cells).
Knock-in mice – an experimental line of mice, produced from embryonic stem cells in which a reporter gene has been inserted into the genome, in such a position that the expression, or activity, of a gene under investigation can be monitored.
Knockout mice – a commonly used type of animal model, a mouse population resulting from embryonic stem cells in which a normally functional gene has been switched off, or replaced by a non-functional form of the gene. The function of such a gene can be understood by studying the characteristics of animals unable to produce the gene product.
Latency – a state in which a pathogenic organism, or a tumour, is present in the body, but not actively replicating or causing illness. EBV and HIV are examples of organisms which can be latent for many years.
Leucocytes – or leukocytes- lit. “white cells” – a broad term referring to the white cell population of the blood, including B-cells, T-cells, monocytes, macrophages, basophils, eosinophils, neutrophils, and NK cells. While in the bloodstream, many of these cells are relatively undifferentiated (immature) and only activated at the site of an infection, once exposed to an antigen.
Leukaemia – lit. “white blood” – cancer of the developing cells of the bone marrow, leading to massive overproduction ofleucocytes.
Lymphocytes – immune system cells, produced in the bone marrow at a rate of about 109 per day, that play a major role in the body’s immune system. There are four broad classes of lymphocytes, B cells, T cells, NK cells, and NKT cells, all with differing roles and responses to the presence of an antigen. Collectively, they are responsible for antibody production, direct cell-mediated killing of virus infected cells and tumour cells, and for the regulation of many other components of the immune system.
Macrophage – a large phagocytic (cell and particle ingesting) type of immune system cell present in tissues and lymph nodes. Macrophages assist in activating T cells, by presenting fragments of antigen bound to cell surface molecules to these cells.
Mast cells – large immune system cells, present in the tissues and blood, capable of mounting an immune response toparasite and bacterial infection. This is partially achieved by activating other cells such as neutrophils and T cells, and partially by phagocytosis, or ingestion, of the offending antigen. Mast cells release histamines and are responsible for allergy symptoms and asthma.
Melanoma – cancer of a type of skin cell called melanocytes, often metastasising to internal organs. Melanomas are induced by exposure to high levels of UV radiation, and are of particular concern in Queensland and at QIMR Berghofer.
Meiosis – during embryonic development, a complex process of cell division occurring after fertilisation of egg with sperm, in which chromosomic material is exchanged and recombined such that the resulting embryo is a unique genetic entity, different genetically to either parent.
Memory cells – long-lived B cells and T cells, residing in the bone marrow, that retain the ability to respond to a previously encountered antigen, and therefore can initiate a rapid “secondary” immune response upon reinfection. The aim of vaccination is to induce production of memory cells without creating the disease itself.
Messenger RNA – see mRNA.
Microarray technology – a method of determining how a cell can control the expression of large numbers of genessimultaneously. Up to 10,000 different cDNA segments are spotted on to a glass slide, making a DNA “chip”. When a solution of fluorescently labelled DNA fragments is added to the chip, fluorescence occurs in the spots where gene activity is present.
Mitochondria – rod-shaped organelles within a cell, responsible for energy production. Mitochondria also contain a small amount of DNA.
Mitochondrial inheritance – in humans, mitochondria are only inherited from the mother (maternal inheritance), not from the father, because they are absent from sperm cells. Therefore, diseases arising from mutations in mitochondrial DNA are inherited differently to diseases resulting from mutations in nuclear DNA.
Molecular mimicry – a phenomenon associated with some pathogens, where the antigens evoking an immune responsehave enough similarity to the body’s own proteins to cause an autoimmune reaction, such as in rheumatoid arthritis, mediated by “cross reactive” T cells and/or circulating antibodies.
Monoclonal antibody – a quantity or culture of a single antibody type, produced in vivo (in the body) or in vitro (in the lab), directed against a specific epitope, and produced by a single clone of B cells, or a myeloma (cancer) cell line.
mRNA – messenger RNA – the end product of transcription of a gene. Both introns and exons are initially transcribed to form a pre-RNA, which undergoes splicing by nuclear enzymes to remove the introns and create mRNA, which is then used as a template for protein production on the ribosomes of the cell. Also see gene expression.
Mouse model – see animal model.
Mutation – a mistake in the cell’s DNA, produced by miscopying during cell reproduction, radiation damage, or environmental factors. These mistakes are perpetuated when the DNA replicates, and result in imperfect gene products (proteins) being produced.
Naïve – when referring to cells of the immune system, ones that have not been subjected to antigenic stimuli, and are therefore undifferentiated or immature.
Natural killer (NK) cells – a type of lymphocyte that attacks and kills infected and tumour cells. NK cells respond to “absence of self” on cell surfaces, a feature of cancer cells.
Neutrophil – a type of immune system cell, present in the blood and in tissues, able to phagocytose (ingest) foreign cells. The attraction of neutrophils out of the blood and into a foreign organ, a phenomenon known as sequestration, is of particular importance during transplantation.
NKT cells – natural killer T cells – a type of T-cell, only recently described, whose function is clearly different from NK cellsand T-cells. They are immune effector cells with cytotoxic anti-tumour activity.
Northern blot – a cellulose or nylon membrane onto which RNA molecules have been spotted. The transferred RNA is hybridized to single-stranded DNA probes. Northern blot technique is often used to measure the expression of a gene for which a specific cDNA is available for use as a probe.
Oncogenes – genes, implicated in the development of cancer, which are mutant forms of genes (proto-oncogenes) whose normal function is to regulate cell growth and proliferation. The ATM gene which is associated in breast cancer, is an example.
Pathogen – an organism capable of causing disease. Examples of pathogens include some bacteria, viruses, fungi, helminths (worms) and protozoa. Many different types of pathogen are being studied at QIMR.
Peptide – a small chain of amino acids, part of a protein. Part of the immune response involves the processing or metabolising of antigens into peptide fragments of 8-20 amino acids in length, which are then presented to the immune system.
Perfusion – the supplying of blood or fluids, in transplantation or surgical procedures, to an organ or a part of the body. See ischaemia.
PCR – polymerase chain reaction – a method of producing large amounts of a specific segment of DNA in the laboratory, by incubating a template DNA with primer DNA and adding a polymerase enzyme. Also see cDNA.
Phagocytosis – the ability of certain cells, such as macrophages and dendritic cells, to engulf and ingest, and therefore destroy, foreign matter or organisms. Most of the end products of this degradation are used for nutritional purposes within the cell.
Phase I, Phase II trial – see clinical trial.
Phenotype – the visible appearance or set of traits of an organism, resulting from the combined action of genotype and environment. Phenotype also can refer to a specific displayed characteristic which is coded for by one or a small number ofgenes, e.g. eye colour.
Plasmid – an extrachromosomal, circular DNA molecule found in certain bacteria, capable of independent replication to the nuclear DNA. Plasmids can transfer genes between bacteria, and are useful tools in genetic manipulation.
Platelet – an anuclear (without a nucleus) cell type, produced in the bone marrow, and playing a major role in the blood clotting mechanism. Platelets also contain secretory granules active in the tissue immune response to some pathogens.
Ploidy – the number of sets of chromosomes in a cell, e.g. haploid (one), diploid (two), tetraploid (four), polyploid (many). Most human cells are diploid. Some cancer cells are tetraploid or even polyploid. Some cells can have partial ploidy – for example, Down’s syndrome sufferers have an extra chromosome 21 (known as trisomy 21).
Polymorphism – the existence of two or more alternative forms (alleles) of a gene, or other DNA segment, that differ in base sequence, or that have variable numbers of repeated sequences.
Polytope/polyepitope – a DNA construct, consisting of segments of viral DNA spliced together to form a sequence coding for a multi-antigen, which can be used to stimulate vaccine production. The DNA segments represent the code for antigenic fragments which are most effective in stimulating antibody responses. QIMR is investigating a polytope vaccine for malaria and other diseases.
Probe – a specific sequence of single-stranded DNA or RNA, typically labelled with a radioactive or fluorescent tag, which is designed to bind to, and thereby identify, a particular segment of DNA (or RNA).
Promoter region – the part of a gene, upstream from the exon, which binds RNA polymerase and transcription factors in order to begin transcription. Promoter regions also bind regulatory proteins such as repressors, which displace RNA polymerase and prevent transcription occurring. A commonly found promoter sequence in human DNA is the sequence of fourbases, TATA (thymine-adenine-thymine-adenine).
Protein – a macromolecule composed of one or several polypeptides. Each polypeptide consists of a chain of amino acids linked together by covalent (peptide) bonds.
Proteomics – the field of study encompassing the identification and quantification of proteins, and the effect of their modifications, interactions, activities, and function, during cancer, disease states, and treatment.
Receptor – a molecular structure on the cell surface, which allows the attachment of specific extracellular molecules, such asantigens and cytokines, in order to allow communication with other cells and the environment. Receptors are a starting point for signal transduction.
Recessiveness – in gene pairs, the lack of expression of one allele’s coded characteristic, because the other allele is dominant. Recessive genes must be present as a pair in order to exhibit the trait that they code for.
Recombinant DNA – a DNA sequence produced by introducing a segment of DNA into the genome of a different organism, e.g. recombinant IL-2. It is a method by which large or even commercial quantities of a protein of interest may be produced.
Reporter gene – a gene that codes for a product that can readily be measured, such as a fluorescing protein. The fluorescence generated by the protein can indicate, for example, whether a DNA construct has been successfully introduced into a cell. GFP (green fluorescing protein) is one example used in flow cytometry and fluorescence microscopy.
Repression – inhibition of the transcription of a gene by the binding of a repressor protein (the product of a regulatory gene) to its promoter region (the transcription initiation site). Repressor proteins block RNA polymerase from binding to the promoter region, thus “switching off” the gene and preventing mRNA production.
Restriction enzymes – a group of enzymes used to cleave (cut) DNA strands, each having a characteristic base sequence at which it cleaves. These enzymes are used in DNA manipulation studies, for example, in the insertion of DNA constructsinto a genome, or the insertion of a gene into a plasmid. Ligases are then used to join the ends.
Reverse transcription – the synthesis of DNA from an RNA template, using the reverse transcriptase enzyme. In the lab, reverse transcription is used to make fluorescently labelled cDNA probes to study expression profiles of genes, e.g. in microarrays.
Ribonucleic acid – see RNA.
RNA – ribonucleic acid – single-stranded chains made up of adenine, cytosine, guanine and uracil bases. There are various types of RNA, with different functions. Messenger RNA (mRNA) is the product of transcription of DNA, enabling the code for aprotein to be transferred from the nucleus to the ribosomes. Transfer RNAs (tRNAs) contain single codons and bind the corresponding amino acid, participating in the translation of mRNA into protein. Ribosomal RNA (rRNA) is a structural component of the ribosome. Also see gene expression.
RT-PCR – reverse transcriptase polymerase chain reaction (PCR) – a two-step process. First, complementary DNA (cDNA) is made from an RNA template, using a reverse transcriptase enzyme, and then some of it is used in a PCR reaction to produce large quantities.
Seronegative – not present in the blood (strictly, the serum), especially with respect to antigens, antibodies and a large range of molecules produced by the body.
Signal transduction – communication inside the cell, and also, how a cell reacts to an external signal by transmitting it across the cell membrane to the interior of the cell. Proteins on the cell surface function as receptors for specific molecules (such as the hormone, insulin). The binding of the molecule to the receptor initiates an interlinked series of biochemical events inside the cell, involving enzymes, proteins and ions (especially calcium). Impairment or absence of any part of this chain causes signal transduction to break down.
Splicing – a stage in the processing of mRNA, in which intervening sequences (introns) are removed from a primary RNAtranscript (pre-RNA) and the coding exons are joined together to form the mature mRNA molecule. Splicing can also be carried out as an experimental procedure to join or insert DNA segments.
Stem cell – an undifferentiated type of body cell found in bone marrow, growing tissues, and embryonic tissue. The physical location of the stem cell, and the hormonal or growth influences that surround it, will determine what type of adult cell it will become.
Surface antigens – molecules located on the surface of a cell, such as HLAs.
T cells – a class of lymphocytes named for their partial maturation in the thymus, and responsible for the cell-mediated or cellular immune response. T cells attack and destroy body cells that have become infected or become cancerous, and also secrete cytokines. The main types of T cells are CTLs (cytotoxic or killer T cells), helper T cells, and suppressor T cells.
Target gene – a gene of experimental study or biological importance.
Trafficking – transport or relocation, particularly of molecules, between or within cells, or from an external environment, e.g. the intestine, into a cell. Trafficking is often assisted by specialised proteins, specific for the molecule being moved.
Transcription – the process of reading and copying a gene or a DNA sequence to make new DNA or RNA. A transcription complex refers to the complex of RNA polymerase and transcription factors bound to the promoter region of a gene.
Transgenesis – the introduction of a gene or genes into cells, which leads to the transmission of the input gene (transgene) to successive generations.
Transport proteins – proteins of various types, found in the blood, in the cell, or on the cell membrane, responsible for carrying or translocating (“trafficking“) specific molecules. For example, DMT1 is a cell surface protein, which allows iron to be transported from the intestine into the intestinal lining cells.
Trisomy – an abnormal condition in cells where there are three copies, instead of two, of a particular chromosome. For example, Down’s syndrome sufferers have trisomy of chromosome 21.
Tumour suppressor genes – genes that are normally responsible for restraining unlimited cell division, but, when missing or mutated, allow cells to grow uncontrolled, resulting in a tumour.
Vaccine – A preparation designed to confer immunity against a disease, usually by single inoculation. Each vaccine is different, containing weakened or dead pathogens, or parts of these, that stimulate the immune system into antibodyproduction, i.e. immunity, without causing the disease. Probably the most famous – and the first – vaccine is that for smallpox, made by using a preparation of the less pathogenic but similar cowpox. Also see memory cells.
Vector – a physical means of transmitting disease, such as the Aedes aegypti mosquito, which carries dengue fever. A vector is also a constructed segment of DNA able to carry a gene or region of experimental interest into a target organism. For example, a plasmid containing an antibiotic gene can be introduced into a bacterial culture, which will subsequently produce the antibiotic.
Virus – one of the most primitive types of organism, consisting only of a DNA or RNA genome and a protein coat or “capsid”. Viruses can only replicate when they have infected another organism, utilising the host’s cellular machinery to cause disease and/or allow proliferation of the virus. Many viruses are being studied at QIMR – some examples are Epstein-Barr virus (EBV), human cytomegalovirus (HCMV), Ross River Virus (RRV), and Barmah Forest virus (BF).
Western blot – a method of quantifying the amount of a protein of interest in a cell extract, by first separating the cell proteins using gel electrophoresis (PAGE), then “blotting” the resultant spots onto a thin membrane.
X-chromosome – a chromosome associated with sex determination. In most animals, the female has two X-chromosomes, and the male has one.
X-linked – present (as in a gene) on the X-chromosome.
X-linked disease – an inheritable disease caused by an abnormal gene present only on the X-chromosome. In X-linked recessive conditions, such as XLP (X-linked lymphoproliferative disease) a son, having only one X-chromosome, will exhibit the disease associated with the abnormal gene, whereas a daughter who has one normal and one abnormal gene will not. She is a carrier of the gene – however, her sons will inherit her gene and have XLP.
X-chromosome inactivation – a developmental process in female mammals where one complete X-chromosome is decommissioned or inactivated, to compensate for their double dose of X-linked genes, in comparison to males.
Y-chromosome – a chromosome associated with sex determination. Human males have one Y- and one X-chromosome. Females have two X-chromosomes, but no Y. The Y-chromosome contains fewer genes than an X-chromosome.