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Glossary

Affinity – The strength of a bond between a binding site on a molecule (e.g. an antibody) and ligand (e.g. an antigen).

Anaphylatoxin - Molecules that induce a pro-inflammatory response. This includes the stimulation of mast cells to release histamine, and the recruitment of immune cells via chemotaxis.

Antibody – A glycoprotein also known as an immunoglobulin (Ig), produced by B-lymphocytes that binds antigens, often with a high degree of specificity and affinity.

Antigens – A molecule capable of inducing an immune response.

Antigen presenting cells – A group of cells that display peptide fragments of antigens in association with MHC molecules on their surface, and activate T-lymphocytes. In addition to displaying peptide-MHC complexes, APCs also express co-stimulatory molecules to activate T-lymphocytes optimally. Can be professional or atypical.

Apoptosis – A process of cell death characterized by DNA cleavage, nuclear condensation and fragmentation and plasma membrane blebbing. Cell fragments are removed by phagocytosis.

Autoimmunity – A state of responsiveness to self-antigens by the immune system that occurs when mechanisms of self-tolerance fail.

B-cell receptor – The cell surface antigen receptor found on B-lymphocytes, which is a membrane-bound immunoglobulin molecule.

Bone marrow – The central cavity of bone that is the site of production of all circulating blood cells and the site of B-lymphocyte maturation.

Caspase pathway – Involves intracellular proteases called caspases which form an enzymatic cascade that results in the apoptosis of cells.

Clusters of differentiation (CD) molecules – Cell surface molecules expressed on various immune cells that are designated by their “cluster of differentiation” or CD number e.g. CD4+.

Cell-mediated immunity – Form of adaptive immunity that is mediated by T-lymphocytes without the involvement of antibodies.

Central tolerance - A form of tolerance to ‘self’, induced in primary lymphoid organs as a result of the deletion or inactivation of self-reactive immature lymphocytes. Central tolerance development prevents the release of lymphocytes with high-affinity receptors for the self-antigens.

Chemokines – A large family of structurally homologous, low molecular weight cytokines that stimulate leukocyte movement (chemotaxis).

Chemotaxis – The movement of a cell directed by a chemical concentration gradient. This chemical gradient is created by chemokine release.

Class I Major Histocompatibility Complex (MHC I) – One of the two forms of the major histocompatibility complex responsible for antigen presentation. Found on all nucleated cells within the human body, and displays peptide antigens derived from endogenous (or intracellular) sources.

Class II Major Histocompatibility Complex (MHC II) - One of the two forms of the major histocompatibility complex responsible for antigen presentation. Found on antigen presenting cells, and displays peptides derived from extracellular sources that have been internalized via endocytic or phagocytic vesicles.

Complement - A cascade of proteolytic enzymes that interact with one another and with other molecules in the immune system to generate (for example) inflammatory mediators and opsonins. The common endpoint of the complement cascade is the formation of the membrane attack complex (MAC).

Complementary Determining Regions (CDRs) – Short segments found on antibody, BCR and TCR proteins that are hypervariable and represent specific antigen binding sites.

Cytokines – Proteins produced by many different cells that mediate inflammatory and immune reactions. Act as the principle mediators of communication between immune cells.

Damage Associated Molecular Patterns (DAMPs) – Endogenous molecules that are produced or released from damaged or dying cells that bind to pattern recognition receptors. An example of a DAMP is ATP.

Diapedesis – The movement of leukocytes from blood vessels to the tissues surrounding them. Also known as leukocyte extravasation.

Effector cell – Cells that perform effector functions during an immune response, such as secreting cytokines (helper T lymphocytes), or producing antibodies (plasma cells).

Endocytosis - The process by which a cell engulfs molecules into its cell by the invagination of part of its cell membrane to form a vacuole.

Endogenous – Substances that originate from within an organism, tissue or cell.

Exogenous - Substances that originate from outside that organism.

Fragment antigen binding (Fab) region – The portion of an Ig molecule that includes the variable region of the antibody, and is composed of a light chain paired with a section of the heavy chain.

Fas (CD95) – A ‘death receptor’ of the TNF receptor family that can be expressed on the surface of many cell types. When activated by binding to its ligand (FasL), it initiates a signaling cascade that results in apoptosis of the fas-expressing cell. Important for the maintenance of self-tolerance.

Fas ligand (FasL or CD95 ligand) – Membrane protein expressed on activated T cells, which binds to Fas to initiate apoptosis of the Fas-expressing cells.

Fc region – A fragment of an Ig that contains only the terminal regions of the two heavy chains that acts as the ‘constant” region of the Ig. The Fc region acts as a binding site for immune cell receptors or the C1q complement protein.

Fc receptors – A cell surface receptor specific for the constant region of an Ig molecule. Fc receptors mediate many of the effector functions of antibodies, such as phagocytosis of antibody-bound antigens, and activation of mast cells, complement and NK cells.

Granzyme – Serine protease enzyme that is found within the granules of Tc cells (cytotoxic T-cells) and NK cells. It enters target cells and activates the caspase cascade to induce target cell apoptosis.

Haematopoesis – The development of mature blood cells from pluripotent stem cells in the bone marrow and foetal liver.

Histones – Proteins found within eukaryotic cell nuclei responsible for packaging and ordering DNA into nucleosomes.

Human Leukocyte Antigen (HLA) – Another name for the major histocompatibility complex in humans.

Humoral immunity – The type of adaptive immune response mediated by antibodies.

ICAM-1 – Otherwise known as Intercellular Adhesion Molecule 1. Cell surface glycoprotein expressed on endothelial cells and cells of the immune system responsible for cellular adhesion.

Immune complex – A complex comprising of multiple antibody molecules bound to antigens. They can activate effector mechanisms of the immune system (e.g. the complement cascade), and aim to facilitate antigen neutralisation and elimination via the reticuloendothelial system. Immune complexes vary greatly in size and solubility. Their pathological deposition, for example in blood vessels or the renal glomerulus, can lead to inflammation and disease.

Immune system – A system of molecules, cells, tissues and organs that collectively function to provide protection to the body from foreign organisms.

Immunoglobulin class switching – The process by which a B-lymphocyte changes the class or isotype of the antibody it produces by changing the heavy chain. The antigen specificity of the antibody that is produced during this process remains unchanged.

Immunological memory – A property of the adaptive immune system that allows it to react more rapidly and aggressively to an antigen on subsequent exposure compared with the response produced on first encounter.

Inflammation – A complex reaction of vascularised tissue to infection or toxin exposure that involves the accumulation of plasma proteins and leukocytes in the affected tissue. Common result of innate immune responses. Serves a protective function in controlling infections and promoting tissue repair, though it can also cause tissue damage and disease.

Interleukins – Cytokines named with a numerical suffix in order of discovery or molecular characterisation.

Leukocytes – Another name for white blood cells.

Leukocyte extravasation – The movement of leukocytes from blood vessels to the tissues surrounding them. Also known as diapedesis.

Lymphatic system – A system of vessels in the body that collect fluid called lymph, originally derived from the blood, it is returned through the lymphatic ducts back into the circulation.

Lymph nodes – Small nodular capsules containing aggregates of lymphocytes and antigens situated along lymphatic vessels. Act as sites of antigen presentation where adaptive immune responses are primed.

Lymphatic duct – A great lymphatic vessel that empties lymph back into the circulation via the subclavian veins.

Lymphatic vessels – Vessels making up the lymphatic system responsible for the movement of lymph.

Lymphocytes – Type of white blood cells originating from the lymphoid lineage. Two main types are the T-lymphocytes and B-lymphocytes.

Lymphoid organs – Tissues responsible for producing lymphocytes and antibodies.

Major Histocompatibility Complex (MHC) – A heterodimeric membrane protein encoded in the MHC locus on human chromosome 6 that serves as a peptide display molecule for recognition by T lymphocytes. Also known as the human leukocyte antigen (HLA).

Mucociliary escalator - A defence mechanism involving ciliary action and flow of mucus from bronchioles through the bronchi and trachea up to the larynx. It forms a method by which particulate matter (including pathogenic organisms) is removed from the respiratory tract.

Opsonin – A molecule that becomes attached to the surface of a microbe to increase the efficiency of phagocytosis. Opsonins can be recognized by surface receptors on neutrophils and macrophages. Examples of opsonins are; IgG antibodies and complement proteins (e.g. C3b).

Opsonisation – The process of attaching opsonins, such as IgG or complement proteins, to the surface of pathogens to target them for phagocytosis.

Pathogen – A causative agent of disease e.g. bacteria or virus.

Pattern Recognition Receptors (PRRs)– Receptors that recognise PAMPs and DAMPs, and thereby activate innate immune responses. Examples include Toll-like receptors and Nod-like receptors.

Pathogen Associated Molecular Patterns (PAMPs) – Structures produced by microorganisms but not mammalian host cells, which are recognised by and stimulate the innate immune system. Examples include bacterial lipopolysaccharide (LPS) and viral double stranded RNA.

Perforin – A protein, which is homologous to the C9 complement protein, that is present in the granules of Tc cells (cytotoxic T-cells) and NK cells. When released, perforin promotes the entry of granzymes into target cells by puncturing holes in their cell surface, leading to apoptotic death of the target cell.

Peripheral tolerance – A form of tolerance that maintains the unresponsiveness of lymphocytes to self-antigens present in peripheral tissues.

Phagocyte – A cell capable of phagocytosis. Examples include macrophages, neutrophils and dendritic cells.

Phagocytosis – The process by which phagocytes engulf large particles, such as intact microbes, and degrade them.

Proteasomes – Protein complexes that degrade unneeded or damaged proteins by proteolysis.

Reticuloendothelial System (RES), or Mononuclear Phagocytic System (MPS) – A network of tissue-based phagocytes found throughout the body (e.g. in liver and spleen). Functions include; destruction of ‘old’ or damaged circulating cells, and the detection and phagocytosis of invading microbes.

Selectin – Carbohydrate-binding proteins that mediate the adhesion of leukocytes to endothelial cells.

Self-antigen – A molecule of an organism which can act as an antigen in inducing antibody formation in another organism, but to which the normal healthy immune system of the parent organism is tolerant to.

Self-tolerance – The unresponsiveness of the adaptive immune system to self-antigens via the inactivation or destruction of self-reactive lymphocytes.

T-cell receptor – Antigen receptor found on CD4+ and CD8+ T lymphocytes that recognises complexes of foreign peptides bound to self-MHC molecules.

Thymocyte – Precursor cell for mature T-lymphocytes found within the thymus.

V(D)J recombination – Unique mechanism of genetic recombination that occurs only in developing lymphocytes during the early stages of T and B-cell maturation. Involves the somatic rearrangement of various genetic sequences, resulting in the development of a highly diverse repertoire of BCRs and TCRs.

Common Cytokines, Chemokines and Molecules

IL-1:

– Produced by activated macrophages, neutrophils, endothelial and epithelial cells
– Causes fever, lymphocyte activation, production of acute phase proteins, mobilisation of PMNs and activates the endothelium

IL-2:

– Produced by activated T cells
– Induces proliferation of T, B and NK cells

IL-4:

– Produced by Th2 cells and mast cells
– Induces B cell activation and IgE production, Th2 cell proliferation and mast cell proliferation
– Inhibits Th1 response and important in allergy

IL-5:

– Produced by Th2 cells and mast cells
– Induces eosinophil growth and differentiation, B cell activation and IgA response

IL-6:

– Produced by T cells, macrophages and endothelial cells
– Responsible for B lymphocyte activation, fever, and acute phase protein production
– Acts as both a pro-inflammatory and anti-inflammatory cytokine

IL-8:

– Produced by macrophages, monocytes, keratinocytes and fibroblasts
– Also known as chemokine CXCL-8 as its involved in chemotaxis of PMNs such as neutrophils

IL-10:

– Produced by macrophages and T cells (mainly Treg cells)
– Inhibits the expression of IL-12, co-stimulators and class II MHC

IL-12:

– Produced by B cells, dendritic cells, neutrophils and macrophages
– Induces Th1 and activates NK cells. Inhibits Th2 response

IL-13:

– Produced by CD4+ T cells, particularly Th2 cells, NK cells, mast cells, eosinophils and basophils
– Both pro- and anti-inflammatory properties
– Causes IgE secretion by B cells, goblet cell hyperplasia, mucus hypersecretion and airway hyperresponsiveness
– Mediator of allergic inflammation and different diseases e.g. asthma

IL-15:

– Produced by macrophages
– Released by virally infected phagocytes and causes the proliferation of NK cells and promotes the survival and proliferation of memory CD8+ Tc cells

IL-17:

– Produced by Th17 cells
– Causes the increased production of chemokines by endothelial cells and macrophages

CXCL-8

– Otherwise known as IL-8 or Chemokine C-X-C motif ligand 8
– Released by macrophages, monocytes, keratinocytes and fibroblasts
– Causes chemotaxis of polymorphonucleic cells, such as neutrophils, to site of infection/inflammation and stimulates degranulation and phagocytosis
– Potent promoter of angiogenesis.
– Important in psoriasis disease.

CXCL -10:

– Also known as Chemokine C-X-C motif ligand 10 or Interferon gamma-induced protein 10
– Produced by cells such as monocytes, endothelial cells and fibroblasts
– Attracts monocytes, macrophages, T cells, NK cells and dendritic cells
– Important in T cell adhesion to endothelial cells

CCL-2

– Also known as chemokine c-c motif ligand 2 (or monocyte chemoattractant protein 1)
– Secreted by monocytes, macrophages and dendritic cells.
– Recruits monocytes, memory T cells, and dendritic cells to the sites of inflammation.
– Important in the pathogenesis of several immune system related diseases such as psoriasis and rheumatoid arthritis.

CCL-3

– Also known as chemokine c-c motif ligand 3 or Macrophage inflammatory protein 1 alpha
– Produced by many cells but in particular, macrophages, dendritic cells, B cells and T cells.
– Responsible for recruitment and activation of neutrophils, eosinophils, and basophils.
– Important suppressor in HIV.

CCL-4

– Also known as chemokine c-c motif ligand 4 or Macrophage inflammatory protein 1 beta
– Produced by monocytes, B Cells, T Cells, fibroblasts, endothelial cells, and epithelial cells.
– Attracts a variety of immune cells such as natural killer cells and monocytes.
– Important suppressor in HIV.

CCL-5

– Also known as RANTES (regulated on activation, normal T cell expressed and secreted)
– Produced by immune cells such as macrophages
– Recruits T cells, eosinophils and basophils
– Important suppressor in HIV

CCL-11

– Also known as Eosinophil chemotactic protein
– Produced by T cells, macrophages, eosinophils and bronchial epithelial cells
– Recruits eosinophils
– Important in allergic reactions

Tumour necrosis factor-alpha (TNF-α):

– Produced by most immune cells, mainly macrophages, NK and T cells
– Involved in systemic inflammation and the acute phase reaction
– Increases vascular permeability and induces fever and apoptosis
– Inhibits tumourigenesis and viral replication

Transforming growth factor-beta (TGF-β):

– Produced by many cells, including regulatory T lymphocytes
– Controls cell growth, proliferation, differentiation and apoptosis

Interferon-gamma (IFN-gamma):

– Produced by Th1 cells, NK cells
– Activates macrophages and PMNs
– Induces Th1 and inhibits Th2 response

Histamine:

– Increases vascular permeability
– Smooth muscle contraction

Bradykinin:

– Inflammatory mediator protein
– Causes vasodilation

Prostaglandins and leukotrienes:

– Increase vascular permeability
– Smooth muscle contraction
– Stimulate mucus secretion
– Chemoattract T cells, eosinophils, mast cells and basophils

Nitric oxide:

– Produced by macrophages, PMNs
– Vasodilation
– Smooth muscle relaxation
– Cytotoxic to pathogens {footer}