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56 Cards in this Set
- Front
- Back
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Activation-induced cytidine deaminase (AID)
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Cytidine deaminase capable of carrying out targeted deamination of C to U and shows strong homology with the RNA-editing enzyme APOBEC-1. Essential for both somatic hypermutation and class-switch recombination.
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Adjuvant
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Any substance that, when incorporated into a vaccine formulation, acts generally to accelerate, prolong, or enhance the quality of specific immune responses to vaccine antigens.
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Adjuvant mechanisms of action
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(1) increasing the biological or immunologic half-life of vaccine antigens; (2) improving antigen delivery to antigen-presenting cells (APCs), as well as antigen processing and presentation by the APCs; and (3) inducing the production of immunomodulatory cytokines
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Advantages to using vaccine adjuvants
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: (1) their ability to direct and optimize immune responses that are appropriate for the vaccine; (2) to enable mucosal delivery of vaccines; (3) to promote cell-mediated immune responses; (4) to enhance the immunogenicity of weaker immunogens, such as highly purified or recombinant antigens; (5) to reduce the amount of antigen or the frequency of immunization required to provide protective immunity; and (6) to improve the efficacy of vaccines in individuals with reduced or weakened immune responses, such as newborns, the aged, and immunocompromised vaccine recipients.
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Depot effect
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: gel-type adjuvants, such as aluminum hydroxide, or emulsion-based adjuvants, such as Freund’s incomplete adjuvant, associate with antigen and facilitate the transport of antigen to the draining lymph node, where immune responses are generated. This allows the immunogenicity of small antigens such as synthetic peptides that otherwise would be rapidly cleared from the injection site and from draining lymph nodes to be improved by the use of adjuvants that form particles or otherwise associate with and hold antigen.
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Enhancement of antigen presentation
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Immunologic adjuvants can act directly or indirectly on APCs, such as macrophages and dendritic cells. MF59 has recently been shown to be internalized by DCs. Purified saponins, immunostimulatory complexes, and liposomes, have been shown to greatly improve the induction of major histocompatibility complex (MCH) class I-restricted CD8+ cytotoxic T lymphocyte (CTL) responses over that induced by Ag alone or with alum adjuvants. This may occur due to direct delivery of Ag to the cytosol for presentation with MHC class I molecules, by allowing it to bypass endosomal antigen delivery and subsequent MHC class II processing, which occurs with Ag alone or with alum, which results in primarily antibody responses. Various adjuvants can also stimulate the production of cytokines that can drive either Th1 or Th2 responses. Adjuvants that enhance Th1 immune responses through the induction of IFNg and DTH also elicit the production of IgG subclasses that fix complement and bind with high affinity to Fc-g-1 receptors (e.e., IgG2a in mice, IgG1 in humans). These immunoglobulins are the most active in complement-mediated lysis and in antibody-dependent cell-mediated-cytotoxicity effector mechanisms.
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Affinity maturation
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As B cells with higher affinity immunoglobulins can more successfully compete for limited amounts of antigen present, an increase in the average affinity of the antibodies produced during an immune response is observed.
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Allotypes
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Variants that are inherited as alternatives and therefore not all healthy members of a species inherit a particular allotype. They occur mostly as variants of heavy chain constant-region genes.
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Antibody bond to antigen
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Non-covalent interaction
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Major antibody response determinant
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Accessibility of the epitope on the protein surface
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Antibody specificity
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1. the antibody has high affinity for antigen;
2. the antibody is able to discriminate between molecules |
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Antigenicity
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The ability to be recognized by antibody
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Cell shutdown
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AKA lymphocyte trapping. The dramatic fall in the output of cells in the efferent lymphatics after antigen reaches a lymph node in a primed animal. It is thought to result from the antigen-induced release of soluble factors from T cells
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Class-switch recombination
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Allows the IgH constant region exon of a given antibody to be exchanged for an alternative exon, giving rise to the expression of antibodies with the same antigen specificity but of differing isotypes, and therefore of differing effector functions. Occurs through a deletional DNA recombination event at the IgH locus. Constant regions for IgG, IgA, and IgE isotypes are located downstream of the IgM exon and CSR occurs between switch (S) regions. Breaks are introduced into the DNA of the two S regions and fusion of the S regions leads to a rearranged Ch locus
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Collectins (collagen + lectin)
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Proteins characterized by their amino (N)-terminal collagen-like regions that have a repeating triple helix of Gly-X-Y triplets, where X denotes any amino acid and Y is often a hydroxyproline residue. The N-terminal domain also confers structural stability on the protein, owing to its disulphide-bonding patter. The carboxy-terminal domains of the collectins all have C-type (calcium-dependent) lectin activity. The lectin domains mediate the interaction of collectins with a wide variety of pathogens. The most well-understood consequence of this interaction is pathogen opsonization and enhanced uptake by phagocytes. The collectin conglutinin agglutinates erythrocytes coated with antibody and complement. Studies have shown their ability to bind Gram-positive and Gram-negative bacteria, viruses, fungi, and allergens.
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Clonal selection
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Both T-cells and B-cells possess antigen-specific receptors and clones of these lymphocytes will be selected to proliferative when specific antigen is encountered.
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Combinatorial diversity
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The creation of diversity in the immunoglobulin repertoire through the joining of various gene segments.
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Complement
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Complex series of some 20 proteins which, along with blood clotting, fibrinolysis, and kinin formation, forms one of the triggered enzyme systems found in plasma. It is a highly amplified cascade phenomenon where the product of one reaction is the enzymic catalyst of the next. The most abundant and pivotal component is C3.
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Cross-presentation
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Occurs when exogenous antigens that have been phagocytosed or endocytosed gain access to the cytoplasm by exiting the vacuole and are processed via MHC class I. In this manner, APCs are able to present antigen (such as viral proteins) from organisms that are not tropic for them. It is also possible for MHC class II to pick up endogenous proteins in the ER.
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Defensins
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3.5-4 kDa cationic peptides that are rich in arginine and reach high concentrations in the neutrophil phagosome. They have an amphipathic structure which allows them to insert into microbial membranes to form destabilizing voltage-regulated ion channels. They act against a wide spectrum of Gram-negative and –positive bacteria, many fungi, and a number of enveloped viruses.
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Dichloromethylene diphosphonate
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Macrophage depleting drug when given in liposomes that are phagocytosed by the macrophages
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Epitope
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Molecular shape on an antigen that is recognized by antibody. The better the fit of the epitope to the antibody combining site, the more favorable the interaction and the higher the affinity of the antibody for antigen.
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Fc region
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composed of the C-terminal segments of the heavy chains. Mediates the secondary consequences of Fab binding to antigen.
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Guanidinium salts
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Used for stabilizing and destabilizing proteins
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Haplotype restriction
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T cells bearing ab receptors only respond when the APCs express the same MHC haplotype as the host from which the T cells were derived.
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Hapten
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A low molecular weight molecule that is recognized by preformed antibody but is not itself immunogenic unless conjugated to a ‘carrier’ molecule which provides epitopes recognized by helper T cells.
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Iccosomes
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Immune complex-coated bodies. One to three days after secondary antigen challenge, the filamentous dendrites on the FDCs to which the immune complexes are bound, form into beads which break off as iccosomes. These then bind to germinal center B cells which then endocytosed and process the antigen for presentation by the B cell MHC class II, and subsequent stimulation of T helper cells to kick off the secondary response.
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Immunogenicity
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The ability to elicit antibodies when used to immunize an animal.
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Immunological memory
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Hallmark of the adaptive immune response. Adoptive transfer experiments have shown that it is a property of the small lymphocyte.
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Immunologically privileged sites
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Certain locations in the body in which antigens do not provoke reactions against themselves, such as brain, anterior chamber of the eye, and the testis. They are generally protected by strong blood-tissue barriers. High levels of immunomodulators (i.e. IL-10) endow macrophages with an immunosuppressive capacity. In general, immune responses in these areas could prove more destructive than the antigen if left alone.
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IgG
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Monomeric and the major antibody in serum and non-mucosal tissues, where it inactivates pathogens directly and through interaction with effector triggering molecules such as complement and Fc receptors. It activates the classical complement pathway.
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IgM
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Pentameric and is found in serum and is highly efficient at complement triggering (classical pathway). A monomeric form of IgM with a membrane-tethering sequence is the major antibody receptor used by B lymphocytes to recognize antigen. IgM differs from IgG in having an extra pair of constant domains instead of the hinge region
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IgA
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Exists in three soluble forms. Monomeric and small amounts of dimeric IgA (formed from two monomers linked by an extra polypeptide called J chain) are found in the serum where they can help link pathogens to effector cells via Fc receptors specific for IgA. Secretory IgA is formed of dimeric IgA and an extra protein known as secretory component and is crucial in protecting the mucosal surfaces of the body against attack by microorganisms. IgA exists as two subclasses in humans. IgA2 has a much shorter hinge than IgA1 and is more resistant to attack by bacterially secreted proteases.
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Secretory IgA
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approximately 40mg/kg of body weight is transported daily through the human intestinal crypt epithelium (compare this to a total daily IgG production of 30mg/kg). The IgA is synthesized locally by plasma cells and dimerized intracellularly together with a cystein-rich polypeptide called J chain. Dimeric IgA binds strongly to the pIgR present in the membrane of mucosal epithelial cells. The complex is then actively endocytosed, transported across the cytoplasm and secreted into the external body fluids after cleavage of the pIgR peptide chain. Secretory component is the fragment of the pIgR that remains attached to the dimeric IgA.
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IgE
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Monomeric antibody typically found at very low concentrations in serum. Most IgE is probably bound to IgE Fc receptors on mast cells. Antigen binding to IgE cross-links IgE Fc receptors and triggers an acute inflammatory reaction that can assist in immune defense. IgE, like IgM, has an extra pair of constant domains instead of the hinge region.
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IgD
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Primarily found on the surface of B cells as an antigen receptor together with IgM, where it likely serves in the control of lymphocyte activation and suppression. It is monomeric and has a large hinge region
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Idiotype
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An idiotype of an antibody consists of a set of idiotypic determinants which individually are called idiotopes. Idiotypic determinants are the unique areas in the variable region that distinguish it from most other antibodies of that species. Idiotypes are the collection of epitopes on the variable region of an immunoglobulin which are recognized by a collection of antibodies directed against them (the so-called anti-idiotypic serum).
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Invariant chain
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Has several functions: acts as a dedicated chaperone to ensure correct folding of the nascent class II molecule; an internal sequence of the luminal portion of invariant chain sits in the MHC groove to inhibit the precocious binding of peptides in the ERE before the class II molecule reaches the endocytic compartment containing antigen; combination of invariant chain with the ab class II heterodimers inactivates a retention signal and allows transport to the golgi; targeting motifs in the N-terminal cytoplasmic region of invariant chain ensure delivery of the class II-containing vesicle to the endocytic pathway.
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Isotypes
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Variants present in all healthy members of a species (e.g. antibody classes and subclasses).
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Lck
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Tyrosine kinase bound to the cytoplasmic portion of CD4. Initiates the signaling cascade that follows T cell encounter of antigen.
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Lymph nodes
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Encapsulated tissue of the lymph node contains a meshwork of reticular cells and their fibers organized into sinuses. These act as a filter for lymph draining the body tissues, and possibly bearing foreign antigens, which enters the subcapsular sinus by the afferent vessels and diffuses past the lymphocytes in the cortex to reach the macrophages of the medullary sinuses and thence the efferent lymphatics. T and B lymphocytes are largely separated into different anatomical compartments, which is accomplished by differential chemokine production.
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Mannose-binding Lectin
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Ca-dependent acute phase opsonin which can react with several sugars. It has the ability to trigger the classical C3 convertase through two novel associated serine proteases (MASP-1 and MASP-2) and is the basis of the lectin pathway of complement activation. It is a collectin. The lectin domain recognizes foreign carbohydrate patters, while the collagen domain binds to and activates phagocytic cells through complementary receptors.
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Memory
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The clonal proliferation that occurs during a primary immune response produces both effector lymphocytes and memory cells. These memory cells constitute an expanded population of specific lymphocytes which form the basis of the secondary immune response.
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Missing self recognition
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The process by which NK cells recognize cells that have lost MHC class I expression, generally due to malignance or infection.
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Pattern Recognition Receptors (PRRs)
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TLRs are included. C-type (calcium-dependent) lectins are also PRRs displayed by phagocytes. An example would be the macrophage mannose receptor. These transmembrane proteins possess multiple carbohydrate recognition domains whose engagement with their cognate microbial PAMPs generates an intracellular activation signal. Scavenger receptors are another class of phagocyte PRRs which recognize some anionic polymers and acetylated low density proteins.
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Peptidoglycan
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also known as murein, is a polymer consisting of sugars and amino acids that forms a homogeneous layer outside the plasma membrane of eubacteria. The peptidoglycan layer is substantially thicker in Gram-positive bacteria (20 to 80 nm) than in Gram-negative bacteria (7 to 8 nm), with the attachment of the S-layer.
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poly I:C
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A synthetic chemical that resembles the RNA of infectious viruses and is used to stimulate the production of interferon by the immune system.
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Recombination-activating genes
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Lymphocyte-specific enzymes essential for V(D)J recombination. The RAG complex binds the recombination signal sequences, and in association with high mobility group (HMG) proteins, the two RSS are brought together. Post-cleavage, the RAG complex remains associated with the free-DNA ends.
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Recombination signal sequence
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Noncoding sequence which flanks coding gene segments. It is make up of a conserved heptamer and nonamer sequences which are separated by an unconserved 12- or 23-nucleotide spacer.
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Respiratory burst
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The production of reactive oxygen intermediates
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Specific antibody appearance in serum
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5-7 days after initial contact with antigen.
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Somatic hypermutation
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The introduction of non-templated point mutations into V regions of rapidly proliferating B cells in the germinal centers of lymphoid follicles. Antigen-driven somatic hypermutation of variable immunoglobulin genes can result in an increase in binding affinity of the B-cell receptor for its cognate ligand.
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Spleen
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The lymphoid tissue forming the white pulp of the spleen is seen as circular or elongated gray areas within the erythrocyte-filled red pulp which consists of splenic cords lined with macrophages and venous sinusoids. T and B cell areas are segregated. The spleen is a very effected blood filter removing effete red and white cells and responding actively to blood-borne antigens, the more so if they are particulate. Plasmablasts and mature plasma cells are present in the marginal zone extending into the red pulp.
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Superantigens
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A special class of molecule which stimulate 5-20% of the total T cell population expressing the same TCR Vb family structure. These molecules do this irrespective of the antigen specificity of the receptor. An example is the pyogenic toxin superantigen family which includes S. aureus enterotoxins and streptococcoal superantigen. They are strongly mitogenic in the presence of MHC class II accessory cells. MMTV are another example. Microbes can provide B cell superantigens (ex. staphylococcal protein A).
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Surfactant
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Mostly composed of phospholipids that are essential for reducing surface tension at the air-liquid interface of the lung. Four surfactants have been identified, two of which are collectins (SP-A and SP-D). Both of these bind LPS. Sp-A can bind the P2 outer-membrane component of H. influenzae and a lipid component of Mycoplasma pneumoniae. SP-D binds lipoarabinomannan of the Edman strain of M. tuberculosis. Studies indicate that these lung collectins recognize many pathogens by using various binding motifs that are frequently targets for the collectin CRDs. Binding of collectins to receptors can induce a variety of responses that are receptor dependent. The lung collectins can enhance the uptake of particles and pathogens by opsonizing pathogens, by functioning as activation ligands, and by regulating cell-surface-receptor expression.
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Tolerance
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Specific immunological non-responsiveness.
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