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63 Cards in this Set
- Front
- Back
molecules that interact specifically with antigen-specific immune response molecules via antigenic determinants.
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antigens
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antibodies, B cell receptors (BCRs), T cell receptors (TCRs) or Antigen-presenting cell receptors (ACRs)
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Ag-specific immune response molecules
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the portions of antigen molecules that physically interact with paratopes of immune response molecules and therefore actually "determine" antigen specificity
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antigenic determinants (epitopes)
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combining sites
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paratopes
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Linear epitopes
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continuous and found in polysacchs as well as in both native (nondenatured) and denatured proteins, especially fibrillar proteins
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typical size is 5-6 subunits in length
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linear epitopes
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specificity depends upon primary sequence
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linear epitopes
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specificity depends upon conformation, or three-dimensional shape, which is a combination of tertiary and quaternary structure ... supported by primary and secondary structure, of course
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conformational epitopes
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typical size is hard to pinpoint, but sequences of up to 16 amino acids in certain protein antigens have been shown to interact with their complementary paratope
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conformational epitopes
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discontinuous (involve multiple subunits, often located far apart in the primary sequence of the antigen molecule) and are thus found only in native (globular) proteins
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conformational epitopes
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have antigenic determinants, but cannot induce immune responses because they lack one or more of the important attributes needed for this function
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incomplete antigens
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incomplete antigen; artificial monovalent epitope
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hapten
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complete antigens which are able to interact with specific immune response molecules,and can also induce immune responses
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immunogens
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determined by foreigness, molecular size, composition and chemical complexity, & processing and presentation susceptibility
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immunogenicity
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Why molecular size is important
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larger molecules are more complex and therefor more like to contain foreign epitopes and are also more like to be readily engulfed and processed.
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must be processed and presented to trigger T cell responses
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protein immunogens
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must be reduced greatly by the immune system if immune responses are to occur
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Ag Molecule Concentration
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generally the most potent immunogens
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proteins
(potency) |
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immunogen potency
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proteins first, polysacchs and distant second, nucleic acids generally not immunogenic unless attached to a protein or polysacch.
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The more chemically complex an immunogen is...
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the more likely it is to have numerous foreign epitopes, and the smaller it can be and still induce an immune response
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requires its processing and presentation by APCs
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T cell recognition of antigen
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Often necessary to prevent tolerance, in which development of an immune response is prevented, sometimes due to the presence of too many immunogen molecules
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Removal of excess Antigen
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form complexes with fragments of immunogen molecules in responsive animals, but not in non-responsive animals
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ACR's and immune responses
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controls immune responsiveness by determining the structure of ACRs present on immune cells
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genotype & immune response
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may cause a lack of responsiveness referred to as tolerance because they "swamp-out" the immune system
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high immunogen dosage
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generally the best immune response inducers
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intermediate doses of immunogen
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may not induce immune responses because they:
constitute too few molecules to adequately stimulate enough cells to yield an immune response ... or induce tolerance |
low immunogen dosage
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Routes of immunogen administration
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Parenteral & Non-parenteral (enteric = ingestion)
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parenteral admin: stimulate immune cells in the spleen first
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Intravenous (iv) and intraperitoneal (ip) injections
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pareteral admin: stimulate immune cells in the lymph node that "drains" the site of injection first
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Intradermal (id), subcutaneous (cs) and intramuscular (im) injections
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Preferred route for intestinal parasite immunogens & Frequently induces B cell tolerance rather than an immune response
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Non-parenteral administration
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Function by causing one or more of these effects:
Prolonged persistence of immunogen molecules at the site of injection, Enhancement of co-stimulatory signals, Induction of granuloma formation, Stimulation of lymphocyte proliferation in a non-specific manner |
Adjuvants
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immune response enhancers
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Adjuvants
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Developed the methods leading to the three-dimensional structure of Abs
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Poljak ( 1970s, 1980s)
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This required a sequence of studies and x-ray crystallography to develop
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3-D structure of Abs
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Quaternary aggregates of globular protein domains
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Antibodies
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Antibodies are arranged so that ____ are accesible to antigenic determinants and the ____ can bind to complement and/or ____ receptors on phagocytic cells
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a) Fabs
b) Fc c) Fc |
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Ab domains are comprised of ...
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three dimensionally folded polypeptide structures
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These are universal in antibodies and other immuno-relevant structures
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domains
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This is comprised of the N-terminal domains of Fab
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Fv (fragment variable)
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The antibody combining sites are loated near the N-terminal regions of the heavy and lght chains that make this up
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Fv (fragment variable)
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Certain AA's in these sites make up the floor and sides of a shallow groove (or slight projection) on the surface of them that actually interact with antigenic determinants
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Fv (fragment variable)
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This is responsible for determining the structure, and thus assuring the specificity, of Fv
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Immunoglobulin fold
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Comprised of ~110 amino acids and are arranged in antiparallel sets of beta-pleated sheets.
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Immunoglobulin fold
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in the Ig fold, loops that connect the beta-pleated sheets contain amino acids that comprise these
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Hypervariable regions (HVRs) or complementarity-determining regions (CDRs) of Abs
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Interaction of CDR amino acids with antigenic determinant constituents occurs via
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multiple noncovalent interactions
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multiple noncovalent interactions include
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hydrogen bonding
electrostatic interactions van der waal's forces hydrophobic interactions |
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These determine the specificity and affinity (strength of binding) of Ab combining sites
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CDRs
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these are the result of the unique arrangements of AAs that make up Ab combining sites
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idiotypic determinants
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Biological activities
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IgG and IgM complement binding
IgG and IgE FcR binding IgG transplacental transport IgA transport through mucous membrane epithelial cells |
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These are associated with structures in the Fc portion of Ab molecules
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Biological activities
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Due to mutation-induced changes in a restricted number of AAs, mostly in the constant portions of heavy and light chains
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allotypic differences
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Genetic basis of Ab combining site diversity
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many gene segments or fragments
gene segments are rearranged during B cell maturation |
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Present in the 5' and 3' ends of each intron, these separate the gene fragments and allow rearrangement to occur in an orderly manner
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recognition signal sequences (RSSs)
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two types of RSS
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heptamer...12(or 23) bp spacer...nonamer
nonamer...12(or 23) bp spacer...heptamer |
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hybridize with one another, forming the recognition signal for RAG 1 and RAG2
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RSS
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RAG1 and RAG2
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Recombination-activation genes; responsible for the actual rearrangement process
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the cut out unused intervening sequences of DNA
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RAG 1 and RAG2
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splice seleted DNA sequences to form AB V region transcriptional units
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RAG 1 and RAG2
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Ab V region transcriptional units
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V-J (light chain)
V-D-J (heavy chain) |
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These two events activate antibody genes:
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generation of a novel V region gene
and strengthening the V region promoter |
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How to generate the novel V region gene
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by combination of one of many V region gene segments w/one of several J gene segments or one of several D and one of several J gene segments (heavy)
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Strengthens by moving closer to the enhancer found 3' to the J ene segments on the chromosome
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the V region promoter
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