Immunology Chapter 4

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antigenic but incapable by themselves of inducing a specific immune response

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haptens

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infiltration of cells at the site of the adjuvant injection often results in formation of a dense, macrophage-rich mass of cells called a ...

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granuloma

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on naive proteins
generally are composed of hydrophilic amino acids on the protein surface that are topographically accessible to membrane-bound or free antibody

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B-cell epitopes

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epitope type with contiguous amino acids

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sequential

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epitope type with residues far apart in the primary amino acid sequence but close together in the tertiary structure of the molecule
such epitopes are only present when the protein is in its native conformation

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nonsequential
conformational determinants

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tend to be located in flexible regions of an immunogen and often display site mobility

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B-cell epitopes

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polypeptides in antibodies of about 22,000 Da

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light (L) chains

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polypeptides in antibodies of about 55,000 Da

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heavy (H) chains

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highly variable first 110 or so amino acids of the amino-terminal region of a light or heavy chain

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V region

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constitute the antigen binding site of the antibody molecule
most of differences among antibodies fall within these areas of the V regions

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complementarity-determining regions (CDRs)

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two fragments of IgG in which were identical (45,000 each) and had antigen-binding activity

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Fab fragments

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other fragment of IgG w/o antigen-binding activity
found to crystallize during cold storage

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Fc fragment (fragment, crystallizable)

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this fragment consists of a portion of heavy plus an intact light chain

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Fab fragment

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this fragment consists of only heavy-chain components

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Fc fragment

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cancer of antibody-producing plasma cells

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multiple myeloma

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two types of light chains in humans

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kappa and lambda
kappa -- 60%
lambda -- 40%

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variability definition (equation)

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number of different amino acids at a given position
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frequency of the most common amino acid at a given position

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V domains which exhibit comparitively less variation

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framework regions (FRs)

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3 regions in light and heavy chains (in V domain) which display maximum variation
loops that join the beta strands

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complementarity-determining regions (CDRs)
hypervariable regions

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this antibody region is rich in proline residues and is flexible, giving IgG, IgD, and IgA segmental flexibility
two Fab arms can assume various angles to each other when antigen is bound

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hinge region

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sIg

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secreted immunoglobulin

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mIg

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membrane-bound immunoglobulin

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protein molecules that can bind the constant region of Ig molecules, are present on the surfaces of macrophages and neutrophils as well as other cells not involved in phagocytosis

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Fc receptors (FcR)

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important byproduct of the complement activation pathway
protein fragment which binds nonspecifically to cell- and antigen-antibody complexes near the site which complement was activated
red blood cells and macrophages have receptors for this

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C3b

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in this process the antibody acts as a newly acquired receptor enabling the attacking cell to recognize and kill the target cell
linking w/ Fc receptors of numerous cell types, but particularly NK cells

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antibody-dependent cell-mediated cytotoxicity

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movement of immunoglobulin across epithelial layers

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transcytosis

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acquisition of immunity by receipt of preformed antibodies rather than by active production of antibodies after exposure to antigen

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passive immunization

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most abundant immunoglobulin class in serum
consists of two gamma heavy chains
four subclasses

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IgG

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distinguished by different germ-line heavy-chain constant regions
structural characteristics that distinguish these from each other are the size of the hinge region and the number and position of the interchain disulfide bonds between the heavy chains

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four IgG subclasses

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activates classical complement pathway

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IgG1, IgG2, IgG3, IgM

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crosses placenta

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IgG1, IgG2, IgG3, IgG4

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present on membrane of mature B cells

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IgM, IgD

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binds to Fc receptors of phagocytes

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IgG1, IgG2, IgG3, IgG4

possibly IgM

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antibodies that undergo mucosal transport

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IgA1, IgA2, IgM

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antibodies that induce mast cell degranulation

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IgE

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accounts to 5-10% of total serum immunoglobulin
expressed as membrane-bound antibody on B cells
secreted by plasma cells as a pentamer
first immunoglobulin class produced in a primary response to an antigen
more efficient than IgG in activating complement, creating agglutination
does not diffuse well, found in very low concentrations in the intercellular fluids
accessory role as a secretory immunoglobulin

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IgM

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10-15% of total serum immunoglobulin
predominant immunoglobulin class in external secretions such as breast milk, saliva, tears, and mucus of the bronchial, genitourinary, and digestive tracts

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IgA

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facilitates polymerization of immunoglobulins

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J-chain

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expressed on the basolateral surface of most mucosal epithelia and on glandular epithelia in the mammary, salivary, and lacrimal glands
receptor for polymeric immunoglobulin molecules

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poly-Ig receptor

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potent biological activity despite extremely low average serum concentration
mediate the immediate hypersensitivity reactions that are responsible for the symptoms of hay fever, asthma, hives, and anaphylactic shock
binds to Fc receptors on membranes of blood basophils and tissue mast cells

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IgE

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serum from allergic person intradermally injected into a nonallergic individual
appropriate antigen later injected at same site, swelling and reddening developed there
basis for first biological assay for IgE activity

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P-K reaction

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first discovered by a when a patient developed a multiple myeloma whose myeloma protein failed to react w/ the then-known isotypes
serum constitution of .2%
w/ IgM, this is the major membrane-bound immunoglobulin expressed by mature B cells
no biological effector function has been identified

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IgD

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constant-region determinants that collectively define each heavy-chain class and subclass and each light-chain type and subtype w/in a species

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isotype

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encode subtle amino acid differences
occur in some, but not all, members of a species

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allotype

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each individual antigenic determinant of the variable region

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idiotope

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sum of the individual idiotopes

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idiotype

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a transmembrane protein complex composed of mIg and disulfide-linked heterodimers called Ig-alpha/Ig-beta.

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B-cell receptor (BCR)

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responsible for the movement of antibodies across cell membranes and the transfer of IgG from mother to fetus

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Fc receptors (FcR)

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all members contain at least one or more stretches of about 110 amino acids, capable of arrangement into pleated sheets of antiparallel beta strands, usually with an invariant intrachain disulfide bond that closes a loop spanning 50 to 70 residues

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immunoglobulin superfamily

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created by fusing a normal activated, antibody-producing B cell with a myeloma cell (cancerous plasma cell)
possesses immortal-growth properties of myeloma cell and secreted the antibody produced by the B cell

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hybridoma