Immunology Chapter 4

heteroconjugates ‐

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humanized antibody ‐

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Isotypes

1. An antibody class, which is determined by the constant‐region sequence of the heavy chain. The five human isotypes, designated IgA, IgD, IgE, IgG, and IgM, exhibit structural and functional differences. Also refers to the set of isotypic determinants that is carried by all members of a species. 2. One of the five major kinds of heavy chains in antibody molecules (α, γ, δ, ε, and μ)

IgA

10‐15% of immunoglobulin in serum; predominant class in external excretions (breast milk, saliva, tears, and mucus of bronchial , genitourinary, and digestive tracts)

aminopterin

4‐amino analog of folic acid; an antineoplastic drug with immunosuppressive properties used in chemotherapy

IgM

5‐10% of the total serum; expressed as membrane bound antibodies on B cells

myeloma cell

A cancerous plasma cell

heterokaryon

A cell with two separate nuclei formed by the experimental fusion of two genetically different cells.

ADCC (antibody‐dependent cell‐mediated cytotoxicity)

A cell‐mediated reaction in which nonspecific cytotoxic cells that express Fc receptors recognize bound antibody on a target cell and subsequently cause lysis of the target cell

hybridoma

A clone of hybrid cells formed by fusion of normal lymphocytes with myeloma cells; it retains the properties of the normal cell to produce antibodies or T‐cell receptors but exhibits the immortal growth characteristic of myeloma cells. Hybridomas are used to produce monoclonal activity

Fc fragment

A crystallizable, non‐antigen‐binding fragment of an immunoglobulin molecule that consists of the carboxy‐terminal portions of both heavy chains and possesses binding sites for FC receptors and the C1q component of complement. It is obtained by brief papain digestion

mIg (Membrane Bound Immunoglobulin)

A form of antibody that is bound to a cell as a transmembrane protein. It acts as the antigen‐specific receptor of B cells

secretory component

A fragment of the poly‐Ig receptor that remains bound to Ig after transcytosis across an epithelium and cleavage

immunoglobulin superfamily

A group of proteins that contain immunoglobulin‐fold domains, or structurally related domains; it includes immunoglobulins, T‐cell receptors, MHC molecules, and numerous other membrane molecules

Polyclonal

A mixture of antibodies produced by a variety of B-cell clones that have recognized the same antigen. Although all of the antibodies react with the immunizing antigen, they differ from each other in the amino acid sequence

Plasmacytomas

A plasma cell cancer

multiple myeloma

A plasma‐cell cancer

J chain (joining chain)

A polypeptide that links the heavy chains of monomeric units of polymeric IgM and di‐or trimeric IgA. The linkage is by disulfide bonds between the J chain and the carboxy‐terminal cysteines of IgM or IgA heavy chains

framework regions (FR)

A relatively conserved sequence of amino acids located on either side of the hypervariable regions in the variable domains of immunoglobulin heavy and light chains

Idiotypic

A single antigenic determinant in the variable domains of an antibody or T‐cell receptor; also called idiotypic determinant. Idiotopes are generated by the unique amino acid sequence for each antigen.

Chimera

An animal or tissue composed of elements derived from genetically distinct individuals. The SCID‐human mouse is a chimera. Also, a chimeric antibody that contains the amino acid sequence of one species in one region and the sequence of a different species in another (for example, an antibody with a human constant region and a mouse variable region)

Allotypic

An antigenic determinant that varies among members of a species. The constant regions of antibodies possess allotypic determinants

Isotypic

An antigenic determinant within the immunoglobulin constant regions that is characteristic of a species

structure

Antibodies consist of 2 light and 2 heavy chains held together with disulfide bonds

Domains

Binding regions of an antibody

immunoglobulin fold

Characteristic structure in immunoglobulins that consists of a domain of 100 to 110 amino acids folded into two β‐pleated sheets, each containing three or four antiparallel β strands and stabilized by an intrachain disulfide bond

Papain

Cleaves near the amino end above the disulfide bond; creates 3 molecules

B‐cell receptor

Complex comprising a membrane‐bound immunoglobulin molecule and two associated signal‐transducing Iga/Igb molecules

Opsonization

Deposition of opsonins on an antigen, thereby promoting a stable adhesive contact with an appropriate phagocytic cell

Tiselius and Kabat

Did an experiment to see where the antibodies were in serum. Found that the antibodies were contained in the gamma‐globulin

Serum

Fluid portion of the blood which is free of cells and clotting factors

Immunotoxins

Highly cytotoxic agents produced by conjugating an antibody with a highly toxic agent, usually a protein such as ricin

monoclonal antibody

Homogeneous preparation of antibody molecules, produced by a single clone of B cell lineage, often a hybridoma, all of which have the same antigenic specificity

complement activation

IgG can activate the complement system

SCID‐human mice

Immunodeficient mouse into which elements of a human immune system such as bone marrow and thymic fragments have been grafted. Such mice support the differentiation of pluripotent human hematopoietic stem cells into mature immunocytes and so are valuable for studies on lymphocyte development

light (L) chains

Immunoglobulin polypeptides of the lambda or kappa type that join with heavy‐chain polypeptides to form the antibody heterodimer

Valency

Numerical measure of combining capacity, generally equal to the number of binding sites. Antibody molecules are bivalent or multivalent. Whereas T‐cell receptors are univalent

Immunoglobulins

Protein family with antibody activity

Passive immunization

The acquisition of immunity conferred by the transfer of immune products. Such as antibody or sensitized T cells, from an immune individual to a non‐immune one

Agglutination

The aggregation of clumping of particles

Plasma

The cell-free fluid portion of the blood which contains all the clotting factors

Heterogeneous

The epitopes are not all the same on a given antigen

sIg (Secreted Immunoglobulin)

The form of antibody that is secreted by cells of the B lineage, especially plasma cells. This form of Ig lacks a transmembrane domain

hinge region

The segment on an immunoglobulin heavy chain between the Fc and Fab regions. It gives flexibility to the molecule and allows the two antigen‐binding sites to function independently

F(ab')2

Two Fab units linked by disulfide bridges between fragments of the heavy chain. They are obtained by digestion of antibody with pepsin

Fab fragments

a monovalent antigen‐binding fragment of an immunoglobulin molecule that consists of one light chain and part of one heavy chain, linked by an interchain disulfide bond. It is obtained by brief papain digestion

salvage pathway

a pathway in which nucleotides are synthesized from intermediates in the degradative pathway for nucleotides

HAT media (hypoxanthine‐aminopterin‐thymidine)

a selection medium for mammalian cell culture

IgD

about 0.2% of the total immunoglobulin in serum; with IgM are expressed in mature B cells

MADGE

acronym for the 5 different isotypes of the heavy chain sequences (Mu, Alpha, Delta, Gamma, Epsilon)

Secondary structure

alpha helix and beta pleated sheets add to the protein

Primary Structure

amino acid structure

variable region

amino‐terminal portions of immunoglobulin and T‐cell receptor chains that are highly variable and responsible for the antigenic specificity of these molecules

conformational changes

changes in the conformation (shape) of the molecule

Subtypes

classification of differences in light chain antibodies

Pepsin

cleaves near the carboxylic group end above the disulfide bond

MOPC (mineral oil induction of plasmacytoma cells)

clones of malignant plasma cells

tertiary structure

complex folding creates a 3D molecule

myeloma protein

denotes the source of antibodies with patients with multiple myeloma

Edelman experiment

discovered the chemical structure of antibodies; noticed that antibodies were not one continuous chain

Porter experiment

discovered the chemical structure of antibodies; split an immunoglobulin obtaining an active fragment

immunoglobulin classes

distinguished by unique amino acid sequences in the heavy‐chain constant region that confer class‐specific structural and functional properties

carboxy‐terminal

end with a free carboxy group. When the protein is translated from messenger RNA, it is created from N‐terminus to C‐terminus.

Bence‐Jones protein

excess amount of light chains first discovered in the urine of myeloma patients

IgG

gamma heavy chain class of antibodies

beta‐globulin

globular protein in plasma

alpha‐globulin

globular protein in plasma. Inhibit certain protease and inhibitor activity

Ig‐a/Ig‐B

heterodimer on the B‐cell receptor

IgE

low average serum composition; mediates the immediate hypersensitivity reactions. Responsible for symptoms like hay fever, asthma, hives, and anaphylactic shock

affinity labeling

method for tagging molecules that allow them to be studied

quaternary structure

more than one peptide chain link together

IgG

most abundant class in serum (80%); consists of 2 heavy λ chains and 2 κ or 2 λ light chains

Lambda

one of the two types of light chains

kappa

one of the two types of light chains.

hypervariable region

one of three regions within the variable domain of each chain in immunoglobulins and T‐cell receptors that exhibits the most sequence variability and contributes the most to the antigen‐binding site; also called complementarity‐determining region

complementarity‐determining region (CDR)

portions of the variable regions of antibody molecules that protrude from the V domains and have the potential to contact antigens. The antigen‐binding sites of antibody molecules are composed of CDR's.

Albumin

protein in serum encoded by the ALB gene. Most abundant plasma protein

Mercaptoethanol

reducing agent that breaks the disulfide bonds heavy (H) chains - The larger polypeptide of an antibody molecule; it is composed of one variable domain VH and three or four constant domains (CH1, CH2, CH3, ect.). There are five major classes of heavy chains in humans (α,γ, δ, ε, and μ), which determine the isotype of an antibody

antigenic determinants on Igs

specific for one antigen

constant region domains

take part in the various biological functions determined by the amino acid sequence of each domain

gamma‐globulin

the electrophoretic fraction of serum that contains most of the immunoglobulin classes

constant region

the nearly invariant portion of the immunoglobulin molecule that does not contain antigen‐binding domains. The sequence of amino acids in the constant region determines the isotype (α, γ, δ, ε, and μ) of heavy chains and the type (κ and λ) of light chains

contact areas

where the antibody comes into contact with the antigen