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38 terms

Antibodies

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Antibodies
plasma glycoproteins produced by plasma cells in response to antigen
-bind to their specific antigens in both the recognition phace (as membrance Igs [BCR] and effectro phase (secreted )
% of total plasma protein
~20%
Half-life
-depends on the status of the oligosaccharide side chain
-when neuraminic acid is removed the (now) terminal galactose binds to a receptor on liver cells, triggering endocytosis of the Ig.
Structure of Ab's
four polypeptie chains: 2 identical light chains, and 2 identical heavy chains held together by disulfide bonds
-Each chain contsists of a variable and constant region
Light chain
-consists of one variable and one constant domain (no known effector fnx)
-two isotypes: Kappa [κ] and lamda [λ]
-a given Ig molecule will have either or, never both
Heavy chain
-consists of one variable and 3 (IgA, IgG and IgD) or 4 (Ig E and IgM) constant domains
Hing region
-Proline rich region between the Ch1 and Ch2 domains.
-Confers segmental flexibility on the Ig molecule, allowing the two antigen combining sites to simultaneously bind two epitopes separated by varying distances
-IgE and IgM do not possess
The Bifunctional Nature of Immunoglobulins
the antigen recognition functions and the effector functions are spatially separated from eachother
Isotypes (classes) and subisotypes (subclasses)
-bases on the amino acid sequence of the constant region
Hyprvariable Regions (Paratopes)
-3 sites within the VL and VH chains where the amino acid sequences are highly variable
-form the antigen binding site
-aka complementarity determining regions (CDR's 1, 2 and 3)
CDR 3
the most variable CDR, thus the most extensive contact with antigen occurs here
Affinity
refers to the strength of the binding between one Fab fragement of Ab and an epitope of an antigen
Avidity
The sum total of the strength of binding of two molecules, such as antibody and antigen
-takes into consideration binding of Fabs to all the available epidtopes
Isotopes
-Refers to the antigenic (amino acid) differences in the CL and CH regions
-variants produced are present in all healthy members of a species
Allotypes
-additional antigenic features of CL and CH regions that vary among individuals.
Idiotypes
antigenic determinants formed by the amino acids in the hypervariable regions
-each one is unique for the antibody produced by a specific clone of B cells
Fc receptors
cell surface receptors that bind the Fc portion of an antibody molecule.
-signaling receptors that are specific for antibodies of different classes
IgG
-Immunoglobin Gamma
-major Ig in serum
-major Ig produced in the 2° immune response
-found in blood, tissue spaces and extravascular spaces
-only antibody to cross the placenta in some species
Fcϒ receptors
-cell surface receptors that bind the Fc portion of IgG
-There are 3: FcϒRI, FcϒRII (A and B) and FcϒRIII
FcϒRIIB
-found on B cells
-expresses an inhibition motif
-when cross linked to the BCR it delivers inhibitory signals to the B cell, blocking B cell activation
FcϒRI (CD64)
-High affinity
-macrophages, neutrophils (low levels) and eosinophils
-fnx in phagocytosis, ADCC
FcϒRII (CD32)
-Medium affinity
-macrophages, FDC's, neutrophils, platelets, eosinophils, B cells
-fnx in phagocytosis, ADCC, feedback inhibition of B cells
FcϒRIII (CD16)
-low affinity
-NK cells, eosinophils, macrophages
-fnx in phagocytosis, ADCC
Functions of IgG
-opsonization; agglutination of particulate antigens and precipitation of soluble antigens
-neurtralization of viruses and microbial toxins
-complement activation
IgM
-Immunoglobulin Mu
-first Ig class produced both during the development of B cells and during the primary immune response
-In serum it is a pentamer
-highest avidity
-large size confines it to blood
-predominat Ig produced by the fetus
IgM functions
-because it has 10 Fabs, it is the most efficient Ig in agglutination, complement activation etc
-monomeric form is an antigen receptor on naive
b cells
-neutralization of viruses and mcrobial toxins
-Not an opsinin itself
IgA (Immunoglobulin Alpha)
- synthesis occurs mainly in mucosal lymphoid tissues, especially in the GI tract and Respiratory tract
-most abundant Ig in body
-present in two forms, serum and secretory
Serum IgA
-present mostly as a monomer
-minor component of the systemic humoral immunity
Secretory IgA
-present as a dimer plus a joining chain and secretory component
-major effector Ig ate the mucosal level
-predominant Ig in various secretions, eg, saliva, tears, milk etc
-protects mucosal surfaces by preventing the attachment of microbes and microbial toxins to mucous membranes
Secretory component of Secretory IgA
polypeptide synthesized by epithelial cells that helps transport IgA to the mucosal surface
-protects IgA from proteolytic degradation
IgE (Immunoglobulin Epsilon)
-poseesse 4 CH domains
-Fc portion binds to FcεR's on mast cells, basophils and eosinophils
-reaginic antibody
-Heat labile at 56° for 30 min
IgE functions
mediates immediate hypersensitivity (anaphylaxis) by causing release of mediators, eg histamine from mast cells and basophils upon exposure to antigen
-defense against some helminth infestations by causing release of enzymes from eosinophils onto the parasite
IgD (Immunoglobulin delta)
-only known fnx is as an antigen receptor (together with IgM) on naive B cells
-activation provokes loss from cell membran
-daughter cells do not express
-also heat-labile at 56° for 30 min
ADCC
-Antibody-Dependent Cell Mediated Cytotoxicity
-the killing of antibody-coated target cells by nonspecific cells with Fc receptors that recognize the Fc region of the bound Ab
-Most is mediated by NK cells that have CD16 on their surface
-Macrophages and neutrophils express FcϒRs and kill target cells via IgG mediated
-Eosinophils express FcεRs and kill helminth parasites via IgE mediated
Monoclonal antibodies
-antibodies that arise from a single clone of cells, are homogenous and are directed at only one epitope
Hybridoma
-a cell that is formed by the fusion of a B cell and a myeloma cell
-wil grow in cell culture and maintain the ability to produce antibodies
Papain
-cleaves IgG above the S-S bond at the hinge region
-produces two FAB's and one Fc
Pepsin
-cleaves IgG below the S-S bond at the hinge region
-produces two FAB's still attached at the hinge region
-FC is decgraded