Term
|
Definition
Ab are built from 2 H chains, 2 L chains
2 types of L: lambda, kappa
5 types of H: mu, gamma, delta, alpha, epsilon
-give rise to: IgM, IgG, IgD, IgA, IgE
The H & L chains are held together by disulfide bonds & noncovalent interactions |
|
|
Term
| the immunoglobulin domains |
|
Definition
Ig domain consists of 110 AA, 2 cysteine residues which form intrachain disulfide bond
N domain of H & L chains are the "variable" domains, others are "constant"
each L chain has 1 VL and 1 CL
each H chain has 1 VH, CH1, CH2, CH3 |
|
|
Term
Fab and Fc fragments
Proteolytic cleavage:
-papain
-pepsin |
|
Definition
Fab: Two fragments of IgG, contain Ag-binding activity
Fc: readily crystallizable
papain: cleaves IgG -> 2 Fab, Fc
pepsin: IgG -> F(ab')2, several other fragments, largest called pFc' |
|
|
Term
|
Definition
Segment of 10-15 AA residues b/t CH1 & CH2
rich in cys & pro residues, allows segmental flexibility so that Ab can bind repetitive antigens simultaneously
found in alpha, gamma, delta chains but absent in mu and epsilon chains |
|
|
Term
| CDRs (Complementarity Determining Regions) |
|
Definition
Hypervariable regions
Wu and Kabat plot: 3 distinct hypervariable regions (HV1, HV2, HV3) are found in the variable domains
CDRs: hypervariable residues form the antigen binding site, interact with Ag on the basis of structural complementarity
-CDR1, CDR2, CDR3
-most variable part is in the HV3 (CDR3) region
flanked by less variable regions: framework regions
-FR1, FR2, FR3, FR4 |
|
|
Term
| Compare and contrast the effector functions of major isotypes of immunoglobulins |
|
Definition
IgG
-75% of Ig
-IgG1 (70%): neutralization. opsonization, sensitization for killing by NK cells, complement activation
-IgG2 (20%): neutralization
-IgG3 (8%): neutralization, complement activation, opsonization, NK sensitization
-IgG4 (4%): neutralization
-can cross placenta (passive immunity to newborn)
-*Erythroblastosis fetalis*: hemolytic disease of the newborn, caused by IgG ab (anti-Rh), cross placenta & destroy fetal RBC (mom is Rh-, fetus is Rh+)
IgM
-the first Ab produced in a humoral immune response
-complement activation
-a pentamer, has 10 active antigen binding sites
-each contains a joining piece (J), disulfide-linked to molecule
-activates complement
IgA
-mucosal secretions, colostrum
-IgA1, IgA2
-neutralization
-monomeric & dimeric forms (dimeric has the J chain)
-secretory IgA is bound with "secretory piece" (derived from poly-Ig receptor on epithelial cells), protects dimeric IgA from proteolytic cleavage
IgD
-low serum conc (<1%)
-found on surface of B cells
-fn not well characterized
IgE
-lowest conc in serum
-allergic reactions
-mast cell sensitization
-binds to R on mast cells & basophils, release mediators (eg histamines) upon binding of antigens |
|
|
Term
| Production of monoclonal antibody |
|
Definition
used as treatment (rituximab, herceptin, elotzumab)
B cells are immunized with antigen + myeloma cells -> fusion -> grow, only hybrid cells live -> select for Ag-specific hybridoma -> clone selected hybridoma cells |
|
|
Term
| Describe the generation of diversity in immunoglobulins |
|
Definition
combinatorial diversity: random combo of VJ (L chain) & VDJ (H chain) segments
junctional diversity: intro of additional nucleotides (P & N) at junctions b/t gene segments during recombination
-recombination of V,J,D is imprecise
-i/c by endonuclease cleavage of DNA loops at break point, creates P-nucleotides
-N-nucleotides are added at break point by Tdt
Combinatorial association of H & L chains
somatic hypermutation
-introduces point mutations into the V regions of L & H chains
-occurs after VJ or VDJ joining, cont throughout life of B cell (thus more observed in IgG than IgM)
-B cells that express somatic variants with i/c affinity for antigen are preferentially stimulated to mature into AFC: affinity maturation |
|
|
Term
| Define Immunoglobulin Class switching |
|
Definition
mature B cells express both IgM & IgD at cell surface
-mu and delta mRNAs are made by differential splicing of hnRNA
upon stimulation by antigen, B cells proliferate, cont to differentiate
VDJ joined by another C gene, B cell may switch from expressing IgG to any other isotype (isotype switching)
involves recombination b/t switch regions and the DNA b/t the switch regions are deleted |
|
|
Term
|
Definition
Serum glycoproteins - i/c when exposed to antigen or immunogen
expressed on B cells as BCR
secreted by AFC or plasma cells
All are bifunctional
-Fab binds antigen
-Fc involved in effector function |
|
|
Term
|
Definition
reversible, non-covalent
electrostatic forces, hydrogen bonds, Van der Waals forces, hydrophobic forces
do not involve covalent bonds |
|
|
