MB - Immunoglobulins Flashcards
What are immunoglobulins (Ig)?
Immunoglobulins (Ig) are proteins produced by B lymphocytes
as part of the humoral immune response to non-self molecules
2 forms:
- B cell membrane receptor
- Secreted form (antibody) – 20% of blood protein
What are 4 characteristics of Igs?
- Stable and durable structure
- High affinity, high specificity binding sites for a nsm
- Cross-linking ability→aggregate nsm (agglutinate cells)
- Signal nsm presence to immune system cells/complement
Describe the structure of Igs
Overall Y-shaped structure, with binding sites at the end of each arm.
Describe the secondary and quarternary structure of Igs
Secondary and supersecondary structure
- β strand rich
- β strands are arranged into immunoglobulin domains
- Heavy chain - 4 Ig domains
~450aa - Light chain - 2 Ig domains
~220aa
Quaternary structure
Tetramer (150kDa)
- 2 Heavy chains (50kDa)
- 2 Light chains (25kDa)
→H2L2
Disulphide bridges join H and L chains
Describe the Ig fold domain structure
Consists of a small beta barrel of 7 or 8 anti-parallel beta strands with a disulphide bridge connecting a 4 sheet to a 3 sheet
What are the different classes of Igs
Ig have several different classes (A,D,E,G,M) with differing
structure, role, and numbers of Ig domains
- Different heavy chains determine the class
Light chains come in two types:
- κ and λ (kappa and lambda) – found in all classes
What are some characterisitcs about the IgA class? (7)
- In intestinal tract, saliva, sweat, tears, colostrum and milk
- Offers newborn defence against gastrointestinal infections
- Binds to pathogens and blocks their attachment to epithelial surfaces
- 0.9 - 4 mg / ml
- Monomer, dimer or trimer
- Disulphide bridges + J(oining) chain
- Subtypes A1 and A2
How does IgA move across the epithelial lining
Transcytosis moves IgA across the epithelial lining for secretion outside the body
IgA coating to mucous membranes acts as a protective barrier against pathogens
What are some characterisitcs about the IgD class? (6)
- Function in serum is not clear
- 0.003 - 0.4 mg / ml
- Acts as cell-surface receptor on B lymphocytes
- Mr = 175kDa (more CHO)
- Only one disulphide bridge between H chains
Absent or diminished in some mammals:
- (✔️) Primates, mice, rats, dogs
- (✖️) Swine, sheep, cattle, cats
What are some characterisitcs about the IgE class? (6)
- Found in minute quantities in serum
- Involved in response to parasites and in the allergic response (binds mast cells)
- 0.0001 - 0.001 mg / ml
- Mr = 200kDa
- 5 Ig domains
What are some characterisitcs about the IgG class? (7)
- Gamma globulin
- Major class of Ig in serum (75%)
- Also found in interstitial fluid
- Crosses placenta via receptor mediated endocytosis in weeks 18-20
- 6 - 18 mg/ml
- Mr = 150kDa
- Several sub-types (G1-G4) differing in number and position of disulphide bridges
What are some characterisitcs about the IgM class? (6)
- Found in serum
- First Ig to be raised
- 0.5 - 1.9mg/ml.
- Pentamer - 5 Ig joined by disulphide bridges and a J chain.
- Mr = 950kDa
- 5 Ig domains
What fragments are found in Igs? (3)
Papain digestion
3 fragments:
- 2x Fab (50kDa)
- 1x Fc (50kDa)
Fab = Antigen Binding
Fc = Crystal
What did Pepsin digestion do?
Split Fc into many small fragments leaving 1x (Fab)2 (100kDa)
What are the function of these fragments (3)
- Fab fragments can bind antigen
- (Fab)2 fragments can bind antigen and cross-link nsm
- Fc fragments can’t bind antigen, but can bind and activate immune cells and complement (class dependent)
