Immunoglobulin Effector Function Flashcards
What Ig class to B cells initially make?
What does class switching do?
All B cells begin by making IgM.
Memory cells produce IgG, IgA or IgE with same antigen specificity.
Retain same variable domains (same antigen binding specificity).
Change constant part.
How are antibody classes distributed in the body?
IgM, IgG, and monomeric IgA protect the internal tissues of the body-predominate in blood.
IgG and monomeric IgA- major isotypes in extracellular fluid.
Dimeric IgA protects the mucosal surfaces of the body- predominates in secretions.
IgE provides a mechanism for the rapid ejection of pathogens from the body- found mainly in connective tissue beneath skin, respiratory and GI tracts.
Brain devoid of Igs- too large to cross blood brain barrier.
In fluid and tissue- no IgM- larger, can’t diffuse into tissues.
Dimeric IgA is secretory.
Which antibody classes are passed from mother to child, before and after birth?
Before: During pregnancy, IgG from maternal circulation is transported across the placenta.
Delivered directly into foetal circulation.
Mother passes any IgG response she has to baby- baby will already have this protection when it is born.
At birth, human babies have as high a level of blood IgG as mothers.
This IgG has wide range of antigen specificities.
Helps protect baby until it makes its own Abs.
After: After birth, GI tract of baby is protected by dimeric IgA in breast milk, especially in colostrum (first milk) – example of passive transfer of Ig (i.e. of preformed Ab).
What happens to infant Ab levels in the first year of life?
In first year of life infants have transient decrease in IgG levels.
Although infants produce IgM soon after birth, IgG production does not begin for ~6 months.
IgA in breast milk can help protect during period of lower IgG levels.
At birth, IgG is the main antibody class in babies. As it decreaes, and baby makes its own Abs, IgM becomes the dominant class.
What do high affinity neutralising antibodies do?
Prevent viruses infecting host.
Comparison of vaccinated with non-vaccinated individuals.
Vaccinated:
Adult with anti-influenza virus IgA antibodies.
Dimeric IgA (in respiratory tract) blocks viral interaction.
Virus can’t infect cells. Adult remains healthy.
Non-vaccinated:
Adult without anti-influenza virus antibodies.
Haemagglutinin on viral surface binds to sialic acid on cell surface. Internalization into endosome.
Fusion of viral lipid envelope with endosome membrane.
Release of viral RNA into cytoplasm.
Virus infects cells and replicates.
Adult gets severely sick for two weeks.
Antibodies can protect by simply binding to pathogens- neutralisation.
How do neutralising antibodies prevent bacterial infections eg. at mucosal surfaces? Use an example.
One child has had previous exposure to ‘strep throat’ caused by S. pyogenes but another has not.
Abs coat bacteria and prevent them from attaching to fibronectin in extracellular matrix.
Child with antibodies:
Antibodies prevent attachment of bacteria to the tissue- most bacteria are swept into the gut.
bacterial population is limited and kept at a steady state- child remains healthy.
Child without antibodies:
Bacteria stay in the pharynx and multiply.
Bacterial population expands out of control and damages its environment- child suffers a sore throat.
Will be IgA playing the main role here because of mucosal secretion.
How are microbial toxins neutralised?
Bacterial toxins often cause disease by disrupting normal cell function.
IgG and IgA are efficient at binding to soluble toxins preventing them from binding to cell surface receptors = Neutralizing antibodies.
Binding to toxins that pathogens produce.
Cells poisoned if toxins bind to cell receptor rather than antibody.
Toxin binds to cellular receptors.
Endocytosis of receptor:toxin complex.
Dissociation of toxin to release active chain which poisons cell.
Antibody protects cell by blocking binding of toxin.
Binding to toxin will have a strong effect in preventing disease.
What are the dual functions of antibodies?
Recognition function- Binding to antigen mediated by Fab arms.
Effector function- Clearance mechanisms mediated by interaction of Fc region with effector molecules. (Fc receptors and complement).
What is IgG?
Most abundant Ig in plasma (10 mg/ml). Four subclasses - IgG1, IgG2, IgG3, IgG4. Only Ig class to cross placenta. Predominant antibody of secondary response.
4 Ig genes that make the different kinds.
Difference in sequences in constant regions.
Differ significantly in hinge regions.
Crosses placenta by interacting with particular Fc receptors.
IgG1 and IgG4 have similar hinge regions.
IgG2 has a slightly longer hinge region.
IgG3 has a very long hinge region.
Differ in effector function capabilities.
The four subclasses of IgG have different and complementary functions
What does human IgG4 do?
Undergo Fab arm exchange.
In circulation IgG4 molecules become functionally monovalent.
4 can split in half.
Not just Fab arms that exchange- whole arm can.
No formation of disulphide bridges in hinge- arms dissociate and reassociate with another half of a different IgG molecule.
Each half may recognise a different antigen.
Similar things seen in animals too.
Antibodies are flexible molceules due to hinge.
Why does the IgG molecule need to be flexible?
The flexibility of the IgG molecule is crucial for its function for binding simultaneously to pathogens and effector molecules and receptors of the immune system.
Parts of the molecule can move freely, relative to one another.
Important for antibody function- allow is to bind to adjacent molecules that may be a varying locations.
What is IgM?
Present only in plasma and secretions - too large to enter tissues.
Pentamer- Made of five monomer units joined by J (joining) chain and disulphide bridges. μ chain has extra domain in place of hinge.
Has 10 binding sites for antigen - very good at agglutinating particles e.g. viruses.
Predominant antibody of primary response.
What does IgM binding do?
Binding of IgM to antigen on a pathogen’s surface activates complement
by the classical pathway.
Adopts planar structure normally.
Adopts staple structure when bound to antigen.
Biding sites for C1q would fit perfectly with size of c1q molecules.
How is the classical complement pathway activated by IgG?
IgG molecules bind to antigens on the bacterial surfaces.
C1q binds to at least two IgG molecules.
Need at least two antibodies for head parts of C1q to engage before activation of classical pathway.
How well can each IgG class activate complement?
IgG1- very well.
IgG2- weak activation.
IgG3- very well.
IgG4- no activation.
