Antibody interaction with antigen Flashcards
What does the Ab recognise?
Conformational antigens composed of several sequentially discontinuous segments brought together by folding of the molecule
What is the epitope?
The part of the antigen which is recognized by the antibody
What is the paratope?
The complimentary part of the antibody
What is each V region made of?
3 hypervariable regions
What are complimentary determining regions?
6 hypervariable regions of light and heavy chains
Describe the hypervariable region
CDR loops interact with antigen
Poke out of the beta sheets of Ig domain
How does the binding happen?
Neither the antibody nor the antigen is changed by binding
One antibody binding site binds to one epitope on the antigen
The binding is non-covalent and is reversible
What bonds are involved in the binding?
Non-covalent interaction due to Ionic bonds
H-bonds
Hydrophobic bonds
Van der Waals forces
Lots of small forces add up to a strong interaction.
All critically dependent on the distance apart
What forces are present in antibody-antigen binding?
Electrostatic
Hydrogen bonds
Hydrophobic bonds
Van der Waals
What is the strength of interaction?
Each force acts over short distance that can be measured (affinity)
What is meant by avidity?
Avidity = total binding strength
Different from affinity (binding strength at a single binding site)
Avidity functionally more important than affinity
What else is required for antibody production?
Additional signals from the B cell once BCR is ligated and IgAlpha and IgBeta signal is sent
How do T cells contribute to Ab production?
Cytokine production
What does neutralisation of viruses depend on?
type of virus, target cell and class of Ab
What is the importance of antibodies in neutralisation?
May be important in limiting viral infectivity - bind to a virus to block infection
Vaccine efficacy often assessed by measuring circulating, neutralising Abs
Why is neutralisation important?
May inhibit virus-cell interaction
Prevent endocytosis of virus
Prevent uncoating inside endosome
What makes neutralisation more effective?
Complement
How are toxins neutralised?
Abs bind bacterial exotoxins: neutralise their effect by preventing attachment to cellular receptors (e.g. binding of cholera toxin to ganglioside GM1)
What antibodies are important in neutralisation?
IgG and IgA
What receptor mediates toxin clearance?
Fc-receptor
What is opsonisation?
The coating (binding) of particles by either Ab,
complement or APP (eg CRP)
Ab bind microorganisms via the Fab and to cells
by the Fc
What does opsonisation do?
Increases the efficiency of the
phagocytic process, allowing the organism to be
cleared more effectively
What is complement?
The complement system is a collection of circulating membrane-associated proteins
Important in defence against microbes
What are the pathways of complement?
Classical and alternate pathways
What are the functions of complement?
Chemotaxis
Opsonisation
Lysis of target cells
Priming of adaptive immune response
How do antibodies interact with cells?
Via Fc receptors
What do Fc receptors associate with?
G-chain
How does activation of Fc receptors occur?
Due to aggregation of receptors and signalling via Immunoreceptor Tyrosine-
based Activation or Inhibition Motifs
What does Fc receptor activation cause?
ADCC (antibody-dependent cellular cytotoxicity)
Phagocytosis
Apoptosis
Mediator release
Can enhance antigen presentation
What does CD64 bind?
Monomeric IgG1 and IgG3 with high affinity and IgG4 with low affinity
No binding to IgG2
Where is CD64 expressed?
On mononuclear phagocytes
What is CD64 involved in?
Phagocytosis of immune complexes and mediator release
What is the structure of CD64?
3 extracellular Ig domains
Associated with gamma chain ITAM
Describe CD32
2 types = FcgRIIa and FcgRIIb
Describe FcgRIIa
Wide cellular distribution
Moderate affinity for monomeric IgG1 and IgG3.
High affinity for complexed IgG
Has ITAM
Describe FcgRIIb
Same specificity for Ig but has ITIM
How is the antibody response inhibited?
Secreted antibody forms complex with antigen
Antigen-antibody complex binds to B cell Ig and Fc receptor
Block in B cell receptor signalling due to ITIM -ve signal
Inhibition of B cell response
Describe CD16
Has FcgRIIIa and FcgRIIIb
Describe FcgRIIIa
Transmembrane molecule with moderate affinity for monomeric IgG
Associated with g-, b-, z- h- chains of the CD3 complex as ITAMs
Expressed on monocytes, macrophages, NK cells and some T cells
ADCC
Describe FcgRIIIb
GPI (glycophosphatidilelinositol) linked with low affinity for monomeric IgG
Expressed on neutrophils and basophils
Activates by lipid raft formation and associates
Describe CD89
Associated with g-chain
Expressed on myeloid cells
Can trigger phagocytosis, cell lysis and the release of inflammatory mediators
Binds both IgA1 and IgA2
Describe Fc-epsilon-RI
Very high affinity receptor for IgE
Associates with g-chains and b-chain (abg2
receptor unit)
Expressed on mast cells and basophils.
Receptors always saturated (low serum IgE)
X-linking of these Ab molecules bound to FceRI
leads to mediator release e.g histamine
Describe CD23
Low affinity receptor for IgE
Expressed on leukocytes and lymphocytes.
Not a member of the Ig-Superfamily, similar to C-type lectins (eg mannose binding lectin)
Where is CD23a expressed?
B cells and involved in IgE production
Where is CD23b expressed?
Many cell types and induced by IL-4
