Immunology 4 - Antibodies Flashcards
What is an antibody?
- An antibody is a protein that is produced in response to a foreign molecule (antigen), and has the property of binding specifically to that antigen
- Antibodies form the class of proteins known as immunoglobulins, and are a large family of soluble glycoproteins
What are the secondary effector functions of antibodies following antigen binding?
- Complement activation
- Opsonisation (promotion of phagocytosis)
- Cell activation via specific antibody-binding receptors (Fc receptors)
Explain with the aid of a diagram the structure of immunoglobulin molecules.
- Intramolecular disulfide bridges, 2 Intermolecular disulfide bridges
- 2 short chains and 2 long chains + hinge region
- Fab has antigen binding activity, Fc is a constant region recognised by phagocytes
How does the structure of antibodies link to their function?
- Hinge region allows binding to widely spaced as well as closely spaced cell surface determinants
- Light and heavy chains split into variable regions and constant regions -variable regions bind to antigens
What are the forces involved in antibody/antigen binding?
- Hydrogen bonds
- Ionic bonds
- Hydrophobic interactions
- Van der Waals interactions
- Ionic bonds
Define antibody affinity
The strength of the total noncovalent interactions between a single antigen binding site and a single epitope on the antigen
Define antibody avidity
The overall strength of multiple interactions between an antibody with multiple binding sites and a complex antigen with multiple epitopes, a better measure of binding capacity.
What is antibody cross-reactivity?
- Antibody elicited in response to one antigen can sometimes recognise a different antigen of similar structure
- Eg. Cowpox vaccination also works for smallpox
List the classes of antibodies
IgG, IgA, IgM, IgE, IgD
Describe the structure and function of the IgG antibody.
- Most abundant immunoglobulin
- Occurs as a monomer with 4 subclasses (variability mainly located in hinge region and effector function domains)
- Actively transported across the placenta
- Found in blood and extracellular fluids
- Major activator of classical complement pathway (mainly IgG1 and IgG3)
Draw the structure of IgG
Simple antibody structure
Describe the structure and function of IgA antibodies.
- Second most abundant immunoglobulin
- Occurs as a monomer (blood) and as a dimer (secretions)
- Major secretory immunoglobulin
- Protects mucosal surfaces from bacteria, viruses and protozoa
Draw the structure of the secretory IgA
Dimer joined at constant/Fc region by a J chain
Describe the structure and function of IgM antibody
- Large pentameric molecule of 5 monomers joined by J chain (10 x Fab)
- Mainly confined to blood (80%)
- First Ig synthesised after exposure to antigen
- Primary antibody response
- Multiple binding sites compensate for low affinity
- Efficient at agglutination
- Activates complement system
Describe the structure and function of the IgD antibody.
- Extremely low serum concentrations
- Surface IgD expressed early in B cell development
- Involved in B cell development and activation
Describe the structure and function of IgE
- Present at extremely low levels
- Produced in response to parasitic infections and in allergic diseases
- Binds to high affinity Fc receptors of mast cells and basophils
- Cross-linking by antigen triggers mast cell activation and histamine release
Summarise the selective Ig distribution
- IgG & IgM in blood
- IgG in extracellular fluid
- Dimeric IgA in secretions across epithelia, including breast milk
- Maternal IgG in foetus via placental transfer
- IgE with mast cells below epithelia
What are the consequences of antibodies binding to the antigen?
- Neutralisation
- Agglutination
- Opsonisation
- Complement activation
- Bound by cells expressing Fc receptors (predominantly cells of innate immunity: phagocytes, NK cells)
What other roles, apart from host defence, are there for antibodies?
- Used in medicine in diagnosis (monoclonal antibodies), monitoring, therapy and in cancer treatment.
- Used in the lab with diagnostic and research applications
Why must the antigen and antibody be very similar in shape?
The non-covalent bonds can only form close together, so there must be a close complementarity.
How do different classes of antibody differ?
In their constant region
