Antibodies Flashcards
What is an antibody?
Protein produced in response to antigen
What is the immunoglobulin superfamily?
Many proteins express similiar domains structurally
What secondary function does it initiate?
- complement activation
- Opsonisation
- cell activation via Fc receptors (bind to FC part of antibody)
What is the structure of an antibody?
- Light and heavy chains divided into variable and constant
- Each domain has an internal inter and intra chain disulphide bonds - immunoglobulin domains
- Fc part change conformation when antigen bound and can perform effector functions e.g activating complement
- Constant region have barrel shaped beta sheet held together by highly conserved internal disulphide bonds
- Forces are non covalent
- Different antibody classes differ in constant regions of their heavy chains
- All classes use lambda light chain (one per antibody because is symmetrical)
Hinge region: flexible allowing antibody binding
- Can be wide apart of closely spaced together
What are complementarity determining regions?
- 3 hypervariable regions determines specificities
- Located at loops at protein end and interact with antigen
- approximately flat surface with undulations
Define antibody affinity?
- strength of total non covalent interactions between single anitgen binding site and single domain
Define antibody avidity?
overall strength of multiple interactions between antibody with multiple binding sites
What is the relationship between binding sites and avidity?
- more sites means more avidity
- Large number of interactions over small distances
- NO covalent bonds so individually weak need lots of them
Define antibody cross reactivity
- Antibodies produces in response to 1 antigen can cross react and bind to different antigen of similar structure
Difference between isotopes and allotypes?
Isotopes: present in everyone, different in the constant region
the kappa and lambda light chains, the different heavy chains, the immunoglobulin classes and sub-classes)
Allotypes: polymorphic variables, some have then others don’t, can spread anywhere within constant region
How antibodies kill virus?
- Binds to virus: prevents attachment to cell
- Opsonization. Virus coated in antibody and more easily phagocytosed
- Complement: mediated lysis of membrane bound virus
- Antibody dependent cell mediated cytotoxicity (ADCC): mediated by NK like cell viral membrane proteins in membrane coated with antibody
- Bound by cells expressing Fc receptors (innate immunity , phagocytes, NK)
IgM:
- Mainly in blood
- 1st one produced after antigen exposure
- Big pentamer
- Low affinity but high avidity
- Efficient at agglutination, activated complement, primary response
- Held together by disulphide bonds
- subclasses have different F.C. receptors
IgG:
- gammy heavy chain
- 4 Subclasses vary mainly in hinge region and effector function
- Major activator in classical complement pathway
- Some have disulphide bonds
- Subclasses have different effector function -one is more abundant than others
- Differ in ability to activate complement
- 75% of serum IG, monomeric antibody
- cross placenta to give newborn immunity
- Long half life in serum
- Blood and ECF
IgA
- alpha heavy chain
- Dimer (Y structure joijed together by disulphide bonds and joining chain)
- Second most abundant
- Blood form mononer
- Mucosal surfaces dimer
- Protects mucosal surfaces
- Joined by J chain
How does IgA from below the epithelial layer enter the lumen?
- IgA produced in plasma cell
- Binds to poly-Ig-receptor on basolateral membrane
- Triggers endocytosis
- Poly Ig receptor cleaved leaving secretory component attached to dimer IgA
IgD
IgD: delta heavy chain
- Low serum concentration
- Surface IgD expressed in B cell development
- Involved in B cell development and activation
- Involved in membrane bound form on B lymphocyte signaling
Selective Ig distribution:
Blood: IgG and IgM ECF: IgG Secretion across epithelia: dimeric IgA Foetus: IgG Mast cells below epithelia: IgE
IgE
- e heavy chain
- Very Low blood concentration
- Produced in response to parasitic infections and allergic diseases
- Bind to high affinity Fc receptors of basophils and mast cells
- Cross linking by antigen triggers mast cell activation and histamine release
- involved in allergic responses
- Binds to basophils and mast cells to trigger histamine release
What are the subclasses of IgG
IgG1 (70% of total IgG),
IgG2 (20%)
IgG3 (7%)
IgG4 (3%).
IgG1 and 3 are more active than IgG2 and 4. Antibodies to bacterial carbohydrates are often IgG2.
