Antibodies Flashcards
Antibodies classes, structure, and diversity
What is the definition of antibodies?
Glycoproteins found in serum and tissues that are produced in large amounts after contact with immunogenic foreign molecules
What part of immunity are antibodies involved in?
Humoural
How many antibody classes are there? State them.
5 subclasses.
IgG, IgA, IgM, IgE, and IgD
What is an alternate name for the Fab fragments combined?
Variable region
Alternate name for Fc fragment/region
Constant region
At what amino acid positions are the three hypervariable regions?
30, 50, and 90.
What localised regions form the antigen binding site?
Framework regions and hypervariable sequences
‘Antibody affinity’ refers to the interaction of:
A single antigenic determinant
Single Ab combining site
Product of the summation of forces
3 main functions of the Fc region
Bind to Fc receptors on effector cells
Activate complement cascade
Regulate secretion so antibodies can widely distribute
Complement cascade
Series of reactions that occurs on the surface of pathogens and generates active components with various effector functions
Predominant Ab of primary immune response
IgM
Affinity & avidity of IgM
+ why?
Low affinity because they are produced before B cells have undergone somatic hypermutation, but pentameric molecule so a large no. of binding sites and therefore high avidity
Distribution of IgM
Limited to circulation due to large size
First antibody produced and why
IgM because it can produces w/o class switching
IgM heavy chain type
“mu”
IgG heavy chain type
gamma
Most abundant Ab in serum
IgG (70-75%)
How many subclasses of IgG are there and how do they differ?
4 subclasses.
Differ in structure of the hinge region.
IgG is:
a. Dimeric
b. A pentamer
c. Monomeric
d. A Hexamer
c. Monomeric
Distribution of IgG
Extravascular (can cross into tissues easily)
Widespread distribution
Ig1, 3, and 4 can cross placenta for foetal immunity
Opsonisation process
Fab binds to pathogen
Fc binds to phagocytic cells
Speeds up phagocytosis
How many IgA subclasses are there?
2
Type of heavy chain for IgA
alpha
Where is IgA predominant?
Secretions like saliva and colostrum (first breast milk received by neonate)
Generally places w/o cells
Secretory IgA is specialised for
Transport to areas w/o antibody-producing B cells
How does IgA reach areas that don’t have B cells?
When a B cell cannot pass it secretes dimeric IgA
IgA uses secretory component polypeptide to bind to polymeric immunoglobulin receptor
It can then be transported across to neutralise pathogenic toxins
IgD heavy chain type
delta
Signal transduction
Process by which a cell responds to substances outside the cell through signalling molecules on surface and inside the cell
Function of IgD
Acts in signal transduction to stimulate B cell proliferation
Where is IgD found?
The surface of circulating B lymphocytes
Lowest serum level Ab
IgE
What type (like genre) of cells does IgE interact with?
Granulocytes
IgE and inflammation
Stimulates release of granules, which are pro-inflammatory agent by binding to Fc receptor on granulocytes.
Associated w allergy.
How do antibodies help fight infection? (4 things)
Antigen binding stimulates B cell activation
Antibodies neutralise key receptors or pathogen products
Block adhesion receptors
Enhance Fc-mediated phagocytosis
Antibodies and NK cells
Antibody binds to pathogen antigens
Fc receptors on NK cells recognise bound antibody and cross-link -> sends signals
Target cell dies by apoptosis
Resting vs activated mast cells
Resting mast cell has granules that contain histamine and other inflammatory mediators
Activated -> Multivalent antigen cross links bound IgE antibody, causing release of granule contents
Base postulates of clonal selection hypothesis
Each lymphocyte bears a single type of receptor w unique specificity
Binding w pathogen activates lymphocyte
Differentiated effector cells from activated lymphocyte bear parental cell receptor
Lymphocytes bearing receptors specific for ubiquitous self molecules are deleted at early stage of lymphoid development and are therefore absent from repertoire of mature lymphocytes
Somatic recombination (Ab)
Rearrangement of genetic material that encodes Ab heavy or light chains
Antigen-independent process that occurs in bone marrow
Another name for somatic recombination is
V(D)J recombination
How is rearrangement controlled?
Enzymes (recombinase activating genes expressed only during the process)
DNA sequences (RSS)
Junctional diversity
Cutting is imprecise when the segments are joined together, giving loss or gain of some nucleotides - P nucleotides
N-region addition
template independent random addition catalysed by terminal deoxy transferase - heavy chain only
RNA splicing
enables generation of IgM and IgD with specificity for same antigen