4 Antibodies - specificity and function Flashcards
antigen origin name
from antibody generator
epitope
Many antibodies may bind the same antigen, each a separate site termed an antigenic determinant or epitope – antibodies recognise epitopes
what epitopes do antigens show
can also show repeated epitopes
what structure are antigens
can be diverse molecular structures
two effector cell types
B lymphocytes
T lymphocytes
B lymphocytes (B cells)
- make antibodies (immunoglobulins) - cell surface and secreted
- can improve the antibodies made over time
- protection against extracellular pathogens & toxins
T lymphocytes (T cells)
- express T cell receptors (TCR)
- interact with other cells
- can kill cells, or facilitate immune responses by other cells
- Killer T cells (CD8+), Helper T cells and regulatory T cells (CD4+)
variable region
antigen-binding site
constant region
binds to cellular receptors – effector function
heavy chains have a hinge region in middle that gives a flexibility to the antibody
adaptive immune system
It changes over time!
immunoglobins examples
Serum glycoproteins also found in tissue fluids
B lymphocytes
antibodies
B lymphocytes
> surface antigen receptor (B cell receptor; BCR)
> associates with other cell surface proteins
Plasma cells produce
secretory immunoglobulin (antibody)
antibody classes
five classes of antibody: IgG, IgA, IgM, IgD & IgE
what is the first antibody line of defence
IgM
bonds in antiobodies
disulphide
what enzymes can be used in enzymatic cleavage
papain
pepsin
what happens if us papain enzyme for cleavage
- 2x Fab, (Fragment- antigen binding)
- Fc (Fragment-crystallizable)
what happens if use pepsin enzyme for cleavage
- Fab(2), bivalent binding
- Fc fragments
why is an antibody bifunctional
- antigen binding
- ability to trigger effector functions
what light chains could be in a B cell
any one b cell will only use either kappa or lambda chain
constant region of a light chain
CL
variable region of a light chain
VL
variable domain of a heavy chain
CH1, CH2, CH3, sometimes CH4
constant domain of a heavy chain
VH
antibody flexibility
Hinge regions
hinge of IgG subclasses is what makes them differ
Serum concentrations and half-life of IgG1
High concentration for IgG1 in serum
Half-life varies in subtypes – IgG1 usually longest
Serum concentrations and half-life of IgG3
IgG3 not found in serum is found in the skin = low concentration in serum
what makes up the domain structure of antibodies
- Variable (V)
- Constant (C)
what is the complementarity determining region
Peptide loops (hypervariable regions) are involved in interactions with antigen Hypervariable regions (loops) interact with antigen
how many complementarity determining regions does the heavy and light chains have each
3 CDRs each
what forms a paratope
Combination of H+L CDRs produces the unique antibody combining site
where is a paratope
within the antibody
what holds the antigen into place
non-covalent interactions of the paratope with the antigenic epitope
Size of antigens and area of interaction varies
Small, can fit into the antibody
Lay across the antibody
Globular, antibody can open up slightly and sit on it
Conformational specificity of an antibody
an antibody may recognise a specific 3D conformation of protein
primary sequence recognised by antibodies
linear epitope
secondary sequence recognised by antibodies
constrained secondary structure epitope (e.g. a loop or turn)
tertiary structure recognised by antibodies
discontinuous epitope (tertiary structure epitope) Tertiary structure gives the epitope
affinity
strength of a single antibody (Fab)/antigen bond
avidity
- Binding of a multivalent antibody to a multivalent antigen
- Avidity is likely to be the physiologically relevant affinity (functional affinity)
effect of bivalent antibody
equilibrium constant higher, functional ability increased as avidity higher
Fab binding
affinity
IgG bindings
affinity or functional avidity
IgM binding
affinity and avidity
how do antibody isotopes differ
hinge regions
IgM antibody structure
form a pentameric structure – using a joining chain protein and disulphide bonds – how circulates in body
why has IgM got a higher molecular weight
circulating as a pentamer
IgA antibody structure
dimer in the body
isotope physical differences
- CH1-CH2 hinge length
- Interchain disulphide bond location and number
- Number of CH domains
- Variable glycosylation
- Multimer capability
what is a multimeric immunoglobin
When antibodies come together some can become relatively large
Tissue distribution of IgG isotopes
IgG in most places
Tissue distribution of IgM isotopes
IgM when secreted mainly in peripheral blood
Tissue distribution of IgA isotopes
Dimeric IgA in mucosa – upper respiratory tract and gut
Tissue distribution of IgE isotopes
IgE mainly in skin, as allergic reactions take place here e.g. basophils and mast cells
Tissue distribution of IgD isotopes
IgD expressed in upper respiratory tract, possibly more important than IgA
Effects of pathogen specific antibodies
- Neutralize toxins
- Block virus binding and entering cells
- Opsonise pathogens
- Activate complement
where are Antibody receptors present
Fc receptors present on phagocytic cells
Antibody function
Different classes have different functions
antibody capabilities
> Neutralisation
Complement activation
Opsonization cytotoxicity
what occurs at IgG
location of effector function sites
