5 - antibody structure and function Flashcards
humoral immunity
involves soluble substances
mediated by macromolecules in extracellular fluid
e..g secreted antibodies, complement proteins, antimicrobial peptides
antibody defn
host protein produced in response to the presence of foreign molecules in the body
antibodies produced by
plasma cells
lymphoid lineage
B cell effector cells
antibodies
antibody-antigen complex
antibodies bind to Fc regions of antigens and opsonise the cells
linus pauling 1940s importance
interested in antibody polypeptide structure and its ability to recognise antigens
proposed one immunoprotein that changed its conformation
clonal selection for self tolerance
B cells producing antibodies against self antigens are tested and deleted
clonal expansion
B cells producing correct specific antibody for the target antigen is activated and multiplied
B cells after infection is over
become memory cells and wait in lymphatics
antibodies are
glycoproteins
shared functional properties of antibodies
all bind to both antigens and immune cells
shared structural properties of antibodies
all have Y shaped unit
where do antibodies bind to on an antigen
epitope
epitope
amino acid sequence on a polypeptide coat protein
paratope
antigen-binding region of antibody
where do antigens bind to on an antibody
paratope
features of antibody antigen binding
reversible
non-covalent
antibodies can change places for a better fit
CDR
complementarity determining region
describe structure of an antibody
4 polypeptide chains
held together by disulphide bridges and non-covalent bonds
importance of hinge region of antibody
enables contortion allowing binding
importance of CDRs
hypervariability regions
porter (1959) and Edelman (1961)
worked on structure of IgG used enzymes to break up antibody (papain cleavage and pepsin cleavage) 3 fractions (Fab) showed that there were 4 polypeptides
classes of immunoglobulin
IgG IgM IgA IgE IgD
how are classes of immunoglobulin distinguished
by their number of y-units
by their type of heavy chain polypeptide
how many types of light chain polypeptide are there
2
no of light chains =
no of heavy chains
subclasses of IgG
IgG1
IgG2
IgG3
IgG4
valency of 2
2 potential binding sites to target antigen
IgM
first response
low affinity binding
(hypermutation of B cell receptor causes class to switch to IgG)
pentameric –> 5 Y units
IgG
secondary response
principal antibody –> high serum concentration
heavy chain = gamma
IgA
protects mucous membranes
secreted in breast milk and other secretions (tears, mucous, saliva)
heavy chain = alpha
IgE
protects against parasites and allergies
Fc receptors on mast cells, basophils, eosinophils
J chain
holds 5 Y components to make pentameric IgM
M cells
relay info to DCs
subclasses of IgG
IgG1
IgG2
IgG3
IgG4
valency of 2
2 potential binding sites to target antigen
IgM
first response
low affinity binding
(hypermutation of B cell receptor causes class to switch to IgG)
pentameric –> 5 Y units
IgG
secondary response
principal antibody –> high serum concentration
IgA
protects mucous membranes
IgE
protects against parasites
J chain
holds 5 Y components to make pentameric IgM
M cells
relay info to DCs
transcytosis
movement of antibody across the epithelium into the lumen side of the gut
movement stimulated by docking of antibody to polymeric Ig receptor (with secretory component) on epithelial cell
describe release of IgA after transcytosis into gut
protease cleaves the Ig receptor near the membrane
IgA - secretory component - polymeric Ig receptor complex
role of secretory component
protects and anchors antibody complex at desired location
so phagocytic cell can bin to the Fc receptor and destroy
Fc receptor
found on immune cells
binds to Fc component of antibodies that are attached to pathogenic cells
binding triggers phagocytosis
ITAM
immunoreceptor tyrosin-based activation motif
important signalling molecule
lectin activation pathway of complement
recognition and binding of carbohydrates by collectins
e.g. ficolin or mannose-binding lectin is a collecting that binds to mannose on the surface of a pathogen
C4 and C2 components are cleaved
C2a and C4b bind to form classical C3 convertase on pathogen cell membrane
classical activation of complement
triggered by antibody binding to antigen or pentraxins
antibody-antigen complex forms
series of proteins form C3 convertase
cleaves C3 protein
C3b binds to C3 convertase to form C5 convertase
cleaves C5 protein
cleaved products attract phagocytes to site of infection
assembly of membrane attack complex
conformational change
‘fluid-phase’ C3 convertase forms
cleaves multiple C3 proteins into C3a and C3b
CMC
complement mediated cytotoxicity
ADCC
antibody attracts to cytotoxic cells via Fc receptors
target cell antigens become bound to lots of antibodies
effector immune cell lyses target cell
Complement mediated cytotoxicity
antibody binding results in fixation of complement onto target cell
results in membrane attack complex and cell lysis
complement system
formed by soluble/humoral components of serum
3 activation pathways
effects of complement (4)
triggers inflammatory response
attracts phagocytes
degrades membranes
stimulates antibody production
3 activation pathways
lectin
classical
alternative
lectin activation pathway of complement
recognition and binding of carbohydrates by collectins
e.g. mannose-binding lectin is a collecting that binds to mannose on the surface of a pathogen
C4 and C2 components are cleaved
they bind to form classical C3 convertase on pathogen cell membrane
alternative activation of complement
occurs directly at microbial cell surfaces
triggered when C3b protein binds to a microbe
conformational change 'fluid-phase' C3 convertase forms cleaves multiple C3 proteins into C3a and C3b C5 convertase forms all pathways follow the same
ficolin
collectin that binds to N-acetylglucosamine
MASP
mannose-binding lectin associates serine protease
MAC
membrane attack complex
terminal complement complex that ruptures wall of pathogen
3 types of Fc receptor
Fc- gamma
Fc-alpha
Fc- epsilon
