Week 17: (C) Immunoglobulins Flashcards
Where is IgA found?
major antibody where?
seromucous secretions
e.g. saliva, milk, colostrum, gut, tracheobronchial system & genito-urinary system
When is IgA encountered?
first encountered by many invading pathogens.
2most prevalent antibody in serum after IgG
What is the most abundant antibody?
IgA
found in serums
What are the 2 sub-classes of IgA?
1 and 2
What 2 forms can IgA have?
monomeric and dimeric forms
What structure is IgA in serum?
monomeric
How much is IgA1 and IgA2 in monomeric form?
90% IgA1
10% IgA2
What structure is IgA in secretions?
mostly dimeric
What percents of IgA1 and IgA2 are in secretions?
40% IgA1
60% IgA2
What additional component is in the secretory IgA?
additional polypeptide (secretory component). derived from receptor mediating sport to the secretions. Carries IgA into the secretions
What is the secretory component?
Additional polypeptide in the secretory IgA.
Carries IgA into secretions
What does the secretory component protect IgA from?
harsh environment
extremes of pH and proteolytic enzymes present.
Are IgA’s N-linked?
GLYCOSYLATED, decorated with N-liked oligosaccharides.
What additional oligosaccharides does IgA1 have?
O-linked sugars, attached thing region
What are O-linked oligosaccharides attached to?
Ser or Thr residues
Where is secretory IgA produced?
locally at the mucosal surfaces
What structure is secretory IgA?
dimeric
What holds the SIgA together?
- J-chain (middle the tails)
- Secretory component CH2 through the J-chain to the other CH2 of other chain
how many globular domains does the secretory component have?
5
Where is the secretory component derived from?
receptor that carried the dimeric IgA out into the secretions
IgA has 4 ABS, what is this called?
polyvalent
What can IgA be described as?
antiseptic paint. Agglutinates pathogens.
Pathogens prevented from crossing the epithelium and rushed from body
How many heavy chain globular domains does IgE have?
5
How many heavy chain globular domains does IgA have?
4
Does IgE have a lotto oligosaccharides attached?
YES
What response is ice associated with?
allergic response
protection in parasitic infections
What immunoglobulin done know the least about?
IgD
What concentration is IgD in serum
Low conc
Where is IgD found?
surface lymphocytes
What is the function of IgD?
unclear, may be involved control of antibody response
OR// mucosal immune system
How do antibodies block virus from binding to and invading host cell?
1) block binding receptors on virus–> block fusion event
2) agglutination–>multiple ab and viruses clumped together
How do antibodies block entry of pathogens into host cells?(bacterial)
antibodies block colonisation
Also agglutinate
What do bacterial pathogens bind to?
colonise on cell surface via bacterial adhesions
What is the action of town poisoning a cell?
1) toxin binds to receptor
2) endocytosis of toxin- receptor complexes
3) Dissociation of toxin to release the active chain, poisoning cell
How do antibodies block the binding of toxin?
bind to toxin and block
Neutralisation
What antibodies are efficient in binding soluble toxins?
IgG & IgA
What are antibodies called that prevent a toxin binding to cell surface receptors?
neutralising antibodies
It’s not only the recognition site on the Fab region that is associated with protective function, but what does the Fc region do?
effector function
interact with effector molecules
What 3 pathways can result in complement activation?
classical, lectin & alternative
What complement pathways can be activated directly via pathogen?
lectin & alternative
What compliment pathway does IgM and IgG need to recognise pathway before activation?
Classical
What activation any of the 3 compliment pathways lead to?
C3 convertase enzymatic activity.
cleavage of C3 —>c3b+C3a
What can C3b initiate?
1) feedback to alternative pathway
2) opsonisation
3) C5–>C5b+C5a …
C6-C9 … membrane stack process (punch hole into membrane) = LYSIS
What conformational change does IgM undergo when binding to antigenic surface?
planar to staple confo
When IgM is in stable confo, what can recognise and bind to it?
C1q
How many IgG molecules are bound to antigenic surface?
6
What conformation does the IgG make when bound to antigen cell surface?
cluster together
Fab arms facing the outside
Fc create a platform in the middle
What does the C1q recognise in the IgG?
the Fc platform
What stops inappropriate activations of the C1q complement to IgG?
need a cluster of 6, individual IgGs cannot activate
What does activation of C1q activate?
C1r –> cleaves and activates C1s.
further steps trigger lysis of target cell
What are the 2 types of effector molecules can interact with the Fc region?
C1q & fc receptors (specific to different types Igs)
How can Fc receptor- mediated pathways cause clearance of pathogen?
1) free Ig bind to Fc receptors but don’t cross-link (no neighbouring Fc R activated). macrophage not activated.
2) Specific IgG recognise antigenic determinants on a bacterial cell, closely associated together.
Engagement of neighbouring Fc receptors = cross-linked on surface of the cell —> signal passed into cell, phagocytose
What is a bacterial cell coated with in bacterial opsonisation?
specific IgG
C3b
In bacterial opsonisation what receptors recognise C3b and IgG?
C3b = CR1 IgG = Fc receptors
What happens after binding of C3b and IgG to their receptors?
internalised into a vesicle, dude with lysosome, lysosome contents release. lysis of cell.
What is the Fc receptor present inmost cells called?
Fc (epsilon) R1 receptor
When does the IgE bind to the Fc(epsilon) receptor?
allergic responses
(innocuous antigen)
cross-linked–> release inflammatory responses e.g histamine
