Humoral immunity Flashcards
(47 cards)
what are the antigen-dependent responses of B cells?
occurs in secondary lymphoid tissue:
- activated by antigen divide and differentiate into plasma cells secreting soluble antibody.
- Affinity maturation and class switching may also occur via AID gene
Soluble antibodies mediate humoral immunity
what are the antigen-independent responses of B cells?
occurs in bone marrow
- Antibody genes undergo rearrangement; “naïve” B cells expressing membrane IgM +/- IgD are generated
how are immunoglobulins classified?
- by their different constant region amino acid sequence of their heavy chains
- Antibodies of different classes act in distinct location and have distinct effector functions
what is the structure of IgG?
- monomeric, m.wt 150kDa
- long hinge region, carbohydrate helps antibody be soluble
- 2 carbohydrates linked to CH2 domains to keep them apart
when is IgG most prevalent?
in secondary/memory responses
what is the difference between the primary and secondary immune response?
First time we encounter antigen, we make low amounts of IgM and IgG – primary response
Second time we encounter antigen, we make some IgM and lots of IgG – secondary/memory response
why is IgM important in primary immune responses?
IgM antibodies usually low affinity but high avidity so can bind lots of antigen at once
other classes tend to be higher affinity and bind more tightly and specifically to antigen (due to somatic hypermutation and affinity maturation)
what facilitates the transition from primary to secondary immune response?
Facilitated by class/isotype switching:
- IgM –> IgG, IgA or IgE
- T cell help (cytokines) and AID required
what are the subclasses of IgG? how are they classified?
subclasses: IgG1 (most common), IgG2, IgG3, IgG4 (least common)
- differ mainly in length and number of disulphides of hinge region
- differ in sequence in constant region of heavy chain, in the hinge region
-IgG1 and IgG3 are the most active and have the longest hinge region
what are the main functions of IgG?
- can activate complement
- binds Fc receptors on phagocytes and NK cells
- crosses placenta (binds FcRn on trophoblast) – occurs in third trimester, so premature babies do not have this protection
- long serum half-life (20-24 days) – useful for the memory response and newborns
why are IgG1 and IgG3 the more active IgG subclasses?
IgG1 and IgG3 are more active due to their amino acid composition, and that their long hinge region separates the functions of the antibody – separates Fc from Fab arms – good for innate interaction
what is FcRn?
The neonatal receptor for IgG:
- Present on trophoblast, permitting transfer of maternal IgG antibodies
- protects foetus and newborn
- also present on neonatal gut – IgG can be transferred through breast milk
FcRn is also present in adults in gut, liver and endothelial cells – binds and recycles IgG, preventing excretion (improves half-life) – prevents breakdown of IgG by sequestering it
what is the structure of IgM?
- pentamer (5 antibody subunits + J chain holds together)
- m.wt. 970,000 d, so usually serum-restricted
- no defined hinge region – has an extra pair of domains instead
- ‘functional hinge’ – some flexibility
what are the key properties of IgM?
- low affinity, but high AVIDITY (can bind up to 10 antigens)
- high valency (deca-/pentavalent) = good agglutinator of particulate antigen
what are the functions of IgM?
- can activate complement very efficiently – most potent complement activator
- important in primary antibody responses
what is the structure of IgA?
- monomer when in serum, dimer in secretions e.g. milk, tears, saliva
- secretions and at mucosal surfaces: secretory IgA = IgA dimer + J chain + secretory component wrapped around Fc regions
- Secretory component protects IgA from proteolysis
what are the subclasses of IgA?
subclasses: IgA1 and IgA2 (primates) – differ in hinge region
- evolved to deal with proteases
- IgA1 is resistant to bacterial proteases, while IgA2 is resistant to self-proteases
what are the functions of IgA?
- high valency when in secretions (bind 4 antigens at once)
- rapid catabolism – broken down quickly
- does not activate complement
- monomer, but not secretory IgA, binds Fc receptors on phagocytes
how is IgA moved from lymphoid tissue to secretions?
Specialised transport mechanism
- plasma cells in submucosa make IgA, and this must be transported to lumen
what is the process of the specialised transport mechanism of IgA?
Poly-Ig receptor – IgA binds to this for transport
- binds polymeric IgA/IgM
- member of immunoglobulin gene superfamily
IgA is internalised into a vesicle, and traverses the cell to be released on the other side – transcytosis
- During this process, IgA is cleaved to form its secretory form
- Transport system allows secretion of IgA (and IgM) into lumen
*- bacteria that penetrate mucosa can be transported back to lumen
how much IgA does mucosal lymphoid tissue produce? why?
produces 5g IgA per day because:
- IgA has high valency – good for agglutination
- Secretory component can interact with bacteria non-specifically
-IgA has a passive role in preventing adhesion/infection of pathogens - IgA coats pathogens and prevents them adhering to cells – immune exclusion
which immunoglobulin is important for immune exclusion?
IgA = coats pathogens to prevent them from adhering to cells
what is the structure of IgD?
- monomeric, m.wt 184,000
- extended hinge is glycosylated – flexible molecule so can bind antigen at different distances apart
- present as antigen receptor on many B lymphocytes, together with IgM
what is known about IgD?
- <1% serum Ig
- present as antigen receptor on many B lymphocytes, together with IgM
- Produced by B cells/plasma cells in upper respiratory tract; interacts with receptors on basophils, inducing antimicrobial, inflammatory and B cell stimulatory factors
function is unknown
