12 - Biological Roles of Immunoglobulins - Partridge Flashcards
List the 6 biological roles of Immunoglobulins including the Abs that allow each of these functions to occur (sometimes an example isn’t give)
- label pathogen for elimination/destruction
- reduce its movement. eg IgM binds to flagella to immobilise bacteria
- form immune complexes when multiple Abs bind to soluble antigen eg IgM/IgG
- agglutinate particles (bacteria) so they’re easily cleared by defence molecules
- neutralise toxins (IgA, IgG)
- prevent interaction of pathogen with host cells (IgA, IgG)
Describe the difference between avidity and affinity and give an example of a molecule with high avidity but low affinity
AVIDITY;
relates the size and the no. binding sites of the Ab to its ability to bind to pathogen
AFFINITY;
strength of the interaction between the Fab arm and the antigen
eg IgM
When talking about multivalency, Abs are at least ____
divalent
What are the 3 Fc effector functions?
- invoke the destruction of the pathogen
- activate complement (IgG/IgM)
- bind Fc receptors on leucocyte surfaces (IgG/A/E)
What do the 3 Fc effector functions depend on? (2)
- stages of the immune response (1ry/2ndry)
- site of infection and the types of pathogen involved
What are the 3 pathways of complement activation and what is the central event in all of these?
classical, alternative, MB lectin
cleavage of C3 component -> C3a + C3b
Describe the classical pathway in terms of the no. Abs needed to activate it, the components involved and draw a diagram
- involves C1 molceule = C1q + C1r + C1s
- requires C1q making at least 2 interactions to Fc regions (eg 2 IgGs or pentameric IgM)
- binding to Fc -> activates C1r which then cleaves and activates C1s -> cleaves C2 and C4 -> C4bC2a (C3 converts)
- C1r + s = Ser proteases. exist as complex with C1qr2s2 with Ca2+ holding complex together
List the order in which the Abs (and their subclasses) can activate the classical pathway with the most potent being first
IgM > IgG3 > IgG1 > IgG2
What are the results of complement activation?
- lysis of cells
- activation of leucocytes
- inducer of inflammation (allowing immune cells to reach the location where theyre needed)
- opsonisation of pathogen
give examples of the effector cells that express FcRs
- NK cells
- mononuclear phagocytes
- granulocytes eg basophils, mast cells
Describe the complex of an FcR
Overall; multisubunit complex
different iso forms depending on the Ig they bind (IgG/A/E) eg FceR has many intracellular domains invovled in signalling
- alpha chains bind Fc regions
- associated chains have functions in downstream signalling and cell surface expression
- ITIM/ITAM intracellular motifs (immunoreceptor tyr inhibitory/activation motifs). have roles in activating/suppressing immune response once pathogen has been dealt with
Why is the activation of an FcR dependent upon it binding to Ab bound to antigen?
Ab is cross linked when bound to antigen
FcR is cross linked when binding to Ab
What are the 2 Ig classes that can bind to FcRs on phagocytes and list the affinity of the subclasses to these FcRs
IgG, IgA
IgG1=3>4
What are the 5 results when the FcRs on phagocytes are bound by Abs?
- cell activation (inducing phagocytosis etc)
- opsonisation of the Ab-bound pathogen
- respiratory burst and release of O2 intermediates in the phagosome
- clearance of immune complexes
- frustrated phagocytosis - release of lysosomal contents in the pathogen is too big to be phagocytosed
IF FcRs are present on APC eg DCs, then the bacterial peptides produced can be presented on the surface associated w/ MHC molecules
Draw a diagram illustrating how phagocytosis occurs of an opsonised pathogen
dont forget about the cross linking of the FcRs