Humoral Effector Functions Flashcards
What is humoral immunity?
A branch of adaptive immunity mediated by Abs produced by B cells and plasma cells. Humoral immunity is the principle defense against extracellular pathogens!
Where are Abs produced and where do they perform their effector function?
Abs are produced by plasma cells in the lymphoid tissues/organs and perform their function at sites distant from where they are produced.
How are the effector functions of Abs mediated?
They are mediated by the Fc region
All functions are triggered by the binding of […] to the […] region.
Ag
Fab’(V)
How does Ab affinity differ between the primary and secondary immune responses?
Primary response: Lower average affinity and more variable
Secondary response: Higher average affinity through affinity maturation
What are some of the effector functions of Abs?
Neutralization of microbes and toxins, complement activation, opsonization and phagocytosis of microbes, ADCC, phagocytosis of microbes opsonized w/ complement fragments, inflammation, and lysis of microbes
What are two distinct functions of the Fc region?
Deliver Ab to inaccessible anatomical sites.
Link bound Ag to molecules/cells that effect destruction
Ag-bound Abs will bind to […] in order to act as opsonins or to activate cells!
Fc receptors
How can Abs neutralize the infectivity and potential effects of infection?
An Ab can block penetration of a microbe through the epithelial barrier, block a microbes ability to bind and infect a cell, or block the binding of toxin to cellular receptors
How can an Ab work as an opsonin?
A microbe has IgG Ab bound to its surface → Ab-microbe complex binds to phagocyte via FcγRI → Fc receptor signals activate the phagocyte → phagocytosis of the microbe occurs → killing of ingested microbe
How does opsonization allow for the clearance of immune complexes (IC)?
CR1 on RBCs binds circulating ICs w/ attached C3b and C4b and transports the complexes to the liver and spleen.
There, resident phagocytes remove the immune complexes from the RBC surface and allow the RBC to continue circulating
How do Abs allow for the activation of NK cells via ADCC?
IgG abs bound to surface Ags of a cell can bind to the low-affinity FcγRIII (CD16) present on NK cells triggering activation and destruction of Ab-coated cell
How could IVIG therapy be used to suppress the immune system?
Abs injected can engage the inhibitory FcR on B cells and possibly dendritic cells thus suppressing the immune response
How does IgE Abs aid a Th2 cell (which is secreting IL-5) in elimination of helminths?
IgE bound to a helminth will bind to the FcεRI present on mast cells triggering degranulation of the mast cell leading to helminth death.
What two Abs are involved in mucosal immunity and what is the mechanism by which IgA does this?
An IgA producing plasma cell will secrete dimeric IgA Abs which bind to poly-Ig that can be endocytosed by the mucosal epithelial cells and secreted into the lumen to act on microbes
How can IgG be transported from maternal circulation and across the placental barrier?
An IgG receptor known as FcRn, upon binding of IgG, will undergo transcytosis which transports the IgG Ab to where it needs to go
Where can FcRn surface receptors be found?
Surface of endothelial cells, macrophages, and other cell types.
In a newborn, when do we start to see the production of IgM, IgG, and IgA
IgM is produced around birth
IgG and IgA lag for 6-12 months leaving a vulnerable period when a baby is not immunocompetent
What are some functions of C’?
Triggering and amplification of inflammation reactions, attraction of phagocytes by chemotaxis, clearance of immune complexes, cellular activation, direct microbial killing, and play an important role in the development of humoral responses
Which complement complexes have enzymatic activity?
C1qrs
C4b2a3b in the classical pathway
C3bBb3b in the alternative pathway
Why would the alternative pathway be capable of providing immunity even if the host has not had prior exposure to an Ag, but the classical pathway would not?
Cause the classical pathway is activated by an Ab being bound to a pathogen
Which C’ pathway is the most rapid and efficient in its response?
The classical pathway
Which Abs can trigger the classical pathway?
IgG or IgM
Which C’ protein binds to the Fc portion of the Ab?
C1
How does C1 become enzymatically active?
A C1q subunit is associated with two C1r and two C1s molecules. Binding of Ab-Ag complex to multiple globular domains of C1q triggers conformational changes causing the autocleavage of C1r and C1s yielding an enzymatically active C1qrs complex
What is the job of C1qrs in the activation of C’ ?
It cleaves C4 → C4a and C4b. C4b then showers down on the target cell and attaches to the cell membrane.
What is the role of C4b once bound to the membrane?
C2 is attracted to a membrane bound C4b. C1qrs can then cleave C2 → C2a and C2b. C2a then associates with C4b in the membrane.
Which C’ protein is responsible for the distinction between self and non-self? How does it do this?
C3
Self-cell surfaces can limit the deposition of C3b on their surface, but non-self cell surfaces allow the rapid deposition of C3b.
This is cause self-cells have high levels of sialic acid which rapidly inactivates bound C3b molecules on host cells
What is the main amplification step of the classical complement pathway?
C3 convertase cleaving many molecules of C3
How is the lectin pathway initiated?
MBL can bind mannose residues on bacterial surface polysaccharides. MBL then binds MASP which creates a complex that is structurally similar to C1q
What pathways does the C1inh control? How so?
Controls both classical and lectin pathways.
It binds to both C1r and C1s and causes dissociation from the C1q complex. Additionally, it can remove MASP enzymes from the MBL complex
How does factor I regulate C’?
Factor I is also known as the C3b inactivator, and it is a plasma protein which cleaves . C4b or C3b preventing the formation of C3 and C5 convertases
How does decay-accelerating factor (DAF) regulate C’?
Promotes dissociation of the C3 convertase
How does CD59 regulate C’?
It blocks C9 binding to the C5b678 complex on the cell surface
What is the major opsonin from the complement pathway?
C3b
