Humoral Effector Functions

Question 1

What is humoral immunity?

Answer 1

A branch of adaptive immunity mediated by Abs produced by B cells and plasma cells. Humoral immunity is the principle defense against extracellular pathogens!

Question 2

Where are Abs produced and where do they perform their effector function?

Answer 2

Abs are produced by plasma cells in the lymphoid tissues/organs and perform their function at sites distant from where they are produced.

Question 3

How are the effector functions of Abs mediated?

Answer 3

They are mediated by the Fc region

Question 4

All functions are triggered by the binding of […] to the […] region.

Answer 4

Ag

Fab’(V)

Question 5

How does Ab affinity differ between the primary and secondary immune responses?

Answer 5

Primary response: Lower average affinity and more variable

Secondary response: Higher average affinity through affinity maturation

Question 6

What are some of the effector functions of Abs?

Answer 6

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

Question 7

What are two distinct functions of the Fc region?

Answer 7

Deliver Ab to inaccessible anatomical sites.

Link bound Ag to molecules/cells that effect destruction

Question 8

Ag-bound Abs will bind to […] in order to act as opsonins or to activate cells!

Answer 8

Fc receptors

Question 9

How can Abs neutralize the infectivity and potential effects of infection?

Answer 9

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

Question 10

How can an Ab work as an opsonin?

Answer 10

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

Question 11

How does opsonization allow for the clearance of immune complexes (IC)?

Answer 11

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

Question 12

How do Abs allow for the activation of NK cells via ADCC?

Answer 12

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

Question 13

How could IVIG therapy be used to suppress the immune system?

Answer 13

Abs injected can engage the inhibitory FcR on B cells and possibly dendritic cells thus suppressing the immune response

Question 14

How does IgE Abs aid a Th2 cell (which is secreting IL-5) in elimination of helminths?

Answer 14

IgE bound to a helminth will bind to the FcεRI present on mast cells triggering degranulation of the mast cell leading to helminth death.

Question 15

What two Abs are involved in mucosal immunity and what is the mechanism by which IgA does this?

Answer 15

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

Question 16

How can IgG be transported from maternal circulation and across the placental barrier?

Answer 16

An IgG receptor known as FcRn, upon binding of IgG, will undergo transcytosis which transports the IgG Ab to where it needs to go

Question 17

Where can FcRn surface receptors be found?

Answer 17

Surface of endothelial cells, macrophages, and other cell types.

Question 18

In a newborn, when do we start to see the production of IgM, IgG, and IgA

Answer 18

IgM is produced around birth

IgG and IgA lag for 6-12 months leaving a vulnerable period when a baby is not immunocompetent

Question 19

What are some functions of C’?

Answer 19

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

Question 20

Which complement complexes have enzymatic activity?

Answer 20

C1qrs
C4b2a3b in the classical pathway
C3bBb3b in the alternative pathway

Question 21

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?

Answer 21

Cause the classical pathway is activated by an Ab being bound to a pathogen

Question 22

Which C’ pathway is the most rapid and efficient in its response?

Answer 22

The classical pathway

Question 23

Which Abs can trigger the classical pathway?

Answer 23

IgG or IgM

Question 24

Which C’ protein binds to the Fc portion of the Ab?

Answer 24

C1

Question 25

How does C1 become enzymatically active?

Answer 25

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

Question 26

What is the job of C1qrs in the activation of C’ ?

Answer 26

It cleaves C4 → C4a and C4b. C4b then showers down on the target cell and attaches to the cell membrane.

Question 27

What is the role of C4b once bound to the membrane?

Answer 27

C2 is attracted to a membrane bound C4b. C1qrs can then cleave C2 → C2a and C2b. C2a then associates with C4b in the membrane.

Question 28

Which C’ protein is responsible for the distinction between self and non-self? How does it do this?

Answer 28

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

Question 29

What is the main amplification step of the classical complement pathway?

Answer 29

C3 convertase cleaving many molecules of C3

Question 30

How is the lectin pathway initiated?

Answer 30

MBL can bind mannose residues on bacterial surface polysaccharides. MBL then binds MASP which creates a complex that is structurally similar to C1q

Question 31

What pathways does the C1inh control? How so?

Answer 31

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

Question 32

How does factor I regulate C’?

Answer 32

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

Question 33

How does decay-accelerating factor (DAF) regulate C’?

Answer 33

Promotes dissociation of the C3 convertase

Question 34

How does CD59 regulate C’?

Answer 34

It blocks C9 binding to the C5b678 complex on the cell surface

Question 35

What is the major opsonin from the complement pathway?

Answer 35

C3b