A7: Humoral Immune Response

Question 1

What are two ways that cross linking of Ig molecules?

Answer 1

Occurs if two antigen molecules bind adjacent Ig OR if there are repeating epitopes on a single microbe and it can activate both

Question 2

What molecules make up the BCR complex?

Answer 2

The membrane antibody receptor, the Ig alpha and Ig beta (similar to zeta and CD3 in TCR complex)

Question 3

What type of region do both Ig alpha and beta have that allow it to conduct signaling?

Answer 3

They have ITAM sequences so when cross linking of receptors occurs, they phosphorylate tyrosines of the ITAMs which leads to Syk tyrosine kinase recruitment, phosphorylating adaptor proteins

Question 4

What are haptens?

Answer 4

Small molecules that bind to larger substances and react with specific TCRs or BCRs and elicit an immune response. eg penicillin

Question 5

Which antibody heavy chain isotype mediates antibody dependent cellular cytotoxicity (ADCC)?

Answer 5

IgG

Question 6

What antibody heavy chain isotype mediates complement activation?

Answer 6

IgM primarily, but also IgG. IgM is best because clustering due to its pentameric structure allows excellent complement deposition

Question 7

How are B and T cells brought together if they respond to the same antigen?

Answer 7

The migrate towards each other because T cells migrate to edge of follicles when they reduce expression of CCR7 and increase expression of CXCR5. B cells upregulate CCR7 and downregulate expression of CXCR5 and thus move towards where T cells are

Question 8

Through which receptor:signal mechansim does T helper cells help B cells?

Answer 8

CD40L on T helper cells binds to CD40 receptors on B cells, stimulating more B cell proliferation and Ig production. Also induces isotype switching

Question 9

What is the name of the area of the follicle where B cells are proliferating?

Answer 9

Germinal center (proliferating B cells where somatic hypermutation occurs reside in dark zone of germinal center, selection of B cells and class switching occurs in the light zone of the germinal center)

Question 10

What reaction is IgG most effective at? What about IgE?

Answer 10

IgG is best for opsonization. IgE is best for parasite elimination because IgE activates eosinophils which are key for eliminating parasites

Question 11

What is the only Ig to cross the placenta, and how does it cross?

Answer 11

IgG is the only one that crosses. This is because they are able to bind to a specialized Fc receptor called the FcRn

Question 12

What are the two signals required for isotype switching?

Answer 12

CD40L from T helper cells binding to CD40 on B cells, as well as cytokines

Question 13

Which cytokines induce IgG switching, and where do they come from? IgE? IgA?

Answer 13

IgG is stimulated by IL-10 produced by Tfh cells
IgE stimulated by IL-4 by Tfh cells
IgA in mucosal lymphoid tissues occurs because TGF-beta is prevalent here

Question 14

What are two distinct kinds of responses that a B cell can undergo in response to antigen?

Answer 14

Rapid plasmablast differentiation (extrafollicular response) or can form germinal centers

Question 15

What is the main type of Ig antibody produced in an extrafollicular response?

Answer 15

Rapid IgM production

Question 16

What type of response (of the two main types of B cell activation) requires T-dependence?

Answer 16

Germinal center responses are dependent on T cells

Question 17

What is a key enzyme that has a role both in isotype switching in germinal center responses and in affinity maturation?

Answer 17

AID (activation induced cytidine deaminase)

Question 18

How does feedback inhibition of B plasma cell production of antibodies occur?

Answer 18

IgG that is available in the blood is recognized by FcgammaRIIB that is on the B cell. Binding of this receptor causes it to shut off its response.