B Cell Mediated Immunity

Question 1

What are the Co-BCRs found on B cells?

Answer 1

CD19, CD20, CD40, CD81, and CR2 (CD21)

Question 2

What is the difference between the two major types of B-2 cells?

Answer 2

Follicular B cells: re-circulating B cells, majority in body.
Marginal B cells: reside in spleen, recognize blood-borne polysaccharide antigens.

Question 3

What is the role of B-1 cells?

Answer 3

Found in mucosa. Limited antigen specificity.

Question 4

Describe the migration of naive B cells into secondary lymphoid tissues (SLTs). What protein helps localize it?

Answer 4

Enters through HEV or lymphatics, then migrates to primary follicle via CXCR5.

Question 5

What are follicular dendritic cells (FDCs)?

Answer 5

In lymphoid organs, they capture antigens and displays them for B cells to bind to.

Question 6

What are the two signals required for B cell activation?

Answer 6

1. Antigen crosslinks 2 or more BCRs, leading to Igα and Igβ phosphorylating Syk.
2. Class switching, proliferation, and differentiation by T-dependent mechanism. T-independent mechanism is similar but does not cause class switching.

Question 7

What is the significance of C3b bound to an antigen during B cell activation?

Answer 7

C3b will bind to CR2 on B cell and provide cross-linkage signal via CD19. Similar signaling can occur via TLR. This is used to enhance the first signal.

Question 8

What are the main outcomes of the first activation signal of B cells?

Answer 8

Increased proliferation/survival. Increased B7 expression for interaction with Th cells. Increased expression of cytokine receptors. Increased expression of CCR7, prompting B cell to leave follicle and migrate to T cell zone of lymph node. Also begins to secrete IgM.

Question 9

Describe T cell dependent activation of B cells.

Answer 9

B cell processes antigen and presents to Th cell via HLA II. Additionally, B7 and CD40 on B cell bind to CD28 and CD40L on T cell, respectively. This leads class switching and affinity maturation (somatic hypermutation).

Question 10

What is the role of activation-induced deaminase (AID) enzyme?

Answer 10

Causes to somatic hypermutation and class switching of secreted antibodies. Expression of AID is induced by T cell dependent activation of B cells.

Question 11

What happens once B cells are activated by T cells?

Answer 11

B cells change their chemokine receptors and migrate back to follicular area to establish germinal centers where class switching and affinity maturation occurs. Re-arrangements are then selected by Tfh and FDCs.

Question 12

What is the purpose of the cytokines released by Th cells during T-dependent activation of B cells?

Answer 12

To induce H chain class switching and to augment B cell differentiation and proliferation.

Question 13

Explain how class switching occurs in B cells.

Answer 13

CD40:CD40L ligation and cytokines lead to AID expression. AID rearranges VDJ gene with downstream C region gene. Intervening DNA is deleted. T-dependent activation only.

Question 14

What is the purpose of T follicular helper cells (Thf)? What do they secrete?

Answer 14

They secrete IL-21, which facilitates differentiation of germinal center B cells into plasmablasts. ICOS is needed for germinal center reaction. Also provides IFN-γ and IL-4 for class switching.

Question 15

What are the cell markers increased/decreased on plasma B cells?

Answer 15

Increased CD27. Decreased CD19, CD20, and HLA II.

Question 16

How does T-independent B cell activation differ from T-dependent activation?

Answer 16

They are activated by large number of surface IgM binding to polysaccharide/non-protein antigen. Leads to mainly IgM secretion (because no class switching). Short lived.

Question 17

What is the difference between B-1 cells and B-2 cells in T-independent antigen activation?

Answer 17

B-1: responds to non-protein antigen in mucosal tissues.

B-2: responds to blood-borne polysaccharides in spleen.

Question 18

What are the main surface markers found on memory B cells?

Answer 18

CD27 and CD45R(O)

Question 19

What is the purpose of Bcl-2 in memory B cells?

Answer 19

To prevent apoptosis

Question 20

How does antibody feedback work in B cells?

Answer 20

Excess antibodies bind next to BCR and blocks further antibody production. IgG only.

Question 21

Describe how antibody-mediated neutralization works.

Answer 21

Antibodies bind to microbe, preventing penetration of epithelial barrier and infection of cells. They can also bind to toxins, preventing toxins from binding to cell receptors.

Question 22

Describe how waste management of immune complexes work.

Answer 22

Antibody:antigen complex forms and is activated by complement (coated with C3b). CR1 on erythrocyte binds C3b-tagged complex and carries it to liver/spleen. There, resident phagocyte removes and takes up complex from erythrocyte.

Question 23

Describe antibody dependent cell-mediated cytotoxicity (ADCC).

Answer 23

NK cells bind to antibody-covered cells via FcR and destroys infected cell.

Question 24

What is the clinical significance of natural antibodies?

Answer 24

Individuals produce natural antibodies against other blood types. Produced by B-1 and marginal zone B cells. IgM mainly, but also some IgG.

Question 25

Which antibodies are involving in mucosal immunity, preventing microbes from entering epithelial tissues?

Answer 25

IgA and IgM

Question 26

What antibodies are transferred from the mother to the fetus/child?

Answer 26

During pregnancy, fetus receives IgG from maternal circulation. Additional protection gained through IgA secreted in breast milk.

Question 27

How does IgG cross the placenta during pregnancy?

Answer 27

IgG binds to FcRn (FcRb) on endothelial cell. An endocytic vesicle is formed and the IgG is transferred across the cell.

Question 28

What are hyper IgM (HIGM) syndromes?

Answer 28

X linked disorder affecting the presentation of CD40L on T cells. Leads to the inability to class switch in B cells. Also leads to macrophage defect due to no opsonization.

Question 29

Describe how leprosy affects the immune response.

Answer 29

M. leprae colonizes macrophages and other host cells and multiplies within them. Can only be eliminated by intracellular killing by activated macrophages. Grows best at 86 F, hence predominant growth of lesions on extremities.

Question 30

What is the difference between Tuberculoid and Lepromatous leprosy?

Answer 30

Tuberculoid: Caused by Th1 response. Low infectivity.
Lepromatous: Caused by Th2 response. High infectivity.