Jitt # 10 CD40 Ligand Deficiency

Question 1

After recognizing an antigen, what is the first antibody to appear?

Answer 1

IgM

Question 2

What antibodies predominate in the serum and extravascular spaces?

Answer 2

IgG

Question 3

What type of antibody is present in the gut and respiratory tract?

Answer 3

IgA

Question 4

Where is IgE produced?

Answer 4

In the mucosal tissues

Question 5

What type of cells undergoes class switching? How is class switching induced?

Answer 5

B cells, induced by T cells (T cell dependent)

Question 6

How is T cell independent class switching induced?

Answer 6

Induced when microbial antigens or repeated epitopes are recognized by TLRs

Question 7

How is T cell dependent class switching induced?

Answer 7

T cells express CD40L, B cells have CD40 R when activated, both bind together; T cells secrete cytokines to help B cells grow and proliferate. B cells are activated when T cells recognize antigens on B cells in the context of MHC

Question 8

What cytokine is important for the production of IgE?

Answer 8

IL-4

Question 9

CD40L gene and consequence of mutation

Answer 9

CD40LG; located on the X chromosome at Xq26; people who have a mutation in this gene are only able to produce IgM or IgD and are unable to switch to other Ig sub classes; Disease, Hyper IgM syndrome, CD40 deficiency,

Question 10

On what cells are CD40 expressed?

Answer 10

Macrophages, DCs, FDCs, Mast cells and some epithelial and endothelial cells. In CD40 deficiency cases, there is no interaction between these APCs and the T cells. Antigen specific T cells are produced in very low numbers.

Question 11

Characteristics of CD40L Deficiency

Answer 11

Low WBC count, severe neutropenia (causes sores and blisters in the mouth), normal levels of lymphocytes, High number of monocytes, absence of secondary follicles and germinal centers; recurrent infection with pyogenic bacteria; Can make antibodies for T- Cell independent bacteria, but cannot make antibodies against T cell dependent antigens; also have defects in cell mediated immunity (No T cell activation of Macrophages); persistent inflammation of the liver (leads to liver failure);

Question 12

How do you treat severe neutropenia?

Answer 12

G-CSF; granulocyte colony stimulating factor

Question 13

Treatment for CD40 Deficiency

Answer 13

Antibiotics to control infections, Ig replacement therapy, prophylaxis, avoiding waters contaminated with bacteria; HSC transplantation is a cure.