Isotype Switching
CD40 ligand deficiency leads to a lack of isotype/class switching and impairment of macrophage function
The process by which the B-cell changes the class of immunoglobulin it makes while preserving the antigenic specificity of the immunoglobulin
What is CD40 Ligand
Deficiency?
Impediment of CSR
Clinical Characteristics
Hyper IgM Syndrome
&
Macrophage Activation
Lack of GM-CSF
Neutropenia
Common Symptoms include: upper and lower respiratory tract infections, chronic diarrhea, liver disease/inflammation, and neutropenia
Isotype Switching: CSR
Defects in both humoral and cell-mediated immunity
Detection:
Method 1: Flow Cytometry
Case Study 2: CD40 Ligand Deficiency
Reference
Method 2: Lymph node Biopsy
Geha, R., & Rosen, F. (2008). Case studies in immunology: A clinical companion (6th ed.). New York, New York: Garland Science, Taylor and Francis Group.
Parham, P. (2015). The immune system. Garland Science, Taylor & Francis Group, LLC. Fourth Ed. (London & New York).
http://www.bloodjournal.org/content/103/3/1152?variant=full-text&sso-checked=true
http://www.nature.com/nm/journal/v4/n11/pdf/nm1198_1253.pdf
http://www.ncbi.nlm.nih.gov/pubmed/9255191
http://adc.bmj.com/content/84/6/508.full
Sang Won Choi
Macaire Grobe
Questions?
Treatment Methods:
- Short term:
- Immunoglobulin Replacement Therapy
- Long Term:
- HSC Transplant
- Gene Therapy
Case Study: Dennis Fawcett
Summary:
5 years old:
- No antibody against strep and recurrent sinus infections
- DPT booster did not work
- Raised monocyte counts
- Low IgA and IgG, but high IgM anti-A and anti-B antibodies
- No follicles or germinal centers and no T-cell binding of soluble CD40
15 Years Old
- Being treated with IV gamma globulin
- Had complications in the liver (cholestasis, sclerosing cholangitis)
21 years old
- The CD40L protein is expressed after T cell receptor recognizes MHC complex on an antigen-presenting cell.
- CD40-CD40L ligation is required to signal class switching of antibodies and the activation of certain macrophage functions.
- Lack of diversity in immunoglobulin classes as well as impaired macrophage function leads to defects in both humoral and cell-mediated immunity.