Académique Documents
Professionnel Documents
Culture Documents
Biology 430
Klinefelter Syndrome
o Contributes to female susceptibility
o Hypogonadotrophic hypogonadism
(Dorner et al. 2011; Mok and
Lau. 2003; Hu and Deng 2014)
Two Stage Disease
o Loss of self-tolerance/Auto-Abs generation
o Immune complex formation, causes inflammation/disease
Role of Apoptosis
o Impaired clearance of apoptotic cells
o Results from defective complement system
C2, C4, C1q defects
Reduced CR1 receptors
o Cells serve as immunogens
(Ahmadpoor et al. 2014; Dorner
o Induce auto-reactive T/B cells et al. 2011; Mok and Lau. 2003)
Aberrant DC activity
o DCs present self antigens from apoptotic cells
Mostly nucleosomes, apoptotic blebs
o DCs present to CD4 cells
Autoantibody Production
o 95% are antinuclear Abs (anti-Sm, Anti-DNA)
(Ahmadpoor et al. 2014; Dorner et al. 2011; Mok and Lau. 2003)
(Dorner et al. 2011)
Stage Two: Immune Complex Formation
o Auto-Abs bind to:
Pieces of DNA
Nucleosomes
Proteoglycans
o Immune complex formation
Accumulate in organ basement membranes
Corticosteroids
o Reduce inflammation
o Used after significant organ damage
Antimalarial Drugs
o Hydroxychloroquine (Plaquenil), chloroquinone (Aralen)
o Reduces inflammation, protects against organ damage
o Used for skin symptoms, joint pain
Dorner T, Giesecke C, Lipsky PE. 2011. Mechanisms of B cell autoimmunity in SLE. Arthritis Research and Therapy.
13(243): 1-12.
Hu, ZD, Deng AM. 2014. Autoantibodies in pre-clinical autoimmune disease. Clinical Chimica Acta. 435: 14-18.
Lau CS, Yin G, Mok MY. 2006. Ethnic and geographical differences in systemic lupus erthematosus: an overview.
Lupus. 15: 715-719.
Mok CC, Lau CS. 2003. Pathogenesis of systemic lupus erythematosus. Journal of Clinical Pathology. 56(7): 481-490.
Perl A. 2009. Overview of signal processing by the immune system in systemic lupus erythmatosus. Autoimmunity
Reviews. 8:177-178.
Sang A, Zheng YY, Morel L. 2014. Contributions of B cells to lupus pathogenesis. Molecular Immunology. 62: 329-338.
Schur P, Shmerling R, Ramirez M. 2014. "Patient Information: Systemic Lupus Erythematosus (SLE) (Beyond the
Basics)." Systemic Lupus Erythematosus (SLE). UpToDate Health. Web.
<http://www.uptodate.com/contents/systemic-lupus-erythematosus-sle-beyond-the-basics?view=print>.
Shiel W, Stoppler MC, Driver CB. 2014. "Lupus Symptoms, Causes, Treatment - What Is the Treatment for Systemic
Lupus?" MedicineNet. Web.
<http://www.medicinenet.com/systemic_lupus/page5.htm#what_is_the_treatment_for_systemic_lupus_eryth
ematosus>.
"What Is Lupus?" 2014. Lupus.org. Lupus Foundation of America, Web.. <http://www.lupus.org/answers/entry/what-
is-lupus>.
Multiple Choice Questions:
Essay Response
o Key points to mention:
o Clearance of apoptotic cells/cell fragments is impaired because of defective
complement system.
o DC cells encounter and present portions, particularly nuclear portions, of
apoptotic cells as self-antigens to CD4 cells.
o T cell dependent B cell activation is unregulated and B cells that have self-
antigen specificity are not eliminated as they should be.
o B cells are activated into plasma cells. These cells secrete auto-reactive
antibodies that can migrate anywhere in body. Some will migrate to kidney.
o In kidney, antibodies will encounter self antigens, bind, and form immune
complexes. These immune complexes will lead to an inflammatory response
by immune system. Inflammation is local and will occur in portions of the
kidney, such as the nephron, causing nephritis.