Deficiency of C8

• what does complement do?

  • produce opsonins

  • produce the membrane-attack complex (MAC) of C5 through C9

• young adult female or male admitted for meningococcal septicemia (a disaster, often fatal) and meningitis

  • when Dr. Baird was in medical school, Fort Ord had continuous problems with meningococcal infections in their troops

  • this was because the beds were so close together that those who sneezed would infect their neighbors

  • a capsular form of the bacteria was also found in the dirt; it is fairly resistant to phagolysosome formation and even phagocytosis

• previous history of the same infection. however, patients do make antibodies appropriately, so it is a problem downstream of antibody formation

• CH50 titer of 0. CH50 is a test where you serially dilute patient’s plasma. add this to sheep RBC and measure how far you can dilute the plasma and still lyse the sheep red cells. the CH50 refers to dilution at which you pop half of the red cells

• about half of siblings have CH50 = 0; one parent has 50% activity

Principles you should understand

• attack complex of C5, 6, 7, 8, 9 pokes holes in susceptible bacteria. this is necessary to combat Neisseria (in gonorrhea, for example) and Meningococcus infections

• when C5, 6, 7, 8, or 9 are deficient, the patient has low or absent CH50 (MAC depends on all of these)

• deficiencies of C3 increase susceptibility to all bacteria because there is no opsonization

  • so is the problem phagocytosis and lack of hole-poking (MAC),

  • or is the problem only a lack of hole-poking?

• deficiencies of C1q, r, s, C2, or C4 cause immune complex disease (cf. slide 21). this can cause infarcts in peripheral microvasculature

Formation of the membrane-attack complex

• C5a is one of the best chemokines

• C5b binds to the pathogen surface, attracting C6, 7

• then, C8 attaches

• then, one to 16 C9 molecules bind to the complex and polymerize; this forms the pore of the membrane-attack complex

Getting rid of immune complexes

• immune complexes such as C43b bound to antibodies bind to CR1 on RBC surfaces

• when the “RBC goes sailing through the spleen,” phagocytes nip off the immune complex and a bit of the RBC

• after this happens a bunch of times, RBCs get eaten away (so they get smaller and smaller) and die off after a few months

Category: Pathology Notes