Inflammation, Fever, and Complement - Anatomy and Physiology
- What is the complement system?
- A group of plasma proteins that circulate inactive and, when activated in a cascade, promote inflammation, opsonize microbes and lyse cells.
- Which two complement fragments act as anaphylatoxins that trigger mast cell degranulation?
- C3a and C5a. C5a is also a strong chemoattractant for neutrophils.
- What is a pyrogen?
- A fever-inducing substance. Endogenous pyrogens include IL-1, IL-6 and TNF-alpha released by immune cells; exogenous ones include bacterial products.
- How does aspirin reduce a fever?
- It inhibits cyclooxygenase (COX), blocking prostaglandin E2 synthesis, so the hypothalamic set point returns toward normal.
- What does the membrane attack complex do, and which complement proteins form it?
- It forms a pore in the target cell membrane, causing lysis. It is assembled from C5b, C6, C7, C8 and multiple C9 molecules.
- At fever onset, the set point rises to 39 degrees C while core temperature is still 37 degrees C. What does the person experience?
- Feeling cold, with shivering and skin vasoconstriction, because the body is below its new set point and works to produce and conserve heat.
- Which complement fragment is the major opsonin that coats microbes for phagocytosis?
- C3b. Phagocytes have receptors for C3b, so coated microbes are engulfed more easily.
- Which complement pathway is triggered when C1 binds antibody attached to an antigen?
- The classical pathway. It links the antibody response to the complement cascade.
- How does a moderate fever help limit bacterial growth?
- It causes the liver and spleen to sequester iron and zinc that bacteria need, and it speeds up the body's repair processes.
- Which complement pathway begins when a plasma lectin binds mannose-containing carbohydrates on microbes?
- The lectin pathway, started by mannose-binding lectin. It, like the alternative pathway, needs no antibody.
- When a fever breaks, the set point returns to normal while core temperature is still high. What response follows?
- Sweating and skin vasodilation (flushing), which release heat until core temperature falls to the restored set point.
- How do pyrogens raise body temperature at the level of the brain?
- They trigger prostaglandin E2 production in the hypothalamus, which raises the thermoregulatory set point.