Microbiology, 2021

696 17 • Innate Nonspecific Host Defenses
Figure 17.9
The three complement activation pathways have different triggers, as shown here, but all three result in the activation of the
complement protein C3, which produces C3a and C3b. The latter binds to the surface of the target cell and then works with other
complement proteins to cleave C5 into C5a and C5b. C5b also binds to the cell surface and then recruits C6 through C9; these molecules
form a ring structure called the membrane attack complex (MAC), which punches through the cell membrane of the invading pathogen,
causing it to swell and burst.
Although each complement activation pathway is initiated in a different way, they all provide the same
protective outcomes: opsonization, inflammation, chemotaxis, and cytolysis. The term opsonization refers to
the coating of a pathogen by a chemical substance (called an opsonin) that allows phagocytic cells to recognize,
engulf, and destroy it more easily. Opsonins from the complement cascade include C1q, C3b, and C4b.
Additional important opsonins include mannose-binding proteins and antibodies. The complement fragments
C3a and C5a are well-characterized anaphylatoxins with potent proinflammatory functions. Anaphylatoxins
activate mast cells, causing degranulation and the release of inflammatory chemical signals, including
mediators that cause vasodilation and increased vascular permeability. C5a is also one of the most potent
chemoattractants for neutrophils and other white blood cells, cellular defenses that will be discussed in the
next section.
The complement proteins C6, C7, C8, and C9 assemble into a membrane attack complex (MAC), which allows
C9 to polymerize into pores in the membranes of gram-negative bacteria. These pores allow water, ions, and
other molecules to move freely in and out of the targeted cells, eventually leading to cell lysis and death of the
pathogen (Figure 17.9). However, the MAC is only effective against gram-negative bacteria; it cannot penetrate
the thick layer of peptidoglycan associated with cell walls of gram-positive bacteria. Since the MAC does not
pose a lethal threat to gram-positive bacterial pathogens, complement-mediated opsonization is more
important for their clearance.
Cytokines
Cytokines are soluble proteins that act as communication signals between cells. In a nonspecific innate
immune response, various cytokines may be released to stimulate production of chemical mediators or other
cell functions, such as cell proliferation, cell differentiation, inhibition of cell division, apoptosis, and
chemotaxis.
When a cytokine binds to its target receptor, the effect can vary widely depending on the type of cytokine and
the type of cell or receptor to which it has bound. The function of a particular cytokine can be described as
autocrine, paracrine, or endocrine (Figure 17.10). In autocrine function, the same cell that releases the
cytokine is the recipient of the signal; in other words, autocrine function is a form of self-stimulation by a cell.
In contrast, paracrine function involves the release of cytokines from one cell to other nearby cells,
stimulating some response from the recipient cells. Last, endocrine function occurs when cells release
cytokines into the bloodstream to be carried to target cells much farther away.
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