This chapter has described the preexisting, constitutive components of innate immunity. The body’s epithelial surfaces are a constant barrier to pathogen entry and have specialized adaptations, such as cilia, various antimicrobial molecules and mucus, that provide the simplest form of innate immunity. The complement system is a more specialized system that combines direct recognition of microbes with a complex effector system.  Of the three pathways that can activate complement, two are devoted to innate immunity. The lectin pathway relies on pattern recognition receptors that detect microbial membranes, while the alternative pathway relies on spontaneous complement activation that is down-regulated by host molecules expressed on self membranes. The main event in complement activation is accumulation of C3b on microbial membranes, which is recognized by complement receptors on phagocytic cells to promote microbial clearance by cells recruited to sites of infection by C3a and C5a. In addition, C5b initiates the membrane-attack complex that is able to lyse some microbes directly. The complement cascade is under regulation to prevent attack on host tissues, and genetic variation in regulatory pathways can result in autoimmune syndromes and age-related tissue damage.
Questions.
2.1 Multiple Choice: The widely used β-lactam antibiotics are mainly active against Gram-positive bacteria. These inhibit the transpeptidation step in synthesis of peptidoglycan, a major component of the bacterial cell wall that is critical for the survival of the microorganism. Which of the following is an antimicrobial enzyme that functions to disrupt the same bacterial structure that β-lactams ultimately target?
A. Phospholipase A
B. Lysozyme
C. Defensins
D. Histatins 2.2 Short Answer: Why is the capacity of mannose-binding lectin (MBL) trimers to oligomerize important for their function?
2.3 Multiple Choice: Choose the option that correctly describes ficolins.
A. C-type lectin domain, affinity for carbohydrates such as fucose and N-acetylglucosamine (GlcNAc), synthesized in the liver
B. Fibrinogen-like domain, affinity for oligosaccharides containing acetylated sugars, synthesized in the liver
C. C-type lectin domain, affinity for oligosaccharides containing acetylated sugars, synthesized in the liver
D. Fibrinogen-like domain, affinity for carbohydrates such as fucose and N-acetylglucosamine (GlcNAc), synthetized in the liver and lungs 2.4 Fill-in-the-Blanks: For each of the following sentences, fill in the blanks with the best word selected from the list below. Not all words will be used; each word should be used only once.
Like MBLs, ficolins form oligomers with ________ and ________. Such interaction allows the oligomer to cleave the complement components ________ and ________. Once these are cleaved, they form ________, a C3 convertase, which cleaves ________ and permits the formation of the membrane-attack complex.
2.5 Short Answer: One way in which the alternative pathway activates is by spontaneous hydrolysis of the C3 thioester bond that is normally used to covalently attach to the pathogen’s surface. How can the alternative pathway proceed to form a membrane-attack complex if the C3 convertase that initiates this process is soluble?
2.6 Fill-in-the-Blanks: Paroxysmal nocturnal hemoglobinuria, a disease characterized by episodes of intravascular red blood cell lysis, is the result of red blood cells losing the expression of ________ and ________, which renders them susceptible to lysis by the ________ pathway of the complement system.
2.7 Matching: Match each of the following complement-regulatory proteins with the pathological manifestation that would develop if this factor were defective: