Exam 2: Innate Immunity: the First Lines of Defense

The production of antimicrobial peptides is one of the most evolutionarily ancient mechanisms of defense for multicellular organisms, and most eukaryotic species make many different forms of these proteins. For instance, human paneth cells in the gastrointestinal epithelium make 21 different defensins. The reason for this diversity of antimicrobial peptides is:

Epithelial surfaces provide the first line of defense against infection by the use of several types of mechanisms. One of the chemical mechanisms used by epithelia is:

The C3 convertase of the alternative complement pathway amplifies the overall magnitude of complement activation regardless of which of the three pathways initiated the complement activation initially.

Neutrophils regulate the production of active cathelicidins (a class of antimicrobial peptides) by segregating the inactive propeptide from the processing enzyme that cleaves and activates it in two different types of cytoplasmic granules. These two types of granules are induced to fuse with phagosomes after ingestion of microbes, bringing the processing enzyme and the propeptide together.

Opsonization of pathogens by both antibodies and complement proteins (C3b) leads to uptake and destruction of the pathogen by phagocytic cells that express both Fc receptors and complement receptors. Which of the following in Figure is the most efficient form of dual opsonization of the pathogen by antibody and C3b to maximize phagocytosis?

The importance of complement activation as an innate immune defense against infections is illustrated by:

Streptococcus pneumoniae is a Gram-positive bacterium that colonizes the mucosal surface of the upper respiratory tract in humans. The presence of this bacterium in the nose and throat is widespread in the population, and in most people, colonization with Strep. pneumoniae is asymptomatic. Figure shows a comparison of in vitro growth curves of the wild-type strain of Strep. pneumoniae, as well as a Strep. pneumoniae mutant strain with a defect in one bacterial gene. The graph on the right shows the growth curve following addition of lysozyme during the logarithmic phase of bacterial growth. Which statement could account for the data in these graphs?

Mannose binding lectins (MBL) and ficolins are the two classes of proteins that can initiate the lectin pathway of complement activation. These proteins are selective for activating complement on the surfaces of microbial pathogens rather than host cells because:

Although the complement cascade can be initiated by antibodies bound to the surface of a pathogen, complement activation is generally considered to be an innate immune response. This is because:

The C3 convertase amplifies the process of complement activation by generating large amounts of C3b and cleaving large numbers of C5 molecules.

Although homozygous deficiencies in complement regulatory proteins cause serious diseases, more subtle alterations in the balance of complement activation versus inhibition have been found to contribute to disease susceptibility. Describe the genetic evidence linking subtle alterations in complement regulatory proteins to disease susceptibility.

B cells express a complement receptor that binds to C3b cleavage products, such as iC3b and C3dg. When a B cell with an antigen receptor that specifically recognizes that pathogen also has its complement receptor stimulated because the pathogen is opsonized with these C3 fragments, B cell activation is greatly enhanced. Due to this mechanism, B cells can be activated by much lower concentrations of antigen (in this case, the pathogen) than if the antigen is devoid of complement components. This mechanism functions to:

Mucosal surfaces and external epithelia are major routes of pathogenic infection. Mucosal surfaces are found in tissues such as the gastrointestinal tract, the reproductive tract and the mouth and respiratory tract. While the mouth and respiratory tract are routes of virus but not bacterial infections, the gastrointestinal tract is the route for bacterial but not virus infections.

In vertebrates, complement activation generally involves a pathogen recognition step followed by a proteolytic cascade that produces the effector proteins that function in opsonization, membrane attack, and inflammation. a) Which of these is likely to be the most evolutionarily primitive aspect of the complement system? b) Which pathway of complement initiation is likely to be the one that most recently evolved?

Antibodies, complement proteins, and phagocytic cells provide effective protection against all of the following types of infections in Figure , except:

Even when the complement cascade fails to proceed beyond generating the C3 convertase, complement activation is effective at inducing pathogen uptake and destruction. This process of immune protection is mediated by:

The classical and lectin pathways of complement activation converge at the step of C3 activation. However, the initiating steps of each pathway use protein components and enzymatic mechanisms that share no similarity with each other.

Women with urinary tract infections caused by

Pathogenic infections induce damage to the host by a variety of mechanisms. While many mechanisms are direct effects of the pathogen, some damaging mechanisms result from the immune response to the infection, as illustrated in Figure . Examples of damage caused by the host immune response are:

Patients with recurrent infections of Neisseria meningitidis, an extracellular bacterial pathogen that causes meningitis, were examined to determine the underlying cause of their immunodeficiency. A subset of these patients were found to have defects in complement activation on the bacterial surface, a process that for this bacterium is dominated by alternative complement activation leading to C3b deposition on the pathogen surface. When neutrophils from these patients were examined in vitro, the results in Figure were obtained. Based on these data, the identity of the green neutrophil mediator in Figure is likely to be: