Complement activation is a cascade reaction, with each component sequentially acting on others, in a similar way to the blood-clotting system. Discuss the effects that occur when peptides are generated from the activation by either the classical or the alternative pathway.
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Complement activation is a cascade reaction, with each component sequentially
acting on others, in a similar way to the blood-clotting system. Discuss the effects
that occur when peptides are generated from the activation by either the classical
or the alternative pathway.
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- Complement activation is a cascade reaction, with each component sequentially acting onothers, in a similar way to the blood-clotting system. Discuss the effects that occur whenpeptides are generated from the activation by either the classical or the alternative pathwayComplement is an integral part of the innate immune response to bacteria . One of its mechanisms of action is to behave as an anaphylatoxin Describe the anaphylatoxic effects of complement identifying which components are activated.Neutralizing antibodies are effective at preventing infection or toxicity mediated by pathogens or their toxic products. In fact, nearly all vaccines currently in use function by eliciting neutralizing antibodies. One example is the tetanus vaccine, in which neutralizing antibodies are generated against an inactivated form of the tetanus toxin (the tetanus toxoid). The most important feature of a neutralizing antibody is having high affinity for the antigen. being efficient at activating the complement cascade. having a high degree of multivalency, such as being a pentamer or hexamer of immunoglobulin monomers. being present at a high concentration in the circulation. 0 0 0 0
- A patient has many allergic reactions. As part of the treatmentscheme, doctors try to identify the allergen that stimulates theimmune system’s response. A series of solutions, each containing anallergen that commonly causes a reaction, is composed. Each solution is injected into the skin at different locations on the patient’sback. The following results are obtained: (a) At one location, theinjection site becomes red and swollen within a few minutes;(b) at another injection site, swelling and redness appear 2 dayslater; and (c) no redness or swelling develops at the other sites.Explain what happened for each observation by describing whatpart of the immune system was involved and what caused the redness and swelling.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: Their higher-order oligomeric structure can be assembled only after the monomers first bind to pathogen membranes. They only recruit MASP (MBL-associated serine proteases) proteins when bound to pathogen surfaces and not when bound to host cells. They only undergo the conformational change needed to activate MASP proteins when bound to a pathogen and not when bound to a host cell. They only bind to carbohydrate side chains and oligosaccharide modifications found on pathogen surfaces but not on host cell membranes. The activated MASP proteins are rapidly inactivated by hydrolysis when present on the surface of a host cell.The formation of the C3 convertase is a key step in complement activation that occurs in all three complement pathways. This enzyme cleaves C3 in blood plasma, leading to a conformational change in the C3b fragment that exposes its reactive thioester group. The activated C3b is potentially harmful to the host, if it becomes covalently attached to a host cell, rather than to the surface of a pathogen. This deleterious outcome is largely avoided by: The inability of active C3b to diffuse away in the blood plasma. The inability of active C3b to covalently attach to the membranes of eukaryotic cells. The rapid hydrolysis of active C3b in solution, rendering it inactive. The tight binding of active C3b to the C3 convertase. The ability of active C3b to recruit phagocytic cells.
- It would be disastrous if a complement attack werenot confined to the surface of the pathogen that is the tar-get of the attack. Yet, the proteolytic cascade involved inthe attack liberates biologically active molecules at severalsteps: one that diffuses away and one that remains boundto the target surface. How does the complement reactionremain localized when active products leave the surface?The current view in the field of immunology is that dendritic cells are the primary antigen-presenting cells for stimulating naive T cells. One piece of evidence supporting this conclusion is the observation that IRF8-deficient individuals, which retain their tissue-resident macrophages, are susceptible to a range of severe opportunistic infections caused by intracellular bacteria, viruses, and fungi. Explain the reasoning behind this argument.Complement components and the C-reactive protein are some of the acute phase reactants. Aside from these, enumerate five (5) other acute phase reactants.
- The alternative pathway is an amplification loop for C3b formation that is accelerated by properdin in the presence of pathogens. The alternative pathway of complement activation has an important role in innate immunity, due to its ability to greatly amplify the amount of C3b deposited onto the pathogen surface. This amplification occurs because: The C3 convertase of the alternative pathway is much more active than those of the classical and lectin pathways. The C3 convertase of the alternative pathway works as a soluble enzyme in the plasma. The C3 convertase of the alternative pathway cannot be inactivated by complement regulatory factors in the host. The C3 convertase of the alternative pathway is more efficiently recruited to pathogen surfaces than the C3 convertases of the classical and lectin pathways. The C3 convertase of the alternative pathway contains C3b, and can generate more of itself.Which of the following is true about complement? Check all that apply. Three pathways of complement, where classical and alternative, are activated by antibodies and lectin by spontaneous hydrolysis of C3 Complement pathways are activated in response to infections and involved in opsonization, phagocytosis and lysis of microbes The"b" subunit of complement such as C3b or C5b is deposited on the microbes, whereas the "a" subunit, C3a or C5a recruits phagocytic cells to the site of infection and promotes inflammation Alternative pathway is activated immediately due to presence of C3b because of spontaneous hydrolysis of C3, whereas classical pathways in several days after secretion of pathogen-specific antibodies Seven complement(C) proteins are made by liver and C5 is found in abundanceAdjuvants are substances that slow but do not stop the release of anantigen from an injection site into the blood. Suppose injection A isgiven without an adjuvant and injection B of the same amount ofantigen is given with an adjuvant that causes antigen to be releasedover a period of 2–3 weeks. Does injection A or injection B result inthe greater amount of antibody production? Explain.