Ch 8 Effector Mechanisms of Humoral Immunity Flashcards
What regions of antibody molecules are involved in the functions of antibodies?
The N-terminal variable regions of antibodies are involved in antigen binding. The Fc portion of the heavy-chain constant region is involved in binding and activating complement and binding to Fc receptors in various cells, which is important for phagocytosis, antibody-mediated cellular cytotoxicity by NK cells, transplacental transport, and maintenance of prolonged half-life in the blood.
How do heavy-chain isotype (class) switching and affinity maturation improve the abilities of antibodies to combat infectious pathogens?
Class switching allows antibodies to perform different effector functions that are particularly suited to certain infections, and it allows delivery of the antibody to certain sites of infection. For example, some IgG subclasses bind well to Fc receptors on phagocytes, permitting internalization and killing of extracellular microbes. IgA antibodies are secreted into the lumen of the gut, where they can bind to pathogenic microbes and prevent them from invading through the intestinal epithelial barrier.
Affinity maturation improves the ability of antibodies to bind tightly to pathogens and therefore more effectively neutralize the microbes and target them for destruction by complement or phagocytes.
In what situations does the ability of antibodies to neutralize microbes protect the host from infections?
Neutralization prevents microbes located in mucosal secretions, blood, or extracellular tissue fluid from binding to cell surfaces, which is a first step in infecting cells. For example, viruses must enter cells to replicate, and viral entry requires binding to specific cell surface receptors, which vary depending on the virus and cell type. Antibody neutralization blocks the virus from binding to their receptors. Neutralization also inhibits the spread of microbes from an infected cell to another cell.
How do antibodies assist in the elimination of microbes by phagocytes?
IgG antibodies bind to microbial surfaces, a process called opsonization, and at the same time bind to Fc receptors on macrophages or neutrophils. Binding of the antibody to the Fc receptor stimulates internalization of the microbe by phagocytosis and activates the phagocyte, and the microbe is killed by various mechanisms inside the cell.
How is the complement system activated?
The classical pathway of complement is activated when the complement protein C1 binds to the Fc regions of IgG or IgM molecules in antibody-antigen complexes. In the lectin pathway of complement, the first step is binding of the protein mannose-binding lectin (MBL) to mannose residues on microbial surfaces. In the alternative pathway, the complement protein C3 is spontaneously hydrolyzed to form C3b, which then binds covalently to microbial cell surfaces. In all three pathways, the first step is followed by activation of a cascade of protease, generating an enzymatic complex called C3 convertase, which is covalently attached to the microbial surface.
Why is the complement system effective against microbes, but does not react against host cells and tissues?
Host cells have regulatory proteins on their cell surfaces, including decay-accelerating factor (DAF), complement receptor 1 (CR1), and C4-binding protein (C4bp) that prevent the formation of the C3 convertase. These regulatory proteins are not expressed by microbes. Alternative pathway complement proteins also tend not to bind to normal host cells.
What are the functions of the complement system, and what components of complement mediate these functions?
The main functions of the complement system are to promote inflammation, opsonize microbes for phagocyte clearance, and directly lyse microbes. Inflammation is promoted by the complement protein fragments C3a and C5a. Opsonization is mediated by C3b. Lysis is mediated by the membrane attack complex composed of C5b, C6, C7, C8, and C9.
How do antibodies prevent infections by ingested and inhaled microbes?
IgA and some IgM are secreted onto the lumen of the gut or the airways, where they neutralize pathogens.
How are neonates protected from infection before their immune system has reached maturity?
Maternal IgG is transported into the fetal circulation through the placenta, so the baby is born with a full range of antibodies against microbes that mother has been exposed to in the past. Maternal IgA and IgG in breast milk is ingested by the nursing baby and protects against intestinal pathogens.
