Ch2 Innate Immunity Flashcards
How does the specificity of innate immunity differ from that of adaptive immunity?
Innate immunity is directed against microbes and the products of damaged cells and is mediated by cell surface receptors and secreted proteins of limited diversity that recognize microbial patterns and products of damaged cells. Adaptive immunity uses an extremely large and diverse set of antigen receptors to recognize a wide variety of microbial and nonmicrobial antigens.
What are examples of microbial substances recognized by the innate immune system, and what are the receptors for these substances?
Some examples of microbial substances recognized by the innate immune system include lipopolysaccharide recognized by Toll-like receptor-4 (TLR-4), flagellin recognized by TLR-5, double-stranded DNA recognized by TLR-9, and mannans recognized by the mannose receptor as well as by mannose-binding protein.
What is the inflammasome, and how is it stimulated?
The inflammasome is a multiprotein complex found in the cytoplasm of phagocytes and some epithelial cells. It proteolytically cleaves a precursor of the cytokine interleukin-1 (IL-1), generating an active proinflammatory form of IL-1 that is released from the cell. The inflammasome contains a NOD family molecule called NLRP3 and the proteolytic enzyme caspase-1. NLRP3 recognizes several different molecules that indicate cell infection or injury, leading to activation of caspase-1, which then cleaves the IL-1 precursor. Stimuli that activate the inflammasome include various bacterial products, viral DNA, intracellular crystals such as sodium urate, reduced potassium concentration, and reactive oxygen species.
What are the mechanisms by which the epithelium of the skin prevents the entry of microbes?
The skin provides a relatively impermeable epithelial barrier. These epithelial cells secrete antimicrobial peptide antibiotics, and the skin also contains protective intraepithelial lymphocytes.
How do phagocytes ingest and kill microbes?
To recognize microbes, phagocytes use a range of receptors that recognize microbial carbohydrates and Fc receptors that recognize microbes coated (opsonized) by antibodies. Microbes are internalized into phagosomes, which fuse with lysosomes, where the microbes are destroyed by reactive oxygen and nitrogen species and lysosomal enzymes.
What is the role of MHC molecules in the recognition of infected cells by NK cells, and what is the physiologic significance of this recognition?
NK cells express inhibitory receptors that recognize MHC class I molecules on host cells and can then dampen NK cell activation. In virally infected cells, MHC class I molecules are downregulated and therefore fail to engage inhibitory receptors, and thus NK cells can be activated to kill these infected cells.
What are the roles of the cytokines TNF, IL-12, and type I interferons in defense against infections?
TNF stimulates inflammation in part by helping to recruit neutrophils and monocytes to sites of infection. IL-12 made by macrophages and dendritic cells contributes to NK cell and T cell activation. Type I interferons inhibit viral replication (the antiviral state).
How do innate immune responses enhance adaptive immunity?
Innate immune responses induce the expression of costimulators on dendritic cells that can provide second signals for T cell activation. Innate immune cells make cytokines that modulate the adaptive immune response. Complement activation as part of the innate immune response can lead to the generation of complement fragments that enhance B lymphocyte activation.
