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Innate Immune Responses and Complement Activation

Chapter 2 · Describe PAMPs and PRRs, and how they are involved in the immune response. Pathogens have PAMPS: pathogen associated molecular patterns. They are molecular structures that: o Are not found in multicellular hosts o Present on numerous groups of pathogens o Essential for the microbe and do not undergo frequent mutation Examples: LPS, peptidoglycan, dsRNA PRR: Pattern recognition receptors: receptors that recognize PAMPs and help immune system cells recognize self from non self Chapters 2 - Innate Immune Responses Phagocytosis (endocytotic) receptors: when a pathogen binds to this type of PRR, it is engulfed by the cell. Toll-like receptors (TLRs) is a different type of PRR: the binding of the PAMPs initiates intracellular signals that result in: - release of cytokine1 - up-regulation of MHC class II proteins2,3 - up-regulation of B7 co-stimulatory molecule3 (3important in the development of the adaptive immune responses). 1 Later in these slides, Introduced in 2Chapter 8 and 3Chapter 9 20 Toll-like receptors (TLR) Pattern recognition receptors that can initiate the cell's signal transduction pathways when the cell has recognized the presence of a pathogen They recognize common features such as LPS in gram negative bacteria and PG in gram positive bacteria · Describe the key features of the alternative pathway for complement activation. Innate immune responses to pathogens include both a cellular component and a protein component. There are two important types of proteins that are part of innate responses and work on attacking extracellular pathogens a. Some type of soluble PRRs can activate complement. b. Complement: a collection of proteins in the blood that work in a cascade process o Classical pathway: -- > adaptive a. The complement proteins are activated when antibodies made during a previous adaptive immune response bind to the pathogen surface. Antibodies are a type of plasma protein produced by B cells (both antibodies and the classical pathway of complement activation will be discussed in Chapter 6). o Alternative C' pathway -- > innate Complement proteins are a set of plasma proteins that act together in a cascade manner to attack extracellular forms of pathogens a. complement proteins bind directly to the bacteria and initiate the complement activation cascade directly (thereby eliminating the need for antibody recognition to start the cascade). There is a lot of the complement protein C3 in blood and small amounts spontaneously undergo hydrolysis to result in a form of C3b that binds to the pathogen surface. (can also be activated by interacting with IgG bound to surfavce of pathogen) b. C3b is formed from spontaneous breakdown c. It binds to pathogen surface (C3b is deposited in membrane of invading cell) d. Recruits a C3 convertase proteins to breakdown C3 e. C3b recruits C5 convertase to breakdown C5 f. C5b binds to surface and more proteins are formed g. Complex of proteins and molecules polymerize to form a pore and Pathogen is killed because it lysis (loses its cytoplasmic content) Component Function C3a Increases permeability of blood vessels, expression of adhesion molecules to