Pattern Recognition Receptors

Chapter 6 This chapter outlines the concepts of innate immunity, inflammation, and wound healing. Innate immunity refers to the body's initial defense mechanisms against invasion and injury. Inflammation is the body's response to injury and infection, aimed at protecting and healing the body. Wound healing involves several phases, including hemostasis, inflammation, tissue formation, and remodeling. Bullet points Pattern Recognition Receptors (PRRs):  Different types: Toll-like receptors (TLRs), C-type lectin receptors (CLRs), NOD-like receptors (NLRs), Complement receptors, Scavenger receptors  Recognize: Pathogen-associated molecular patterns (PAMPs) and Damage-associated molecular patterns (DAMPs)  Found in: Phagocytic cells, macrophages, dendritic cells, innate immune cells, platelets, epithelial cells, vascular smooth muscle cells, macrophages Recognition of Pathogens  Innate immune cells have pattern recognition receptors (PRRs) that recognize more than 1000 different molecules  Toll-like receptors (TLRs) are an important group of PRRs that recognize various molecules located on the cell wall or surface of microorganisms  C-type lectin receptors (CLRs) bind to both pathogen-associated molecular patterns (PAMPs) and damageassociated molecular patterns (DAMPs)  Nucleotide-binding-like receptors (NLRs) and NOD-like receptors are cytoplasmic receptors that recognize PAMPs and DAMPs  Complement receptors recognize fragments produced through activation of the complement system  Scavenger receptors facilitate recognition and phagocytosis of bacterial pathogens, damaged cells, and lipoproteins Cellular Mediators and Products  Cytokines are small soluble signaling molecules secreted by a variety of cells  They regulate innate or adaptive immunity and can be proinflammatory or anti-inflammatory  Some cytokines have systemic effects, such as inducing fever  Mediators such as histamine, prostaglandins, leukotrienes, and bradykinin are involved in inflammation and immune response  Other mediators like transforming growth factor-beta (TGF-B) and vascular endothelial growth factor (VEGF) are involved in repair and healing  Inflammatory mediators also play a role in pain, angiogenesis, and systemic effects like phagocytosis, fever, and leukocytosis Mediators of Inflammatory Processes:  TNF-α, MCF, IL-8, ENA-78, NCF, ECF-A, kallikrein  IL-4, IL-5 (Mast cells and eosinophils)  G-CSF (Granulocytes) Engulfment and Phagocytosis:  Monocytes (M-CSF)  C3b, IgG (opsonins) Natural Killer Cells:  IL-2  IFN-γ (activates macrophages) Acute Phase Reactants:  TNF-α, IL-1, IL-6, IL-8  CRP (C-reactive protein) and other proteins  TNF-β (increases phagocytosis) Classification of Cytokines:  Cytokines are small signaling proteins secreted by various cell types  Lymphokines and monokines refer to cytokines secreted from lymphocytes or monocytes, respectively  Chemokines are chemotactic cytokines that attract leukocytes to sites of inflammation  Interleukins (ILs) are produced predominantly by macrophages and lymphocytes Effects of Interleukins (ILs):  Regulation of cell adhesion molecules (CAMs)  Attraction of leukocytes to a site of inflammation (chemotaxis)  Induction, proliferation, and maturation of leukocytes in bone marrow  General enhancement or suppression of inflammation and adaptive immune response Proinflammatory Cytokines:  TNF-α, IL-1, IL-6  TNF-α interacts with IL-1 and IL-6  TNF-α is primarily secreted by activated macrophages and contributes to the damaging effects of chronic inflammation Effects of TNF-α:  Chemotaxis and adherence of neutrophils  Phagocytosis  Fever induction  Increase in liver synthesis of acute phase proteins  Muscle wasting (cachexia)  Intravascular thrombosis Effects of IL-1:  Enhances both innate and adaptive immunity  Acts as a growth factor for many cells  Endogenous pyrogen (fever-causing cytokine) Effects of IL-6:  Produced by various cell types  Directly induces hepatocytes to produce many of the acute phase proteins Inflammation and Cytokines  Proteins called acute phase proteins are needed for inflammation  IL-6 stimulates growth and differentiation of blood cells and fibroblast growth for wound healing  Anti-inflammatory cytokines like IL-10 and TNF-B control the inflammatory response  IL-10 suppresses activation and proliferation of lymphocytes and limits production of proinflammatory cytokines  TGF-B suppresses lymphocyte activity and production of proinflammatory cytokines  Interferons protect against viral infections and modulate immune response  Type I interferons induce antiviral proteins and protection in neighboring healthy cells  Type II interferon (IFN-y) activates macrophages and enhances immune system response Immunoreactive Cells  Mast cells are significant activators of the inflammatory response  Mast cells release biochemical mediators in response to tissue injury  These mediators include histamine, chemotactic factors, and cytokines  Histamine has potent effects on other cells and can bind to histamine receptors on target cells Vasoactive amines  Molecules like histamine and serotonin cause temporary constriction of smooth muscle  They also cause dilation of postcapillary venules, increasing blood flow within microcirculation  Histamine increases vascular permeability and leukocyte adherence