Preface

When a foreign antigen plans to reside in the body, innate immunity attempts to define the frontier lines of defense and, if necessary, helps to formulate a more specific line of defense. There is a recognition system required for innate immunity to work efficiently in such a highly responsible position. Toll-like receptors (TLRs) are an essential part of this system. They are present on innate and adaptive immune cells making them key switches incorporated in bridging innate and adaptive immunity. The non-immune cells express TLRs and, in turn, their value increases.

This book first provides readers with basic facts about TLR structure, cellular distribution, and signaling pathways. It then discusses in detail the role of natural killer cells expressing TLRs in linking innate and adaptive immunity. Furthermore, the book includes chapters that focus on the role of TLRs in infections and neurodegenerative diseases.

> **Nima Rezaei** Professor of Clinical Immunology, Tehran University of Medical Sciences, Tehran, Iran

**1**

**Chapter 1**

Receptors

**receptors**

family of PRRs.

**2. Toll-like receptors**

*Amene Saghazadeh and Nima Rezaei*

Introductory Chapter: Toll-Like

**1. The first line of defense is filled with a variety of pattern recognition** 

Pattern recognition receptors (PRRs), which are germ line-encoded receptors, probably provided the host with the best possible innate property to identify "nonself" invaders from both exogenous and endogenous sources. PRRs can discriminate self-microorganisms and molecules from nonself ones through recognizing conserved parts of microorganisms—which are known as microorganismassociated molecular patterns (MAMPs). If it is nonself, then they will direct the induction of inflammatory responses. In addition, PRRs allow the innate immunity to identify endogenous danger signals—which are released by stressed, damaged, or dying cells and known as damage-associated molecular patterns (DAMPs)—and thereby help in initiation of sterile inflammation. In this manner, PRRs participate in the clearance of invading pathogens by regulating infectious inflammation and contribute to tissue repair and regeneration in addition to elimination of autoimmu-

nity and tumorigenesis by regulating sterile inflammatory processes.

They display three types of localization. Toll-like receptors (TLRs) are a kind of PRRs located in the membrane along with C-type lectin receptors. Also, nucleotide oligomerization domain (NOD)-like receptors (NLR) and retinoic acid-inducible gene I (RIG-I)-like receptors (RLR) are found in the nucleus and contribute to recognition of intracellular microorganisms. Finally, there are some proteins that their synthesis occurs in the cells and can be used as receptors by various microorganisms. TLRs—which are the subject of this book—were the first discovered

They exist in mammals and insects and mediate actions essential to achieve control over immune homeostasis. The major cells expressing TLRs are antigenpresenting cells (APCs). Activation of TLRs in APCs can affect maturation of these cells and T helper 1 (Th1) cell differentiation for processing more specific immune mechanisms [1]. However, different cell types of the body have the capacity to induce the expression of TLRs, allowing them to carry TLR-mediated signaling pathways and production of inflammatory mediators and type I interferons (IFN). When handling a number of immune and inflammatory pathways, TLRs are able to have a role in the induction of innate immune responses and to link the innate immunity with the acquired immunity. Interfering with TLR function leads inevitably to immunological anomalies seen in common conditions ranging from immunodeficiency and infection to allergy, autoimmunity, cancer and more generally to diseases of many organ systems including the central

### **Chapter 1**
