Diet, Immunity and Inflammation

Philip C Calder, Parveen Yaqoob, Philip C Calder, Parveen Yaqoob

• Publisher: Woodhead Publishing
• Year: 2013
• ISBN:
  9780857095749
• Topic: Technology & Engineering
• Subtopic: Food Science
• Index: Technology & Engineering

Although inflammation is one of the body's first responses to infection, overactive immune responses can cause chronic inflammatory diseases. Long-term low-grade inflammation has also been identified as a risk factor for other diseases. Diet, immunity and inflammation provides a comprehensive introduction to immunity and inflammation and the role that diet and nutrition play with regard to this key bodily response.Part one, an introductory section, discusses innate and adaptive immunity, mucosal immunity in a healthy gut and chronic inflammatory diseases and low grade inflammation. Chapters in part two highlight the role of micronutrients, including zinc, selenium, iron, vitamin A and vitamin D, in inflammation and immunity. Part three explores other dietary constituents and includes chapters on intestinal bacteria and probiotics, the impacts of prebiotics on the immune system and inflammation, and antimicrobial, immunomodulatory and anti-inflammatory effects of food bioactive proteins and peptides. Further chapters explore the role of olive oil, short and long chain fatty acids and arginine and glutamine in immune functions. Nutrition, immunity and inflammation are discussed from an integrative and life course perspective in part four. Chapters focus on adverse immune reactions to foods, early nutritional programming, the impact of nutrition on the immune system during ageing, the impact of exercise on immunity and the interaction with nutrition, and the effect that malnutrition has on immunity and susceptibility to infection.With its distinguished editors and international team of expert contributors, Diet, immunity and inflammation is a comprehensive resource for those researching immunology or inflammation, nutrition scientists, and professionals in the food and nutrition industries who require an understanding of the effect that diet can have on the immune system and inflammation.

• Provides an overview of key research in the important and connected areas of inflammation, infection, overactive immune responses, diseases and diet
• Outlines the fundamentals of immunity and inflammation and reviews the effects of different food constituents
• Discusses important related issues, such as ageing and exercise

Part I

Immunity and inflammation: an introduction

1

Innate and adaptive immunity

P.S. Noakes, University of Western Australia, Australia

L.J. Michaelis, Royal Victoria Infirmary, UK

Abstract:

The innate and adaptive immune systems are often described as contrasting separate arms of the host response; however, they usually act together, with the innate response representing the first line of host defense and the adaptive response becoming prominent after several days as antigen-specific T and B cells have undergone clonal expansion. Components of the innate system contribute to activation of the antigen-specific cells. Additionally, the antigen-specific cells amplify their responses by recruiting innate effector mechanisms to bring about the complete control of invading microbes. Thus, although the innate and adaptive immune responses are fundamentally different in their mechanisms of action, synergy between them is essential for an intact, fully effective immune response.

Key words

innate immunity

adaptive immunity

B cell

T cell

regulation

1.1 Introduction

The immune system consists of a complex network of specialized cells which each have precise roles. Immunity is generally divided into two parts determined by the speed and specificity of the response: (i) innate and (ii) adaptive immunity. The innate immune response is rapid, non-specific, non-anticipatory and non-clonal, and utilizes germ-line-encoded receptors. In contrast, the adaptive (sometimes referred to as acquired) immune response is specific, anticipatory and clonal and uses receptors that have been generated by somatic DNA rearrangement. The innate response uses an arsenal of cells, which includes phagocytic cells (neutrophils, monocytes and macrophages), inflammatory cells (basophils, mast cells and eosinophils) and natural killer cells. The molecular components of the innate repertoire include complement, acute-phase proteins and cytokines. The adaptive response involves the binding of antigen to surface receptors of specific B and T cells via an antigen presenting cell (APC) and the subsequent activation, proliferation and regulation of many immune pathways. In response to this cascade, B cells secrete immunoglobulins (Ig), the antigen-specific antibodies whose key role is to identify and aid destruction of extracellular micro-organisms. T cells assist B cells to produce antibody and are able to eradicate intracellular organisms by triggering macrophages and directly destroying virally infected cells. Innate and adaptive immune responses work together to eliminate organisms, toxins and allergens, while providing normal homeostasis. This chapter will provide an overview of the key mechanisms used by the immune system to respond to invading microbes and other exogenous threats.

1.2 Levels of defense

In order to protect itself from a diverse array of environmental pathogens and toxins, the body has developed a number of barrier mechanisms (e.g. the gut immune barrier and blood–brain barrier) to limit the entry of potential hazards. Although each barrier provides defense in very different environments, there are many similarities in their mechanisms of action. There is a physical barrier formed by a cellular layer that tightly regulates the movement of ions, molecules and cells between two tissue spaces. These barrier cells interact with different cell types, which dynamically regulate their function, and with a different array of immune cells that survey the physical barrier and provide innate and adaptive immunity (for a recent review of these chemical and physical barriers see (Daneman and Rescigno, 2009)).

1.3 Innate immunity

The innate immune system comprises several molecules, cells and processes that work in conjunction with the adaptive immune system to maintain physiological homeostasis of the host and to protect it against potentially pathogenic organisms. Although innate and adaptive immune systems have been traditionally viewed as two separate entities or sometimes as two overlapping entities, it has now become very clear that these are highly integrated and interconnected systems.

1.3.1 Innate immune recognition

Pattern-recognition receptors

Recognition of microbial pathogens is an essential element for the initiation of innate immune response such as inflammation and is mediated by germline-encoded pattern-recognition receptors (PRRs) that recognize molecular structures that are broadly shared by pathogens, known as pathogen-associated molecular patterns (PAMPs). Since these molecular patterns exist in benevolent, neutral and malevolent organisms alike, they should actually be designated as MAMPs (microbial-associated molecular patterns) (Mackey and McFall, 2006). Upon MAMP/PAMP recognition, PRRs initiate a series of signaling programs that execute the first line of host defensive responses necessary for killing infectious microbes. In addition, PRR signaling simultaneously induces maturation of dendritic cells (DCs), which is responsible for alerting induction of the second line of host defense, that is, adaptive immunity.

Toll-like receptors (TLRs) were the first PRRs to be identified (Akira et al., 2001). TLRs are type I transmembrane proteins with ectodomains containing leucine-rich repeats that mediate the recognition of PAMPs, transmembrane domains and intracellular Toll-interleukin 1 (IL-1) receptor (TIR) domains required for downstream signal transduction. They are expressed either on the cell surface or associated with intracellular vesicles (Fig. 1.1). To date, 10 functional TLRs have been identified in humans (reviewed in Kawai and Akira, 2010). Each TLR detects distinct PAMPs derived from viruses, bacteria, mycobacteria, fungi and parasites (Table 1.1). These include lipopolysaccharide (LPS) from gram- negative bacteria, peptidoglycan, lipoteichoic acid, bacterial flagellar proteins, viral double stranded RNA and unmethylated DNA with CpG motifs characteristic of microbial DNA. Interaction between PAMPs and TLRs initiates a signaling cascade upon recruitment of an adapter protein (e.g. MyD88) leading to activation of members of the mitogen activated protein (MAP) kinase family, nuclear factor kappa B (NFкβ) and interferon (IFN) regulatory factors amongst others (Kawai and Akira, 2010).

Table 1.1

Pattern-associated molecular patterns (PAMPs) and their recognition by toll-like receptors (TLRs) and other pattern-recognition receptors (PRRs)

AIM, absent in melanoma; DAI, DNA-dependent activator of interferon; IFI, interferon γ-inducible protein; IPAF, interleukin-1 β-converting enzyme (ICE) protease-activating factor; MDA, melanoma differentiation-associated gene; NAIP, neuronal apoptosis inhibitory protein; NALP, NACHT-, LRR- and PYD-containing proteins; NOD, nucleotide-binding oligomerization domain; RIG, retinoic acid-inducible gene.

Source: Modified from Immunity, 34, T. Kawai and S. Akira, Toll-like receptors and their cross-talk with other innate receptors in infection and immunity, 637–650, Copyright (2011) with permission from Elsevier.

Fig. 1.1 TLR trafficking and signaling. Reprinted from Immunity. 34. T. Kawai and S. Akira, Toll-like receptors and their cross-talk with other innate receptors in infection and immunity. 637–650. Copyright (2011) with permission from Elsevier.

After discovery of TLRs, several classes of cytosolic PRRs, including RIG-I-like receptors (RLRs) and Nod-like receptors (NLRs), were identified. These PRRs, in concert with TLRs, have a critical role in both innate and adaptive immunity. A more detailed discussion of these and other ligands can be found elsewhere (Kawai and Akira, 2011).

1.3.2 Cellular components of the (innate) immune response

All cells of the immune system derive from the bone marrow; in fact, all of the inflammatory and ancillary cells that work in concert with...