Innate Immunity

Published on 09/02/2015 by admin

Filed under Allergy and Immunology

Last modified 09/02/2015

Print this page

rate 1 star rate 2 star rate 3 star rate 4 star rate 5 star
Your rating: none, Average: 0 (0 votes)

This article have been viewed 1541 times

Innate Immunity

Learning Objectives

Key Terms

Acute-phase proteins

Acute-phase response

Adaptive immune response

Complement

Innate immune response

Opsonin

Pyrogen

Toll-like receptor

Introduction

The body is protected from infection by anatomic and physiologic barriers in the skin and in the respiratory, intestinal, and urogenital tracts. If these barriers are breached an innate immune response is generated. In the response, phagocytic cells, antimicrobial proteins and serum enzymes are activated by molecules common to most bacteria. The innate immune response functions to contain an infection until an adaptive response can be mounted against the infective agent. An adaptive response begins 7 to 10 days after infection and consists of antibodies, CD4Th1 inflammatory response or CD8 cytotoxic cells.

Anatomic and Physiologic Barriers

Skin

The skin is an inhospitable environment for bacterial colonization and growth with the exception of staphylococcus epidermidis, bacteria cannot attach to the outer layer of skin or stratum corneum because it is composed of dead keratinocytes, keratin, ceramides, free fatty acid, and cholesterol. Moreover, the stratum corneum is continually shed and renewed by younger keratinocytes pushing up from below. Bacterial colonization is prevented by other factors as well. Perspiration deposits salt on the skin. High salt concentrations create a hypertonic environment that inhibits bacterial growth. Sebaceous glands also produce a waxlike substance called sebum, which contains lactic acid and propionic acid produced by Propionibacterium acnes—a commensal organism found in the sebaceous gland. Sebum reduces the skin pH to between 3.0 and 5.0, and this acidic environment inhibits bacterial growth.

Respiratory Tract

The respiratory tract is protected from infection by ciliated epithelial cells and a mucous layer. Glycosylated mucous proteins cover the entire respiratory tract and trap particulate matter. The coordinated beating of the cilia on respiratory epithelial cilia moves the mucus upward to the glottis, where it is expelled from the airways or swallowed. This mechanism is referred to as the mucociliary escalator. The mucous covering is replaced several times each day, leading to the production of a pint to a quart of mucus per day. Defective escalator function increases the risk of developing respiratory tract infections, sinusitis, and otitis media.

Mucociliary escalator dysfunction can be inherited or can be the result of environmental insults. For example, primary ciliary dyskinesia (PCD) is an inherited syndrome characterized by impaired transport and the abnormal structure of cilia. In this syndrome, lungs and sinuses are prone to repeated infections.

Environmental insults and drugs often affect the function of the mucociliary escalator. For example, halothane, cocaine, and sulfur dioxide are toxic to epithelial cells. Smoking or inhalation of toxic fumes also injures the epithelium causing loss of ciliated cells. Escalator function can be compromised by cold or dry air that often creates a highly viscous mucus that cannot be moved upward by ciliated cells.

Stomach and Intestine

Stomach acid forms a passive barrier to prevent infection of the intestinal tract. With the exception of Helicobacter pylori (the etiologic agent of gastric and duodenal ulcers), most ingested pathogenic bacteria cannot survive in stomach acid. Bile salts found in the intestine also are toxic to bacteria.

Urogenital Tract

The components of the urogenital tract that actively participate in the innate immune response are the urethra and the vaginal mucosa. The urethra is usually sterile because the persistent flushing of urine prevents bacterial attachment to urethral epithelial cells. The acidity of urine also prevents bacterial colonization. In females, the normal flora of the vaginal mucosa prevents colonization by pathogenic microbes. Acids produced by lactobacilli create a slightly acidic mucosal environment that inhibits bacterial growth. The risk of infection increases when the lactobacillus population is reduced, the pH of urine is increased, or both.

Pathogen-Associated Molecular Patterns

Pathogen-associated molecular patterns (PAMPs) are molecular structures or molecules that are shared by most pathogenic bacteria and some viruses. Most components are constituents of microbial cell walls, single-stranded and double-stranded nucleic acids, or unmethylated deoxyribonucleic acid (DNA). Common PAMPs are presented in Table 2-1. In an innate immune response, PAMPs are recognized by several different mechanisms, including the following:

Table 2-1

Common Pathogen-Associated Microbial Patterns in Bacteria, Fungi, and Viruses

Peptidoglycan Gram-positive bacteria
Lipopolysaccharide Gram-negative bacteria
Lipoteichoic acids Gram-positive bacteria
Flagellin Bacteria
Lipoarabinomannan Mycobacteria
Beta 1,3 glycan Fungi
Respiratory syncytial virus (RSV) protein Viruses
Double-stranded ribonucleic acid (RNA) Viruses
Lipopeptides Mycoplasma
Unmethylated CpGDNA Bacteria
Profilin-like molecules Toxoplasma

Unmethylated bacterial deoxyribonucleic acid (DNA) containing cytosine phosphate guanine motifs.

Serum Complement Components and Pathogen-Associated Molecular Patterns

Complement comprises nine serum proteins (Figure 2-1) and produces proinflammatory factors that are chemotactic for phagocytic cells (see Chapter 11). Complement fragments coat bacteria to create opsonins, which are, by definition, molecules that attach to microbes and promote phagocytosis.

Complement can be activated by different mechanisms. In an adaptive response, complement is activated by antigen–antibody complexes (see Chapter 11). Three other mechanisms do not require the presence of antibody and are activated during an innate immune response. Complement can be activated by interaction with select molecules (e.g., zymozan) on microbial surfaces in an alternative complement activation pathway. Lectins (proteins that bind to sugars) also activate the complement cascade in the mannose-binding lectin (MBL) pathway. Some acute phase proteins produced by the liver during inflammation activate the complement cascade (see Acute Phase Response).

Mannose-Binding Lectin Complement Activation Pathway

Collectins are a family of lectins that react with terminal mannose or fructose molecules on microbes and activate complement. The collectin family includes Mannose-binding lectin (MBL), bovine conglutinin, lung surfactants A and D, and bovine collectin 43. Structurally, collectins are multi-meric proteins with a “flower bouquet” or an “X-like” structure (Figure 2-2).

Buy Membership for Allergy and Immunology Category to continue reading. Learn more here