The Innate Immune System: An Overview

THE INNATE IMMUNE SYSTEM

A. THE INNATE IMMUNE SYSTEM VERSUS THE ADAPTIVE IMMUNE SYSTEM: AN OVERVIEW

The overall purpose of this Learning Object is:
1) to introduce what is meant by the innate immune system; and
2) to compare the innate immune system with the adaptive immune system.

LEARNING OBJECTIVES FOR THIS SECTION

The body has two immune systems: the innate immune system and the adaptive immune system.

1. Innate immunity is an antigen-nonspecific defense mechanisms that a host uses immediately or within several hours after exposure to almost any microbe. This is the immunity one is born with and is the initial response by the body to eliminate microbes and prevent infection. In general, the innate immune responses do not improve with repeated exposure to a given infection.

Unlike adaptive immunity, innate immunity does not recognize every possible antigen. Instead, it is designed to recognize molecules shared by groups of related microbes that are essential for the survival of those organisms and are not found associated with mammalian cells. These unique microbial molecules are called pathogen-associated molecular patterns or PAMPS (def) and include LPS from the gram-negative cell wall, peptidoglycan and lipotechoic acids from the gram-positive cell wall, the sugar mannose (a terminal sugar common in microbial glycolipids and glycoproteins but rare in those of humans), bacterial and viral unmethylated CpG DNA, bacterial flagellin, the amino acid N-formylmethionine found in bacterial proteins, double-stranded and single-stranded RNA from viruses, and glucans from fungal cell walls. In addition, unique molecules displayed on stressed, injured, infected, or transformed human cells also act as PAMPS. (Because all microbes, not just pathogenic microbes, possess PAMPs, pathogen-associated molecular patterns are sometimes referred to as microbe-associated molecular patterns or MAMPs.)

Most body defense cells have pattern-recognition receptors or PRRs (def) for these common PAMPS and so there is an immediate response against the invading microorganism. Pathogen-associated molecular patterns can also be recognized by a series of soluble pattern-recognition receptors in the blood that function as opsonins and initiate the complement pathways. In all, the innate immune system is thought to recognize approximately 10³ of these microbial molecular patterns.

Innate immunity involves the following:

phagocytic cells: leukocytes such as neutrophils, eosinophils, and monocytes; tissue phagocytic cells in the tissue such as macrophages (def);

cells that release inflammatory mediators: inflammatory cells in the tissue such as macrophages and mast cells (def); leukocytes such as basophils and eosinophils;

natural killer cells (NK cells (def)); and

molecules such as complement proteins (def), acute phase proteins (def), and cytokines (def).

Examples of innate immunity include anatomical barriers, mechanical removal, bacterial antagonism, antigen-nonspecific defense chemicals, the complement pathways, phagocytosis, inflammation, fever, and the acute-phase response. In this current unit we will look at each of these in greater detail.

Concept Map for Innate Versus Adaptive Immunity

2. Adaptive (acquired) immunity refers to antigen-specific defense mechanisms that take several days to become protective and are designed to react with and remove a specific antigen (def). This is the immunity one develops throughout life. Adaptive immune responses often improve upon repeated exposure to a given infection.

An antigen (def) is defined as a substance that reacts with antibody molecules and antigen receptors on lymphocytes. An immunogen is an antigen that is recognized by the body as nonself and stimulates an adaptive immune response. For simplicity we will use the term antigen when referring to both antigens and immunogens. The actual portions or fragments of an antigen that react with antibodies and lymphocyte receptors are called epitopes (def).

The body recognizes an antigen as foreign when epitopes of that antigen bind to B-lymphocytes (def) and T-lymphocytes (def) by means of epitope-specific receptor molecules having a shape complementary to that of the epitope. The epitope receptor on the surface of a B-lymphocyte is called a B-cell receptor and is actually an antibody molecule (def). The receptor on a T-lymphocyte is called a T-cell receptor (TCR).

It is estimated that the human body has the ability to recognize 10⁷ or more different epitopes and make up to 10⁹ different antibodies, each with a unique specificity. In order to recognize this immense number of different epitopes, the body produces 10⁷ or more distinct clones of both B-lymphocytes and T-lymphocytes, each with a unique B-cell receptor or T-cell receptor. Among this large variety of B-cell receptors and T-cell receptors there is bound to be at least one that has an epitope-binding site able to fit, at least to some degree, any antigen the immune system eventually encounters. With the adaptive immune responses, the body is able to recognize any conceivable antigen it may eventually encounter.

The downside to the specificity of adaptive immunity is that only a few B-cells and T-cells in the body recognize any one epitope. These few cells then must rapidly proliferate in order to produce enough cells to mount an effective immune response against that particular epitope, and that typically takes several days. During this time the pathogen could be causing considerable harm, and that is why innate immunity is also essential.

Adaptive immunity involves the following:

antigen-presenting cells (APCs) such as macrophages (def) and dendritic cells (def)
;

the activation and proliferation of antigen-specific B-lymphocytes (def);

the activation and proliferation of antigen-specific T-lymphocytes (def); and

the production of antibody molecules (def), cytotoxic T-lymphocytes (CTLs) (def), activated macrophages (def), and cytokines (def).

Concept Map for Innate Versus Adaptive Immunity

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