THE INNATE IMMUNE SYSTEM: AN OVERVIEW
During the first one and one-half units we looked at microorganisms: how they replicate, why some are potentially more pathogenic than others, and how we can control them with antimicrobial agents. The remainder of Unit 2 and all of Unit 3 is devoted to the ways in which the body defends itself against microbes and other potentially harmful cells and molecules.

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

The second half of Unit 2 deals with innate immunity while Unit 3 will cover adaptive immunity. Let's first briefly compare acquired and innate immunity.

 

1. 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. This is the immunity one develops throughout life.

An antigen 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.

The body recognizes an antigen as foreign when epitopes of that antigen bind to B-lymphocytes and T-lymphocytes 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 called surface immunoglobulin (sIg). The receptor on a T-lymphocyte is called a T-cell receptor (TCR).

 It is thought that the human body has the genetic ability to recognize 107 - 109 different epitopes. In otherwords, the body has 107 - 109 distinct clones of both B-lymphocytes and T-lymphocytes, each with a unique B-cell receptor or T-cell receptor. In this 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.

Adaptive immunity usually improves upon repeated exposure to a given infection and involves:

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

  • the activation and proliferation of antigen-specific B-lymphocytes;
     

  • the activation and proliferation of antigen-specific T-lymphocytes; and
     

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

Acquired immunity includes humoral immunity and cell-mediated immunity and will be the topic of Unit 3.

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.

2. Innate immunity refers to antigen-nonspecific defense mechanisms that a host uses immediately or within several hours after exposure to almost any antigen. This is the immunity one is born with and is the initial response by the body to eliminate microbes and prevent infection.

Unlike adaptive immunity, innate immunity does not recognize every possible antigen. Instead, it is designed to recognize a few highly conserved structures present in many different microorganisms. The structures recognized are called pathogen-associated molecular patterns and include LPS from the gram-negative cell wall, peptidoglycan, lipotechoic acids from the gram-positive cell wall, the sugar mannose (common in microbial glycolipids and glycoproteins but rare in those of humans), bacterial DNA, N-formylmethionine found in bacterial proteins, double-stranded RNA from viruses, and glucans from fungal cell walls. Most body defense cells have pattern-recognition receptors for these common pathogen-associated molecular patterns. 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 molecular patterns.

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