The Immune System in Health and Disease: Volume I

Introduction to Immunology

It is said that the field of immunology began with Edward Jenner who discovered in 1796 that cowpox could be used to induce protection against human smallpox. Jenner called this procedure vaccination, and this term is still used to describe individuals who have been injected with weakened or attenuated strains of disease-causing agents to confer protection from (often) fatal diseases. Almost two centuries later, from the initial pioneering work of Jenner, the smallpox vaccine was universal and in 1979, the World Health Organization declared smallpox eradicated.

In the late 19^th century, Robert Koch proved that infectious diseases are caused by microorganisms, with each one responsible for a particular disease. In fact, Koch defined what is now known as Koch's Postulates (which every basic course on immunology loves to test).

1. The microorganism suspected of causing pathology must be found in abundance in all organisms suffering from the disease, but should not be found in healthy animals.

2. The microorganism must be isolated from a diseased organism and grown in pure culture.

3. The cultured microorganism should cause disease when introduced into a healthy organism.

4. The microorganism must be reisolated from the inoculated, diseased organism and identified as being identical to the original specific causative agent.

Currently, disease-causing organisms or pathogens, can be grouped into four broad categories: viruses,bacteria, pathogenic fungi and parasites.A proteinaceous infectious particle, or prion, is an infectious agent composed primarily of misfolded protein and is sometimes considered as another category of pathogen.

Further advancements came in the 1800s, Louis Pasteur developed a vaccine against cholera in chickens, and also developed a rabies vaccine. Emil von Behring and Shiasaburo Kitasato discovered that serum from animals that were immune to diphtheria or tetanus contained an "antitoxic activity" that could confer short-term immunity to unimmunized animals. This "antitoxic activity" would later be termed antibodies.

Components of the Immune System

The immune response can be broadly classified into the innate and adaptive immune responses. The innate immune system comprises the cells and mechanisms that defend the host from infection in a non-specific manner. The innate immune system responds rapidly against infectious agents but unlike the adaptive immune system, it does not confer long-lasting or protective immunity to the host. The innate system is thought to constitute an evolutionarily older defense system, and is the dominant immune system found in plants, fungi, insects, and in primitive multicellular organisms. Elie Metchnikoff discovered that many microorganisms could be engulfed and digested by specialized phagocytic cells. These cells, now called macrophages, are a key component of the innate immune system and will be studies in more detail later. The major functions of the vertebrate innate immune system include:

1. Recruiting immune cells to sites of infection, through the production of chemical factors, including cytokines andchemokines.

2. Activation of the complement cascade to identify bacteria, activate cells and to promote clearance of dead cells or antibody complexes.

3. The identification and removal of foreign substances present in organs, tissues, blood and lymph, by specialized white blood cells.

4. Activation of the adaptive immune system through antigen presentation.

The adaptive immune system is composed of highly specialized, systemic cells and processes that eliminate or prevent pathogenic challenges. It provides specific immune responses, such as the production of antibodies against particular pathogens and it can retainimmunological memory because it confers immunity against the same pathogen during the lifetime of the individual. The adaptive immune system is highly adaptable because of somatic hypermutation (a process of accelerated somatic mutations), and V(D)J recombination (an irreversible genetic recombination of antigen receptor gene segments). These mechanisms allow a small number of genes to generate a vast number of different antigen receptors, which are then uniquely expressed on each individual lymphocyte, and confer the ability to recognize millions of pathogenic organisms and mount a specific response to each.