Historical Overview

They ruled this planet for at least 3 billion years before the evolution of eukaryotic life forms. Their descendants are within our cells as the mitochondria and in plants as the chloroplasts.
"Adam had 'em"

The basic idea of immunology was known to the early Greeks and recorded by the historian Theophrastus as he observed soldiers dying or recovering from both wounds and other infections.

The term "immune" was first applied to those soldiers who survived the Black Death (bubonic plague) and were therefore immune from battle field service. It was their chore to cart off and burn the dead bodies of plague victims. A tough way to start as the first male nurses.

1660's William Harvey discovers that blood circulates in a closed system of arteries, capillaries, and veins - thus disproving the early ideas of the Roman physician Galen

1798 Edward Jenner, an English country doctor, develops a vaccine for smallpox and initiates attenuation studies

1882 Pasteur, using some of Jenner's ideas, attenuates the agent responsible for fowl cholera and goes on to develop vaccines for anthrax and rabies

This work represents the beginning of what is called active immunization.

1884 Metchnikoff, a Russian scientist, describes "phagocytosis" by white blood cells (neutrophils); this work establishes a cellular aspect of immunology; Metchnikoff joins Pasteur

1884 Nuttal demonstrates the bactericidal action of serum: Bordet who later discovers the causative agent of whooping cough, explains the serum's action is due to special serum proteins called "antibodies"and other proteins with enzyme-like qualities called complement

1888 Roux and Yersin, both of whom work with Pasteur, isolate and describe the toxin produced by the diphtheria microbe

1890 von Behring and Kitasato isolate and describe the toxin produced by the tetanus organism

This work sets the stage for the development of passive immunization techniques.

1906 Wasserman adapts the "complement-fixation" reaction for use in syphilis testing

1930 Frobisher and Davis use the complement-fixation test for yellow fever testing

Since the 1960's the amount of information has increased dramatically. It has been suggested that during the 1980's the amount of information about immunology doubled every 2-3 years. Probably a lot sooner since the advent of computer databases.

The initial development of microbiology would not have been possible without the ability to see the microbes. From the time of Leeuwenhoek and earlier, crude microscopes were available. In the 20th and 21th centuries the types of microscopes that have been and will be developed has changed dramatically. These new microscopes now have the capability to see individual molecules and even individual atoms.

Labelled Photograph of Compound Brightfield Microscope Some Additional Types of Microscopy - A Brief Review The initial development of microbiology would not have been possible without the ability to see the microbes. From the time of Leeuwenhoek and earlier, crude microscopes were available. In the 20th and 21th centuries the types of microscopes that have been and will be developed has changed dramatically. These new microscopes now have the capability to see individual molecules and even individual atoms. Visit this site to see a comparison of standard light, dark field and phase contrast microscopy. Microscopes Help Scientists Explore Hidden Worlds. This web site, located on the Nobel site, includes succinct information on microscopy, as well as interative simulators. This site provides an excellent model for what is possible on the web. The simulator requires the latest Shockwave Player (free from Macromedia at http://www.macromedia.com/), portraying phase contrast and transmission electron microscopy with surprising accuracy. Single page summaries are available on the history of microscopy, resolution limits, and four types of microscopy: phase contrast, fluorescence, transmission electron and scanning tunneling microscopy. This site is supported by Zeiss. (****) -S Darkfield - look for picture of Buccal (Mouth) Epithelium The darkfield microscope uses a modified CONDENSER so that light is prevented from passing directly through the specimen. The light is directed at the specimen from the sides and thus the only light seen is that which is scattered from the cells. This is similar to moonlight. This type of scope makes possible the observation, in the living state, of particles and cells so tiny that they are invisible in a conventional brightfield microscope. The Negative staining technique gives a similar result. This scope might be used for viewing the syphilis organism, Treponema pallidum, a small spiral microbe. Fluorescent The fluorescent microscope makes use of the fact that certain chemicals and dyes give off light of one color when they are subjected to light of another color (wavelength). A filter in the light source absorbs the fluorescent light so that only the light coming from the organism or molecule comes through to be seen. The dye auromine has been used for TB organisms and gives a yellow light at a wavelength of 600 nm. Fluorescent staining is sometimes done to detect antibodies against syphilis and for detection of the rabies virus. One limitation is that the work must be done in a completely darkened area. A great deal of work in recent times has used green fluorescent protein (GFP) from a jellyfish and luciferin from the firefly for identifying molecules and parts of eukaryotic cells. The photomicrographs of human cheek cells show the use of GFP. It is also being used for extraction and separation of molecules. Note the bacteria on the surface of this white blood cell.*Used with permission from Purdue Cytometry. Note bacteria on surface of cheek cell shown with fluorescent dyes Phase-Contrast The phase-contrast microscope uses a modified DIAPHRAGM to place light out of phase. No staining is required and this scope allows visualization of living, unstained organisms. It is often used with wet mounts and hanging drop slides. It will show motility of organisms and the internal cellular structures will appear as darker, contrasting structures. ELECTRON MICROSCOPY Transmission Electron Microscope (TEM) Visit the site and note the pictures. Instead of a visible light source the TEM uses an electrical current to heat a tungsten filament to 20000 C, causing clouds of electrons to boil off around the wire. An Electron gun accelerates the electrons through the vacuum chamber of the scope. Streams of electrons pass through two (2) electromagnets known as CONDENSER LENS. This lens shapes the electron beam so that it passes through the material to be magnified. The material to be examined is mounted on a fine copper wire mesh. The electron beam passes through the material and enters two (2) more sets of electromagnets: the OBJECTIVE LENS and the PROJECTOR LENS. Both of these bend the electron beam and produce high magnification. The extremely short wavelengths of the electron beam are not visible. However, they strike a phosphorus-coated plate, enclosed in a leaded glass for safety. The plate glows and produces a visible image. This is the principle of the picture on a TV picture tube. The operator uses the image on the view plate to position materials and focus the electron beams. He usually exposes a photographic negative from which a photographic print can be made for study. The amount of magnification is determined by the electromagnets used. Magnifications range from 1,400X to 200,000X. The negative can be enlarged several times without loss of resolution producing a final magnification of over 1,000,000X. The major limitations of this technique include: long preparation time of the specimen; a need for very thin slices of the specimen; the use of the vacuum tube means materials must be dehydrated and thus no living materials can be studied. Scanning Electron Microscope (SEM)Visit the site and note the pictures. This scope was developed as an offshoot of work done during the space program to land a man on the moon. See how a SEM works at this site. Electrons do not pass through the specimen, but scan back and forth across it, allowing a view of the specimen surface in 3-D detail. The electron beam projected from a filament is focused into a fine pencil line by two (2) electromagnetic condenser lens and concentrated on the specimen which is held in a tilted mount. The current from the scanning generator causes this beam to scan back and forth across the specimen while at the same time causing a light spot to sweep across a cathode ray tube where the image will be seen. At this stage the tube looks similar to a TV screen just before the picture comes on. Then the beams that are scanning the specimen are caught by a signal detector and passed through a video amplifier the increases their volume. The signal produced modulates the brightness of the spot moving across the tube and the result is a TV-like image up to 50,000X specimen size. This same principle is used in getting pictures from the moon and other planets. Scanning Tunneling Microscope (STM) Since the STM was developed in 1981, it has made a dramatic impact on the understanding of surface structures of molecules. It can magnify molecules several billion times. Most biological molecules are too small to be seen with the light microscope and the electron beam of electron microscopes often damages their structure. The STM produces 3-D images of atoms and molecules without the use of destructive electron beams. The microscope works by using a procedure called electron tunneling. A sample must conduct electrons if it is to be imaged with the STM. The samples are coated with metals and the STM detects electrons jumping or "tunneling" from the surface of the specimen. An electrically conductive, needlelike probe, usually made of tungsten, scans the surface billionths of a millimeter above the sample. It follows the sample's surface outline by maintaining a constant distance from the surface. The probe is attached to a computer that projects a 3-D image onto a fluorescent screen. A team of scientists in California recently used the STM to obtain the first direct image of DNA. These new images show the three-dimensional structure of DNA and provide support for theories that DNA exists in several helical variations.

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