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Defense against infections

Last update 2-7-2009

Introduction

About this website on the defense against infections

Occurrence of infection is the result of microbial offense and major defense variables that all developed in evolution. With increasing complexity of life (living organisms) the defense system had to get updated (adapted) in order to safe the species involved. In higher animals and man, much of the original defense mechanisms remained. In the digestive tract for example, a magnitude of different microorganisms in enormous numbers still forms a self-maintaining stable system as long as the host organism that depends on it remains in good condition and takes its role in the control of its composition and maintenance.

Bacteria have developed an alarming resistance to antimicrobial drugs. Resistance to antibiotics appears inevitable; even to the most recently developed ones as well as to combinations of them. An international group of scientist assembled in 1992 in Herborn (Germany) [1] in response to the recognition that development of resistance to antibiotics is becoming a serious, worldwide problem. Mankind once thought that it could control or even conquer infectious diseases. It was thought that antibiotics would solve the problem of infections and resistance to antibiotics seemed a minor nuisance.
However, since anti-microbial drugs became available, resistance has developed and has continued to develop to practically every new anti-microbial drug within four to five years. Furthermore, immuno-compromised patients have increased gradually in numbers so that they now present a majority of hospitalized patents.
It was decided to study factors involved in the normal defense to infection and search for ways to maintain the defense system (artificially) well-functioning in order to minimize the use of antimicrobial drugs. The group stopped its activities recently after having been unsuccessful, largely due to research funding priorities.

We decided to take another approach to study the normal defense, Thus this website presents an - as comprehensive as possible - overview of the defense against infections. As such it goes beyond standard works on immunology and bacteriology in scope as it tries to bring all aspects of the defense in view, rather than those that have historically become associated with a specific discipline. So there are elements from paleontology, evolution biology, medical biology and ecosystem dynamics as well as more traditional medical disciplines such as histology, immunology and bacteriology.

In creating this site we have not attempted to provide all the answers. Rather we have tried to enlarge the scope so important aspects and interrelations can be brought into the limelight that up to now have fallen between disciplines. A good example is the interrelation between the intestine wall, the indigenous micro flora, non-indiginous (transient) microflora and potential pathogens, as described in the specific model of the defense against infections.

Purpose

The purpose of this website is twofold:

  1. To provide an easily accessible and increasingly comprehensive source of information on the defense against infections.
  2. To provide an opportunity for Dick van der Waaij to share his ideas on the defense against infections as he has developed them over the last decade as an emeritus professor.

We hope that this core of ideas and this website will develop into a joint effort between many people; a place where ideas are exchanged and information is shared. The subject is too complex and too little understood for one person to handle.

Structure

This website has several story lines that become intertwined at deeper levels:

These story lines are available as links in the menu-bar at the top of each page.
The wiki environment is provided for you, so you can participate by adding your ideas, comments, references to literature and so on.

The 5 main components of the defense against infections

5 main components of the defense against infections

The defense against infections has evolved over time into a very complex system. 5 main components can be discerned:

  1. Microflora (ecological) dynamics
  2. Innate defense
  3. Ideotype defense
  4. Adaptive defense
  5. Neuro-endocryno-immonulogical control

Microflora (ecological) dynamics

The microflora that lives on and in the body plays an active role in the defense against infections. The microorganisms compete for food, oxygen and space with newly arriving microbes. The latter may try to find a niche for survival and expansion of its kind along the body wall so that an invasion can be attempted. There is also large scale chemical warfare between endogenous species and newly arriving microbes through 'defensins'. If a newly arriving potential pathogen microorganism successfully establishes and attaches to the body wall they may penetrate in sufficient numbers to cause infection.

Innate defense

The innate defense is the oldest type of the defense system in evolution. It consists of phagocytic cells which have the ability to produce defensins, engulf and destroy microorganisms. Binding proteins enhance the binding of phagocytes with bacteria and other foreign material.

Ideotype defense

The idiotypic network consists of multi-specific antibodies representing phylogenetically the oldest kind of adaptive immunity. The ideotypic system could be regarded as an interface between innate and adaptive immunity. The role of this 'early' multi-specific system is self-maintainance.
Not very much is known about the ideotype defense.

Adaptive defense

The most recent evolutionary development is the adaptive defense system. A key difference with the other defense systems is that it must be trained by experience. It has very effective defense mechanisms that can be targeted at known pathogens. Drawbacks are that it needs several days to learn to recognize a new potential pathogen and that it can also be misled in to attacking body tissues.

Neuro-endocryno control

There are complex interrelations between the defense systems (immunological systems), the endocrynological system(s) and the neurological systems. These cross-influence each other in many ways that are not yet well understood. An example is the hormone adrenaline that dampens the immunological defense.

Observation

The 5 defense components model is a way to structure the very complex defense against infections. It is not proven to be true. It can be that a model with 4 or for example 7 defense components will develop that describes the defense against infections in a better way. There is a lot of work to be done here.


References

[1] Zentralblatt Review: Araneo B.A., Cebra J.J, Beuth J., Fuller B., Heidt P.J., Midvedt T., Nord C.E., Nieuwenhuis P. Manson W I., Pulverer G., Rusch V.D., Tanaka R. , Van der Waaij D.,Walker R.I., Wells, C.I.: Problems and Priorities Controlling Opportunistic Pathogens with new Antimicrobial Strategies; an Overview of Current Literature. Zbl. Bakt. 283 (1996) 431-465.