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Defense against infections

Last update 1-11-2008

A simplified model of the defense against infections

This part of the site provides a simplified model of the defense mechanisms against infections. The intention is to provide an insight how all these different elements of the defense against infections work together.

Below the general model there is a more specific model that describes the details of the defense against infections in the upper part of the gut. The focus is on the evolutionaty earlier, less advanced elements of the defense against infections. The specific model is described in more detail here, together with an account how colonization resistance works.

General model of the defense against infections

The model below shows a generalized vertebrate (human) body with the elements of the defense against infections plotted in it. Behind each element a more extensive story is told. Please click through.

A simplified model of the defense against infections

The brain, central nervous system and associated glands govern the immune system using hormones to carry messages back and forth Phagocytosis by marcophages is one way to eliminate microorganisms that have penetrated into the body The food one eats also brings a range of microorganisms The Thymus is where T-cells mature The bone marrow is where the white bloodcells are generated Hormones carry signals between the immunesystem and the Neuro-endocrino-immune-system Hormones carry signals between the immunesystem and the Neuro-endocrino-immune-system The liver synthesizes most of the complement proteins Complement proteins form a chemical cascade that triggers inflammation Produces adrenalin that inhibits the immune system The epithelial cells that line the gut wall grow rapidly and shed into the gut lumen after a few days thereby preventing microorganisms to attach to the gut wall The spleen houses lymphocytes for early trouble detection Hormones carry signals between the immunesystem and the Neuro-endocrino-immune-system Houses lymphocytes that scan for penetrating microorganisms Houses lymphocytes that scan for penetrating microorganisms Movements of the gut that send the food mass forwards thereby also removing microorganisms Defensins are broad-spectrum antimicrobial peptides Defensins are broad-spectrum antimicrobial peptides Defensins are broad-spectrum antimicrobial peptides Defensins are broad-spectrum antimicrobial peptides Defensins are broad-spectrum antimicrobial peptides Defensins are broad-spectrum antimicrobial peptides The gastro-intestinal wall provides a physical barrier that blocks microorganisms to enter the body The skin provides a barrier blocking microorganisms to enter the body Complement proteins form a chemical cascade that triggers inflammation By shedding rapidly epithelial cells prevent microorganisms to attach to the gut wall The gut houses enormous amounts of microorganisms T-cells and B-cells migrate through the body while fighting microorganisms Massive numbers of microorganisms live on the skin Massive numbers of microorganisms live on the skin The Gut Associated Lymphoid Tissue houses white blood cells Generic symbol for a microorganism Microorganisms that are accepted as 'self' and are part of the colonization resistance Microorganisms that can potentially cause disease (infections) Immuboglobulins are complex molecules that perform a key role in the adaptive immune system White blood cells is a generalized name for various cells specializing in fighting microorganisms T-cells and B-cells migrate through the body while fighting microorganisms

The model shows a very much simplified model of a human body (advanced vertebrate) where the large oval representing the body and the body wall (skin) and the cylinder in the center represents the gut (from mouth to anus).
The body parts that play a role in the defense against infections are shown - all other body parts are left out. Arrows represent various chemicals, such as hormones, defensins and immunoglobulines.

By clicking on the various parts, or even pointing at them with the cursor, more information is provided about each part.

Specific model of the defense against infections in the gut

The model below depicts a small part of the small intestinal wall and the microorganisms living close to it. This area of the gut was chosen as an example because the existence of Paneth cells that only occur here. Other parts of the gut have a similar defense mechanism although less intense.

Specific model of the defense against infections Immunoglobulins, produced by B-cells, transfer the epithelial layer and are inactivated beyond the 
			mucosa Immunoglobulins, produced by B-cells, transfer the epithelial layer and are inactivated beyond the 
			mucosa Immunoglobulins, produced by B-cells, transfer the epithelial layer and are inactivated beyond the \			
			mucosa Immunoglobulins, produced by B-cells, transfer the epithelial layer and are inactivated beyond the 
			mucosa Macrophages eliminate microorganisms that penetrate the basal membrane by phagocytosis Macrophages eliminate microorganisms that penetrate the basal membrane by phagocytosis Macrophages eliminate microorganisms that penetrate the basal membrane by phagocytosis B-cells produce immunoglobulins to help eliminate specific microorganisms B-cells produce immunoglobulins to help eliminate specific microorganisms T-cells act as early warning system for the adaptive defense system B-cells produce immunoglobulins to help eliminate specific microorganisms B-cells produce immunoglobulins to help eliminate specific microorganisms Mass produced defensins are inactivated as soon as they leave the submucosa Mass produced defensins are inactivated as soon as they leave the mucosa Paneth cells exist in the duodenum and mass-produce defensins Paneth cells exist in the duodenum and mass-produce defensins Mass produced defensins are inactivated as soon as they leave the submucosa Mass produced defensins are inactivated as soon as they leave the submucosa Paneth cells exist in the duodenum and mass-produce defensins Microorganisms live en masse in the gut lumen Paneth cells exist in the duodenum and mass-produce defensins Autochtonous microflora in mucosa Epithelial cells line the gut wall and produce defensins, that are inactivated as soon as they reach 
			the gut lumen The basal membrane provides the foundation for the epithelial cells and limits microorganisms 
			transfer  LINK TO BE DONE Legenda defensins .... Immunoglobulins, produced by B-cells, transfer the epithelial layer and are inactivated beyond the 
			mucosa The basal membrane provides the foundation for the epithelial cells and limits microorganisms 
			transfer   LINK TO BE DONE Epithelial cells line the gut wall and produce defensins The submucosa consists of mucus (slime) and autochtonous microorganisms that have managed to take 
			permanent residence  LINK TO BE DONE Paneth cells exist in the duodenum and mass-produce defensins legenda_microorganisms White blood cells (macrophages, B-cells and T-cells) play an active role in the defense against 
			infections Autochtonous micro flora .... Potential pathogen microorganisms ... Specific model of the defense against infections

The most striking part of the specific model is that the submucosa (slime layer) covering the gut wall (shown as epithelial cells) is home to indigenous microorganisms only. As compared to real life this is probably a simplification. It is shown here to make a point. The point is: indigenous microflora survives on the submucosa because it is resistant to (can handle) the defensins are produced by the epithelial cells in the colon, in the small intestines by the Paneth cells in the crypts. The result is a submucosa that is occupied by the indigenous microflora which makes it more difficult to colonize the site by other microorganisms (such as potential pathogens). This effect is called colonization resistance.
An important reason why this is so can be found in defensin inactivation. As soon as defensins get into contact with the gut lumen, they get inactivated and hence become ineffective.
Production of defensins and inactivation of defensins, is part of the continuous chemical warfare between microorganisms among each other and with their host.

A detailed description of the specific model can be found here.