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The Complement System: Let me help with some proteins

I have written a number of blogs on the immune system. I have simplified the discussion focusing primarily on the timing of activity of members of the immune system, as this explains differences between the 3 major forms of gadolinium toxicity: acute hypersensitivty reaction, GDD, and NSF.

Essentially the immune system is also categorized into the innate immune system and the adaptive system. The most basic difference is that the innate system are designed to kill invaders and don't show much variation. The key members are neutrophils, which act early, and the principle combatants with infection (also result in the formation of pus), and macrophages which handle invaders in a more subacute fashion. As the name suggests, the adaptive system can change cell function/members based on adjusting to different types of invaders. The principle members are B-cells, which generate antibodies, and T-cells that are more direct cell based killers.

The Complement system are a collection of small proteins, about 30 are recognized, which means there probably are atleast 100 different types, that work in concert with immune cells to fight invaders, hence complement the immune cells. There is the conventional pathway of complement activation, that is remarkable if for no other reason that it is highly choreographed, and requires atleast 3 well defined events to occur. There are two common variant pathways.

Hepatocytes have been considered to be the cells that manufacture complement proteins, but it turns out a number of other cells can also make them, such as monocytes (precursor to macrophages and other immune cells).

Antibodies are often essential to activate the complement system, which in turn assists in B-cells making antibodies.

The essential take home points are:

1) to emphasize the remarkable level of cell choreography involved in immune system function - so it is easy to see how small errors can disrupt normal immune system behavior, and at the same time.

2) there are a number of parallel tracks of cells, proteins, other cell products that act in concert or in parallel, so that if something goes wrong, there are other cells that can help.

3) there is generally at least one common pathway for a cellular reaction to occur, but there are often a number of variants as well.

4) there may be no more deadly killers than the cells that we produce ourselves, that can kill enemies ruthlessly, if we can train them to recognize foes (such as cancer) this is likely the best cancer therapy, but if there is a glitch and our immune cells turn on ourselves, we are in big trouble. This last point is happening with GDD.

Richard Semelka MD Consulting

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