The Beautiful Immune System Lesson 7: The Beginning Innate Immune Response to a Microbe

Before reading this post, you may want to go back and read about innate immunity and the cell types that carry out these types of responses. Here.

The innate immune system is our first line of defense against microorganisms. It not only blocks the entry of such things, but also can limit or completely eliminate the growth of these organisms on our tissues.

The skin is one of the most important barriers in the innate system, as well as the tissues along the gastrointestinal tract and the respiratory tracts. The continuous epithelial tissues along these tracts also serve as barriers from the organisms of our outside environment. I like to think about it this way: the opening of the mouth and nose down to the exit point in our backside is a tube, and this tube   needs protection from microorganisms that may attempt to enter it.

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Should an organism successfully breach these barriers, the innate immune system brings in cells to take care of the situation.

Once inside the body, the microorganism may encounter a macrophage (Mφ) that can bind to and ingest it (phagocytosis). Once this happens, the macrophage is termed active. Activated macrophages start to produce chemicals that will digest destroy the microorganism. These chemicals include:

  • Reactive Oxygen Species (ROS) – Strong oxidants that can
    damage other molecules and cellular structures. (Portrayed in red.)
  • Lysosomal Enzymes – Enzymes released by the lysosome (LYS), a small organelle within the macrophage cell. These enzymes (in blue) break down larger molecules such as bacteria.

Some macrophages also start signaling other cells. Signaling macrophages release cytokines–the protein “messenger molecules” of the immune system–which start the recruitment of leukocytes such as neutrophils to the site of infection. The local accumulation and activation of the leukocytes from both the innate and adaptive immune system and the destruction of the microorganism is what creates inflammation.

Should the microorganism invading the body be a virus, the macrophages release anti-viral cytokines. These cytokines are called interferons. And interferons activate natural killer cells, which kill our body cells that have become infected with the virus.

If the microorganism manages to escape the macrophages and enter the blood stream, the innate immune system is hard at work there, as well. Plasma proteins of the innate immune system, called complement proteins, can become activated when they encounter a microbial surface. (This is called the alternative complement pathway of activation, should you need to know that.) When the compliment proteins become activated they generate cleavage products (more on this later). The cleavage products ultimately stimulate inflammation, coat the microbes for phagocytosis, and create holes in the microbial membranes leading to their lysis.

But, pathogens have evolved the ability to resist the innate immune system and invade and replicate in our cells. Can you imagine that some microbes can still resist all of this?  A more powerful and specialized defense mechanism is often required to eliminate disease. And that’s when the innate immune system calls in for back up from the adaptive immune system.


  1. Abbas, Abul K., Andrew H. Lichtman, and Shiv Pillai. Cellular and Molecular Immunology. Philadelphia: Saunders Elsevier, Inc., 2010.