Immunodeficiencies: Phagocyte and complement dysfunction: Pathology review

Alyssa is a 3 week old newborn baby girl that’s brought to the clinic by her parents. They’re a bit concerned because they’ve noticed that Alyssa’s umbilical cord stump hasn’t fallen off yet.

On physical examination, you notice that the stump looks red and swollen, but there’s no pus. You decide to run a blood test, which reveals an increased level of neutrophils.

Finally, you perform flow cytometry, which shows that these neutrophils have reduced expression of CD18.

Next comes Eddie, a 2 year old boy who has a fever that won’t go away after 2 weeks. His parents also mention that he has frequent infections involving the respiratory tract, and he once also had an infection of the knee joint.

Upon physical examination, the first thing you notice is that Eddie has extremely light skin, hair, and eyes. Then, you find swollen lymph nodes all around the body, and you palpate an enlarged liver and spleen.

So again you run some blood tests, but now you find decreased white blood cells, especially neutrophils, and a prolonged bleeding time.

Finally, you do a peripheral and bone marrow smear, which shows abnormally large granules within the white blood cells and platelets.

Based on the initial presentation, both cases seem to have some form of immunodeficiency, meaning that their immune system's ability to fight pathogens is compromised.

Immunodeficiencies can be classified according to the component of the immune system that is defective.

In this video, we’ll be focusing on phagocyte dysfunction and complement disorders. Okay, let’s start with phagocyte dysfunction.

First we have leukocyte adhesion deficiency, which is an autosomal recessive disorder, meaning that an individual needs to inherit two copies of the mutated gene, one from each parent, to develop the condition.

Normally, when there’s an infection or inflammatory process, as well as for wound healing, chemical signals are released by cells in the affected area, to attract leukocytes such as phagocytes that are circulating in the blood, and this is called chemotaxis.

But to actually get to the affected area, they first have to squeeze and pass through the endothelial cells that line the blood vessel wall.

To do this, what’s important to know is that there’s a tight interaction between cellular adhesion molecules on the surface of endothelial cells, and the integrins on the surface of the phagocytes.