Tissue Macrophages Provide a First Line of Defense Against Infection. Within minutes after inflammation begins, the macrophages already present in the tissues, whether histiocytes in the subcutaneous tissues, alveolar macrophages in the lungs, microglia in the brain, or others, immediately begin their phagocytic actions. When activated by the products of infection and inflammation, the first effect is rapid enlargement of each of these cells. Next, many of the previously sessile macrophages break loose from their attachments and become mobile, forming the first line of defense against infection during the first hour or so. The numbers of these early mobilized macro phages often are not great, but they are lifesaving.

Neutrophil Invasion of the Inflamed Area Is a Second Line of Defense. Within the first hour or so after inflammation begins, large numbers of neutrophils begin to invade the inflamed area from the blood. This invasion is caused by inflammatory cytokines (e.g., tumor necrosis factor and interleukin-1) and other biochemical products produced by the inflamed tissues that initiate the following reactions:

1. They cause increased expression of adhesion molecules, such as selectins and intercellular adhesion molecule–1 (ICAM-1) on the surface of endothelial cells in the capillaries and venules. These adhesion molecules, reacting with complementary integrin molecules on the neutrophils, cause the neutrophils to stick to the capillary and venule walls in the inflamed area. This effect is called margination and is shown in Figure 1 and in more detail in Figure 2.

2. They also cause the intercellular attachments between the endothelial cells of the capillaries and small venules to loosen, allowing openings large enough for neutrophils to crawl through directly from the blood into the tissue spaces by diapedesis.

3. They then cause chemotaxis of the neutrophils toward the injured tissues, as explained earlier. Thus, within several hours after tissue damage begins, the area becomes well supplied with neutrophils. Because the blood neutrophils are already mature cells, they are ready to immediately begin their scavenger functions of killing bacteria and removing foreign matter.

Acute Increase in the Number of Neutrophils in the Blood—“Neutrophilia.” Also within a few hours after the onset of acute, severe inflammation, the number of neutrophils in the blood sometimes increases fourfold to fivefold—from a normal of 4000 to 5000 to 15,000 to 25,000 neutrophils per microliter. This is called neutrophilia, which means an increase in the number of neutrophils in the blood. Neutrophilia is caused by products of inflammation that enter the blood stream, are transported to the bone marrow, and there act on the stored neutrophils of the marrow to mobilize these into the circulating blood. This makes even more neutrophils available to the inflamed tissue area.

Second Macrophage Invasion into the Inflamed Tissue Is a Third Line of Defense. Along with the invasion of neutrophils, monocytes from the blood enter the inflamed tissue and enlarge to become macrophages. However, the number of monocytes in the circulating blood is low. Also, the storage pool of monocytes in the bone marrow is much less than that of neutrophils. Therefore, the buildup of macrophages in the inflamed tissue area is much slower than that of neutrophils, requiring several days to become effective. Furthermore, even after invading the inflamed tissue, monocytes are still immature cells, requiring 8 hours or more to swell to much larger sizes and develop tremendous quantities of lysosomes; only then do they acquire the full capacity of tissue macrophages for phagocytosis. After several days to several weeks, the macrophages finally come to dominate the phagocytic cells of the inflamed area because of greatly increased bone marrow production of new monocytes, as explained later.

As already pointed out, macrophages can phagocytize far more bacteria (about five times as many) and far larger particles, including even neutrophils and large quantities of necrotic tissue, than can neutrophils. Also, the macrophages play an important role in initiating the development of antibodies, as discussed in Chapter 35.

Increased Production of Granulocytes and Monocytes by the Bone Marrow Is a Fourth Line of Defense. The fourth line of defense is greatly increased production of granulocytes and monocytes by the bone marrow. This action results from stimulation of the granulocytic and monocytic progenitor cells of the marrow. However, it takes 3 to 4 days before newly formed granulocytes and monocytes reach the stage of leaving the bone marrow. If the stimulus from the inflamed tissue continues, the bone marrow can continue to produce these cells in tremendous quantities for months and even years, sometimes at a rate 20 to 50 times normal.

Fig1. Movement of neutrophils by diapedesis through capillary pores and by chemotaxis toward an area of tissue damage. 

Fig2. Migration of neutrophils from the blood into inflamed tissue. Cytokines and other biochemical products of the inflamed tissue  cause increased expression of selectins and intercellular adhesion molecule-1 (ICAM-1) in the surface of endothelial cells. These adhesion  molecules bind to complementary molecules/receptors on the neutrophil, causing it to adhere to the wall of the capillary or venule. The neutrophil then migrates through the vessel wall by diapedesis toward the site of tissue injury.

اخر الاخبار

اخبار العتبة العباسية المقدسة

لتعزيز الوعي الديني… قسم الشؤون الدينية يقدم دوراته الفقهية لمنتسبي العتبة العباسية المقدسة الجدد

لأكثر من 150 طالبًا.. قسم الشؤون الفكرية ينظم مسابقة معرفية في بغداد

جامعة الكفيل تكرم المشاركين في فعاليات المؤتمر الطلابي السادس لمشاريع تخرج الطلبة

إعلان أسماء الفائزين في مشاريع التخرج ضمن اليوم الثاني للمؤتمر الطلابي السادس

المزيد

الآخبار الصحية

سرّ بسيط لصحة القلب.. أطعمة تخفض الكوليسترول خلال أسابيع

سبب خفي لإعتام عدسة العين ؟

عوامل خفية تسرّع شيخوخة الدماغ

أسباب الرغبة الشديدة في تناول الحلويات والأطعمة النشوية

المزيد

الآخبار التكنلوجية

كندا تصنع كاسحة جليد من جيل جديد

رواد "أرتيميس 2" يكشفون تفاصيل حياتهم في الفضاء

حفريات صينية تكشف كائنات بحرية عاشت قبل 546 مليون عام

روسيا تطلق صاروخ "سويوز-2.1 إيه" من قاعدة بليسيتسك الفضائية

المزيد

مواضيع ذات صلة

Formation of Pus

Feedback Control of the Macrophage and Neutrophil Responses

Natural Killer Cells

Integrins and Integrin Ligands

Selectins and Selectin Ligands

Anatomy and Functions of Lymphoid Tissues : Spleen

Eosinophils

Phagocytosis

Leukocytes (White Blood Cells)

Toll-Like Receptors

Anatomy and Functions of Lymphoid Tissues : Lymph Nodes

Anatomy and Functions of Lymphoid Tissues : Bone Marrow