Acute inflammatory responses are initiated when sentinel cells, including mast cells, tissue-resident macrophages, and DCs, which are present in tissues before infection, use TLRs and cytosolic innate pattern recognition receptors to sense microbes and injured cells (see Fig. 1). Mast cells respond to PAMPs and DAMPs by secreting histamine and prostaglandins that cause vasodilation and increased capillary permeability, which increases blood flow through tissues and increases movement of plasma proteins such as complement proteins, pentraxins, collectins, and antibodies out of the blood vessels. These soluble innate effector molecules work in tandem with leukocytes that are recruited into tissue from the circulation.

Fig 1. Acute inflammatory response. Acute inflammatory responses begin when microbes transgress epithelial barriers or when tissue is injured (1), and then pathogen-associated molecular patterns and damage associated molecular patterns activate sentinel cells, such as macrophages, dendritic cells, mast cells (2), to secrete cytokines and other mediators (3). Some of these mediators (e.g., histamine, prostaglandins) increase the permeability of capillaries (4), leading to the entry of plasma proteins (e.g., complement proteins) into the tis sues (5), and others (interleukin-1, tumor necrosis factor) increase expression of endothelial adhesion molecules and chemokines that promote the movement of leukocytes from the postcapillary venules into the tissues (6), where the leukocytes destroy microbes, clear damaged cells (7), and promote more inflammation and repair.

Recruitment of large numbers of neutrophils, followed by monocytes, from blood into tissues typically occurs as part of the acute inflammatory response to infections and tissue injury. The vasodilation caused by mast cell–derived histamine and prostaglandins increases the number of these leukocytes entering affected tissues and also changes blood flow characteristics that enhance physical interactions of circulating leukocytes with blood vessel walls. TNF, IL-1, IL-6, and chemokines, all of which are produced by sentinel cells at the sites of infection or tissue injury, have multiple effects on capillaries, venules, leukocytes, and bone marrow, which together increase the local delivery of cells that can fight infections and repair tissues (see Figs. 1 and 2).

Fig2. Local and systemic actions of cytokines in inflammation. TNF, interleukin-1 (IL-1), and IL-6 have multiple local and systemic inflammatory effects. TNF and IL-1 act on leukocytes and endothelium to induce acute inflammation, and both cytokines induce the expression of IL-6 from leukocytes and other cell types. TNF, IL-1, and IL-6 mediate protective systemic effects of inflammation, including induction of fever, acute phase protein synthesis by the liver, and increased production of leukocytes by the bone marrow. Systemic TNF can cause the pathologic abnormalities that lead to septic shock, including decreased cardiac function, thrombosis, capillary leak, and metabolic abnormalities due to insulin resistance.

TNF and IL-1 act on postcapillary venule endothelial cells to increase surface expression of adhesion molecules for leukocytes. Expression of E-selectin and ligands for integrins, including intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1), are induced by TNF and IL-1 activation of transcription factors, including NF-κB. P-selectin stored in endothelial cell cytoplasmic granules may be mobilized to the cell surface in response to thrombin generated by the coagulation cascade.

TNF and IL-1 also stimulate various cells to secrete chemokines, such as CXCL8 and CCL2, which bind to receptors on neutrophils and monocytes, respectively. As discussed in Chapter 3, these chemokines increase the affinity of leukocyte integrins for their ligands and stimulate directional movement of leukocytes. The result of increased selectin, integrin, and chemokine expression is an increase in neutrophil and monocyte adhesion to endothelial cells and transmigration through the vessel wall. The leukocytes accumulate in the tissues, forming an inflammatory infiltrate. The actions of TNF on endothelium and leukocytes are critical for local inflammatory responses to microbes. If inadequate quantities of TNF are present (e.g., in patients treated with drugs that block TNF or in TNF gene knockout mice), a consequence may be failure to contain infections.

In addition, TNF, IL-1, and IL-6 produced at inflammatory sites may enter the blood and be delivered to the bone marrow, where they work in concert with colony-stimulating factors to enhance production of neutrophils from bone marrow progenitors and release of mature neutrophils into the blood. In this way, these cytokines increase the supply of cells that can be recruited to the sites of infection and replace leukocytes that are consumed during inflammatory reactions (see Fig.2).

Typically, the leukocytes that are recruited first into sites of inflammation are neutrophils because they are the most abundant leukocytes in the blood and the most rapid responders to chemo tactic signals. Blood monocytes, which become macrophages in the tissue, become increasingly numerous over time and may be the dominant population in some reactions because they have longer lifespans than neutrophils and are capable of local proliferation. Neutrophils and monocyte-derived macrophages phagocytose and kill microbes, discussed later, and these functions are enhanced by the opsonization of microbes by complement proteins, antibodies, and other soluble mediators of innate immunity. Furthermore, the recruited phagocytes, especially the macrophages, respond to microbes and injured cells by secreting more inflammatory cytokines and chemokines, which promotes more leukocyte recruitment and amplifies the acute inflammatory response.

Acute inflammation develops in minutes to hours and lasts for days. Chronic inflammation is a process that takes over from acute inflammation if the infection is not eliminated or the tissue injury is prolonged. It usually involves recruitment and activation of monocytes and lymphocytes. Chronic inflammatory sites also often undergo tissue remodeling, with angiogenesis and fibrosis. Although innate immune stimuli contribute to chronic inflammation, the adaptive immune system is usually also involved and cytokines produced by T cells are powerful inducers of chronic inflammation.

اخر الاخبار

اخبار العتبة العباسية المقدسة

قسم الصيانة يقيم دورة تدريبية عن آلية تنصيب مطافئ الحريق اليدوية وإدامتها لملاكاته

قسم الشؤون الخدمية ينفذ حملة لغسل محيط العتبة العباسية المقدسة وتنظيفه

ضمن برنامج تأهيل المنتسبين الجدد.. قسمُ الشؤون الدينية يطلق دورته الفقهية الـ59 لمنتسبي العتبة العباسية المقدسة

ضمن مقتنياته التراثية.. متحف الكفيل يوثّق تاجًا ذهبيًّا مرصَّعًا بالأحجار الكريمة

المزيد

الآخبار الصحية

المركز الاوروبي : كل ركاب سفينة "هانتا" مخالطون معرضون لخطر كبير

ألمانيا.. رئيس الأطباء يدعو للإسراع بتطبيق "ضريبة السكر"

بين الفائدة والضرر.. جدل حول تأثير الشاي والقهوة على العظام

أمراض خطيرة.. أبحاث تكشف مخاطر الجلوس لفترة طويلة

المزيد

الآخبار التكنلوجية

سبع حقائق غير متوقعة عن موجات الراديو

الأجسام الغريبة.. ماذا رأى رواد "أبولو 17" على القمر؟

حرارة المحيطات عند مستويات مقلقة.. وعودة "إل نينيو" تقترب

باحثون يحددون تأثير القهوة على الميكروبيوم والمزاج

المزيد

مواضيع ذات صلة

Immuno microscopy

V(D)J Recombination

Role of Macrophages in Tissue Repair

Ingestion and Killing of Microbes by Activated Phagocytes

Double Antibody Sandwich ELISA (DAS ELISA)

Enzyme Immunosorbent Assays

Antibody Structure and Function

Apoptosis in the Immune System

The Major Proinflammatory Cytokines of Innate Immunity: Interleukin-6

The Major Proinflammatory Cytokines of Innate Immunity: Interleukin-1

The Major Proinflammatory Cytokines of Innate Immunity: Tumor Necrosis Factor

The Immune Receptor Family