chronic inflammation pathology

1. CHRONIC INFLAMMATION
DR KAMALESH LENKA

2. CHRONIC INFLAMMATION
• Chronic inflammation is a response of prolonged duration
• (weeks or months) in which inflammation, tissue
• injury, and attempts at repair coexist, in varying combinations.

3. Causes of Chronic Inflammation
• Persistent infections
• Hypersensitivity diseases
• Prolonged exposure to potentially toxic agents, either exogenous or
endogenous
• Others-
• alzheimer disease,
• metabolic syndrome
• associated type 2 diabetes

4. persistent infection
• Persistent infections by microorganisms
• such as mycobacteria and certain viruses, fungi, and parasites.
• These organisms often evoke an immune reaction called delayed-type
hypersensitivity
• The inflammatory response sometimes takes a specific pattern called
granulomatous inflammation

5. Hypersensitivity diseases
• Chronic inflammation plays an important role in a group of diseases
that are caused by excessive and inappropriate activation of the
immune system
• autoimmune diseases-antigens evoke a self-perpetuating immune
reaction that results in chronic inflammation and tissue damage
• allergic diseases-chronic inflammation is the result of excessive
immune responses against common environmental substances, as in
bronchial asthma.

6. Prolonged exposure to potentially toxic agents,
either
exogenous or endogenous.
• Silica-inflammatory lung disease called silicosis
• Atherosclerosis-endogenous cholesterol and other lipids

7. Morphologic Features
• Infiltration with mononuclear cells, which include macrophages,
lymphocytes, and plasma cells
• Tissue destruction, induced by the persistent offending agent or by
the inflammatory cells
• Attempts at healing by connective tissue replacement of damaged
tissueaccomplished by angiogenesis (proliferation of small blood
vessels) and, in particular, fibrosis

8. (1) collection of chronic inflammatory cells, (2) destruction of parenchyma (normal alveoli are
replaced by spaces lined by cuboidal epithelium (3) replacement by connective tissue

9. Cells and Mediators of Chronic Inflammation
• Role of Macrophages-
• The dominant cells in most chronic inflammatory reactions are
macrophages
• contribute to the reaction by secreting cytokines and growth factors
that act on various cells, by destroying foreign invaders and tissues,
and by activating other cells, notably T lymphocytes

10. • Macrophages are professional phagocytes-filters for particulate
matter, microbes, and senescent cells.
• function as effector cells that eliminate microbes in cellular and
humoral immune responses

12. There are two major pathways of
macrophage activation
• classical
• alternative

13. classical pathway
• Classical macrophage activation may be induced by
• microbial products such as endotoxin, which engage TLRs and other
sensors, and by T cell–derived signals
• produce NO and ROS and upregulate lysosomal enzymes,
• all of which enhance their ability to kill ingested organisms, and
secrete cytokines that stimulate inflammation

14. Alternative macrophage activation
• Alternative macrophage activation is induced by cytokines other
than IFN-γ, such as IL-4 and IL-13, produced by T lymphocytes and
other cells.
• These macrophages are not actively microbicidal;
• instead, the principal function of alternatively activated (M2)
macrophages is in tissue repair
• They secrete growth factors that promote angiogenesis, activate
fibroblasts, and stimulate collagen synthesis

16. • The products of activated macrophages eliminate injurious agents
such as microbes
• initiate the process of repair, but are also responsible for much of the
tissue injury in chronic inflammation

17. • Macrophages secrete mediators of inflammation, such as cytokines
(TNF, IL-1, chemokines, and others) and eicosanoids.
• Macrophages display antigens to T lymphocytes and respond to
signals from T cells, thus setting up a feedback loop

18. Role of Lymphocytes
• Microbes and other environmental antigens activate T and B
lymphocytes, w hich amplify and propagate chronic inflammation
• By virtue of their ability to secrete cytokines, CD4+ T lymphocytes
promote inflammation and influence the nature of the
inflammatory reaction

19. • There are three subsets of CD4+ T cells
• TH1 cells produce the cytokine IFN-γ, which activates macrophages by
the classical pathway
• TH2 cells secrete IL-4, IL-5, and IL-13, which recruit and activate
eosinophils and are responsible for the alternative pathway of
macrophage activation
• TH17 cells secrete IL-17 and other cytokines, which induce the
secretion of chemokines responsible for recruiting neutrophils into
the reaction

21. Other Cells in Chronic Inflammation
• Eosinophils-
• abundant in immune reactions mediated by IgE and in parasitic
infections
• recruitment is driven by adhesion molecules similar to those used by
neutrophils,
• Eosinophils have granules that contain major basic protein, a highly
cationic protein that is toxic to parasites
• but also injures host epithelial cells.

22. A focus of inflammation containing numerous eosinophils.

23. • Mast cells-
• widely distributed in connective tissues
• participate in both acute and chronic inflammatory reactions

24. • Although neutrophils are characteristic of acute inflammation, many
forms of chronic inflammation lasting for months, continue to show
large numbers of neutrophils,
• Eg-In chronic bacterial infection of bone (osteomyelitis), a
neutrophilic exudate
• chronic damage induced in lungs by smoking and other irritant stimuli

25. Granulomatous Inflammation
• Granulomatous inflammation is a form of chronic inflammation
• characterized by collections of activated macrophages,
• often with T lymphocytes, and sometimes
• associated with central necrosis.

26. • The activated macrophages may develop abundant cytoplasm and
begin to resemble epithelial cells, and are called epithelioid cells
• Some activated macrophages may fuse, forming multinucleate giant
cells.

28. • Granuloma formation is a cellular attempt to contain an offending
agent that is difficult to eradicate.
• In this attempt there is often strong activation of T lymphocytes
leading to macrophage activation, which can cause injury to normal
tissues.

29. There are two types of granulomas
• Immune granulomas
• Foreign body granulomas

30. Immune granulomas
• are caused by a variety of agents that are capable of inducing a
persistent T cell–mediated immune response.
• This type of immune response produces granulomas usually when the
inciting agent cannot be readily eliminated,
• Eg-persistent microbe or a self antigen.

31. • In such responses, macrophages activate T cells to produce cytokines,
such as IL-2, which activates other T cells, perpetuating the response,
and IFN-γ, which activates the macrophages

32. Foreign body granulomas
• are seen in response to relatively inert foreign bodies,
• in the absence of T cell– mediated immune responses.
• granulomas form around materials such as talc (associated with
intravenous drug abuse), sutures, or other fibers
• Epithelioid cells and giant cells are apposed to the surface of the
foreign body
• The foreign material can usually be identified in the center of the
granuloma,