what is chronic inflammation ? Robbins basic pathology important points

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Chronic inflammation

Ø The Inflammation is prolonged (from months to years).

Ø Chronic inflammation undergoes four processes simultaneously.

1. Continous inflammation

2. Infiltration with mononuclear cells i.e macrophages etc

3. Tissue injury

4. Tissue repair, by angiogenesis followed by fibrosis.

Ø Acute inflammation may go to chronic if the acute inflammation process cant be resolved because of the two reasons

Ø either persistancicny of the infectious agent or interference with the normal process of healing

chronic inflammation may arise in the following conditions;

1) persistent infectious microbes- causing delayed-type hypersensitivity immune response i.e mycobacterium tuberculosis.

2) Immune-mediated inflammatory diseases like autoimmune diseases (rheumatoid arthritis), and hypersensitivity (anaphylactic shocks, bronchial asthma ). All these will cause self tissue damage.

3)Prolonged exposure to potentially toxic agents. i.e silica causes chronic inflammation in the lungs and cholesterol crystals can cause atherosclerosis.

4)  Mild form of chronic diseases. It may help in the pathogenicity of diseases.

 Chronic inflammatory cells and mediators

1)MACROPHAGES:

Ø The dominant cells of chronic inflammation.

Ø Macrophages are named according to their location-based in different tissues

 

Tissue	Cells name
Lungs	Alveolar macrophage
CNS	Neuroglial cells
Liver	kupffer
Spleen & lymph nodes	Sinus histiocytes

 

Ø  And together these cells are called mononuclear phagocytes or reticuloendothelial cells.

Ø  Monocytes circulates in the blood for only about a day after the formation form precursor cells

Ø Under  the influence of the chemokines and adhesion molecules monocytes go toward the site of the injury within 24 to 48 hrs after the onset of the acute inflammation

Ø When monocytes reach the extravascular tissues they undergo morphologic changes forming macrophages.

Ø  Now macrophages have longer half-life and greater capacity for phagocytosis as compared to monocytes.

Ø They are activated by two pathways

The classical pathway

Alternative pathway

·      Classical macrophage activation pathway

Ø Microbicidal pathway

Ø This pathway is induced by microbial products like endotoxin, Tcell derived signal, IFN gamma cytokine, and foreign substances.

Ø Activated macrophages have NO, ROS, and lysosomal enzymes which kill the microbes.

Ø They secret cytokines that stimulate inflammation.

Ø They are important in phagocytosis and many chronic inflammation reactions.

·      Alternative macrophage activation pathway

Ø It is induced by cytokines other than INF gamma like IL4, IL3- produced by  T cells, mast cell,, eosinophils,s, and other cells.

Ø   Anti microbicidal pathway.

Ø Causes the tissue repair

Ø Secret growth factors which cause the angiogenesis, fibroblast and stimulate collagen synthesis

Ø It may be that in response to most injurious stimuli, macrophages are initially activated by the classical pathway, designed to destroy the offending agents, and this is followed by alternative activation, which initiates tissue repair.

Ø But this doesn't happens in such a precise way.

 

Role of macrophages

Ø Ingest and eliminate microbes and dead tissues.

Ø They give response to activating signal from T lymphocytes

Ø They initiate the process of tissue repair and are involved in scar formation and fibrosis

Ø Their secret mediators such as IL1, chemokines, and TNF, they are central to the initiation ad propagation of all inflammatory reactions.

Ø They display antigens to T lymphocytes and respond to them

Ø In chronic inflammatory sites,
however, macrophage accumulation persists

Ø they are the most important phagocytes in the cell-mediated arm of adaptive immune
responses

Role of lymphocytes

Ø they help in both immunological and nonimmunological inflammation, i.einfectious or necrotic.

Ø the major drivers of inflammation in many autoimmune and other chronic inflammatory diseases.

Ø The activation of T and B lymphocytes is part of adaptive immunity.

Ø In the tissue the B lymphocytes develop into plasma cells and produce antibodies

Ø While the T cells or CD+ 4 are activated to secret cytokines.

Ø Cd4 secret cytokines which influence the nature of inflammation and promote inflammation

Ø  There are 3 subsets of helper T cells each secret different cytokines and affect inflammation

 

 

T helper cell	cytokines	function
TH1	IFN gamma	Activate macrophages in the m1 pathway
TH2	IL4,IL5 & IL13	Recruit & activate eosinophils & activate M2 pathway
TH17	IL17 & other cyt	Induce secretion of chemokines, which recruit neutrophils and monocytes to the inflammation site

 

Ø Both TH1 and TH17 cells are involved in defense against many types of bacteria and viruses and in autoimmune diseases

Ø TH2 cells are important in defense against helminthic parasites and in allergic inflammation.

Ø  Lymphocytes and macrophages work in a bidirectional way which is like

Ø Macrophages show antigens on their surface toward the T cells then the T cells activate membrane molecules

Ø  They secret cytokines like IL12 and others which causes in turn the other T cells activation.

Ø Now the activated T lymphocytes inturn recruit and activate the macrophages and cause more antigens presentation and cytokines release and help in chronic inflammation.

Ø This cycle fuel and sustain chronic inflammation.

 

Role of eosinophils

Ø Eosinophils are found in inflammation sites around the parasitic infection specifically and as a part of immune reactions mediated by IgE.

Ø  They are typically associated with allergy

Ø They are brought toward the inflammation site by the adhesion molecule as those for leukocytes(neutrophils) and by specific chemokines called eotaxin  derived from epithelial cells and leukocytes

Ø Eosinophils contain highly toxic cationic protein which is toxic for parasites but also causes endothelial cell necrosis.

 

Role of mast cells

Ø They are like the watchman cells they are distributed all over the body in connective tissues.

Ø They are present both in acute and chronic inflammatory responses.

Ø  In atopic persons (those who are more likely to develop allergic diseases) mast cells is armed with IgE antibodies specific for some

environmental antigens.

Ø  When these antigens are  stimulated then mast cells coated with IgE antibodies are triggered to release histamine and amino acids metabolites which causes the early vascular changes of the acute inflammation.

Ø IgEarmed mast cells are central players in allergic reactions, including anaphylactic shock.

Ø Mast cells can also elaborate cytokines such as TNF and chemokines and may play a beneficial role in combating some infections

Ø Lastly although neutrophils are prominent cells in acute inflammation they also can be present in chronic inflammation as a result of the persistent infectious agent or necrotic cells, or also if chronic inflammation is elaborated by the.

 

 

 Granulomatous inflammation

Ø  It is a type of chronic inflammation, like when chronic inflammation cant removes be able to removed the causative agent/microbes mean they aren't killed by the macrophages.

Ø So the macrophages change their structure to a type of cells called epithelioid its name is because they look like epithelial cells.

Ø These epithelioid have more microbial killing ability.

Ø But these cells or granulomatous inflamation is more dangerous than chronic inflammation because of the high killing ability which causes the destruction of the tissue too

Ø Granuloma formation can occur because of the following three settings

Ø With persistent T-cell responses to certain microbes

Ø Granulomas may also develop in some immune-mediated inflammatory diseases,

Ø They are also seen in a disease of unknown etiology called sarcoidosis,

Ø  The formation of a granuloma effectively “walls off” the offending agent and is, therefore, a useful defense mechanism

Ø granulomatous inflammation with subsequent fibrosis may even be the major cause of organ dysfunction in some diseases, such as tuberculosis.

 

Diseases having granulomatous inflammation

Ø Following table shows some diseases which are having the granulomatous inflammation.

 

Diseases	Causative agents
tuberculosis	Mycobacterium tuberculosis
Syphilis	Treponema pallidum
Leprosy	Mycobacterium leprae
Cat-scratch disease	Gram-negative bacillus
sarcoidosis	Uknown cause
Crohn disease	Autoimmunity against intestinal antigens

 

Ø Due to hypoxia and free radicals injury the center of the giant cells or epithelioid become necrotic and on gross examination, it appears as a granular cheesy appearance and is therefore called as caseous necrosis

Ø The granulomas associated with Crohn diseases, sarcoidosis, and foreign body reactions do not have necrotic centers and are said to be non caseating.

 

 

 

Summary of chronic inflammation

·     Pronolonged host response to a continual stimulus.

·     Caused by microbes that resist elimination.

·     Immune responses against foreign antigens and immune complexity against self-antigens.

·     Characterized by continual inflammation and tissue injury.

·     Cellular infiltration with macrophages, lymphocytes, and plasma cells with prominent fibrosis.

·     It is mediated by cytokines secreted by macrophages and lymphocytes (mainly T lymphocytes). These cells are having a bi directional interaction.

 

 

 

•  NOTE; some tables are not showing will here so click here to get the original pdf