Chronic Inflammation Flashcards
Define chronic inflammation
Is inflammation of long duration(weeks or months) in which inflammation, tissue injury and repair attempts coexist.
•It could follow acute inflammation or insidious in onset.
Causes of chronic inflammation
1.Persistent infections e.g mycobacteria, fungi,viruses and parasites.
•2.Immune-mediated disease e.g rheumatoid arthritis, multipe sclerosis, bronchial asthma.
•3.Prolonged exposure to potentially toxic exogenous or endogenous agents e.g silica or atherosclerosis (plasma lipid component).
MORPHOLOGY of chronic inflammation
•1. infiltration by monocytes such as macrophages, lymphocytes and plasma cells
•2.Tissue destruction due to inflammatory cells or persistent agent.
•3. Healing by connective tissue ,with proliferation of small blood vessels(angiogenesis) and in particular fibrosis.
MORPHOLOGY of chronic inflammation
•1. infiltration by monocytes such as macrophages, lymphocytes and plasma cells
•2.Tissue destruction due to inflammatory cells or persistent agent.
•3. Healing by connective tissue ,with proliferation of small blood vessels(angiogenesis) and in particular fibrosis.
MACROPHAGES ROLE IN INFLAMMATION
•A component of mononuclear phagocyte system (Reticuloendothelial system).
•Phagocyte arise from bone marrow common precursor to blood monocytes.
•From blood, differentiate into
macrophages in various tissues aided by growth, cytokines, adhesion molecules etc.
Examples of macrophages
Examples of macrophages are: kupffer cells(liver), sinus histiocytes (spleen and lymph node), alveolar macrophages (lung), central nervous system (microglia).
Transformation of monocytes to macrophages in extravascular tissue activated by________________
various stimuli as TLRS (toll-like receptors), cytokines and chemical mediators.
Action of macrophages
Many are toxic to microbes and even human, others causes angiogenesis, collagen deposit ,fibroblast proliferation, tissue repairs, tissue injury in inflammation.
What do classically activated (M1) macrophages respond to? And what is their major role?
Classically activated macrophages respond to microbial products and T-cell cytokines such as IFN-γ
Role: they have strong microbicidal activity and induce inflammation.
What do alternatively activated (M2) macrophages respond to? And what is their major role?
Alternatively activated macrophages respond to cytokines such as IL-4 and IL-13 (typically, the products of the TH2 subset of T-cells, and are mainly involved in tissue repair and fibrosis
Role: anti-inflammatory, tissue repair & fibrosis
What is a granuloma
Defintion: a circumscribed tiny lesion composed predominantly of epithelioid cells rimmed peripherally by other lymphoid cells.
A granuloma is a focus of chronic inflammation consisting of a microscopic aggregation of macrophages that are transformed into epithelium-like cells, surrounded by a collar of mononuclear leukocytes, principally lymphocytes and on occasion plasma cells.
*A granuloma is a cellular attempt to contain an offending agent that is difficult to eradicate.
*In this attempt, there is strong activation of T-lymphocyte leading to macrophage
What is granuloma inflammation
- Granulomatous inflammation is a form of chronic inflammation characterized by focal accoumulations of activated macrophages, often with T lymphocytes, and sometimes associated with central necrosis.
*It is immune mediated, leading to granuloma
*Seen in both infectious and non infectious conditions.
Purpose of granulamatous inflammation
An attempt by the immune system to contain (at a location) offending irritants- antigens, infective agents, foreign inanimate matter that it cannot eliminate
What are some examples of granulomatous inflammation?
*Tuberculosis
*Sarcoidosis
*cat-scratch disease
*lymphogranulomatous disease
*Leprosy
*Brucelosis
*Syphilis
*Beryllosis
*Mycosis
*autoimmune disease
*reactions to irritant lipids.
Granulomatous inflammation can arise in response to what?
Could also arise in response to the presence of antigens that survived the action of the first line defender inflammatory cells eg, neutrophils, eosinophils
Giant cell
Giant cell: are formed by fusion of epitheliod cells either in the periphery or in the center of granulomas.
(Epithelioid cells are derivatives of activated macrophages resembling epithelial cells)
Giant cells are cells with large mass of cytoplasm having 20 or more small nuclei arranged either peripherally (Langhans-type ) or haphazardly (Foreign body-type).
What are the 2 types of granuloma?
- Foreign body granuloma
- Immune granulomas
What is Foreign body granuloma?
Foreign body granuloma-are incited by relatively inert foreign bodies such as talc, sutures, or fibers large enough to preclude phagocytosis without inciting specific inflammatory or immune response. At the granuloma center is observed the foreign material using polarised light.
What is immune granuloma?
Immune granulomas: Caused by agent that induce cell- mediated immune response.
Macrophage engulf foreign protein antigen, process it, and present peptides to specific T lymphocytes causing their activation.
The activated T cells produce cytokines such as IL-2,IFN-y.
Example :TB (central caseous necrosis)
How can granulomas be classified?
a. Nodular type
b. Diffuse Granulomatous inflammation
What is Nodular type?
a. Nodular type
Nodular caseating type- classically seen in human tuberculosis infection.
Nodular non-caseating type seen in tuberculoid leprosy, sarcoidosis, berylliosis, rheumatoid arthritis, crohn’ disease, foreign body granulomata.
Nodular Gummatous non-caseating granuloma as seen in syphilis- a central coagulative necrotic foci surrounded by fibrous tissue enmeshed with numerous plasma cells, lymphocytes and evidence of end-arteritis.
What is Diffuse Granulomatous inflammation?
Diffuse suppurative granulomatous inflammation: focal micro-abscesses are present in addition to the granulomatous reaction. This is encountered in fungal infections (blastomycosis, coccidiodomycosis etc) and some bacterial infections (actinomycosis, cat scratch disease and early phase of tularaemia etc).
Diffuse Non-specific granulomatous inflammation: this may be encountered in histoplasmosis, lepromatous leprosy etc.
What are the conditions favouring the development of granulomatous inflammation?
Types of foreign bodies that can initiate granulomatous inflammation and exmaples?
The presence of poorly digestible irritant which may be biologic or inanimate
Presence of active cell-mediated immunity to the irritant suggesting the role of hypersensitivity reactions
Parasites, larvae, eggs and wormsSyphilis
Foreign bodies
-Endogenous, e.g. keratin, necrotic bone, cholesterol crystals, sodium urate
-Exogenous, e.g. talc, silica, suture materials, oils, silicone
Specific chemicals e.g. Beryllium. Drugs
Hepatic granulomas due to allopurinol, phenylbutazone, sulphonamides
Unknown
Crohn’s disease Sarcoidosis Wegener’s granulomatosis
How does granulomatous inflammation arise from acute inflammation?
It’s initiation is centered on what?
Granulomatous inflammation can arise from acute inflammation in which the inflammatory response cannot eliminate the injurious agent or more commonly, it may be a chronic inflammation at the outset.
The initiation of the granulomatous reaction is centred on the interplay between the immune system (particularly macrophage), endothelial cells, stroma and the inciting indigestible agent/material.
How are macrophages recruited?
Recruitment of macrophages is first triggered off by the activation of CD4+T cells which release lymphokines (IL—1, IL-2), growth factors (IFN-Y, IFN-@) and Monocyte chemotactic factors (MAF, MIF).
What is the outcome of granulomatous inflammation?
The outcome of granulomatous inflammation is variable.
This depends upon the toxicity and immunogenicity of the inciting agent.
Outcome of granulomatous inflammation: Using tuberculosis as a prototype example:
Lesion could liquefy (caseous material and heightened digestion from enzymes packaged in macrophages) leading to discharging sinuses
Coalescing of adjacent granulomata with extensive fibrosis.
