Chronic Inflammation

Question 1

Define chronic inflammation

Answer 1

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.

Question 2

Causes of chronic inflammation

Answer 2

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).

Question 3

MORPHOLOGY of chronic inflammation

Answer 3

•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.

Question 4

MORPHOLOGY of chronic inflammation

Answer 4

•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.

Question 5

MACROPHAGES ROLE IN INFLAMMATION

Answer 5

•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.

Question 6

Examples of macrophages

Answer 6

Examples of macrophages are: kupffer cells(liver), sinus histiocytes (spleen and lymph node), alveolar macrophages (lung), central nervous system (microglia).

Question 7

Transformation of monocytes to macrophages in extravascular tissue activated by________________

Answer 7

various stimuli as TLRS (toll-like receptors), cytokines and chemical mediators.

Question 8

Action of macrophages

Answer 8

Many are toxic to microbes and even human, others causes angiogenesis, collagen deposit ,fibroblast proliferation, tissue repairs, tissue injury in inflammation.

Question 9

What do classically activated (M1) macrophages respond to? And what is their major role?

Answer 9

Classically activated macrophages respond to microbial products and T-cell cytokines such as IFN-γ

Role: they have strong microbicidal activity and induce inflammation.

Question 10

What do alternatively activated (M2) macrophages respond to? And what is their major role?

Answer 10

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

Question 11

What is a granuloma

Answer 11

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

Question 12

What is granuloma inflammation

Answer 12

• 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.

Question 13

Purpose of granulamatous inflammation

Answer 13

An attempt by the immune system to contain (at a location) offending irritants- antigens, infective agents, foreign inanimate matter that it cannot eliminate

Question 14

What are some examples of granulomatous inflammation?

Answer 14

*Tuberculosis
*Sarcoidosis
*cat-scratch disease
*lymphogranulomatous disease
*Leprosy
*Brucelosis
*Syphilis
*Beryllosis
*Mycosis
*autoimmune disease
*reactions to irritant lipids.

Question 15

Granulomatous inflammation can arise in response to what?

Answer 15

Could also arise in response to the presence of antigens that survived the action of the first line defender inflammatory cells eg, neutrophils, eosinophils

Question 16

Giant cell

Answer 16

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).

Question 17

What are the 2 types of granuloma?

Answer 17

1. Foreign body granuloma
2. Immune granulomas

Question 18

What is Foreign body granuloma?

Answer 18

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.

Question 19

What is immune granuloma?

Answer 19

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)

Question 20

How can granulomas be classified?

Answer 20

a. Nodular type
b. Diffuse Granulomatous inflammation

Question 21

What is Nodular type?

Answer 21

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.

Question 22

What is Diffuse Granulomatous inflammation?

Answer 22

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.

Question 23

What are the conditions favouring the development of granulomatous inflammation?

Types of foreign bodies that can initiate granulomatous inflammation and exmaples?

Answer 23

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

Question 24

How does granulomatous inflammation arise from acute inflammation?

It’s initiation is centered on what?

Answer 24

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.

Question 25

How are macrophages recruited?

Answer 25

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).

Question 26

What is the outcome of granulomatous inflammation?

Answer 26

The outcome of granulomatous inflammation is variable.
This depends upon the toxicity and immunogenicity of the inciting agent.

Question 27

Outcome of granulomatous inflammation: Using tuberculosis as a prototype example:

Answer 27

Lesion could liquefy (caseous material and heightened digestion from enzymes packaged in macrophages) leading to discharging sinuses

Coalescing of adjacent granulomata with extensive fibrosis.