Chronic inflammation

Question 1

Identify the 3 causes of chronic inflammation, with examples.

Answer 1

Persistent infection
• Mycobacteria

Hypersensitivity diseases
• Autoimmune diseases
• Allergic diseases

Prolonged exposure to exo/ endogenous substances
• Silica – silicosis; cholesterol – atherosclerosis; others.

Question 2

Describe persistent infection

Answer 2

• Difficult to eradicate due to location and/or virility of agent
• Example is chronic periapical periodontitis
• The inflammatory response takes on a specific pattern called granulomatous inflammation
• Often, unresolved acute inflammation evolves into chronic inflammation, such as when an acute bacterial infection of the lung progresses to a chronic lung abscess.

Question 3

Describe hypersensitivity diseases

Answer 3

• Autoimmune diseases: self (auto) antigens evoke a perpetuating immune response that causes chronic inflammation and tissue damage.
• Allergic diseases: common environmental substances trigger an excessive immune response causing chronic inflammation. It will have morphological patterns of mixed acute and chronic inflammation, and fibrosis tends to dominate later stages.

Question 4

Describe prolonged exposure to exo/ endogenous substances

Answer 4

• Exogenous agent
E.g: Silica - when inhaled for prolonged periods, result in an inflammatory lung disease called silicosis. Silica particles lead to the development of chronic inflammation, followed by extensive fibrosis.

• Endogenous agent
E.g: Cholesterol - excessive production and tissue deposition of endogenous cholesterol and other lipids in the arterial wall induces a chronic inflammatory process resulting in atherosclerosis.

Question 5

Describe granulomatous Inflammation

Answer 5

• Characterised by the aggregation of macrophages, often with T lymphocytes and sometimes with central necrosis.
• Granuloma formation is a cellular attempt to contain an offending agent that is difficult to eradicate
• Macrophages may develop abundant cytoplasm and resemble epithelial cells (called epithelioid cells)
• Some activated macrophages may fuse, forming multinucleated giant cells.

Question 6

Describe immune granulomas

Answer 6

• Caused by persistent T cell – mediated immune response
• Typically caused by an agent that cannot be readily eliminated, such as a persistent microbe or a self antigen.
• Macrophages actually incite the T cell response

Question 7

Describe foreign body granulomas

Answer 7

• Response to inert foreign bodies, in the absence of T-cell mediated immune responses.
• Formed around the implant materials, such as talc, sutures and other fibres

Question 8

What are the two types of giant cells?

Answer 8

Foreign body giant cell

Langhans giant cell

Question 9

Describe foreign body giant cell

Answer 9

• Collection of fused macrophages
• Nuclei overlap and are disorganised
• Present in response to a large foreign body
i.e. implants and tattoos ; where chronic inflammation occurs
• The cells kind of absorb the foreign material like tattoos, but don’t destory it

Question 10

Describe langhans giant cell

Answer 10

• Formed by fusion of epithelioid cells
(epithelioid histiocytes: activated
macrophages resembling epithelial cells)
• Contain nuclei arranged in a horseshoe
shape pattern in the cell periphery
• Found in nearly every form of
granulomatous disease, including
tuberculosis, sarcoidosis, actinomycosisand syphilis.
• Tuberculosis is a great example. It often has; a central zone of necrosis, multinucleated cells, healing of granuloma with fibrosis

Question 11

List the common histological hallmark features of a granuloma

Answer 11

• Macrophage predominated
• Epithelioid macrophage granulomas ( activated
macrophages resembling epithelial cells)
• Maturation of Chronic Inflammatory Granulation Tissue to Scar Tissue

Question 12

Describe the 6 morphological features of chronic inflammation

Answer 12

• Infiltration of mononuclear cells – macrophages, lymphocytes and plasma cells (activated B cells)
• Tissue destruction – induced high persistent offending agent or inflammatory cells
• Attempts at healing – connective tissue replacement of damaged tissues, accomplished by angiogenesis and in particular, fibrosis.
• Suppuration: Chronic pus formation (chronic dental abscess)
• Diffuse
  
  • Mix inflammatory infiltrate of PMN, macrophages, lymphocytes, plasma cells
  • Usually specific immune responses
  • Often has chronic inflammatory granulation tissue with fibrosis
• Granulomatous
  
  • Macrophage predominated
  • Different patterns of granulomatous inflammation

Question 13

List the various mediators of chronic inflammation

Answer 13

Macrophages

• Types of macrophages

Lymphocytes

• Lymphocytes (T cells)

Eosinophils

Mast cells

Neutrophils

Question 14

Describe macrophages

Answer 14

· Dominant cell in chronic inflammation
· Destroys via phagocytosis
· Secretes cytokines and growth factors to activate T lymphocytes.
· Either haemopoietically derived in the bone marrow (stem cells) or from progenitors in the embryonic yolk sack and fetal liver development.

Question 15

Describe types of macrophages

Answer 15

• Classic – M1
  
  • Strongly proinflammatory. Secretes cytokines that stimulate inflammation, including IL-1, TNF, IL-12 and IL-6.
  • Stimulated by microbial products which engage their TLRs OR IFN-y
  • Produce NO and ROS species to enhance killing of ingested organisms

Alternative – M2
• Induced by cytokines (other than IFN-y), including IL-4 and IL-13 – produced by T-cells and other cells.
• Aids in tissue repair
•Secrete growth factors (IL-10, TGF-b) that promote angiogenesis, activate fibroblasts and stimulate fibrosis (non-pathological).

Question 16

Describe lymphocytes

Answer 16

• Very predominate in chronic inflammation during autoimmune and other hypersensitive diseases.
• Microbes and other environmental antigens activate T and B lymphocytes, which amplify and propagate chronic inflammation. Once activated, inflammation tends to be persistent and severe.
• Granulamatous inflammation is dependent upon lymphocyte responses.

Question 17

Describe lymphocytes (T cells)

Answer 17

• T-cells greatly amplify inflammatory reactions
• TH-1 cells produce the cytokine IFN-γ, which activates macrophages by the classical pathway.
• TH-2 cells secrete IL-4, IL-5, and IL-13, which recruit and activate eosinophils and are responsible for the alternative pathway of macrophage activation.
• TH-17 cells secrete IL-17 and other cytokines, which induce the secretion of chemokines responsible for recruiting neutrophils into the reaction
• TH-1 and TH-17 cells: bacteria, viruses and in autoimmune diseases
• TH-2: helminthic parasites and allergic inflammation.

Question 18

Describe eosinophils

Answer 18

• Involved in parasitic infections and mediate IgE production
• Contain major basic protein that is toxic to parasites but also to host epithelial cells!

Question 19

Describe mast cells

Answer 19

• Expresses cell surface receptors to IgE and degranulate to release histamine and prostaglandins.
• Involved in allergic reactions to foods, insect venom, or drugs (anaphylaxis).
• Can promote inflammation by the plethora of cytokines they produce

Question 20

Describe neutrophils

Answer 20

• While it is the major characteristic of acute inflammation, it can persist for months because of continued microbe presence/ cytokine production
• Coined term ‘acute on chronic’

Question 21

Describe the typical immigration pattern of pro-inflammatory cells during the course of inflammation

Answer 21

• In early inflammation, you have a high number of PMNS
• In early - late inflammation, there is a shift to monocytes becoming macrophages
• In late inflammation, there is lymphocyte emigration

Question 22

Describe the functional consequence of bone resorption in the context of microbial clearance

Answer 22

• Sometimes, since bacteria is so small, it can enter the canaliculi (tunnels in osteons)
• Unfortunately, the body’s immune cells aren’t as big and thus they cannot go into the canaliculi to rid the bacteria
Thus, the body’s response is to resorb bone so that it can reach the bacterial insult and kill it