Inflammation Chronic

Question 1

Define chronic inflammation

Answer 1

Prolonged to weeks to months to years 
Distinguished by 
vascular changes
Oedema
Predominant neutrophilic infiltrate

Question 2

This 5 characteristics of chronic inflammation

Answer 2

infiltration and activation of lymphocytes, macrophages, plasma cells and multinucleate giants cells
Necrosis
Proliferation of fibroblasts and deposition of collagens ( desqoplasia and or fibroplasia)
Angiogenesis and neovascularization (granulation tissue formation)
Inition of wound healing (re-epithelialization and tissue repair)

Question 3

List 5 biologic mechanisms resulting in chronic inflammation

Answer 3

Persistence/resistance
Isolation
Unresponsiveness
Autoimmunity
Defects in leukocytic fx

Question 4

Explain how persistence/resistance results in chronic inflammation

Answer 4

Some bacteria once engulfed by inflammatory cells prevent the lysosomes form fusing with them so they dont die

Bacteria resist to death via production of antioxidants or scavenging free radicals

Mycobacteria have a waxy, hydrophobic cell wall containing mycelia acids _ other lipids = hard to attacked by lysosomal enzymes

Question 5

Explain how isolation results in chronic inflammation

Answer 5

These are not naturally resistant to phagocytosis/desctruction but hide in suppurative encapsulated material

Question 6

Explain how unresponsiveness results in chronic inflammation

Answer 6

These foreign material are basically indestructible and are unresponsive to phagocytosis or enzyme breakdown

Eg plant material
Asbestos fibres
Suture materials

Question 7

Explain how autoimmunity results in chronic inflammation

Answer 7

Sometimes immune reactions develop against the affected person own tissue
resulting in = tissue damage and persistent inflammation

Important role in several common chronic inflammatory disease = rheumatoid arthritis, inflammatory bowel disease

Question 8

Explain how defects in leukocytic fx can also results in chronic inflammation

Answer 8

Eg - Chronic granulomatous disease = loss of NADPH oxidative fx imparts leukocyte free radial and oxidative killing allowing persistence of microbial agents and granuloma formation

Question 9

How chronic inflammation can be detrimental?

Answer 9

When chronic inflammation ensues the body attempts to overcome the inciting agent through mononuclear cells

mononuclear infiltrate often displaces and replaces the original tissue
Resulting in collagen deposition and expansion of the lesion
Thus affecting adjacent tissue

Chronic inflammation effect vary depending on where the lesion is located

Question 10

Effector cells of the chronic inflammatory response

Answer 10

Macrophages = dominant cells of chronic inflammation

There are two types of macrophages
ones residing within specific organs (tissue macrophages)
One formed from monocytes from bone marrow (1.5 to 3 days)

Question 11

Explain circulating macrophages

Answer 11

From monocytes during a inflammatory stimuli

Question 12

Explain macrophages residing within specific organs /tissues

Answer 12

They form a monocyte-macrophage system and include free macrophages in the connective tissue, Kupffer cells in the liver, alveolar macrophages, macrophages within lymph nodes, spleen, bone marrow, brain (microglial cells) and skin.

Question 13

Macrophages steps action with inflammation

Answer 13

monocytes are recruited from the blood into the sites of injury in response to inciting agents/substances. Monocytes expressing CCR2 chemokine receptors are attracted by MCP-1 and enter the areas of inflammation in a manner similar to that described for the leukocyte adhesion cascade of neutrophils.

• same as acute Slow rolling is mediated by E- and P-selectins and firm adherence by monocytes to endothelial cells is largely mediated by β2 integrins and ICAM-1. Transmigration between endothelial cells is mediated by PECAM1 and JAM molecules.

Question 14

The two different ways that macrophages can be activated

Answer 14

Classical macrophage activation
microbal products engage TLRs and other sensors by T cell-derived signals, importantly the cytokine IFN-y in immune response or by forge in substance (eg crystals and particular matter)
Macrophages produce NO +ROS and up regulate lysosomal enzymes = all enhance ability to kill ingested organisms + secrete inflammation stimulating cytokines

Alternative macrophage activation
-q1Induced by cytokines IL-4 and IL-13 - these produced by T lymphocytes and other cells
These macrophages are not actively anti microbicidal
May inhibit classical pathway
Primary fx = tissue repair
Secrete - groth factors = promoting angiogenesis, activate fibroblasts and stimulate collagen synthesis

Question 15

What do activated macrophages do?

Answer 15

ingest + elimiinate microbes and dead tissues
Initiate the process of tissue repair and are involved in scar formation and fibrosis
(releasing growth factors as PDGF – Platelet-Derived growth factor, FGF – Fibroblast Growth
Factor, TGFβ-Transforming Growth factorβ).
 Secrete mediators of inflammation, thus are central to the initiation and propagation of 
inflammatory reactions 

 Display antigens to T lymphocytes and respond to signals from T cells, thus setting up a 
feedback loop that is essential for defence against many microbes by cell-mediated immune responses.

Question 16

Other cells involved in chronic inflammation

Answer 16

Lymphocytes and macrophages interact pin a bidirectional way

Macrophages display antigens —> T cells + stimulate T cell responses

Activated T lymphocytes produce cytokines, one of them - IFNy = major activator of macrophages

Neutrophils are often found in chronic inflammation of months because, either by persistent microbes or mediators produced by macrophages and T lymphocytes

Question 17

Morphological patterns of chronic inflammation

Answer 17

Grey to white and firm ( because of infiltration of macrophages and/or lymphocytes, proliferation of fibroblasts and deposition of connective tissue

Question 18

Explain granulomatous inflammation

Answer 18

Most common type of chronic inflammation

macrophages, epithelioid cells (activated macrophages) and multinucleate giant cells predominate

Question 19

Explain epithelioid macrophages

Answer 19

Epithelioid macrophages are larger than normal macrophages, they have abundant cytoplasm and the cell membrane occasionally assumes a polygonal shape, forming sheets. These cells have diminished phagocytic activity but they contain large amounts of RER, Golgi, vesicles and vacuoles suggesting as a main function an extracellular secretion. Multinucleated giant cells are syncytial cells formed by the fusion of two or more activated macrophages. 


Question 20

Two main forms of granulomatous inflammation

Answer 20

Diffuse granulomas (lepromatous)
Nodular tuberculoid

Question 21

Explain diffuse granulomas (lepromatous)

Answer 21

Th2-biased immunologic response

Grossly poorly delineated, without a distinct capsule and lack caseation

Question 22

nodular tuberculoid granulomas

Answer 22

Th1 biased immunologic response
Grossly grey to white road to oval and firm to hard
Eg - mycobacterium bocis or mycobacterium tuberculosis and some deep fungal infections

Question 23

Caseating vs non caveating granulomas

Answer 23

Histologically
- noncaseating (without a necrotic centre) granulomas are composed by numerous macrophages with variable number of epithelioid cells, multinucleated giant cells and peripheral fibroblasts, lymphocytes and plasma cells. Caseating granulomas have the same morphology but the centre is formed by a core of grey-white-yellow necrotic debris.


Question 24

well-formed granulomas has three distinctive morphologic areas

Answer 24

1) central macrophages and MGCs (with or without necrosis); 2) middle area of macrophages, epithelioid cells and MGCs; 3) outermost layer of lymphocytes, plasma cells, macrophages and a fibrous capsule

Question 25

formation of nodular granulomas is tightly regulated by different chemical mediators and requires the active role of

Answer 25

Role of Thelper 1 cells
	IL2 induces proliferation and long-term survival of Th1 lymphocytes 

	 TNF increases the expression of molecules on endothelial cells which further facilitate the 
extravasation of additional inflammatory cells 

	 IFNγ activates macrophages not only to enhance their phagocytic and killing mechanisms 
but also to enhance their ability to present antigen by inducing increased expression of class II MHC molecules 


Question 26

Diffuse granulomas are characterised by?

Answer 26

a widespread distribution, absence of nodular lesions and an inflammatory infiltrate consisting of numerous macrophages and few lymphocytes. These lesions can be observed in feline leprosy and paratuberculosis of ruminants.

Question 27

Other types of inflammation include:

Answer 27

 Lymphoplasmacytic 

 Chronic-active: containing also neutrophils, fibrin and plasma proteins. It occurs when the 
inciting stimulus has not been removed from the exudate and it continues to elicit an acute inflammatory response