Chronic Inflammation I

Question 1

What are the 3 criteria for chronic inflammation?

Answer 1

1. Inflammation
2. Tissue destruction
3. Attempts at repair coexist - evidenced via fibrosis or presence of fibroblasts

Question 2

How does chronic inflammation develop?

Answer 2

Frequently begins insidiously as low grade, smoldering response without signs of acute inflammation (most common and disabling)

Question 3

What are the causes of chronic inflammation?

Answer 3

1. Persistent microbial infections
2. Immune-related inflammatory diseases
3. Prolonged exposure to potentially toxic agents

Question 4

What occurs with persistent microbial infections of chronic inflammation?

Answer 4

Occurs usually with organisms with low pathogenicity

Often evoke delayed hypersensitivity

Hard to eradicate

May be granulomatous reaction

Question 5

What are examples of immune-related inflammatory diseases that cause chronic inflammation?

Answer 5

Autoimmune diseases - RA, MS

Unregulated immune responses (IBD)

Allergic diseases against common environmental antigens

Question 6

What occurs with prolonged exposure to potentially toxic agents and leads to chronic inflammation?

Answer 6

Exogenous (non-biodegradable silica) and endogenous (increased plasma lipid components –> atherosclerosis)

Question 7

What are the 3 morphology criteria for chronic inflammation?

Answer 7

1. Infiltration with mononuclear cells - macrophages, lymphocytes, and plasma cells
2. Tissue destruction - induced by persistent stimulus or by inflammatory cells
3. Attempts at healing - CT replacement of damaged tissue; new vessel proliferation (angiogenesis) and fibrosis

Question 8

What will you see morphologically with chronic pancreatitis?

Answer 8

Extensive fibrosis

Chronic inflammatory cells

Residual ductal structures

Residual islet

No acinar tissue remaining

Question 9

What will you see with chronic inflammation in the lung?

Answer 9

Collection of chronic inflammatory cells, destruction of alveolar spaces and fibrosis

Question 10

What can we interpret about tissue if we see a plasma cell?

Answer 10

Chronic inflammation!

Question 11

What are the role of macrophages?

Answer 11

Key cell in chronic and granulomatous inflammation

Derive from circulating blood monocytes

Monocytes emigrate to site of injury in 24-48 hours after onset of acute inflammation

Act as filters and sentinels for lymphocytes stimulation

Question 12

Where are macrophages located?

Answer 12

Numerous in liver (Kupffer cells)

Spleen

LN’s and lungs (pulmonary or alveolar macrophages)

CNS (microglia)

Bone (osteoclasts)

Question 13

What are features of activated macrophages?

Answer 13

Increased size

Increased number of lysosome

Increased amount of lysosomal enzymes

Increased ability to kill organisms

Question 14

How do macrophages mature and how do they appear?

Answer 14

Monocytes can transform into macrophages and become activated

Activated macrophages appear large and flat, similar to squamous cells

Question 15

What is the maturation of macrophages?

Answer 15

Stem cell

Monoblast

Monocyte

Macrophage

Question 16

What are the macrophage activation signals?

Answer 16

1. Cytokines secreted by activated T cells and NK cells
2. Bacterial endotoxins
3. Microbial products
4. Other inflammatory mediators

Question 17

How do activated macrophages aid in inflammation and tissue injury?

Answer 17

Reactive oxygen and nitrogen species

Proteases

Cytokines and chemokines

Coagulation factors

AA metabolites

Question 18

How do activated macrophages function in repair?

Answer 18

Growth factors (PDGF, FGF, TGFbeta)

Fibrogenic, cytokines

Angiogenic factors (FGF)

Remodeling collagenesis

Question 19

What are the macrophage products?

Answer 19

Acid and neutral proteases, plasminogen activator

Complement components and coagulation factors

ROS and NO

AA metabolites

Cytokines (IL-1 and TNF)

Growth factors - proliferation of smooth muscle cells and fibroblasts

Question 20

When does macrophage activation occur and what happens?

Answer 20

Within 48 hours, may be predominant cell type

Emigration governed by adhesion molecules and inflammatory mediators with chemotactic and activating properties

Question 21

If short-lived acute inflammation, macrophages eventually….

Answer 21

Disappear

Question 22

In chronic inflammation, macrophage accumulation persists, due to

Answer 22

Continuous recruitment

Local proliferation at site of inflammation

Question 23

What is released when macrophages are activated?

Answer 23

TNF

IL-1

Question 24

What does TNF and IL-1 activate after being released by activated macrophages?

Answer 24

Local effects - vascular endothelium, leukocytes, and fibroblasts

Systemic effects

Question 25

What are the systemic effects after being activated by TNF and IL-1?

Answer 25

Fever Leukocytes Increased acute phase proteins Decreased appetite Increased sleep All systemic manifestations of inflammation

Question 26

What occurs in the vascular endothelium upon activation by TNF and IL-1?

Answer 26

Increased expression of leukocyte adhesion molecules Production of IL-1 chemokines Increased procoagulant and decreased anticoagulant activity All lead to inflammation

Question 27

What occurs with the leukocytes upon activation by TNF and IL-1?

Answer 27

Activation Production of cytokines Leads to inflammation

Question 28

What occurs to the fibroblasts upon activation by TNF and IL-1?

Answer 28

Proliferation Increased collagen synthesis

Question 29

What are the roles of lymphocytes in chronic inflammation?

Answer 29

Can be mobilized in setting of specific immune stimulus (infections), as well as non-immune inflammation (trauma)

Question 30

What is the reciprocal relationship that occurs during chronic inflammation?

Answer 30

T cells and macrophages Macrophages initially activate T cells (or vice versa)

Question 31

How do macrophages and lymphocytes interact in chronic inflammation?

Answer 31

Activated macrophages present to T-cells (IL-12) which leads to the T cells activating Activated T cells release TNF, IL-17, chemokines which lead to the recruitment of neutrophils and macrophages This then leads to the activation of more macrophages Activated macrophages then released TNF and IL-1 which stimulate inflammation

Question 32

What are plasma cells and their function?

Answer 32

Terminal product of B cell activation Produce antibodies against persistent antigens in inflammatory site or against altered tissue components

Question 33

Where are eosinophils seen and what does their recruitment depend on?

Answer 33

Most often seen around parasitic infections or as part of immune reactions mediated by IgE (typically associated with allergies) Recruitment depends on chemokine eotaxin

Question 34

What do the granules of eosinophils contain?

Answer 34

Major basic protein (MBP) MBP is toxic to parasites, but leads to epithelial cells lysis Contributes to tissue damage in immune reactions such as allergies

Question 35

What are the roles of mast cell in inflammation?

Answer 35

Participates in both acute and chronic inflammatory reactions Armed with IgE to certain antigens - will release histamine and PG Central role in anaphylactic reactions and helpful in parasitic infections since it may produce cytokines such as TNF that contribute to fibrosis

Question 36

Can neutrophils be found in chronic inflammation? What is that due to?

Answer 36

Even in apparent chronic inflammation, numerous neutrophils may be found: Due to persistent microbes or due to mediators elaborated by macrophages, necrotic cells, and T cells

Question 37

What is it called when neutrophils are found in chronic inflammation due to persistent microbes or due to mediators by macrophages, necrotic cells, or T cells?

Answer 37

Chronic active inflammation Acute and Chronic Inflammation

Question 38

What are the results of chronic inflammation?

Answer 38

Continued tissue damage/destruction Ongoing tissue destruction can activate inflammatory cascade, leading to co-existence of both acute and chronic inflammation

Question 39

What can fuel chronic inflammation?

Answer 39

Can be fueled by lifestyle factors which promote production of inflammatory mediators Some include: Smoking Excessive alcohol intake Physical and emotional stress Obesity Lack of exercise Diet