Immunology self study

Question 1

COPD is characterized by a limitation of expiratory airflow. Why does this occur (in relation to inflammation)

Answer 1

This occurs as a consequence of chronic inflammation that leads to lesions within the lung, loss of lung elastic recoil, fibrosis and narrowing of small airways. In other words, chronic inflammation causes airflow limitation associated with COPD.

Question 2

Where in the respiratory tract do COPD pts usually have inflammation?

Answer 2

lower respiratory tract

Question 3

Inflammation in the small airways and lung parenchyma of COPD pts involves what cell types and inflammatory mediators?

What two processes lead to destruction of alveolar structure and function?

Answer 3

Tissue biopsies, sputum analyses, and postmortem samples of small airways and lung parenchyma from COPD patients produce a profile that associates chronic inflammation and the disease. Inflammation in the small airways and lung parenchyma involves several different cell types (e.g., neutrophils, macrophages, lymphocytes) and inflammatory mediators (e.g., oxidative metabolites, growth factors, cytokines, chemokines, proteinases).

Increased lung proteinase production/activity and alveolar septal cell apoptosis by cells in the immune system lead to destruction of alveolar structure and function.

Question 4

What type of cell is the most numerous type found in chronic inflammation and makes up the vast majority of cells in the lungs of COPD patients?

What two mediators do they release and what are their effects?

Answer 4

Macrophages are the most numerous cells found in chronic inflammation and make up the vast majority of cells in the lungs of COPD patients. The macrophages release mediators that lead to tissue damage- mainly tumor necrosis factor-alpha (TNF-α) and reactive oxygen species.

Question 5

What is the second most abundant leukocyte in the lungs of COPD pts?

Where are these cells located and how does location of these cells change as symptoms increase in severity?

Answer 5

The second most abundant leukocyte in the lungs of COPD patients are neutrophils. They are present in the airway lumen and airway glands of COPD patients and as symptoms become severe, neutrophils are evident in lung tissue.

Question 6

What is the third most abundant leukocyte found in the lungs of COPD pts?

What are the two types within this class of leukocytes? (just list)

Answer 6

Lymphocytes: B and T cells

Question 7

Where do T-cells develop? What do their receptors recognize?

Answer 7

T-cells are lymphocytes that develop in the thymus and have receptors that recognize 8-12 amino acid peptides presented by a cell surface molecule known as major histocompatibility complex (MHC) molecules

Question 8

What proteins to B-cells express? What is the function of this expressed protein?

Answer 8

B-cells express a proteins knows as immunoglobulins. Immunoglobulins interact with pathogen associated macromolecules and leads to their clearance or elimination from the body

Question 9

What role do epithelial cells play in the pathology of COPD?

Answer 9

Epithelial cells in the lung also play an active role in the pathology of COPD since they are the cells that initiate cell infiltration and inflammation by production and release of chemokines and cytokines.

Question 10

In contrast to acute inflammation, _____ and _____ _____ appear to have little roles in the disease and are only present in the lungs of COPD patients when the disease is exacerbated.

Answer 10

eosinophils and mast cells

Question 11

Macrophages appear to play a pivotal role in the pathophysiology of COPD and can account for most of the known feature of the disease.

How does the number of macrophages change in COPD? How does this correlate with COPD severity? Where are increased numbers of macrophages found?

Answer 11

There is a 5–10-fold increase in the numbers of macrophages in airways, lung parenchyma, lung fluid, and sputum in patients with COPD. There is a correlation between macrophage numbers in the airways and the severity of COPD.

Question 12

Macrophages are activated by substances within _____ _____. When activated, what 3 types of mediators may be released?

Answer 12

1. cigarette smoke
2. tumor necrosis factor alpha (TNF-α), Interleukin-8 (IL-
   8) , and monocyte chemotactic peptide (MCP)-1.

Question 13

What effect does TNF-α have in the lung?

What types of molecules are IL-8, CXCL1, and MCP-1? What effects do they have in the lung?

Answer 13

1. TNF-α is secreted by activated macrophages in the lung and increases damage to the epithelial layer.
2. IL-8, CXCL1 and MCP-1 are known as chemokines. They recruit monocytes and neutrophils from the blood into lungs. The monocytes differentiate to macrophages upon interaction with connective tissue and/or exposure to cytokines produced by T-cells.

Question 14

What do chronic bacterial infections lead to? Why does this occur?

Answer 14

Besides irritants in cigarette smoke, which are associated with onset of COPD, chronic bacterial infections lead to increased airway and systemic inflammation as a result of direct effects of bacteria on the macrophages.

Question 15

Several components found in and on bacterai are recognized by specific receptors on what cell type? What pathway is activated and what does this result in?

Answer 15

Several components found in and on bacteria are recognized by specific receptors on macrophages, triggering the NF-κB pathway resulting in the production of pro-inflammatory cytokines and chemokines.

Question 16

Sputum and bronchial-alveolar lavage analyses following chronic bacterial infections have demonstrated increased concentrations of what cell types/factors/proteins? How does this compare to that found in COPD pts?

Answer 16

Sputum and bronchial-alveolar lavage analyses following chronic bacterial infections have demonstrated the increased concentrations of neutrophils, CXCL8, TNF-α, and proteases, such as MMP-9 and neutrophil elastase. All of these factors are also present in COPD patients.

Question 17

True or false: LTB4 and reactive oxygen species are generated by activated macrophages. Reactive oxygen species are very unstable and lead to damage of tissue adjacent to activated macrophages. The reactive oxygen species were primarily produced to destroy ingested microorganisms.

Answer 17

True.

Question 18

What enzymes do macrophages secrete that may be harmful to tissues? What transcription factor causes the upregulation of most of the inflammatory enzymes in COPD macrophages?

Answer 18

Alveolar macrophages also secrete elastolytic enzymes (elastase), including matrix metalloproteases (MMP)-2, MMP-9, MMP-12, and cathepsins K, L, and S. Most of the inflammatory enzymes that are upregulated (increased) in COPD macrophages are regulated by transcription factor nuclear factor-κB (NFκB), which is activated in alveolar macrophages of COPD patients.

Question 19

How are cysteine proteases (capthesins) implicated in COPD?

Answer 19

Cysteine proteases (cathepsins) may lead to tissue destruction by activating metalloproteinase cascades. The levels of matrix metalloproteinase MMP9 and MMP12, metalloproteases with elastolytic activity, are increased in COPD.

Question 20

Other than breaking down elastic tissue in the lungs, what two harmful effects may elastase released by neutrophils have?

Answer 20

Elastases key role in host defense against pathogens has been the breakdown of outmembrane proteins of pathogens and virulence factors produced by pathogens. Unfortunately, elastase also breaks down elastin, an elastic fiber that, together with collagen, determines the mechanical properties of connective tissue in the lung. Moreover, neutrophil elastase can directly stimulate fibroblast contraction, which may account for narrowing of the small airways. Similarly, neutrophil elastase induces activation of the epidermal growth factor (EGF) receptor and lead to goblet cell metaplasia. Goblet cells produce and secrete mucous into the lumen of the airway.

Question 21

The receptors on T-cells are very specific for foreign peptides. What are cytotoxic T-lymphocytes (CTLs)? What 3 damaging effects do they have?

Answer 21

CTLs secrete mediators, which lead to the death of cells when the T cell receptor is triggered. CTLs also secrete mediators known as cytokines, which enhance T-cell proliferation and macrophage activation.

Question 22

What role do T-helper cells play in COPD pts?

Answer 22

Another subset of T-cells that increase the activation of macrophages is known as T-helper cells. T-helper cells are also responsible for amplifying the inflammatory response in COPD patients.

The responses mediated by T-helper cells also contribute locally to the development of B-cell lymphoid follicles in the lungs and immunoglobulin production in the secretions of the airway vessels of the lung, and systemically to the production of elevated IgG antibody levels in serum of COPD patients.

Question 23

Where do B-cells accumulate in COPD pts? What do B-cells differentiate into what types of cells? Once differentiated into these cells, what do they release?

Answer 23

B-cells accumulate in the lung during COPD. B-cells ultimately differentiate to plasma cells, which secrete antibodies.

Question 24

What 3 types of anti-bodes are more prevalent in COPD pts? How does one of these antibodies effect airflow?

Answer 24

Antibodies against primary lung epithelial cells were recorded more frequently in COPD patients than control patients without COPD. Moreover, the serum concentration of anti-lung tissue antibodies was correlated with the severity of airflow limitation. Finally, anti-nuclear autoantibodies (antibodies to self most likely to DNA in the nucleus) were more prevalent in COPD patients than, healthy controls.