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Anatomic And Molecular Pathology > Chronic Inflammation and Granulomatous Inflammation > Flashcards

Chronic Inflammation and Granulomatous Inflammation Flashcards

1
Q

Define chronic inflammation

A

Inflammation of prolonged duration (weeks to months) in which active inflammation, tissue injury and repair coexist

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2
Q

What are the causes of chronic inflammation❓

A
  • Persistent infections by microorganisms that are difficult to eradicate eg mycobacteria that evoke delayed-type hypersensitivity reaction
  • Diseases that are caused by excessive activation of the immune system
  • Prolonged exposure to toxic agents
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3
Q

What are the key events in chronic inflammation❓

A
  • Infiltration by mononuclear cells ie macrophages, lymphocytes and plasma cells
  • Tissue destruction
  • Repair
  • Organization
  • Angiogenesis
  • Fibrosis
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4
Q

Speak shortly about the cells of chronic inflammation

A

Blood Monocytes/Tissue Macrophages:

Liver-Kupffer cells
Spleen-Sinus histiocytes 
Lungs-Alveolar macrophages 
CNS-Microglia 
Bone-Osteoclasts
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5
Q

Macrophages begin to migrate to the site of injury within 24-48 hours after the onset of chronic inflammation

True or false

A

False

24-48 hours after the onset of acute inflammation

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6
Q

What modulates the phenotypic shift of macrophages❓

A

Classically activated macrophages:
•attack on tumor cells or intracellular pathogens
•pro-inflammatory
•seen in cellular immunity

Alternatively activated macrophages:
•As injury ceases, the phenotype shifts to that of alternative activation to dampen inflammation and promote repair
•Seen in humoral immunity

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7
Q

What activates “classically activated macrophages”?

A

•T-helper 1 cells

•Actions are mediated through interferon gamma which:
-produces cytotoxic pro-inflammatory cytokines such as TNF and IL-6

•May also be stimulated by liposaccharide of gram-negative bacteria

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8
Q

What activates “alternatively activated macrophages”?

A

•T-helper 2 cells under the influence of IL-4 and IL-3

•Alternatively activated macrophages have:
Anti-inflammatory properties
Encourage angiogenesis 
Encourage tissue remodeling 
Encourage tissue repair
  • There is a reduced production of TNF, IL-6 and IL-12
  • There is an induction of arginase 1 which diverts arginine catabolism away from nitric oxide synthesis to that of ornithine and urea
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9
Q

What are the cells of chronic inflammation

A 
Macrophages 
Lymphocytes 
Plasma cells 
Eosinophils 
Mast cells
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10
Q

Tell me the relationship between lymphocytes and macrophages in chronic inflammation

A 
Macrophages display antigens to T-cells
⬇️
produce cytokines IL-12
⬇️
Stimulate T-cell responses 
⬇️
Activated T cells produce cytokines (interferon gamma, TNF and IL-17)
⬇️
Interferon gamma ctivates macrophages which produce TNF and IL-1
⬇️
Chronic inflammation is sustained
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11
Q

Tell me about the two types of T-helper cells and the functions they subserve

A 
T-helper 1 cells:
•secrete IL-1 and interferon gamma
•Involved in:
-delayed hypersensitivity 
-macrophage activation
-synthesis of opsonizing and complement-fixing antibodies

T-helper 2 cells:
•secrete IL-4, IL-5 and IL-13
•involved in the synthesis of other antibodies like IgE (mediated by IL-4 and IL-13)
•activate eosinophils (IL-5)
• found in immediate type hypersensitivity reactions

T-helper 17 cells:
•secrete IL-17 and IL-22
•recruit leukocytes-neutrophils and monocytes

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12
Q

The functions of plasma cells, eosinophils and mast cells in chronic inflammation include❓

A

Plasma cells: produce antibodies against antigens, produces by B cells

Eosinophils: found in inflammation involving parasitic inflammation or immune reactions mediated by IgE (allergies)

Mast cells: produce IgE antibodies. Participate in acute and chronic inflammatory responses in individuals with atopy in allergic reactions

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13
Q

What is a granulomatous inflammation❓

A 
It’s:
•A type of chronic inflammation 
•Cells of monocyte-phagocyte system are predominant 
•Characterized by the presence of:
-Macrophages 
-Epitheloid Cells 
-Multinucleated giant cells
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14
Q

List the cells of granulomatous inflammation

A
  • Macrophages
  • Epitheloid Cells
  • Multinucleated giant cells
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15
Q

Causes of granulomatous inflammation❓

A
  1. Infections eg
    - Schistosomiasis
    - TB
    - Leprosy
    - Histoplasmosis
  2. Toxic reactions
  3. Allergic reactions
  4. Autoimmune diseases
  5. Neoplastic diseases
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16
Q

Discuss the pathogenesis of granuloma formation

A
  • Granuloma formation is a defense from persistent irritants (endogenous/exogenous)
  • Agent is walled off and sequestered by cells of macrophages lineage for destruction or containment
  • Usually occurs when irritant is insoluble or resistant to degradation by macrophages
  • Can also occur if irritant is soluble eg beryllium, but combines with endogenous macromolecules to form insoluble, undegradable compounds
  • CD4+T cells secrete mediators like IL-2, interferon gamma, TNF and lymphotoxin
  • There is transformation of macrophages into epitheloid cells and giant cells
  • Activation of macrophages lead to an increased expression of MHC II and CD4+ Th1 lymphocytes
17
Q

Morphology of granulomas

A

•Epitheloid cells

  • pink, finely granular cytoplasm
  • indistinct cell boundary
  • Epitheloid macrophages are surrounded by lymphocytes secreting cytokines responsible for continuous macrophages activation
  • Older granulomas may have fibroblasts and connective tissue
  • multinucleated giant cells
  • 40-50um in diameter
  • large mass of cytoplasm
  • many nuclei
  • fusion of 20 or more macrophages

*in granulomas associated w certain infectious organisms eg tubercle bacillus, hypoxia and free radical injury leads to central zone of necrosis
•grossly- granular, cheesy appearance (caseous necrosis)
•microscopically- amorphous, structureless, granular debris

18
Q

Naive T cells are activated by❓

A

APC and IL-1

19
Q

What happens in delayed type hypersensitivity rxns

A

1At first exposure, production of IL-12

CD 4+
⬇️IL-12
TH1

  1. At second exposure, TH1 memory cells recognize antigen on APC and are activated

TH1 cells produce IL-2 (proliferation of T cells) and IFy (activator of macrophages)

Recognition of CD4 lymphocytes and macrophages
⬇️
Granuloma

20
Q

What are the chemical mediators of fever❓

A

IL-1

TNF

Anatomic And Molecular Pathology (14 decks)

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