Chronic Inflammation and Granulomatous Inflammation Flashcards
Define chronic inflammation
Inflammation of prolonged duration (weeks to months) in which active inflammation, tissue injury and repair coexist
What are the causes of chronic inflammation❓
- 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
What are the key events in chronic inflammation❓
- Infiltration by mononuclear cells ie macrophages, lymphocytes and plasma cells
- Tissue destruction
- Repair
- Organization
- Angiogenesis
- Fibrosis
Speak shortly about the cells of chronic inflammation
Blood Monocytes/Tissue Macrophages:
Liver-Kupffer cells Spleen-Sinus histiocytes Lungs-Alveolar macrophages CNS-Microglia Bone-Osteoclasts
Macrophages begin to migrate to the site of injury within 24-48 hours after the onset of chronic inflammation
True or false
False
24-48 hours after the onset of acute inflammation
What modulates the phenotypic shift of macrophages❓
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
What activates “classically activated macrophages”?
•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
What activates “alternatively activated macrophages”?
•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
What are the cells of chronic inflammation
Macrophages Lymphocytes Plasma cells Eosinophils Mast cells
Tell me the relationship between lymphocytes and macrophages in chronic inflammation
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
Tell me about the two types of T-helper cells and the functions they subserve
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
The functions of plasma cells, eosinophils and mast cells in chronic inflammation include❓
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
What is a granulomatous inflammation❓
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
List the cells of granulomatous inflammation
- Macrophages
- Epitheloid Cells
- Multinucleated giant cells
Causes of granulomatous inflammation❓
- Infections eg
- Schistosomiasis
- TB
- Leprosy
- Histoplasmosis - Toxic reactions
- Allergic reactions
- Autoimmune diseases
- Neoplastic diseases
Discuss the pathogenesis of granuloma formation
- 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
Morphology of granulomas
•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
Naive T cells are activated by❓
APC and IL-1
What happens in delayed type hypersensitivity rxns
1At first exposure, production of IL-12
CD 4+
⬇️IL-12
TH1
- 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
What are the chemical mediators of fever❓
IL-1
TNF
