Chronic Inflammation Flashcards
Acute Inflammation Resolution Requirements (3)
- also talk about how common this is?
1) Short lived, mild injury
2) Very limited damage to ECM
3) Capacity for cell regeneration (this is a limiting factor in many tissues)
Acute inflammation resolution doesn’t happen very often (only in very very mild injuries). Must usually pass through chronic first.
What are the outcomes of acute inflammation?
1) complete resolution (if there is minimal damage)
2) pus formation, leading to an abscess (this occurs in suppurative inflammation - cannot really be solved on its own, must be drained). This usually leads to healing and fibrosis
3) Fibrosis (macrophages clear out damaged tissue, but the cells can’t regenerate properly; fibroblasts create collagen to fill in gaps; loss of function)
4) Progression to chronic inflammation (angiogenesis, fibrosis, mononuclear cells, progressive tissue injury)
Causes of acute vs. chronic inflammation
Acute:
- bacterial infection
- trauma
- infarction (thrombus or embolism)
- toxins
Chronic:
- viral infection
- chronic infections
- autoimmune disorder
- persistent injury
Chronic Inflammation
- definition
- cause (very general); two possibilities; two sub-possibilities
- prolonged inflammation of weeks to months, including inflammation, tissue injury, and attempts at repair
- usually occurs as a continuation of acute inflammation as part of the healing process, but can also appear insidiously (without obvious precursor)
Insidious appearance possibilities:
1) Persistent exposure to damaging things
–> microorganisms that are of low toxicity or resistance to killing
–> potentially toxic agents, inert foreign materials
2) Dysregulated activation of adaptive immune system
Cardinal features of chronic inflammation (3)
- plus comment about acute?
1) presence of non-neutrophil immune cells (lymphocytes, macrophages, plasma cells) plasma cells are fully differentiated B lymphocytes that spit out antibodies (inflammation)
2) Architectural destruction of tissues (damage)
3) Fibrosis (tissue repair)
- -> features of acute inflammation may also be present but diminished
Chronic inflammation leukocyte reactions
- what are the predominant leukocytes involved?
- what about another leukocyte (specific)
- predominant leukocytes in chronic inflammation are macrophages and lymphocytes
- neutrophils may still be present because of persistent activation by cell mediators secreted by macrophages (TNF, IL-1)
Macrophages:
- where are they from (explain progression)
- list all types of different macrophages
- from stem cells in the bone marrow (here they are called monoblasts)
- in the blood, they differentiate to become monocytes
- in tissues, they are macrophages
- types:
- -> kupffer cells (liver)
- -> osteoclasts (bone)
- -> alveolar macrophages (lung)
- -> microglia (CNS)
- -> langerhans cells (skin)
What do macrophages do? (4)
1) phagocytosis of microorganisms or dead cells
2) secrete chemical mediators (TNF, IL-1)
- -> central role in initiation and propagation of inflammatory response
- -> contributes to systemic effects
3) interact with adaptive immune response by presenting antigens to lymphocytes
4) Initiate tissue repair process
Explain process of monocyte to differentiated macrophage (2 examples)
- time?
1) diapedesis of monocytes is same as that of neutrophils
2) once in tissues, macrophages are exposed to cytokines that influence what type of macrophage it will become
If exposed to microbes, IFN gamma, and cytokines (from activated T cells), will become inflammatory macrophage:
- ROS and nitrogen species
-proteases
- cytokines, IL1 and TNF
- coagulation factors
- AA metabolites
If exposed to IL4, will become repair macrophage:
- secrete growth factors (PDGF - platelet derived, FGF - fibroblast, TGF - transforming)
- angiogenic factors
- remodelling collagenesis
- fibrogenic cytokines
Time: macrophages will reach their targets 2 days after acute inflammation (48 hours)
Persistent injurious stimulation
- explain what happens
- persistent injury results in release of interferon gamma by T cells
- IFN gamma activates macrophages
- in certain situation where the stimulation persists, more IFN gamma is released
- this results in a specific pattern of chronic inflammation called granulomatous inflammation
Granulomatous inflammation
- definition
- examples of illnesses that show granulomatous inflammation
- what is the morphologic hallmark (2 types)?
- describe structure
- distinctive pattern of inflammation resulting from an antigen that is difficult to eradicate
examples: - leprosy
- tuberculosis (VERY COMMON)
- sarcoidosis
- crohn’s disease
- syphilis
- cat-scratch disease
- parasites, some fungal organisms
- foreign bodies (toxins, foreign objects)
Hallmark: Granuloma
1) Immune granuloma - poorly degradable antigen or particulate causes cell mediated response (INF gamma and IL-2)
2) Foreign body granuloma - inert object too large for phagocytosis
Structure:
granulomas are collections of activated macrophages called epithelioid cells, surrounded by lymphocytes (pumping cytokines) or fibrosis. They can merge into each other to form “giant cells” (multinucleated). In the middle of the granuloma is the offending organism/agent.
Macrophages have to keep getting replaced. Granulomas just trap and control the agent (can’t kill).
TB: organisms locked into granulomas, stay there for years not doing anything, until something happens to the granuloma and they escape and then you have full blown TB
Giant cells
Foreign body vs. Immune Granuloma
Foreign body: all nuclei are jumbled around in giant cell
Immune: line the walls of the giant cell
Chronic Inflammation summary of types
- 2 main types, (2 subtypes for each)
Persistent injurious stimulus: –> INF gamma –> granuloma
1) Persistent infections
- organism difficult to eradicate (tuberculosis, leprosy, fungi, etc)
- elicit marked granuloma effect (lots of INF gamma)
2) Persistent inert stimulus
- non-digestible
- weaker granulomatous response
Immune mediated: inherent defect in immune system regulation
1) Autoimmunity (lupus, rheumatoid arthritis):
- unnecessary activation of immune system
- fights against self-antigens
- self propagating
2) Immune dysregulation (inflammatory bowel disease)
- unregulated immune response to antigens
3) Hypersensitivity Reactions
