Inflammation Flashcards
What are the 5 cells you would expect to see during inflammation? How can you differentiate between them histologically?
- Eosinophils
- red staining granules in cytoplasm due to increase proteins
- bilobular nucleus - Lymphocytes
- v large nucleus - Macrophages
- large amount of cytoplasm
- nucleus not round - Neutrophil
- multilobular nucleus (5 lobes)
- granules - Plasma cell
- paranuclear hoff= pale area in cytoplasm near nucleus due to there being numerous ribosomes to enable high transcriptional activity
What are the cardinal signs of inflammation?
Heat Redness Swelling Pain Loss of function
What are the basic differences between acute and chronic inflammation? (Incl different cell types)
Acute:
- fast onset
- mainly neutrophils involved
- mild, self-limited tissue injury/fibrosis
- prominent local and systemic signs
Chronic:
- slow onset
- lymphocytes and plasma cells
- severe and progressive tissue injury
- less prominent local and systemic signs
What are the main causes of acute inflammation?
Infection Burns Chemicals Tissue death Immune response
What are the 4 stages of acute inflammation response?
- Recognition of PAMPs and DAMPs
- Vascular changes
- WBC recruitment
- Elimination of microbial and cellular debris
How are PAMPs and DAMPs involved in acute inflammation?
Leads to activation of macrophages, dendritic cells, mast cells and epithelial cells via methods of recognition:
- complement
- Toll-like receptor s
- Inflammasome complex= Intracellular complex for recognising bacteria
PAMPS= recognise pathogen DAMPS= recognise extracellular ATP released from cytoplasm during cell lysis
How are chemical mediators involved in the vascular changes of acute inflammation?
Released in response to DAMPs/PAMPs
Histamine + prostaglandins= vasodilation
C3a + C5a + leukotrienes= increased vascular permeability
What are the vascular changes associated with acute inflammation?
How do these changes lead to blood stasis? Why is this important?
- Vasodilation
- Increased permeability
- Leukocyte margination
-Increased permeability leads to plasma entering extracellular space
-concentration for erythrocytes increased which results in congestion and increased blood viscosity
= blood flow decreased -> blood stasis
Enables leukocytes to migrate to endothelium
What enables leukocyte margination in acute inflammation?
Blood stasis
Loss of axial streaming due to vasodilation causing plasma to enter extracellular space i.e. would normally preferentially occupy periphery of blood stream
Describe the processes involved in the 5 stages of WBC recruitment in acute inflammation and the adhesion molecules involved.
Which molecules establish the chemotactic gradient?
- Margination= WBC move to blood periphery
- no specific adhesion molecules involved i.e. relies on blood stasis and loss of axial streaming - Rolling= weak binding to endothelium
- selectins - Adhesion= firm adhesion
- integrins - Transmigration= Movement to extravascular space
- platelet endothelial cell adhesion molecule-1 (PECAM-1) - Chemotaxis
- chemotactic substances= bacterial products/complement components/leukotrienes/chemokines
How are microbes eliminated as part of acute inflammation?
- Phagocytosis
Opsonins (IgG or C3b) recognise and ATTACH microbe to leukocyte
Pseudopods ENGULF particle to form phagocytic vacuole
RO species and lysosomal enzymes released to KILL AND DEGRADE - NETs
What are the histological features of acute inflammation?
Increased cell wall diameter
Marginalisation of neutrophils to endothelium
Congested, dilated vessels
Scattered macrophages
What is the difference between purulent exudate and an abscess?
PE= formed from neutrophils, liquefactive necrosis and oedema fluid
Abscess= walled-off collection of pus
What are causes chronic inflammation? Try to give examples.
- Progression from acute inflammation
Eg Repeated acute inflammatory episodes (peptic ulcer)
Eg Persistence of injury without resolution (undrained abscess)
2. Primary chronic inflammation Eg Intracellular infection (Hep B and C) Eg Foreign body reaction (exogenous and endogenous) Eg Autoimmune disease Eg Rejection of organ transplant Eg Unknown aetiology
What are the 3 components of chronic inflammation?
- Tissue infiltration by mononuclear cells
- Tissue distribution
- Healing and repair
Give examples of mononuclear cells. What are their roles in chronic inflammation?
T lymphocytes
- CD4+ = activate effector cells and co-operate humoral response
- CD8+ = effector cells i.e. direct apoptosis or cytotoxic cytokines production
B lymphocytes
-differentiate into plasma cells which secrete Igs
Macrophages
-Activated by cytokines or inflammatory mediators
NOTE: also present in late stages of acute inflammation to remove tissue debris + promoting tissue repair
What are the 2 possible origins of macrophage in chronic inflammation?
What are the characteristics of an activated macrophage?
- Circulating monocytes= diff in tissue
- Resident tissue population eg Kupffer cells in liver and Alveolar macrophages in lungs
Increased size
Mobility
Phagocytic activity
Production of substances promoting angiogenesis and fibrosis
Which 3 CD4+ TC subsets are associated with chronic inflammation? What cytokines are release and what functions do they mediate?
Th1
- IFN-gamma
- M1 polarisation
Th2
- IL-4/5/13
- eosinophil recruitment (associated with IgE response i.e. parasite response)
- M2 polarisation
Th17
- IL-17
- neutrophil recruitment
What is a granuloma and what are possible causes?
Aggregation of macrophages with epitheliod morphology, large vesicular nuclei and eosinophilic cytoplasm (can fuse to form giant cells)
- Infection eg TB/Fungi/parasites/Syphilis
- Foreign body (exogenous or endogenous)
- Drugs eg Phenylbutazone (NSAID) + sulfonamides (antibiotics) cause hepatic granulomas
- Crohn’s disease
- Sarcoidosis
What are examples of time when acute inflammation involves lymphocytes rather than neutrophils?
Acute viral hepatitis
Viral meningitis
Viral myocarditis
Acute AI hepatitis
When is chronic inflammation associated with neutrophils?
Acute on chronic inflammation eg cholecystitis
Immune complex mediated glomerulonephritits
What are the local and system effects of inflammation? What causes the systemic effects to occur
LOCAL:
- tissue injury
- fibrosis
- neoplasia
SYSTEMIC:
- Fever= IL-1 and TNF increase prostaglandin prod -> affect temp balance in hypothalamus
- Acute phase proteins (CRP/Fibrinogen/Serum amyloid A)= IL-6, IL-1 and TNF increase prod in hepatocytes
- Leucocytosis
- Pain= prostaglandins and bradykinin
