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INFLAMMATION & REPAIR
Lecture 5 Acute Inflammation: Inflammatory Cell Types
Winter 2013
Chelsea Martin Special thanks to Drs. Hanna and Forzan
1. Vasodilation (increased blood flow) ► CALOR & RUBOR
• arteriolar dilation / opening of capillaries (hyperemia / redness)
• histamine and Nitric Oxide (primarily)
2. Increased microvascular permeability: fluids into tissues ► TUMOR
3. Blood flow slows (stasis) and rbc concentration ► RUBOR
4.Cellular events –
a) margination, rolling and adhesion
b) emigration of WBC into tissue (exudation)
c) accumulation of WBC at sites of injury
TUMOR
d) activation of cells, production of mediators
DOLOR
e) removal of stimulus
5. Tissue damage / Repair ►LOSS OF FUNCTION
SEQUENCE of EVENTS:
43
Leukocytes Cells of the Inflammatory Exudate
Polymorphonuclear Leukocytes • Neutrophils (heterophils)
• Eosinophils
• Basophils/Mast Cells
Mononuclear Cells • Monocytes/Macrophages
• Lymphocytes
• Plasma cells
• Thrombocytes*
Generalities 1. Most leukocytes are in the blood stream (WBCs)
• except: plasma cells, mast cells, macrophages
2. Leukocytes maintained in relative and constant proportion
• modified by systemic response to inflammation
3. Each blood cell plays a distinctive role
4. Each enters into inflammatory response in a definite sequence
Virchow vs. Cohnheim
The Theory of Inflammation
• Rudolph Virchow believed pus was made of connective tissue elements.
• Julius Cohnheim proved they came from the blood.
Erythrocyte
Platelet
Segmented neutrophil
Band neutrophil
Eosinophil
Basophil
Monocyte
Pathologystudent.com
Neutrophils
Synonyms:
• polymorphs, PMNs, Neuts
Characteristics
• highly mobile
• respond to lots of chemotaxins
• phagocytic and bactericidal
• 1º cell against bacteria
• 1st line of defense & crucial
• don’t divide in tissue
• short life-span - in circulation few days (hrs?)
- undergo apoptosis if not utilized
35
Neutrophils in suppurative
bronchitis (tissue - H&E)
Neutrophils
in cytologic preparation
Neutrophils - Where do they live?
• Originate in Bone Marrow
5-10 X 1010 per day
• Blood
Circulating Pool (measured in a CBC)
Marginating Pool (out of the flow)
• Storage pool in bone marrow
• Exit into tissue
die after 1-2 days
Neutrophil - Morphology
Abundant cytoplasmic granules:
• Azurophil Granules (1o granules)
• Myeloperoxidase & others
• Specific Granules (2o granules)
• Lysozyme & other enzymes
• Leukocyte adhesion molecules
• Tertiary granules
• Gelatinase
• Leukocyte adhesion molecules
Other enzymes - elastase, collagenase, plasminogen activators, etc
Neutrophil - Functions
• Phagocytosis ROS
H2O2 - myeloperoxidases - halide
lysosomal enzymes
• Mediate tissue injury
• Regulate inflammatory response release leukotrienes, PAF, etc
Myeloperoxidase (in azurophil granules)
catalyzes:
H2O2 + Cl- HOCl●
HOCl (Hypochlorous acid) is a powerful oxidant and antimicrobial agent
(H2O2-myeloperoxidase-halide system)
Myeloperoxidase
www.medirabbit.com
Heterophils Guinea pig
eosinophil vs heterophil
WHEN DO NEUTROPHILS PREDOMINATE?
• acute inflammatory reactions
• suppurative / purulent exudates
(esp bacterial infections)
Morph. Dx (pig):
Meningitis, suppurative, focally extensive, acute, severe
Morph. Dx (calf):
Hepatitis, suppurative, focal, acute, severe (abscess?)
Eosinophil - Morphology
• granules are basic
– eosin (acid) – red
• slightly larger than neutrophils,
variable size
• phagocytic (less than pmn’s)
26
Eosinophil - Morphology and Granules
Major basic protein
• parasite killing
• induce histamine release (mast cells)
Eosinophilic cationic protein
• parasite killing
• shortens coagulation time
Histaminase
• inactivates histamine
Pro
-in
fla
mm
ato
ry
Anti-I
nfla
mm
ato
ry
• Kill or damage helminths
• Involved in HS reactions
recruited by mast cell degranulation
(histamine & IL-5)
• Regulate inflammation
histaminase
Eosinophil - Functions
Eosinophil - Functions
• tumor-associated eosinophilia
– Mast cell tumors
– T cell lymphoma, etc.
• reduced numbers with corticosteroid therapy
Morph. Dx: Skin, mast cell tumor
with eosinophilic infiltration
http://cal.vet.upenn.edu
Plasmacytic inflammation Mast cell tumor
When do EOSINOPHILS predominate?
1. Parasitic diseases
Clinostomum marginatum
Heron trachea
2. Hypersensitivities and autoimmune conditions
Morph. Dx: Bronchitis, eosinophilic, subacute, severe
When do EOSINOPHILS predominate?
2. Hypersensitivities and autoimmune conditions
Morph. Dx: Myositis, eosinophilic, multifocal to coalescing, severe
Name of condition: Masticatory Myositis (MM)
Morph. Dx: Temporal & masseter muscles, atrophy, severe
When do EOSINOPHILS predominate?
Basophils and Mast Cells Characteristics
• Both have separate lineage in bone marrow
mast cells within tissue
basophils in circulation
• Receptors for IgE
main cell in HS type I (IgE mediated)
• Contain metachromatic granules
Histamine (+ proteases, etc)
• Don’t die after releasing granules
• Produce cytokines & AA metabolites
TNF, IL-3,-4,-5,-10,-13, Interferon
Leukotrienes, PG’s
18
Basophils and Mast Cells - Morphology
Mast cells
• round cells, abundant cytoplasm filled
with granules
• granules stain metachromatically with
toluidine blue or giemsa stains
• can proliferate in tissue
Basophils and Mast Cells - Morphology
Basophils
• nuclei are multilobed
• recruited at sites of HS’s
Neutrophil
Eosinophil
Basophil
Basophils Morphology - Species Differences
web.vet.cornell.edu/.../CPmodules/ heme1/images/basocomp.jpg
Basophils and Mast Cells - Functions
Acute Inflammation
• activated by IgE (parasities & allergies)
and substance P
• release histamine
• tryptase (tissue damage)
• generate cytokines
Recruitment of eosinophils
• IL-5
• LT-C4
Monocytes - Characteristics
Monocyte
• small reserve pool in bone marrow
• in circulation (t1/2 = 24-72 hrs)
• functional cells but require activation
• monocytes migrate into tissues macrophages monocyte
Macrophages - Characteristics
Macrophages (MØ’s)
• derived from circulating monocytes
(or resident MØ’s)
• t1/2 30-60 days in tissue
• motile - but sluggish
Macrophages/Monocytes - Morphology
• larger than neutrophils
• large nuclei (folded or bean-shaped)
• contain lysosomes
Macrophages - Functions
"Most dynamic and gifted of the leukocytes“
• Antimicrobial and phagocytic (O2 radicals)
• Recruit other leukocytes (chemokines/cytokines)
• Stimulate or modulate other cell activity
• Clean up debris
• Induce systemic effects
Source of: • Epithelioid macrophages
• Multinucleated giant cells
Leishmaniasis,Leishmania spp., canine
popliteal lymph node aspirate
Where do we see MACROPHAGES?
Acute Inflammation (in low numbers)
- with neutrophils
Subacute Inflammation
- with plasma cells/lymphocytes
Chronic Inflammation
- predominate in granulomatous inflammation
Repair
multinucleated giant cells
epithelioid macrophages
Lymphocytes and Plasma Cells - Characteristics
• less motile than PMN’s & macrophages
• recirculate (lymph nodes, lymphatics)
8
Lymphocytes and Plasma Cells
Morphology
• Heterogeneous
• T lymphocytes
– Cell mediated immunity
– Produce lymphokines
• B lymphocytes
– Produce plasma cells
– Important in antibody production
• review immunology notes
Lymphocytes and Plasma Cells
Morphology
• Heterogeneous
• T lymphocytes
– Cell mediated immunity
– Produce lymphokines
• B lymphocytes
– Produce plasma cells
– Important in antibody production
• review immunology notes
Where do we see LYMPHOCYTES & PLASMA CELLS?
1. Subacute Inflammation
2. Viral Infections
3. Immune-Mediated Diseases
4. Chronic Inflammation
Morph. Dx:
Encephalitis, lymphoplasmacytic,
multifocal, subacute, moderate
Name of Disease:
Distemper (Canine Morbillivirus)
Platelets - as inflammatory cells!
Contributions to inflammation
• Increase vascular permeability
Histamine
• Produce adhesion molecules
P selectin
• Release of inflammatory mediators activates complement (C5)
attracts neutrophils (chemotaxis)
Kierszenbaum, Histology and Cell Biology p 157, 2002
Cells of Inflammation
• Neutrophils
• Eosinophils
• Basophils/mast cells
• Monocytes/macrophages
• Lymphocytes/Plasma cells
• Platelets
• Endothelial cells
• Fibroblasts
Why are endothelial cells considered cells of the
inflammatory response?
Endothelial cells are the source of:
1. Pro-inflammatory mediators:
• Prostacyclin
• Prostaglandins
• PAF
• Interleukins (IL-1, IL-8)
• Nitric oxide
2. Adhesion molecules
• E-selectin
3. Anti-inflammatory mediators:
• TGF-β (anti-inflammatory, pro-repair)
Why are fibroblasts considered cells of the
inflammatory response?
Fibroblasts are the source of:
1. Pro-inflammatory mediators
• IL-6 B and T cell proliferation
2. Anti-inflammatory mediators
• TGF-β
Cells of Inflammation
• Neutrophils
• Eosinophils
• Basophils/mast cells
• Monocytes/macrophages
• Lymphocytes
• Platelets
• Endothelial cells
• Fibroblasts