INFLAMMATION & INFLAMMATION & REPAIR Lecture 5 Acute Inflammation: Inflammatory Cell Types Winter 2013

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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

    P ro

    -i n

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    A n ti -I

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  • • 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 mot

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