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    Clinical Examples of Leukocyte-Induced Injury: Acute Chronic

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    sharen
    This document discusses leukocyte-induced injury and defects in leukocyte function that can lead to increased vulnerability to infection. It also summarizes the key morphologic features of chronic inflammation, including infiltration by mononuclear cells such as macrophages, lymphocytes, and plasma cells. Activated macrophages play a central role by secreting various products that can destroy tissue if unchecked, but also initiate repair processes. Ongoing tissue damage can perpetuate the inflammatory response.

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    Clinical Examples of Leukocyte-Induced Injury: Acute Chronic

    Uploaded by

    sharen
    19 views17 pages
    This document discusses leukocyte-induced injury and defects in leukocyte function that can lead to increased vulnerability to infection. It also summarizes the key morphologic features of chronic inflammation, including infiltration by mononuclear cells such as macrophages, lymphocytes, and plasma cells. Activated macrophages play a central role by secreting various products that can destroy tissue if unchecked, but also initiate repair processes. Ongoing tissue damage can perpetuate the inflammatory response.

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    Inflammation.Lecture6

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    This document discusses leukocyte-induced injury and defects in leukocyte function that can lead to increased vulnerability to infection. It also summarizes the key morphologic features of chronic inflammation, including infiltration by mononuclear cells such as macrophages, lymphocytes, and plasma cells. Activated macrophages play a central role by secreting various products that can destroy tissue if unchecked, but also initiate repair processes. Ongoing tissue damage can perpetuate the inflammatory response.

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    © All Rights Reserved
    Download as PDF, TXT or read online from Scribd
    Download as pdf or txt
    19 views17 pages

    Clinical Examples of Leukocyte-Induced Injury: Acute Chronic

    Uploaded by

    sharen
    This document discusses leukocyte-induced injury and defects in leukocyte function that can lead to increased vulnerability to infection. It also summarizes the key morphologic features of chronic inflammation, including infiltration by mononuclear cells such as macrophages, lymphocytes, and plasma cells. Activated macrophages play a central role by secreting various products that can destroy tissue if unchecked, but also initiate repair processes. Ongoing tissue damage can perpetuate the inflammatory response.

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    of 17

    Clinical Examples of Leukocyte-

    Induced Injury

    Acute Chronic
    • Acute respiratory distress •Arthritis
    syndrome •Asthma
    • Acute transplant rejection •Atherosclerosis
    • Reperfusion injury •Glomerulonephritis
    • Septic shock •Chronic lung disease
    • Vasculitis •Chronic rejection
    Defects in Leukocyte Function
    • Defects in leukocyte function, both genetic and
    acquired, lead to increased vulnerability to
    infections:
    – Defects in leukocyte adhesion
    – Defects in phagolysosome function. One such
    disorder is Chédiak-Higashi syndrome, an autosomal
    recessive condition characterized by neutropenia
    (decreased numbers of neutrophils), defective
    degranulation, and delayed microbial killing
    – Defects in microbicidal activity. The importance of
    oxygen-dependent bactericidal mechanisms is shown
    by the existence of a group of congenital disorders
    with defects in bacterial killing called chronic
    granulomatous disease
    Defects in Leukocyte Function
    Genetic
    • Leukocyte adhesion deficiency 1
    • β chain of CD11/CD18 integrins
    • Leukocyte adhesion deficiency 2
    • Fucosyl transferase required for synthesis of sialylated
    oligosaccharide (receptor for selectin)
    • Chronic granulomatous disease
    • Decreased oxidative burst
    – X-linked
    • NADPH oxidase (membrane component)
    – Autosomal recessive
    • NADPH oxidase (cytoplasmic components)
    – Myeloperoxidase deficiency
    • Absent MPO-H2O2 system
    • Chédiak-Higashi syndrome
    • Protein involved in organelle membrane fusion
    Defects in Leukocyte Function
    Acquired
    • Thermal injury, diabetes, malignancy, sepsis,
    immunodeficiencies
    – Chemotaxis
    • Hemodialysis, diabetes mellitus
    – Adhesion
    • Leukemia, anemia, sepsis, diabetes,
    neonates, malnutrition
    – Phagocytosis and microbicidal activity
    MORPHOLOGIC FEATURES OF
    CHRONIC INFLAMMATION
    • Infiltration with mononuclear cells include
    – Macrophages
    – Lymphocytes
    – Plasma cells
    – Eosinophils
    • Tissue destruction
    – induced by the persistent offending agent or by
    the inflammatory cells.
    • Healing
    – by connective tissue replacement of damaged
    tissue, accomplished by proliferation of small
    blood vessels (angiogenesis) and, in particular,
    fibrosis
    MORPHOLOGIC FEATURES OF
    CHRONIC INFLAMMATION
    • MONONUCLEAR CELL
    INFILTRATION
    – The macrophage is the dominant cellular
    player in chronic inflammation
    – The mononuclear phagocyte system
    (sometimes called reticuloendothelial
    system) consists of closely related cells of
    bone marrow origin, including blood
    monocytes and tissue macrophages
    mononuclear phagocyte system

    –monocytes begin to emigrate into extravascular tissues quite early in


    acute inflammation and within 48 hours they may constitute the
    predominant cell type
    MONONUCLEAR CELL INFILTRATION
    • Macrophages may be activated by a variety of
    stimuli, including
    – cytokines (e.g., IFN-γ) secreted by sensitized T lymphocytes
    and by NK cells
    – bacterial endotoxins
    – other chemical mediators
    • Activation results in
    – increased cell size
    – increased levels of lysosomal enzymes
    – more active metabolism
    – greater ability to phagocytose and kill ingested microbes.
    • Activated macrophages secrete a wide variety of
    biologically active products that, if unchecked, result
    in the tissue injury and fibrosis
    The roles of activated macrophages in chronic inflammation.
    Products of macrophages
    1.Acid and neutral proteases
    2.Chemotactic factors
    3.Reactive oxygen
    metabolites
    4.Complement components
    5. Coagulation factors
    6.Growth promoting factors
    for fibroblasts, blood vessels
    and myeloid progenitor cells
    7.Cytokines : IL-1, TNF
    8.Other biologic active agents
    ( PAF, interferon, AA
    metabolites)
    MORPHOLOGIC FEATURES OF
    CHRONIC INFLAMMATION
    • The products of activated macrophages serve to
    eliminate injurious agents such as microbes and to
    initiate the process of repair, and are responsible for
    much of the tissue injury in chronic inflammation
    • In chronic inflammation, macrophage accumulation
    persists, this is mediated by different mechanisms:
    1. Recruitment of monocytes from the circulation, which results
    from the expression of adhesion molecules and chemotactic
    factors
    2. Local proliferation of macrophages after their emigration from
    the bloodstream
    3. Immobilization of macrophages within the site of inflammation
    • ongoing tissue destruction can activate the
    inflammatory cascade by diverse mechanisms, so that
    features of both acute and chronic inflammation may
    coexist
    OTHER CELLS IN CHRONIC INFLAMMATION
    • Lymphocytes
    – Both T & B Lymphocytes migrates into inflammation
    site
    –Lymphocytes and macrophages interact in a bidirectional
    way, and these reactions play an important role in chronic
    inflammation

    Activated lymphocytes and macrophages influence each


    other and also release inflammatory mediators that affect
    other cells.
    •Eosinophils
    are abundant in immune reactions mediated by IgE and in
    parasitic infections
    •respond to chemotactic agents derived largely from mast cells
    •Granules contain major basic protein: toxic to parasites and lead
    to lysis of mammalian epithelial cells
    • Mast cells
    – are widely distributed in connective tissues
    – Mast cells express on their surface the receptor that
    binds the Fc portion of IgE antibody ,
    • IgE antibodies bound to the cells' Fc receptors specifically
    recognize antigen, and the cells degranulate and release
    mediators, such as histamine and products of AA oxidation
    OTHER CELLS IN CHRONIC INFLAMMATION

    • GRANULOMATOUS INFLAMMATION
    – Granulomatous inflammation is a
    distinctive pattern of chronic
    inflammatory reaction characterized by
    focal accumulations of activated
    macrophages, which often develop an
    epithelial-like (epithelioid) appearance

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