Acute Inflammation - Cells Flashcards

1
Q

Cells of Inflammation:

Granulocytes

A

Neutrophils

Eosinophils

Basophils

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2
Q

Cells of Inflammation:

Mononuclear Cells

A

Monocytes / Macrophages

Lymphocyters / Plasma Cells

Mast Cells

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3
Q

Neutrophils:
Morphology

A
  • 10-15 micron diameter
  • Segmented, multi-lobular nucleus
  • Cytoplasmic Granules
    • primary (azurophilic) granules
    • Secondary (Specific) granules
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4
Q

Neutrophils:

Primary Granule Content

A

Myeloperoxidase

Lysozyme

Acid Hydrolases

Elastase

Cathepsin G

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5
Q

Neutrophils

Secondary Granule Content

A

Lysozyme

Collagenase

Gelatinase

Lactoferrin

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6
Q

Neutrphils:

Characteristics

A
  • They are highly differentiated
  • THey are no longer able to divide
  • Cellular respiration can be mainly anaerobic
    • contain abundant glycogen stores
    • Can function in low oxygen environments
      • Hypoxia-inducible Factor-1 (HIF-1a)
  • They metabolize large amounts of oxygen in response to activation
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7
Q

Neutrophils:

Kinetics

A
  • Produced in the bone marrow, where they remain for 1.5 days after maturation in a storage pool
    • pool is 5x the circulating concentration
  • Once they enter the blood, they circulate for 5-12 hours
    • Approximately half of the intravascular neutrophils are marginated
  • Once they emigrate the can live 1-4 days in tissues; depending on the situation
    • Apoptosis occurs following withdrawal of growth factors and other stimuli
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8
Q

Neutrophils:

Major Inflammatory Functions:

Phagocytosis and Killing

A
  • Oxygen-independent Killing
    • Phagolysosome formation allows granule content to act upon the inflammatory stimulus
  • Oxygen-dependent Pathways are prominent in neutrophils
    • NADPH - assocaited oxygen radicals
    • Myeloperoxidase dependent killing can occur, making neutrophils the most potent killers of all phagocytes
  • Nitric Oxide Pathways are also present
    • Formulation of highly reactive peroxynitrite
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9
Q

Neutrophils:

Major Inflammatory Functions:

Secretion of Inflammatory Products

A
  • Lysosomal enzymes and oxygen metabolites can be released into the extracellular space
    • can kill extracellular pathogens, but also destroy ECM
  • Cytokines
    • IL-8
  • Products of arachidonic Acid Metabolism
    • LTB4, PGE2, TXA2, PAF
  • Anitmicrobial peptides
  • Neutrophil extracellular traps
    • products of dead neutrophils that trap and possibly kill bacteria
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10
Q

Neutrophil Extracellular Traps

A
  • Web-like matrix of DNA/proteins/ and neutrophil granule products secreted by neutrophils that trap and kill pathogens
    • NETs contain concentrated myeloperoxidase, elastase, cathepsin G, amond others
  • NETs may also be involved in autoimmunity and thrombosis
    • Intracellular products within NETs may stimulate an immune response
    • Platelets regulate and interact with intravascular NETs
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11
Q

Eosinophils:

Morphology

A
  • 15-20 micron diameter
  • Segmented, bilobed nucleus
  • Four types of cytoplasmic granules
    • specific granules have characteristic crystalloid core
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12
Q

Eosinophil:

Granule Content

A

Major Basic Protein (MBP)

Eosinophil cationic protein

Arylsulfatase B

Histaminase

Phospholipase D

Peroxidase

Hydrolytic Enzymes

Collagenase

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13
Q

Eosinophil:
Characteristics

A
  • Not as well understood as neutrophils
    • Phagocytic, but much less so than neutrophils
  • Prominent at sites of allergic reactions or parasitic infections
  • Often occur in association wiht mast cells
    • Respond to eosinophil chemotactic factor and histamine
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14
Q

Eosinophil:

Kinetics

A

Have a 30 minute half life in the blood

Have a 12 day half-life in tissue

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15
Q

Eosinophils:

Major Inflammatory Functions:

Secretion of lysosomal Enzymes

A
  • Damage microbe membranes, but also the ECM
  • Degradation of certain Pro-inflammatory products
    • histaminase and histamine
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16
Q

Eosinophil:

Major Inflammatory Functions:

Secretion of other mediators

A
  • Cytokines
    • Interleukins (1,6,8,12 among others)
    • Transforming Growth Factor (TGF) a and B
  • Chemokines
    • Eotaxin
  • Arachidonic Acid Metabolites
    • LTC4, LTD4, LTE4
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17
Q

Basophil:

Morphology

A
  • 8-12 micron Diameter
  • Multilobed nucleus
  • Cytoplasmic Gramules
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18
Q

Basophil:

Granule Content

A

Histamine

Proteoglycans

Chondrotin

Heparin

Proteases

Elastase

Tryptase

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19
Q

Basophil:

Characteristics:

A
  • Not well understood
  • Associated with sites of IgE-dependent allergic reactions or parasitic infections
    • receptors for IgE and Eotaxin
  • Poorly Phagocytic, and sluggishly motile
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20
Q

Basophil:

Kinetics

A
  • Not well defined
  • Probably similar to neutrophils
    • Recruited into tissue from blood
      • Have a life span of several days once in the tissue
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21
Q

Basophil:

Major Inflammatory Functions:

Secretion of lysosomal Enzymes

A
  • Effects include bronchoconstriction, vasodilation, and ECM degradation
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22
Q

Basophil:

Major Inflammatory Functions:

Secretion of Other Mediators

A
  • Cytokines
    • IL-4, IL-13
      • IL-4 is critical in the IgE response to allergens
  • Arachidonic Acid Metobolites
    • LTD4
  • Chemokines
23
Q

Mast Cell:

Morphology

A
  • 10-15 micron diameter
  • Oval to round nucleus
    • Metachromatic Cytoplasmic granules
24
Q

Mast Cells:

Granule Content

A

Histamines

Serotonin

Proteoglycans

Chondrotin

Heparin

Proteases

Elastase

Tryptase

25
Q

Mast Cell:

Characteristics:

A

Two types:

  1. Connective tissue
  2. Mucosal
  • Prominent at sites of allergic reactions or parasitic infections
    • possess membrane receptors for IgE
  • Functionally very similar to basophils
    • mst cells produce greater numners / varieties of mediators
  • Often Present in conjunction with eosinophils
26
Q

Mast Cells:

Kinetics

A

4-12 week lifespan depending on location and situation

residents in the tissue

27
Q

Mast CellL

Major Inflammatory Functions: Secretion of Lysosomal Enzymes

A

Effects include bronchoconstriction, vasodilation, and ECM degradation

28
Q

Mast Cell:

Major Inflammatory Functions:

Secretion of other Mediators

A
  • Chemotactic Factors
    • Eosinophils, neutrophils, and macrophages
  • Arachidonic Acid Metabolites
    • LTC4, PGD2, TXA2, and PAF
  • Cytokines
    • TNFa
  • Chemokines
29
Q

Mononuclear Phagocytes

A
  • A group of cells that compose the mononuclear phagocytic system
  • This group of cells consists of both circulating and fixed populations
    • Circulating component:
      • monocyte
    • Emigrated monocyte:
      • Macrophage
    • Fixed macrophage components include:
      • Dendritic cells
      • Sinusoidal macrophages of bone marrow and lymphoid
      • Kupffer cells of the liver
      • Alveolar macrophages
      • Microglia of hte CNS
      • Medangial macrophages of renal glomeruli
      • Peritoneal macrophages
30
Q

Monocyte:

Morphology:

A
  • 12-15 micron diameter
  • round to oval, slightly indented nucleus
  • Cytoplasmic granules
  • Abundant cellular organelles
31
Q

Monocytes:

Characteristics:

A
  • Source of macrophges and dendritic cells
    • replenich resident tissue macrophages and dendritic cells
      • physiologic
    • Subsets fo monocytes or certain types of stimuli will drive differentiation into dendritic cells
    • Emigrate in response to inflammatory stimuli
32
Q

Monocytes:

Kinetics

A
  • Circulate for approximately 1-3 days in blood
    • Approximately half of the circulating monocytes are sequestered in the spleen
  • Slower to emigrate than neutorphils
    • Emigrate mainly after 24-48 hours
33
Q

Fixed Macrophages:

Characteristics

A
  • Derived form monocytes
    • These emigrate in response to physiologic cytokines
    • They also replicate locally wihtin the tissues to maintain the fixed population
  • Form the nononuclear-phagocyte system
    • located at sites where microbial invasion is most likely
    • Often the first inflammatory cell to recognize invasion by a microbe or foreign material
  • Contribute to both inflammation and immunity
    • Innate:
      • monokines and otehr macrophage products contribute to innate immunity and inflammation
    • Acquired:
      • macrophages and dendritic cells are important antigen presenting cells in immunity
34
Q

Dendritic Cells:

Characteristics

A
  • Process and present antigen to T-lymphocytes
    • Capture antigen and migrate to areas with T-lymphocytes
    • Express MHC-2 class molecules and T-lymphocyte receptors
  • Non-phagocytic
  • Several Different phenotypes have been described
35
Q

Dendritic Cells:

Kinetics

A
  • Derived form and maintained by blood monocytes
    • emigrates in response to physiological stimuli
36
Q

Macrophages:

Morphology

A
  • 20-50 micron diameter
  • Round to oval, slightly indented nucleus
  • Cytoplasmic granules
  • Abundant cellular organelles
  • Much more pleomorphic than monocytes
37
Q

Macrophages:

Characteristics

A
  • They are highly sophisticated and multifunctional cells
  • Cellular respiration is mainly aerobic
    • contain abundant mitochondria and endoplasmic reticulum
  • They are important for both inflammatory and immunologic events
  • THey are critical components of chonic inflammation and healing
  • Various subtypes exist:
    • inflammatory
    • anti-inflammatory
    • Regulatory
    • Healing
  • Differentiation is dietermined by the local environment
38
Q

Macrophages:

Kinetics

A
  • Derived from monocytes:
    • the bone marrow reserve pool is much smaller than that for neutrophils
    • Monocytes circulate for 1-3 days
  • Macrophages have life span of a week to possibly several months
    • highly dependent on the local cytokine environment
  • Can be divide locally at an inflammatory site
39
Q

Macrophages:

Major Inflammatory Functions:

Phagocytosis

A
  • These are considered the second line of defense after neutrophils
    • generally incease in number the longer the inflammatory stimulus persists
  • More efficient and multipurposed phagocytes than neutrophils
    • play more of a scavenger role
40
Q

Macrophages:

Major Inflammatory Function:

Products and Secretion

A
  • Lysosomal enzymes
    • similar components as neutrophils but lack myeloperoxidase
  • Oxygen metabolites
  • Complement compounds
  • Arachidonic Acid metabolites
  • Monokines
    • regulatory and inflammatory
  • Inflammatory inhibitors
  • Coagulation Factors
41
Q

Macrophage:

Major Inflammatory Function:

Chronic Inflammation

A
  • They play a prominent role when inflammation becomes chronic
42
Q

Macrophages:

Major Inflammatory Functions:

Immunity

A
  • they contribute to both inate and acquired immunity
    • necessary for antigen processing and presentation to lymphocytes
      • express MHC-2
    • Monokines have immunoregulatory functions
  • Macrophages can be cytotoxic and have antiviral and antitumor activity
  • They are important components fo cell-mediated immunity
43
Q

Lymphocytes:

Morphology

A
  • 7-10 micron diameter
  • Prominent, round nucleus
  • Cytoplasm is sparse
44
Q

Lymphocytes:

Characteristics

A
  • There are three major types
    • B-lymphocytes
    • T-lymphocytes
    • Natural killer cells
  • Responsible for immunity
    • NK cells - innate
    • T - acquired
    • B - acquired
  • They are present in the circulation, and present in large numbers in lymphoid tissues
45
Q

Natural Killer Cells:

Characteristics

A
  • cytotoxic cells of innate immunity
    • respond to altered MHC-1 molecules or stress associated proteins on target cells
    • Prior sensitization is not necessary
    • Similar function as cytotoxic t-lymphocytes of the acquired response
  • Lysis of target cells is mediated by perforins and granzyme
  • Early responder to virus-infected or tumor cells
46
Q

T-lymphocytes:

Characteristics and Function

A
  • Defined by expression of the antigen binding T-cell receptor
  • Classified mainly by expression of either CD4 or CD8 molecues
    • CD4+ helper T-lymphocytes
      • recognize antigen bound to MHC-2 molecules
      • Produce lymphokines to promote either cell-mediated antibody or immunosuppressive responses
    • CD8+ cytotoxic T-lymphocytes
      • recognize antigen bound to MHC-1 molecules
      • Bind and lyse altered cells
47
Q

B-lymphocytes:

Characteristics and Functions

A
  • Responsible for humoral immunity
  • Defined by membrane-bound immunoglobulin which binds antigen
    • immunoglobulin is antigen-specific
    • Immunoglobulin interacts with soluble antigens
  • Differentiate into antibody-producing plasma cells following stimulation
48
Q

Lymphocytes:

Kinetics

A
  • Circulate throughout the body and localize in tissues to “scan” the host environment for invaders, non-self antigens, or altered self antigen
  • Emigrate later than neutrophils or macrophages
    • often 48 hours or more after the initial stimuli
49
Q

Lymphocytes:

Major Inflammatory Function:

Immune Reactions

A
  • Production of immunoglobulins
    • important opsonins
    • Produced by plasma cells
  • Production of lymphokines
    • regulate many inflammatory events
      • cell growth and differentiation
      • chemotaxis
      • Macrophage function
  • Innate responses
    • NK cells
50
Q

Lymphocytes:

Major Inflammatory Functions:

Destruction of Altered cells or Intracellular pathogens

A
  • Cytotoxic T-lymphocytes
51
Q

Lymphocytes:

Major Inflammatory Function:

Role in Chronic Inflammation

A

Interactions with macrophages

52
Q

Platelets:

A
  • Primary role in hemostasis
  • Inflammatory roles include:
    • secretion of granule content
      • histamine and serotonin
      • Platelet factor 4
      • Hydrolytic and proteolytic enzymes
    • weakly phagocytic
53
Q

Endothelium

A
  • Forms blood vessels and drives hemostasis
  • Inflammatory Functions include
    • retraction to initiate increased vascular permeability
    • Receptor-mediated adhesion to leukocytes
      • E-selectin, PECAM-1, ICAM-1, VCAM-1
    • Production of inflammatory mediators
      • Arachidonic metabolites
        • PGI2, TXA2
      • Coagulation factors
        • TF, Von Willebrands factor
      • Plasminogen activator
      • Interleukins
        • IL-1