Inflammation: Cells Flashcards

1
Q

What Granulocytes are involved in Inflammation?

A
  • Neutrophils
  • Eosinophils
  • Basophils
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What Mononuclear cells are involved in Inflammation?

A
  • Monocytes/macrophages
  • Lymphocytes/plasma cells
  • Mast Cells
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is the morphology of Neutrophils?

A
  • 10-15 micron diameter
  • Segmented, multilobed nucleus
  • Cytoplasmic granules (lysosomes)
    • Primary (Azurophilic) granules
    • Secondary (Specific) granules
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is the primary granule content of neutrophils?

A
  • Myeloperoxidase
  • Lysozyme
  • Acid hydrolases
  • Elastase
  • Cathepsin G

Varies by species: Birds and reptiles have lower enzyme concentrations compared to mammals

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is the secondary granule content of Neutrophils?

A
  • Lysozyme
  • Collagenase
  • Gelatinase
  • Lactoferrin

Varies by species: Birds and reptiles have lower enzyme concentrations compared to mammals

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What are the characteristics of Neutrophils?

A
  • Highly differentiated
  • No longer abl to divide
  • Cellular respiration may be mainly anaerobic
    • Contain abundant glycogen stores
    • Can function in low oxygen environments
      • Hypoxia-inducible factor 1-alpha
  • They metabolize large amounts of oxygen in response to activation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What does Hypoxia-inducible factor 1-alpha do?

A
  • Induces transcription of genes that enhance phagocytosis and secretion, and inhibit apoptosis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What are the kinetics of Neutrophils?

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
    • ~½ of intravascular neutrophils are marginated
  • Once they emigrate they can live 1-4 days in tissues, depending on the situation
    • Apoptosis following withdrawal of growth factors and other stimuli
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What are Neutrophil’s function in Phagocytosis and Killing?

A
  • Oxygen-independent killing
  • Oxygen-dependent pathways*
  • Nitric oxide pathways
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What are the Oxygen-Independent killing pathways of Neutrophils?

A
  • Phagolysosome formation allows granule content to act upon the inflammatory stimulus
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What is the Oxygen-dependent killing pathway in Neutrophils?

A
  • Oxygen-dependent pathways are prominent in neutrophil
    • NADPH - associated oxygen radicals
    • Myeloperozidase killing can occur making neutrophils the most potent killers of all phagocytes
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What are the Nitric oxide killing pathways with Neutrophils?

A
  • Nitric oxide pathways are also present
    • Formation of highly reactive peroxynitrite
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

How are Neutrophils involved with the 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
  • Antimicrobial peptides (defensins)
  • Neutrophil extracellular traps (NETs)
    • Products of dead neutrophils that trap and possibly kill bacteria
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What are Neutrophil extracellular traps?

A
  • A web-like matrix of DNA/proteins/and neutrophil granule to products secreted by neutrophils that trap and kill pathogens
    • NETs contain concentrated myeloperoxidase, elastase, cathepsin G, among 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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is the morphology of Eosinophils?

A
  • 15-20 micron diameter
  • Segmented, bilobed nucleus
  • 4 types of cytoplasmic granules
    • Specific granules have characteristic crystalloid core
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What is the Granule (lysosome) content of Eosinophils?

A
  • Major Basic Protein (MBP)
  • Eosinophil cationic protein
  • Arylsulfatase B
  • Histaminase
  • Phospholipase D
  • Peroxidase
  • Hydrolytic enzymes
  • Collagenase
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What are the Characteristics of Eosinophils

A
  • Not as well understood as neutrophils
    • Phagocytic, but much less so than neutrophils
  • Prominent at sites of allergic reactions of parasitic infections
  • Often occur in association with mast cells
    • Respond to eosinophil chemotactic factor and histamine
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What are the kinetics of Eosinophils?

A
  • Have a 30 minute half-life in blood
  • Have a 12 day half-life in tissue
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What is the function of Eosinophils in Inflammation?

A
  • Secretion of lysosomal enxymes
  • Secretion of other mediators
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What happens with eosinophil secreted lysosomal enzymes?

A
  • Damage microbe membranes, and the ECM
  • Degradation of certain pro-inflammatory products
    • histaminase and histamine
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What other mediators do Eosinophils secrete?

A
  • Cytokines
    • Interleukins (1, 6 ,8, 12 among others)
    • Transforming Growth Factors (TGF) alpha and beta
  • Chemokines (Eotaxin)
  • Arachidonic acid metabolites
    • LTC4, LTD4, LTE4
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What is the morphology of Basophils?

A
  • 8-12 micron diameter
  • Multilobed nucleus
  • Cytoplasmic (metachromatic granules)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What are the characteristics of Basophils?

A
  • Not well understood
  • Associated with site of IgE-dependent allergic reactions or parasitic infections
    • Have receptors for IgE and exotaxin
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What are the kinetics of Basophils?

A
  • Not well defined
  • Probably similar to neutrophils
    • Recruited into tissue from blood
    • Have lifespan of several days once in tissue
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What are Basophils’ function in Inflammation?

A
  • Secretion of lysosomal enzymes
  • Secretion of other mediators
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

What effects do Basophil secreted lysosomal enzymes have?

A
  • Effects include:
    • bronchoconstriction
    • Vasodilation
    • ECM degradation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

What other inflammation mediators do Basophils secrete?

A
  • Cytokines:
    • IL-4, IL-13
      • IL-4 is critical in the IgE response to allergens
  • Arachidonic acid metabolites
    • LTD4
  • Chemokines
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

What is the morphology of Mast Cells?

A
  • 10-15 micron diameter
  • Oval to round nucleus
  • Metachromatic cytoplasmic granules
    • Granule content includes:
      • histamine
      • Serotonin
      • Proteoglycans
        • Chondrotin/heparin
      • Proteases
        • Elastase
        • Tryptase
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

What are the characteristics of Mast Cels?

A
  • 2 types: located adjacent to small blood vessels and lymphatics
    1. Connective tissue
    2. mucosal
  • Prominent at sites of allergic reactions or parasitic infections
  • Functionally very similar to basophils
    • produce greater #/variety of mediators
  • Often present in conjunction with eosinophils
30
Q

What are the major inflammatory functions of Mast Cell?

A
  • Secretion of lysosomal enzymes
  • Secretion of other mediators
31
Q

What are the effects of lysosomal enzymes secreted by Mast Cells?

A
  • Effects include:
    • Bronchoconstriction
    • Vasodilation
    • ECM degradation
32
Q

What other inflammation mediators do Mast Cells secrete?

A
  • Chemotactic factors
    • for eosinophils, neutrophil, and macrophages
  • Arachidonic acid metabolites
    • LTC4, PGD2, TXA2, and PAF
  • Cytokines (TNF alpha)
  • Chemokines
33
Q

What are Mononuclear Phagocytes?

A
  • Group of cells that compose the mononuclear phagocytic (monocyte-macrophage) system
  • Consists of both circulating and fixed populations
34
Q

What is the circulating component of Mononuclear phagocytes?

A

Monocytes

35
Q

What is an emigrated (tissue) moncyte?

A

Macrophage

36
Q

What are the fixed macrophage components of Mononuclear phagocytic system?

A
  • Dendritic cells
  • Sinusoidal macrophages of bone marrow and lymphoid organs
  • Kupffer cells of the liver
  • Alveolar macrophages
  • Microglia of the central nervous system
  • Mesangial macrophages of renal glomeruli
  • Peritoneal macrophages
37
Q

What is the Morphology of Monocytes?

A
  • 12-15 micron diametr
  • Roundot oval, slightly indented nucleus
  • Cytoplasmic grnules (lysosomes)
  • Abundant cellular organelles
38
Q

What are the characteristics of Monocytes/

A
  • source of macrophages and dendritic cells
    • Replenish resident tissue macrophages and dendritic cells
    • Subsets of monocytes, or certain types of stimuli will drive differentiation into dendritic cells
    • Emigrate in response to inflammatory stimuli
39
Q

What are the kinetics of Monocytes?

A
  • Circulate for approximately 1-3 days in blood
    • Approximately half of the circulating monocytes are sequestered in the spleen
  • Slower to emigrate than neutrophils
    • Emigrate mainly after 24-48 hours
40
Q

What are the characteristics of Fixed Macrophages?

A
  • Derived from monocytes
    • Emigrate in response to physiologic cytokines
    • Replicate locally within the tissues to maintain the fixed population
  • Form mononuclear-phagocyte system
    • Located at sites where microbial invasion is most likely
    • They are often the first inflammatory cell to recognize invasion by a microbe or foreign material
  • Contribute to both inflammation and immunity
    • Innate: monokines and other macrophage products contribute to innate immunity and inflammation
    • Acquired: macrophages and dendritic cells are important antigen presenting cells in immunity
41
Q

What are the characteristics of Dendritic Cells?

A
  • Process and present antigen to T-lymphocytes
    • Capture antigen and migrate to areas with T-lymphocytes
    • Express MHCII class molecules and T-lymphocytes receptors
  • Non-phagocytic
  • Several different phenotypes have been described
42
Q

What are the kinetics of Dendritic Cells?

A
  • Derived from and maintained by blood monocytes
    • Emigrate in response to physiological stimuli
43
Q

What do Kupffer cells look like?

A
44
Q

What do Alveolar Macrophages look like?

A
45
Q

What is the morphology of Macrophages?

A
  • 20-50 micron diameter
  • Round to oval, slightly indented nucleus
  • Cytoplasmic granules (lysosomes)
  • Abundant cellular organelles
  • Much more pleomorphic than monocytes
46
Q

What is the morphology of Macrophages?

A
  • 20-50 micron diameter
  • Round to oval, slightly indented nucleus
  • Cytoplasmic granules (lysosomes)
  • Abundant cellular organelles
  • Much more pleomorphic than monocytes
47
Q

What are the characteristics of Macrophages?

A
  • They are highly sophistacated and multiunctional
  • Cellular respiration is mainly aerobic
    • Contain abundant mitochondria and ER
  • Important for inflammatory and immunologic events
  • Critical components of chronic inflammation and healing
48
Q

What are the subtypes of Macrophages?

A
  • Inflammatory
  • Anti-inflammatory
  • Regulatory
  • Healing
  • Differentiation is determined by the local environment
49
Q

What is the kinetics of Macrophages?

A
  • Derived from monocytes
    • Bone marrow reserve pool is much smaller than that for neutrophils
    • Monocytes circulate for about 1-3 days
  • Macrophages have life spans of a week to possibly several months
    • highly dependent on the local cytokineenvironment
  • Can divide locally at an inflammatory site
50
Q

What are the major inflammatory functions of Mcrophages?

A
  • Phagocytosis
  • Blastomycosis
  • Production and secretion of inflammatory products
  • Chronic inflammation
  • Immunity
51
Q

What is the role of macrophages in Phagocytosis?

A
  • Macrophages are second line of defense after neutrophils
    • Generally increase in number the longer the inflammatory stimulus persists
  • More efficient and multipurpased phagocytes
    • Play more of a scavenger role
52
Q

What is Blastomycosis

A
53
Q

What is the role of macrophages in the Productoin and secretion of inflammatory products?

A
  • Lysosomal enzymes
    • similar componets as neutrophils but lack myeloperoxidase
  • Oxygen metabolites
  • Complement Components
  • Arachidonic acid metabolites
  • Monokines
    • Regulatory and inflammatory
  • Inflammatory inhibitors
  • Cogulation factors
54
Q

What is the role of Macrophges in Immunity?

A
  • Contribute to both innate and acquired immunity
    • They are necessary for antigen processing and presentation to lyphocytes
      • Express MHC class II molecules upon stimulation
    • Many monokines haveimmunoregulatory functions
      • Regulate T-lymphocyte activities
  • Macrophages can be cytotoxic and have antiviral and antitumor activity
  • They are important ccomponents of cell-mediated immunity
55
Q

What is the morphology of Lymphocytes?

A
  • 7 - 10 micron diametr
  • Prominent, round nucleus
  • Cytoplasm is sparse
56
Q

What are the characteristics of Lymphocytes?

A
  • There are 3 major types, numerus subtypes
    • B-lymphocytes
    • T-lymphocytes
    • Natureal killer cells
  • Responsible for immunity
    • NK cell - innate cell-mediated immunity
    • T-lymphocyte - aquired cell-mediated immunity
    • B-lymphocyte - acquired humoral immunity
  • They are present in the circulation, and present in large numbers in lymphoid tisues
57
Q

What are Natural Killer Cells and their function?

A
  • Cytotoxic cell of innate immunity
    • Respond to altered MHC 1 molecules or stress associated proteins on traget 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
58
Q

What are T-lymphocytes?

A
  • Defined by expression of the antigen binding T-cell receptor (TCR)
  • Classified mainly by expression of either CD4 or CD8 molecules
59
Q

What are CD4+ helper T-lymphocytes (TH)

A
  • Recognize antigen bound to MHC II molecules
  • Produce lymphokines to promote either cell-mediated (TH1), antibody (TH2), or immunosuppressive (Treg) responses
60
Q

What are CD8+ cytotoxic T-lymphocytes (Tc or CTL)?

A
  • Recognize antigen bound to MHC I molecules
  • Bind and lyse altered cells
61
Q

What are B-lymphocytes and their functions?

A
  • Responsible for humoral immunity
  • Defined by membrane-bound immunoglobulin which binds antigen
    • Immunoglobulin is antigen-specific
    • Immunoglobulin intrects with soluble antigens
  • Differentiate into antibody-producing plasma cells following stimulation
62
Q

What are the kinetics of Lymphocytes?

A
  • Circulate throughout the body and localized in tissues to “scan” the host environment for invaders, non-self antigens, or altered self antigens
  • Emigrate later than neutrophils or macrophages
    • 48 hours or more after the initial stimulus
63
Q

What are the Major inflammatory functions of lymphocytes?

A
  • Immune reactions
  • Destruction of altered cells or intracellular pathogens
  • Major role in chronic inflammation
64
Q

What is the role of lymphocytes in Immune functions?

A
  • Production of immunoglobulins
    • These are important opsonins
    • Produced by plasma cells
  • Production of lymphokines
    • These regulate many inflammatory events
      • Cell growth and differentiation
      • Chemotaxis
      • Macrophage function
  • Inate responses
    • NK cells
65
Q

What is the role of lymphocytes in cellular destruction?

A
  • Destruction of altered cell orintracellular pathogens
    • cytotoxic T-lymphocytes
66
Q

What is the role of lymphocytes in chronic inflammation?

A
  • Major role in cronic inflammation
    • Interactions with macrophages
67
Q

What are the roles of Platelets?

A
  • Have a primary role in Hemostasis
  • Inflammatory roles include:
    • Secretion of granule content
      • Histamine and serotonin
      • Platelet facto 4
      • Hydrolytic and proteolytic enzymes
    • Weakly phagocytic
68
Q

What is the role of Endothelium in Inflammation?

A
  • Endothelium forms blood vessels and drives hemostasis
  • Inflammatory functions include:
    • Retraction to initiate increased vascular permeability
    • Receptor-mediated adhesion to leukocytes
    • Production of inflammatory mediators
69
Q

What are teh Endothelium receptors that mediate adhesion to leukocytes?

A
  • E-selectin
  • PECAM-1
  • ICAM-1
  • VCAM-1
70
Q

What inflammatory mediators does the Endothelium produce?

A
  • Arachidonic acid metabolites
    • PGI2
    • TXA2
  • Coagulation factors
    • TF
    • von willebrands factor
  • Plasminogen activator
  • Interleukins
    • IL-1