Acute Inflammation - Cells Flashcards
Cells of Inflammation:
Granulocytes
Neutrophils
Eosinophils
Basophils
Cells of Inflammation:
Mononuclear Cells
Monocytes / Macrophages
Lymphocyters / Plasma Cells
Mast Cells
Neutrophils:
Morphology
- 10-15 micron diameter
- Segmented, multi-lobular nucleus
- Cytoplasmic Granules
- primary (azurophilic) granules
- Secondary (Specific) granules
Neutrophils:
Primary Granule Content
Myeloperoxidase
Lysozyme
Acid Hydrolases
Elastase
Cathepsin G
Neutrophils
Secondary Granule Content
Lysozyme
Collagenase
Gelatinase
Lactoferrin
Neutrphils:
Characteristics
- 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
Neutrophils:
Kinetics
- 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
Neutrophils:
Major Inflammatory Functions:
Phagocytosis and Killing
-
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
Neutrophils:
Major Inflammatory Functions:
Secretion of Inflammatory Products
- 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
Neutrophil Extracellular Traps
- 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
Eosinophils:
Morphology
- 15-20 micron diameter
- Segmented, bilobed nucleus
- Four types of cytoplasmic granules
- specific granules have characteristic crystalloid core
Eosinophil:
Granule Content
Major Basic Protein (MBP)
Eosinophil cationic protein
Arylsulfatase B
Histaminase
Phospholipase D
Peroxidase
Hydrolytic Enzymes
Collagenase
Eosinophil:
Characteristics
- 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
Eosinophil:
Kinetics
Have a 30 minute half life in the blood
Have a 12 day half-life in tissue
Eosinophils:
Major Inflammatory Functions:
Secretion of lysosomal Enzymes
- Damage microbe membranes, but also the ECM
- Degradation of certain Pro-inflammatory products
- histaminase and histamine
Eosinophil:
Major Inflammatory Functions:
Secretion of other mediators
-
Cytokines
- Interleukins (1,6,8,12 among others)
- Transforming Growth Factor (TGF) a and B
-
Chemokines
- Eotaxin
-
Arachidonic Acid Metabolites
- LTC4, LTD4, LTE4
Basophil:
Morphology
- 8-12 micron Diameter
- Multilobed nucleus
- Cytoplasmic Gramules
Basophil:
Granule Content
Histamine
Proteoglycans
Chondrotin
Heparin
Proteases
Elastase
Tryptase
Basophil:
Characteristics:
- Not well understood
- Associated with sites of IgE-dependent allergic reactions or parasitic infections
- receptors for IgE and Eotaxin
- Poorly Phagocytic, and sluggishly motile
Basophil:
Kinetics
- Not well defined
- Probably similar to neutrophils
- Recruited into tissue from blood
- Have a life span of several days once in the tissue
- Recruited into tissue from blood
Basophil:
Major Inflammatory Functions:
Secretion of lysosomal Enzymes
- Effects include bronchoconstriction, vasodilation, and ECM degradation
Basophil:
Major Inflammatory Functions:
Secretion of Other Mediators
- Cytokines
- IL-4, IL-13
- IL-4 is critical in the IgE response to allergens
- IL-4, IL-13
- Arachidonic Acid Metobolites
- LTD4
- Chemokines
Mast Cell:
Morphology
- 10-15 micron diameter
- Oval to round nucleus
- Metachromatic Cytoplasmic granules
Mast Cells:
Granule Content
Histamines
Serotonin
Proteoglycans
Chondrotin
Heparin
Proteases
Elastase
Tryptase
Mast Cell:
Characteristics:
Two types:
- Connective tissue
- 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
Mast Cells:
Kinetics
4-12 week lifespan depending on location and situation
residents in the tissue
Mast CellL
Major Inflammatory Functions: Secretion of Lysosomal Enzymes
Effects include bronchoconstriction, vasodilation, and ECM degradation
Mast Cell:
Major Inflammatory Functions:
Secretion of other Mediators
- Chemotactic Factors
- Eosinophils, neutrophils, and macrophages
- Arachidonic Acid Metabolites
- LTC4, PGD2, TXA2, and PAF
- Cytokines
- TNFa
- Chemokines
Mononuclear Phagocytes
- 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
- Circulating component:
Monocyte:
Morphology:
- 12-15 micron diameter
- round to oval, slightly indented nucleus
- Cytoplasmic granules
- Abundant cellular organelles
Monocytes:
Characteristics:
- 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
- replenich resident tissue macrophages and dendritic cells
Monocytes:
Kinetics
- 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
Fixed Macrophages:
Characteristics
- 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
- Innate:
Dendritic Cells:
Characteristics
- 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
Dendritic Cells:
Kinetics
- Derived form and maintained by blood monocytes
- emigrates in response to physiological stimuli
Macrophages:
Morphology
- 20-50 micron diameter
- Round to oval, slightly indented nucleus
- Cytoplasmic granules
- Abundant cellular organelles
- Much more pleomorphic than monocytes
Macrophages:
Characteristics
- 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
Macrophages:
Kinetics
- 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
Macrophages:
Major Inflammatory Functions:
Phagocytosis
- 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
Macrophages:
Major Inflammatory Function:
Products and Secretion
- Lysosomal enzymes
- similar components as neutrophils but lack myeloperoxidase
- Oxygen metabolites
- Complement compounds
- Arachidonic Acid metabolites
- Monokines
- regulatory and inflammatory
- Inflammatory inhibitors
- Coagulation Factors
Macrophage:
Major Inflammatory Function:
Chronic Inflammation
- They play a prominent role when inflammation becomes chronic
Macrophages:
Major Inflammatory Functions:
Immunity
- they contribute to both inate and acquired immunity
- necessary for antigen processing and presentation to lymphocytes
- express MHC-2
- Monokines have immunoregulatory functions
- necessary for antigen processing and presentation to lymphocytes
- Macrophages can be cytotoxic and have antiviral and antitumor activity
- They are important components fo cell-mediated immunity
Lymphocytes:
Morphology
- 7-10 micron diameter
- Prominent, round nucleus
- Cytoplasm is sparse
Lymphocytes:
Characteristics
- 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
Natural Killer Cells:
Characteristics
- 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
T-lymphocytes:
Characteristics and Function
- 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
- CD4+ helper T-lymphocytes
B-lymphocytes:
Characteristics and Functions
- 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
Lymphocytes:
Kinetics
- 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
Lymphocytes:
Major Inflammatory Function:
Immune Reactions
- Production of immunoglobulins
- important opsonins
- Produced by plasma cells
- Production of lymphokines
- regulate many inflammatory events
- cell growth and differentiation
- chemotaxis
- Macrophage function
- regulate many inflammatory events
- Innate responses
- NK cells
Lymphocytes:
Major Inflammatory Functions:
Destruction of Altered cells or Intracellular pathogens
- Cytotoxic T-lymphocytes
Lymphocytes:
Major Inflammatory Function:
Role in Chronic Inflammation
Interactions with macrophages
Platelets:
- Primary role in hemostasis
- Inflammatory roles include:
- secretion of granule content
- histamine and serotonin
- Platelet factor 4
- Hydrolytic and proteolytic enzymes
- weakly phagocytic
- secretion of granule content
Endothelium
- 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
- Arachidonic metabolites
