Inflammation: Cells Flashcards
What Granulocytes are involved in Inflammation?
- Neutrophils
- Eosinophils
- Basophils
What Mononuclear cells are involved in Inflammation?
- Monocytes/macrophages
- Lymphocytes/plasma cells
- Mast Cells
What is the morphology of Neutrophils?
- 10-15 micron diameter
- Segmented, multilobed nucleus
- Cytoplasmic granules (lysosomes)
- Primary (Azurophilic) granules
- Secondary (Specific) granules
What is the primary granule content of neutrophils?
- Myeloperoxidase
- Lysozyme
- Acid hydrolases
- Elastase
- Cathepsin G
Varies by species: Birds and reptiles have lower enzyme concentrations compared to mammals
What is the secondary granule content of Neutrophils?
- Lysozyme
- Collagenase
- Gelatinase
- Lactoferrin
Varies by species: Birds and reptiles have lower enzyme concentrations compared to mammals
What are the characteristics of Neutrophils?
- 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
What does Hypoxia-inducible factor 1-alpha do?
- Induces transcription of genes that enhance phagocytosis and secretion, and inhibit apoptosis
What are the kinetics of Neutrophils?
- 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
What are Neutrophil’s function in Phagocytosis and Killing?
- Oxygen-independent killing
- Oxygen-dependent pathways*
- Nitric oxide pathways
What are the Oxygen-Independent killing pathways of Neutrophils?
- Phagolysosome formation allows granule content to act upon the inflammatory stimulus
What is the Oxygen-dependent killing pathway in Neutrophils?
- Oxygen-dependent pathways are prominent in neutrophil
- NADPH - associated oxygen radicals
- Myeloperozidase killing can occur making neutrophils the most potent killers of all phagocytes
What are the Nitric oxide killing pathways with Neutrophils?
- Nitric oxide pathways are also present
- Formation of highly reactive peroxynitrite
How are Neutrophils involved with the 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
- Antimicrobial peptides (defensins)
- Neutrophil extracellular traps (NETs)
- Products of dead neutrophils that trap and possibly kill bacteria
What are Neutrophil extracellular traps?
- 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
What is the morphology of Eosinophils?
- 15-20 micron diameter
- Segmented, bilobed nucleus
- 4 types of cytoplasmic granules
- Specific granules have characteristic crystalloid core
What is the Granule (lysosome) content of Eosinophils?
- Major Basic Protein (MBP)
- Eosinophil cationic protein
- Arylsulfatase B
- Histaminase
- Phospholipase D
- Peroxidase
- Hydrolytic enzymes
- Collagenase
What are the Characteristics of Eosinophils
- 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
What are the kinetics of Eosinophils?
- Have a 30 minute half-life in blood
- Have a 12 day half-life in tissue
What is the function of Eosinophils in Inflammation?
- Secretion of lysosomal enxymes
- Secretion of other mediators
What happens with eosinophil secreted lysosomal enzymes?
- Damage microbe membranes, and the ECM
- Degradation of certain pro-inflammatory products
- histaminase and histamine
What other mediators do Eosinophils secrete?
- Cytokines
- Interleukins (1, 6 ,8, 12 among others)
- Transforming Growth Factors (TGF) alpha and beta
- Chemokines (Eotaxin)
- Arachidonic acid metabolites
- LTC4, LTD4, LTE4
What is the morphology of Basophils?
- 8-12 micron diameter
- Multilobed nucleus
- Cytoplasmic (metachromatic granules)
What are the characteristics of Basophils?
- Not well understood
- Associated with site of IgE-dependent allergic reactions or parasitic infections
- Have receptors for IgE and exotaxin
What are the kinetics of Basophils?
- Not well defined
- Probably similar to neutrophils
- Recruited into tissue from blood
- Have lifespan of several days once in tissue
What are Basophils’ function in Inflammation?
- Secretion of lysosomal enzymes
- Secretion of other mediators
What effects do Basophil secreted lysosomal enzymes have?
- Effects include:
- bronchoconstriction
- Vasodilation
- ECM degradation
What other inflammation mediators do Basophils secrete?
- Cytokines:
- IL-4, IL-13
- IL-4 is critical in the IgE response to allergens
- IL-4, IL-13
- Arachidonic acid metabolites
- LTD4
- Chemokines
What is the morphology of Mast Cells?
- 10-15 micron diameter
- Oval to round nucleus
- Metachromatic cytoplasmic granules
- Granule content includes:
- histamine
- Serotonin
- Proteoglycans
- Chondrotin/heparin
- Proteases
- Elastase
- Tryptase
- Granule content includes:
What are the characteristics of Mast Cels?
- 2 types: located adjacent to small blood vessels and lymphatics
- Connective tissue
- 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
What are the major inflammatory functions of Mast Cell?
- Secretion of lysosomal enzymes
- Secretion of other mediators
What are the effects of lysosomal enzymes secreted by Mast Cells?
- Effects include:
- Bronchoconstriction
- Vasodilation
- ECM degradation
What other inflammation mediators do Mast Cells secrete?
- Chemotactic factors
- for eosinophils, neutrophil, and macrophages
- Arachidonic acid metabolites
- LTC4, PGD2, TXA2, and PAF
- Cytokines (TNF alpha)
- Chemokines
What are Mononuclear Phagocytes?
- Group of cells that compose the mononuclear phagocytic (monocyte-macrophage) system
- Consists of both circulating and fixed populations
What is the circulating component of Mononuclear phagocytes?
Monocytes
What is an emigrated (tissue) moncyte?
Macrophage
What are the fixed macrophage components of Mononuclear phagocytic system?
- 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
What is the Morphology of Monocytes?
- 12-15 micron diametr
- Roundot oval, slightly indented nucleus
- Cytoplasmic grnules (lysosomes)
- Abundant cellular organelles
What are the characteristics of Monocytes/
- 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
What are the kinetics of Monocytes?
- 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
What are the characteristics of Fixed Macrophages?
- 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
What are the characteristics of Dendritic Cells?
- 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
What are the kinetics of Dendritic Cells?
- Derived from and maintained by blood monocytes
- Emigrate in response to physiological stimuli
What do Kupffer cells look like?
What do Alveolar Macrophages look like?
What is the morphology of Macrophages?
- 20-50 micron diameter
- Round to oval, slightly indented nucleus
- Cytoplasmic granules (lysosomes)
- Abundant cellular organelles
- Much more pleomorphic than monocytes
What is the morphology of Macrophages?
- 20-50 micron diameter
- Round to oval, slightly indented nucleus
- Cytoplasmic granules (lysosomes)
- Abundant cellular organelles
- Much more pleomorphic than monocytes
What are the characteristics of Macrophages?
- 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
What are the subtypes of Macrophages?
- Inflammatory
- Anti-inflammatory
- Regulatory
- Healing
- Differentiation is determined by the local environment
What is the kinetics of Macrophages?
- 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
What are the major inflammatory functions of Mcrophages?
- Phagocytosis
- Blastomycosis
- Production and secretion of inflammatory products
- Chronic inflammation
- Immunity
What is the role of macrophages in Phagocytosis?
- 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
What is Blastomycosis
What is the role of macrophages in the Productoin and secretion of inflammatory products?
- Lysosomal enzymes
- similar componets as neutrophils but lack myeloperoxidase
- Oxygen metabolites
- Complement Components
- Arachidonic acid metabolites
- Monokines
- Regulatory and inflammatory
- Inflammatory inhibitors
- Cogulation factors
What is the role of Macrophges in Immunity?
- 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
- They are necessary for antigen processing and presentation to lyphocytes
- Macrophages can be cytotoxic and have antiviral and antitumor activity
- They are important ccomponents of cell-mediated immunity
What is the morphology of Lymphocytes?
- 7 - 10 micron diametr
- Prominent, round nucleus
- Cytoplasm is sparse
What are the characteristics of Lymphocytes?
- 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
What are Natural Killer Cells and their function?
-
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
What are T-lymphocytes?
- Defined by expression of the antigen binding T-cell receptor (TCR)
- Classified mainly by expression of either CD4 or CD8 molecules
What are CD4+ helper T-lymphocytes (TH)
- Recognize antigen bound to MHC II molecules
- Produce lymphokines to promote either cell-mediated (TH1), antibody (TH2), or immunosuppressive (Treg) responses
What are CD8+ cytotoxic T-lymphocytes (Tc or CTL)?
- Recognize antigen bound to MHC I molecules
- Bind and lyse altered cells
What are B-lymphocytes and their functions?
- 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
What are the kinetics of Lymphocytes?
- 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
What are the Major inflammatory functions of lymphocytes?
- Immune reactions
- Destruction of altered cells or intracellular pathogens
- Major role in chronic inflammation
What is the role of lymphocytes in Immune functions?
- 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
- These regulate many inflammatory events
- Inate responses
- NK cells
What is the role of lymphocytes in cellular destruction?
- Destruction of altered cell orintracellular pathogens
- cytotoxic T-lymphocytes
What is the role of lymphocytes in chronic inflammation?
- Major role in cronic inflammation
- Interactions with macrophages
What are the roles of Platelets?
- 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
- Secretion of granule content
What is the role of Endothelium in Inflammation?
- 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
What are teh Endothelium receptors that mediate adhesion to leukocytes?
- E-selectin
- PECAM-1
- ICAM-1
- VCAM-1
What inflammatory mediators does the Endothelium produce?
- Arachidonic acid metabolites
- PGI2
- TXA2
- Coagulation factors
- TF
- von willebrands factor
- Plasminogen activator
- Interleukins
- IL-1
