Upgrade to remove ads
Only $35.99/year

Assignment #2: Phagocytes

Terms in this set (23)

Describe the phagocytic ability of monocytes, macrophages, and neutrophils
Monocytes have limited phagocytic ability; macrophages are specialized phagocytes; and neutrophils have exceptional phagocytic capability
Describe the differentiation of monocytes in bone marrow
Monocytes secrete GM-CSF, G-CSF, and M-CSF. Describe the role of each
GM-CSF: with IL-3, role in differentiation from a pluripotent stem cell to a myeloid progenitor. By itself, is involved in differentiation of a myeloid progenitor to a GM progenitor in hematopoiesis
G-CSF- Role in differentiation of a GM-progenitor to a granulocytes in hematopoiesis
M-CSF: Role in differentiation of a GM- progenitor to a monocyte in hematopoiesis
Explain the role of CCL2/MCP-1 on monocytes
CCL2/MCP-1 (monocyte chemotactin protein-1) enhances recruitment of monocytes into circulation and migration into tissue where they differentiate into macrophages
Describe macrophages with respect to: (a) differentiation from monocytes, (b) role of MCP-1/CCL2 in absence of infection and during infection
a) Refer to chart
b)
List the two main roles of macrophages
1) Role in phagocytosis
2) Function as antigen presenting cells for CD4+ T cells
PRR
PRR- pattern recognition receptors are receptors on phagocytes that detect different molecular patterns on viruses, bacteria, fungi, and other human pathogens (also molecules released during tissue damage or "stress". They exist as membrane bound receptors, cytosolic receptors, or secreted receptors
DAMPs
DAMPs- Danger associated molecules are molecules originating from dying or damaged cells or other biological molecules that bind to PRRs
PAMPs
PAMPs- pathogen associated molecular patterns are ligands, or molecules expressing the molecular patterns on pathogens that bind to PRRs
Recognition of antigens/pathogens is "Direct" or "indirect". Explain the term "direct recognition". Re: Direct recognition of pathogens: Explain the role of pattern recognition receptors on phagocytes. Name one family of proteins that are classed as PRRs. Explain the role of pathogen associated molecular patterns on pathogens
Direct recognition of pathogens occurs via PRRs, which distinguishes pathogens from self. These receptors trigger cascades of biochemical events that lead to secretion of inflammatory cytokines

Indirect recognition refers to interaction of an intermediary protein (opsonin), which has bound to an antigen, with a receptor on the phagocytes

One family of proteins that are classed as PRRs are toll-like receptors, which are expressed on a variety of cell types including macrophages and neutrophils
Describe steps in phagocytosis & formation of phagosome & phagolysosome
-Recognition and binding of the pathogen is followed by its' ingestion as a portion of the plasma membrane extends outward and surround the microbe, forming a phagocytic vacuole called a phagosome
-Lysosomes, present in the cytosol, fuse with the phagosome to form a fusion product, the phagolysosome, into which lysosomal granules are discharged (contains many enzymes that are cytotoxic to microorganisms)
List the armamentarium (equipment) generated from (i) NADPH oxidase, (ii) lysosomal fusion to phagosome membrane, (iii) iNOS
(i) NADPH armamentarium: superoxide, hydrogen peroxide, hydroxyl radical, hydroxyl ion, hypochlorite

(ii) Lysosomal fusion: lactoferrin, lysozyme, and defensins

(iii) iNOS: NO (can react with reactive oxygen intermediates and generate reactive nitrogen intermediates/RNIs)
Describe the effect of interferon gamma (IFNγ), tumor necrosis factor (TNF), IL-4, IL-10 and transforming growth factor beta (TGFβ) on macrophage activation and the source of these cytokines. Be specific
-IFNγ is secreted by activated cells (NK cells and Th1 cells) that activates iNOS and enhances NADPH oxidase activity

-TNF is a product of activated macrophages and activated Th1 cells that upregulates iNOS to form NO

-IL-4, IL-10 and TGFβ are generated by Th2, a subset of activated T cells which down regulates NO synthesis (with TGFβ being the most effective)
List the chemokines and cytokines secreted by activated macrophages. Identify the target cells for the chemokines and cytokines as well as the role of each of these molecules. See cytokine chart
In general terms describe the inflammasome with respect to signal 1 and signal 2 as well as outcome of the combined effects of these two signals. Include in description: PAMPs, PRRs, DAMPs, pro-IL-1, pro-IL-18, procaspase-1, IL-1, IL-18 and caspase-1. List 5 examples of DAMPs
NALP3 inflammasome is a muli-protein complex that plays a critical role in host defense by mediating conversion of the zymogen, procaspase-1 to caspase-1.

Signal 1 involves PAMP binding to PRR, leading to transciption of pro-IL-1 and pro-IL-18

Signal 2 involved DAMPs binding to PRRs converts procaspase-1 into caspase-1. Caspase-1 converts pro-IL-1--> IL-1 and pre-IL-18-->IL-18 which are both secreted by the macrophage

5 examples of DAMPs are: numerous molecules released during trauma/cell death, reactive oxygen species, ATP, cholesterol crystals, and free fatty acids
Describe the role of IL-1 and TNF on the vascular endothelium in an inflammatory response. Include in your response E-selectins, VCAM-1, ICAM-1, ICAM-2 as well as their relevant counter molecules on neutrophils, lymphocytes, monocytes, and eosinophils
IL-1 and TNF binds to receptors on the vascular endothelium and induces vascular endothelial cells to:
-secrete IL-8/CXCL8, MCP-1/CCL2 (IL-8/CXCL8--> neutrophil migration and chemotaxis; MCP-1/CCL2--> monocyte migration and chemotaxis)
-express de novo VCAM-1, ICAM-1, E-selectin (VCAM interact with VLA-4 on monocytes, lymphocytes, and eosinophiles)
-Upregulate ICAM-2 (ICAM-1 and 2 interacts with LFA-1 (CD11a & CD18) on neutrophils, monocytes, lymphocytes, and eosinophils)
Re: Indirect/Opsonin mediated recognition of pathogens- list three opsonins that may be deposited on a pathogen. List the receptors on the phagocytes that interact with each opsonin
Indirect recognition refers to interaction of an intermediary protein (opsonin), which has bound to an antigen, with a receptor on the phagocytes. Three opsonins and their respective receptors are:
1) Fcγ :FcγR
2) CRP:CRP-Binding site
3) C3b: CR1 (complement receptor-1)
Explain how the opsonins were generated
Opsonins are generated when components, other than phagocytes, are activated in response to the pathogen
Explain why opsonin-mediated recognition is called "indirect recognition"
Opsonin-mediated recognition is called indirect recognition because the molecules opsonin is produced by the host immune system that attaches to antigen and are recognized by receptors. These molecules are not naturally made/on the antigen
Explain the consequence of CD200R interaction with CD200
CD200R are found on the macrophage and when bound to CD200 (expressed primarily on myeloid cells) causes an inhibitory effect on the macrophage
Explain why macrophages are not as effective as antigen presenting cells as dendritic cells
Primary immune responses occur in secondary lymphoid tissue, and not at the site of infection so dendritic cells, unlike macrophages, can capture antigen in the periphery and transport it to the appropriate lymphoid tissue.
Describe neutrophils with respect to: differentiation, % of circulating leukocytes, half-life in circulation, chemotactic factors that attract neutrophils to site of inflammation
-Mature from precursor cells in the bone marrow
-Comprise some 60% of the circulating leukocytes in peripheral blood
-Has a half-life of about 8 hours after being released into circulation
-Chemotactic factors include interleukin-8 (IL-8) and CXCL8 and C5a. Activated macrophages release IL-8/CXCL8
Neutrophil description (4)
1) Do not function as antigen presenting cells
2) Do not secrete cytokines or chemokines
3) Recognition (direct and indirect) is the same as macrophages
4) Armamentarium product and function same as in macrophages
Recommended textbook explanations

Lehninger Principles of Biochemistry

6th EditionDavid L Nelson, Michael M. Cox
616 explanations

Biocalculus: Calculus for the Life Sciences

1st EditionDay, Stewart
5,054 explanations

Fundamentals of Biochemistry: Life at the Molecular Level

5th EditionCharlotte W. Pratt, Donald Voet, Judith G. Voet
980 explanations

Campbell Biology (AP Edition)

9th EditionCain, Jackson, Minorsky, Reece, Urry, Wasserman
715 explanations