Phagocytosis and NADPH Oxidase Overview

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Questions and Answers

What role do reactive oxygen species play in neutrophils and macrophages?

They contribute to energy production.

They help in nutrient absorption.

They are involved in cellular respiration.

They are part of the bactericidal activity. (correct)

Which enzyme is responsible for generating nitric oxide in phagocytes?

NADPH oxidase

Superoxide dismutase

Cyclooxygenase

Inducible nitric oxide synthase (iNOS) (correct)

Which statement correctly describes the production of reactive species in neutrophils and macrophages?

Macrophages produce more nitric oxide than neutrophils. (correct)

Both produce equal amounts of reactive oxygen species.

Neutrophils produce more nitric oxide than macrophages.

Neither cell type produces reactive species.

What is the NADPH phagocyte oxidase primarily responsible for?

Generating superoxide anions. Signup and view all the answers

How are NADPH oxidase and iNOS regulated in phagocytes?

They have independent regulation. Signup and view all the answers

What is a primary characteristic of free radicals?

They have an incomplete electron shell. Signup and view all the answers

Which radical is primarily considered a mitochondrial source?

Superoxide anion radical Signup and view all the answers

Which of the following is a mechanism by which free radicals can cause damage?

Lipid peroxidation Signup and view all the answers

What role do antioxidants like Vitamin E and C play regarding free radicals?

They directly interact with free radicals to neutralize them. Signup and view all the answers

Which of the following is considered a free radical?

Hydroxyl radical Signup and view all the answers

What process is lipid peroxidation primarily associated with?

Oxidative stress Signup and view all the answers

Nrf2 is primarily involved in which of the following processes?

Activation of antioxidant responses Signup and view all the answers

Which of the following describes hydrogen peroxide?

It is a stable molecule with oxidizing properties. Signup and view all the answers

What percentage of O2 consumed is reduced to water during aerobic respiration?

98-99% Signup and view all the answers

Which reactive oxygen species are primarily produced by mitochondria?

H2O2 and O2.– Signup and view all the answers

The process where a small fraction of O2 is reduced to O2.– is known as what?

Electron leak Signup and view all the answers

What is the primary process associated with the consumption of O2 in mitochondria?

Oxidative phosphorylation Signup and view all the answers

Which of the following represents a minor percentage of O2 consumed during aerobic metabolism?

1-2% Signup and view all the answers

What is the consequence of the electron leak process in mitochondria?

Production of reactive oxygen species Signup and view all the answers

What is the major end product of O2 reduction in aerobic respiration?

Water Signup and view all the answers

Which of the following is NOT a reactive oxygen species produced in mitochondria?

H2O Signup and view all the answers

What is the overall efficiency of O2 reduction by mitochondria under normal conditions?

Approximately 98-99% Signup and view all the answers

During oxidative phosphorylation, what is the percentage range of O2 that leaks univalently to form O2.–?

1-2% Signup and view all the answers

Which transition metal is specifically mentioned as catalyzing the Fenton reaction?

Iron Signup and view all the answers

What is the product of the Fenton reaction alongside hydroxyl radical (HO.)?

Hydroxide (HO–) Signup and view all the answers

What is the initial reactant involved in the Fenton reaction?

Hydrogen peroxide (H2O2) Signup and view all the answers

How are reactive oxygen species (ROS) primarily generated in cells?

Enzymatic reactions Signup and view all the answers

What role do superoxides (O2.–) play in the context of oxidative stress?

They can reduce hydrogen peroxide. Signup and view all the answers

What is one cellular source of reactive oxygen species mentioned?

Leukocytes Signup and view all the answers

In the Haber-Weiss reaction, which substance is produced as a result of superoxide and hydrogen peroxide reaction?

Oxygen (O2) Signup and view all the answers

Which enzyme is NOT listed as a source of reactive oxygen species?

Lactate dehydrogenase Signup and view all the answers

What is the final product of the dismutation of superoxide?

Hydrogen peroxide (H2O2) Signup and view all the answers

What is suggested as a mechanism by which oxidants mediate cellular damage?

By causing lipid peroxidation and protein damage Signup and view all the answers

What is the primary role of NADPH oxidase in phagocytic cells?

Activation of bactericidal activity through reactive species Signup and view all the answers

Which component is essential for the respiratory burst in phagocytes?

gp91phox complex Signup and view all the answers

What characterizes the process of NETosis?

Formation of Neutrophil Extracellular Traps Signup and view all the answers

Which molecule is associated with both macrophage polarization and inflammation?

SUCNR1 Signup and view all the answers

What is the function of inducible Nitric Oxide Synthase (iNOS) in macrophages?

Generation of reactive nitrogen species Signup and view all the answers

Which of the following is a key component involved in inflammasome activation?

Reactive oxygen species Signup and view all the answers

Which pathway leads to the expression of inflammatory cytokines IL-1b and IL-18?

Receptor-dependent pathways Signup and view all the answers

What role does mitochondrial DNA (mtDNA) play in the immune response?

Activates inflammasome and leads to interferon responses Signup and view all the answers

Which factor contributes to the antimicrobial activity of Neutrophil Extracellular Traps?

Components of NETs like enzymes and histones Signup and view all the answers

What is the main purpose of using reactive species in inflammation?

To kill pathogens and mediate signaling Signup and view all the answers

Study Notes

Phagocytosis and Intracellular Killing

Phagocytosis is part of the innate immune response.
The NADPH phagocyte oxidase (phox or nox) is responsible for O2.– generation.
The inducible nitric oxide synthase (iNOS) is responsible for the generation of NO.
Neutrophils and macrophages both express NADPH oxidase and iNOS.
Neutrophils produce more O2.– than macrophages, while macrophages generally produce more NO than neutrophils.
NADPH oxidase and iNOS are separate enzyme complexes with independent regulation.

NADPH Oxidase

NADPH oxidase is responsible for generating superoxide radical (O2.–).
The enzyme system is also called phox or nox.
The reaction is: NADPH + O2 ® NADP+ + O2.–
The complex uses NADPH and oxygen to produce superoxide.
NADPH oxidase is a multi-component enzyme complex.
Several components of NADPH oxidase regulate its activity:
- cytosolic component p47phox and p67phox
- membrane-associated components p22phox and gp91phox
During phagocytosis, these components assemble onto a membrane-bound oxidase complex that initiates the respiratory burst (burst of superoxide radical production) and promotes bactericidal activity.
NADPH oxidase is upregulated and its activity is increased during infection and inflammation, producing a burst of superoxide radicals.
gp91phox is crucial for the respiratory burst; it is the catalytic component of NADPH oxidase.

Respiratory burst

Respiratory burst refers to the rapid production of reactive oxygen species (ROS) such as superoxide radical (O2.–) that occurs in phagocytic cells, such as neutrophils and macrophages.
It is triggered by the engulfment of microbes (phagocytosis).
The burst is critical for the destruction of ingested microbes, by generating the superoxide radical.

Role of Superoxide radical

Superoxide radical (O2.–) produced by NADPH oxidase is essential for killing bacteria and other pathogens.
O2.– is produced in the phagosome where bacteria are trapped.
O2.– can also be generated by mitochondria.
O2.– is involved in signaling pathways.

Inducible Nitric Oxide Synthase (iNOS)

Inducible nitric oxide synthase (iNOS) is a calcium-independent enzyme that is induced in macrophages (and other cell types) in response to inflammatory stimuli.
iNOS is responsible for the generation of nitric oxide (NO).
iNOS also uses arginine, NADPH, and oxygen for the reaction: Arginine + NADPH + O2 ® Citrulline + NADP+ + NO.
Nitric oxide production is crucial for defense against bacterial and parasitic infections.
NO reacts with superoxide (O2.–), forming peroxynitrite (ONOO–).
Peroxynitrite is a highly reactive molecule that damages microbial DNA and proteins.
It is thought to contribute to the antimicrobial activity of phagocytes, but also plays a role in inflammation and tissue damage.
NO has a variety of roles in the body, including vasodilation, neurotransmission, and immune regulation.

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Description

This quiz covers key concepts related to phagocytosis and the role of NADPH oxidase in the innate immune response. It explores the production of superoxide and nitric oxide by neutrophils and macrophages, as well as the regulatory mechanisms of NADPH oxidase. Test your knowledge on these essential immune processes!