Enzyme Reactions and Molecular Bindings

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Questions and Answers

Which term describes a molecule that binds to a receptor and activates it?

Agonist (correct)

Antagonist

PAMP

Ligand

What is the primary structural feature of molecules recognized by MAMP receptors, such as DNA and lipopolysaccharides?

A complex of short fatty acid chains

A small, cyclic carbohydrate

A single, linear protein chain

A recurring polymer structure (correct)

What is the main function of the Leucine Rich Repeat (LRR) domain found in many immune receptors?

To activate the TIR domain

To recruit adaptor proteins

To anchor the receptor to the cell membrane

To bind the agonist molecule (correct)

How many transmembrane anchoring sites are typically present in the receptors mentioned in the text?

One (C) Signup and view all the answers

What is the role of the TIR domain in signal transduction?

Recruiting adaptor proteins for signal transmission (B) Signup and view all the answers

What key event typically triggers activation of the TIR domain?

Receptor dimerization (B) Signup and view all the answers

Which of the following is a characteristic of NOD receptors?

They are soluble receptors found in the cytosol (A) Signup and view all the answers

What is the function of procaspase 1 within the inflammasome?

It becomes an active component that is activated during inflammation (B) Signup and view all the answers

What is the primary role of fMet-Leu-Phe receptors in phagocytosis?

To recognize and bind to bacterial peptides, initiating engulfment. (B) Signup and view all the answers

Which protein is responsible for assembling the NADPH oxidase complex on the phagosomal membrane?

Rac2. (A) Signup and view all the answers

What is the direct outcome of the NADPH oxidase reaction?

Generation of superoxide anions (O₂⁻). (D) Signup and view all the answers

What is the role of potassium (K⁺) and hydrogen ions (H⁺) in the phagosome?

To neutralize charged ROS and maintain ionic balance. (B) Signup and view all the answers

What role does ICAM-1 play in leukocyte extravasation?

It binds to integrins on leukocytes, causing them to firmly adhere to the endothelium. (A) Signup and view all the answers

Which enzyme converts superoxide (O₂⁻) into hydrogen peroxide (H₂O₂)?

Superoxide dismutase (SOD). (B) Signup and view all the answers

Which process DIRECTLY contributes to the activation of proteases within the phagosome?

Acidification of the phagosome. (C) Signup and view all the answers

Which event directly follows the firm adhesion of leukocytes to the endothelium during inflammation?

Transmigration (diapedesis). (A) Signup and view all the answers

What is the function of the protease secreted by leukocytes during transmigration?

To break the tight junctions between endothelial cells. (D) Signup and view all the answers

Which of these is NOT a key outcome of the respiratory burst?

Decreased pH environment. (C) Signup and view all the answers

What is the primary mechanism by which neutrophils and macrophages eliminate pathogens?

Phagocytosis. (B) Signup and view all the answers

What is the role of the phagosome in the destruction of pathogens?

It isolates the pathogen within the cell and facilitates its degradation. (B) Signup and view all the answers

What is the role of mannose receptors in phagocytosis?

To specifically bind to mannose found on the surface of many bacteria. (B) Signup and view all the answers

Which of the following describes the correct sequence of events during phagocytosis?

Recognition and binding, invagination and engulfment, phagosome-lysosome fusion, degradation, exocytosis. (D) Signup and view all the answers

What is the 'respiratory burst' in neutrophils primarily responsible for?

Releasing reactive oxygen species (ROS) to destroy pathogens. (C) Signup and view all the answers

What is the primary function of caspase-1?

To cleave specific protein targets, activating them (A) Signup and view all the answers

Which of the following best describes the role of the inflammasome?

To transform inactive procaspase-1 into active caspase-1. (B) Signup and view all the answers

What complex is essential for producing ROS during the respiratory burst?

The NADPH oxidase complex. (A) Signup and view all the answers

What is the role of the adaptor protein in the inflammasome complex?

To bind both NLRP and procaspase-1, bringing them together. (B) Signup and view all the answers

How does active IL-1 contribute to inflammation?

It is secreted from the cell, activating inflammation in nearby cells. (C) Signup and view all the answers

Which of the following is characteristic of necrosis?

A messy cell death where the cellular contents are released. (D) Signup and view all the answers

How does necroptosis differ from apoptosis?

The cell explodes, and releases its contents, similar to necrosis. (D) Signup and view all the answers

Which of the following is NOT a sterile activator of the inflammasome?

Pathogenic bacteria. (C) Signup and view all the answers

What is the primary function of Interleukin-1 (IL-1) in the context of inflammation?

To raise body temperature, enhancing the effectiveness of T cells and inhibiting pathogen survival. (D) Signup and view all the answers

Which of the following factors can activate the inflammasome?

High ATP concentration outside the cell. (C) Signup and view all the answers

How is heat generated in fatty tissues when the body aims to raise its temperature?

By the mitochondria producing heat as a biproduct rather than ATP. (D) Signup and view all the answers

What is the primary function of leukocyte rolling in the context of inflammation?

To enable stronger integrin-mediated adhesion to facilitate migration into tissues. (A) Signup and view all the answers

Why does the body need a signal to maintain the elevated temperature during inflammation?

To prevent the activation of sweating and loss of produced heat. (C) Signup and view all the answers

What is unique about the activation of Tumor Necrosis Factor (TNF)?

It needs to form a homotrimer before it can bind to its receptor. (A) Signup and view all the answers

How does the concentration of cytokines near an inflammation site impact leukocyte adhesion?

Cytokines increase the expression of adhesion molecules on the endothelium, enhancing adhesion. (C) Signup and view all the answers

What causes the release of the extracellular part of TNF from the cell membrane?

The release of proteins that cleave the cytokine. (A) Signup and view all the answers

What is the role of E-selectin in leukocyte movement during inflammation?

It decreases the rolling speed of leukocytes as they approach inflammation zones. (C) Signup and view all the answers

Which adhesion molecule binds with integrin for strong adhesion to the endothelium?

ICAM. (D) Signup and view all the answers

What does Erythropoietin stimulate in the body?

The production of red blood cells in response to low oxygen levels. (A) Signup and view all the answers

What is the main function of GM-CSF?

It stimulates the production and differentiation of granulocytes and macrophages. (C) Signup and view all the answers

What is the function of integrin in the context of leukocyte adhesion?

To bind with ICAM on the endothelial surface for strong adhesion. (A) Signup and view all the answers

What role does IL-6 play during inflammation?

It stimulates the differentiation and proliferation of immune cells and supports the acute-phase response. (B) Signup and view all the answers

Which of the following best describes the interaction between sialyl-LewisX (s-Le^x) and selectins?

They are transient, allowing leukocytes to roll along the endothelium. (A) Signup and view all the answers

During an inflammation, what is the role of proinflammatory cytokines like TNF-α and IL-1β?

To activate endothelial cells and increase selectin expression. (A) Signup and view all the answers

What causes leukocytes to stop rolling and firmly adhere to the endothelium during inflammation?

The high-affinity binding of integrins on leukocytes to ICAM on endothelial cells. (B) Signup and view all the answers

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Study Notes

Recap

Substrate: The substance on which an enzyme acts.
Ligand: A molecule that binds to another molecule; often used pharmacologically to describe agonists and antagonists.
Agonist: A ligand that binds to a receptor and activates it.
Antagonist: A ligand that binds to a receptor but does not activate it, instead inhibiting the agonist's action.
Ligand = PAMP = agonist: These terms are interchangeable in context.

What characterises MAMP's/agonists of all the sensors?

The molecules that bind to the receptors have a repeating polymer structure (e.g., DNA, RNA, lipopolysaccharide).
They have an agonist-binding area rich in leucine (Leucine Rich Repeat). This area is on the outside of the receptor.
The transmembranal area of the receptor has an anchoring site (unlike seven-transmembrane receptors).
The TIR domain is critical for recruiting proteins that relay the signal.
Dimerization of the TIR domain activates the signal cascade, leading to gene activation that triggers inflammation.
Dimerization usually occurs at a certain concentration of the agonist near the cell surface.

Intracellular Sensing

The NOD family of receptors has a Leucine-Rich Repeat domain and a domain for adaptor protein recruitment.
NOD receptors are soluble and found in the cytosol, identifying MAMPs.
NOD receptors detect bacterial entry into the cytoplasm and trigger an immune response.
NODs are similar in structure to other receptors in the cell, making identification of similar receptors relatively straightforward.

The Inflammasome

The inflammasome is a protein complex that initiates inflammation.
It includes components (e.g., macrophages) coloured due to cytoskeletal actin.
The activated inflammasome triggers inflammation.
The inflammasome can lead to the activation of programmed cell death (pyroptosis).

Three Main Components of the Inflammasome

The sensor recognizes the danger signal.
An adaptor protein transmits the signal to an active enzyme (procaspase-1).
Procaspase-1 is activated by the adaptor protein and cleaves other inflammatory proteins.

Cytoplasmic Sensors of Viral RNA

RIG-I and MDA-5 are receptors in the cytoplasm that recognize viral RNA with a triphosphate modification.
They activate the production of inflammatory cytokines and interferons.
These sensors were initially not well understood until the mechanism of their function was better-understood.

Extracellular Sensing

Toll-like receptors (TLRs) are extracellular receptors that recognize pathogen-associated molecular patterns (PAMPs) such as lipopolysaccharide.

Intracellular Sensing (Recap)

NOD-like receptors (NLRs) are intracellular receptors that recognize bacterial components like peptidoglycans, activating inflammation.

Cytokines

Cytokines are small proteins that function as messengers in the immune system, coordinating an immune response:
- Autocrine: effect the current cell releasing them.
- Paracrine: effect adjacent cells.
- Endocrine: effect cells far away.
IL-1 family regulates inflammation and cell responses.

Adhesion Molecules

Selectins (P-selectin, E-selectin) bind to carbohydrate ligands on white blood cells, initiating rolling along endothelial cells.
Integrins (LFA-1, ICAM-1) mediate stronger adhesion and subsequent extravasation of WBCs into tissues. This tight binding allows cells to leave blood vessels and enter tissues effectively.

Elimination

Phagocytes (e.g., neutrophils, macrophages) recognize and eliminate pathogens through phagocytosis, which involves ingestion and destruction of the pathogen.
The respiratory burst is initiated to produce reactive oxygen species which are toxic to pathogens within phagocytes.

Ion Influx and Acidification

K+ and H+ ions move into phagosomes, neutralizing ROS and aiding activation of digestive enzymes
This neutralisation creates a balance of charge and aids in the proper function of the enzyme's action.

Activation of NADPH Oxidase

The NADPH oxidase complex on the phagosome builds up a potent reactive oxygen species (ROS) which effectively neutralizes the pathogen.

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Description

This quiz explores critical concepts related to substrates, ligands, agonists, and antagonists within enzyme reactions. It covers the structural characteristics of MAMPs/agonists and their role in activating receptors. Test your knowledge of these essential biochemical interactions!