class 2 1 Flashcards

1
Q

Describe the proteins involved in directing physiologicalocyte homing and extravasation during inflammatory processes.

A

Proteins involved include adhesion molecules, proteases, cytokines, and chemokines.

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2
Q

What are some mechanisms that regulate leukocyte migration?

A

Mechanisms include up- or down-regulation of chemokine or chemokine receptor gene expression, interaction ofokines with specific glycosaminoglycans, and binding of chemokines to atypical chemokine receptors.

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3
Q

How does modification of the interaction of chemokines with glycosaminoglycans affect chemokine availability?

A

It alters the presentation of chemokines to chemokine receptors on circulating leukocytes.

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4
Q

Define the mechanisms that fine-tune chemokine function.

A

These include synergy or antagonism between chemokines, alternative splicing of chemokine genes, and posttranslational modification of chemokines.

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5
Q

Describe the classification of CXC chemokines based on the presence of an ELR motif.

A

CXC chemokines are subdivided into ELR+ and ELR- CXC chemokines based on the presence of an ELR motif (Glu-Leu-Arg) preceding the CXC sequence.

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6
Q

How are the seven-transmembrane G protein-coupled receptors for chemokines classified?

A

The seven-transmembrane G protein-coupled receptors for chemokines are classified according to the subclass of chemokines they recognize, including CXCR, CCR, CX3CR, and XCR.

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7
Q

Describe the property of redundancy in leukocyte migration within the chemokine network.

A

Despite the cell-specific expression of defined chemokine receptors, chemokines display a high degree of redundancy in leukocyte migration, which is the result of recurrent gene duplications during evolution.

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8
Q

How do chemokines counteract each other in the inflammatory response?

A

Chemokines can counteract each other by reducing the inflammatory response or increasing the selectivity of cell recruitment through heterologous desensitization, internalization, and antagonistic activity for another receptor.

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9
Q

Define alternative splicing in the context of chemokine function.

A

Alternative splicing in chemokine function refers to the process where the pre-mRNA of several chemokine genes undergoes alternative splicing, generating multiple mRNAs that are translated into different chemokine isoforms.

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10
Q

What are the suggested mechanisms through which coin-induced chemokines can synergize?

A

The suggested mechanisms include heteromerization of chemokines or chemokine receptors and synergy at the level of signal transduction.

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11
Q

Describe the process of chemokine production and presentation to leukocytes.

A

Chemokines are produced at the site of infection by local tissue cells and form a concentration gradient by binding to glycosaminoglycan moieties of proteoglycans in the extracellular matrix They pass the endoth cell layer through diffusion transcytosis endothelial DARC glycosaminoglyans

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12
Q

How are chemokines posttranslationally modified, and what impact does this have on their biological activity?

A

Chemokines can be proteolytically cleaved, glycosylated, and citrullinated, with proteolytic processing predominantly occurring at the NH2-terminal region. These modifications affect the biological activity of the chemokines.

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13
Q

Do chemokines have different functions based on their membrane-bound and soluble isoforms?

A

Yes, chemokines have disparate biological functions based on their membrane-bound and soluble isoforms, which are determined by proteolytic processing and other modifications.

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14
Q

Describe the interaction between chemokines and their receptors.

A

Chemokines drive the recruitment specific leukocyte subsets to a site of inflammation by binding to their chemokine receptors.

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15
Q

What are some mechanisms evolved to regulate chemokine availability and function?

A

Mechanisms such as alternative splicing, posttranslational modifications, and glycosaminoglycan binding regulate chemokine availability and function.

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16
Q

How do posttranslational modifications influence chemokine function?

A

Posttranslational modifications can influence binding of chemokines to atypical receptors and glycosaminoglycans, as well as chemokine processing by proteases and possibly chemokine heteromerization.

17
Q

Define the concept of chemokine synergy.

A

Chemokine synergy refers to the highly regulated and specific interplay between chemokines, which allows each chemokine to exert a unique spectrum of functions.

18
Q

Do regulatory mechanisms influence each other in the context of chemokine function?

A

Yes, regulatory mechanisms such as alternative splicing, posttranslational modifications, and glycosaminoglycan binding influence each other, enhancing the complexity of chemokine function.

19
Q

Describe the role of the chemokine system in cancer biology and therapy.

A

The chemok system plays a significant role in cancer biology and therapy, influencing immune responses and tumor progression.

20
Q

Define chemokine receptors and their nomenclature.

A

Chemokine receptors are a class of G protein-coupled receptors involved in immune cell migration and activation. Their nomenclature is standardized by the International Union of Pharmacology.

21
Q

How does the genomic organization of chemokines provide clues for deciphering their functional complexity?

A

The genomic organization of chemokines contains clues for deciphering their functional complexity, offering insights into their diverse roles in immunity and disease.

22
Q

Do platelets release nonallelic variants of chemokines, and what is their potential impact?

A

Yes, platelets release nonallelic variants of chemokines, such as CXCL4L1, which can act as potent inhibitors of angiogenesis.

23
Q

Describe the significance of copy number variation in the chemokine superfamily, specifically the CCL3L-CCL4L genes, in health and disease.

A

Copy number variation in the chemokine superfamily, particularly the CCL3L-CCL4L genes, has implications for both health and disease, impacting immune responses and inflammatory processes.

24
Q

Describe the role of carboxypeptidase N in the cleavage of stromal-derived factor-1alpha.

A

Carypeptidase N is responsible for the C-terminal cleavage of stromal cell-derived factor-1alpha in the circulation.

25
Q

What is the functional diversity of SDF-1 splicing variants?

A

The functional diversity of SDF-1 splicing variants is significant.

26
Q

Define the novel CXCL12gamma isoform and its regulatory properties.

A

The novel CXCL12gamma isoform encodes an unstructured cationic domain which regulates bioactivity and interaction with glycosaminoglycans and CXCR4.

27
Q

How does the alternatively spliced CXCL16 isoform function as a chemoattractant?

A

The alternatively spliced CXCL16 isoform expressed by dendritic cells functions as a secreted chemoattractant for CXCR6+ cells.

28
Q

Do matrix metalloproteinases play a role in modulating inflammation and innate immunity?

A

Yes, matrix metalloproteinases act as modulators of inflammation and innate immunity.