W2-4 WS Cytokines, chemokines, and cell signaling

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According to the text, what are cytokines known as in the context of the immune system?

Workhorses

Which of the following is NOT a function of cytokines?

Treating inflammatory diseases

What is the primary focus of medicine in immunology today?

Controlling immunological processes

Which of the following is NOT a condition that can be treated using pharmacological agents targeting cytokine and cytokine signaling?

Cancer

What are the major classes of cytokines primarily responsible for?

Directing leukocyte development

Which concept refers to the ability of cytokines to act on multiple cell types and have diverse effects?

Pleiotropism

Which receptor family is associated with IL-2, IL-4, IL-7, IL-15, and IL-21 cytokines?

Type I cytokine receptors

What type of receptors are involved in the signaling cascades for TNF receptors?

Type I and Type II cytokine receptors

In the context of MHC I and MHC II molecules, what is responsible for the distribution of MHC I and MHC II on different cells?

$TAP$ (Transporter associated with antigen processing)

Which type of cytokines are biologically active antibodies an example of?

$Polyclonal antibodies including IVIG$

What is the focus of immunologic protection?

Immune response termination mechanisms

What do principles of immunologic protection include?

Mechanisms of vaccine action only

What is the effect of age on the function of components of the immune system?

Decreased immune response to vaccinations in older adults

What is the term for the property of a cytokine exhibiting several different functions?

Pleiotropism

Which property refers to the situation where different cytokines may possess the same biological activity?

Redundancy

What is the term for the situation where the combined effect of two or more cytokines is more or less equal to the sum of the effects of the cytokines taken separately?

Additively

When the effects of a cytokine inhibit the effects of another cytokine, it is said to act:

Antagonistically

What is the term for a cytokine specialized in attracting cells, especially leukocytes?

Chemokine

How are chemokines named based on the spacing of their first cysteine residues?

Spacing-based system

What class of chemokines is represented by the naming convention CXC?

Class B

What represents the amino acids between the first two cysteine residues in the naming convention of chemokines?

'X'

In the naming convention for chemokine receptors, what letter is added at the end to denote that it is a chemokine receptor?

'R'

"CXCL8" is the correct name for which cytokine?

IL-8

What is the term for the situation where many chemokines are ligands for several chemokine receptors?

Promiscuity

In addition to their roles in normal physiological processes and pathophysiology, several cytokines and their signaling are targets for many approved pharmacological...

Therapies

Which of the following is NOT a reason why there is no point in memorizing each cytokine and their respective functions?

Their functions are not context-specific.

In what context can tumor necrosis factor alpha (TNF-α) stimulate the expression of adhesion molecules on the luminal surface of endothelial cells?

At the site of injury

What is the main function of TNF-α in the brain (hypothalamus)?

Inducing fever

What advice does the text give for classifying different cytokines at the beginning of learning?

Classify them according to their general function(s).

What is the main type of response that can help in segregating cytokine functions into functional clusters?

Proinflammatory reactions

In what specific context can tumor necrosis factor alpha (TNF-α) induce energy production through carbohydrate, protein, and fatty acid catabolism?

Systemically

What is the significance of classifying cytokines according to their general function(s) at the beginning of learning?

It allows for immediate understanding of specific cytokine functions.

What is the function of TNF-α at the cellular level, in conjunction with other cytokines or stimuli?

Activating phagocytic cells

What is generally referred to as being involved in preventing or decreasing inflammation?

Antiinflammatory processes

Why is it unnecessary to memorize each cytokine and their respective functions?

They can generally be somewhat segregated according to main type(s) of response(s).

What advice does the text give for learning the specific functions of cytokines within specific contexts?

Learn their specific functions within specific contexts as we progress.

What is the primary communication molecule used within the immune system and between the immune system and other body systems?

Cytokines

What is the primary mode of action for cytokines?

Intracellular signaling pathways

Which statement about cytokine expression is true?

Most cytokines are expressed in soluble form, but some are membrane-bound

What type of signaling occurs when a membrane-bound cytokine interacts with its cognate receptor on the surface of a target cell?

Juxtacrine signaling

Why is the expression of cytokines tightly regulated?

To prevent excessive responses that can be life-threatening

How do cytokines elicit their biological response?

Via intracellular receptor interactions

In what form are most cytokines expressed?

Soluble

What is the primary mechanism by which cytokines mediate their actions?

Receptor engagement and intracellular signaling pathways

Which type of signaling involves the interaction between a membrane-bound cytokine and its cognate receptor on the surface of its target cell?

Juxtacrine signaling

What are the primary factors that lead to cytokine gene transcription, translation, and secretion?

(PRRs) Pathogen-Recognition Receptors and Cytokines

Which statement about cytokines is correct?

Cytokines are synthesized de novo and need to be stimulated for expression

What type of signaling involves the release of cytokines at the site of infection, reaching other tissues to induce physiological responses?

Endocrine signaling

What is the purpose of the tight regulation of cytokine expression?

To avoid excessive responses that can be life-threatening

Which cytokine receptor primarily signals through the Nuclear Factor kappa B (NF-kB) pathway?

Tumor necrosis factor alpha (TNF-α)

Which cytokine receptor family is associated with interferons and primarily signals through the JAK/STAT pathways?

Interferon receptors

Which condition is NOT currently approved for treatment using JAK inhibitors targeting cytokine and cytokine signaling?

Lupus nephritis

Which cytokine receptor family is primarily used by interferons and signals through STAT1 homodimers and STAT1/STAT2 heterodimers?

Interferon receptors

Which of the following is a cytokine mostly known as an anti-inflammatory mediator, although it technically belongs to the interferon family?

Interleukin-10 (IL-10)

Which cytokine is known to signal through STAT1/STAT2 heterodimers?

Interferon-gamma (IFN-γ)

Which receptor family is associated with TNFs and also serves as receptors for other important molecules such as FasL and CD40L?

TNF receptors

What receptor family is primarily used by interferons and also signals through JAK/STAT pathways?

Interferon receptors

What is the main type of response that can help in segregating cytokine functions into functional clusters?

Cytokine response

Which condition is NOT treated using pharmacological agents targeting cytokine and cytokine signaling?

Type 2 diabetes

Which of the following is a function of CXCL10?

Promotion of angiogenesis

Which cytokine receptor family does VEGF-A signal through?

Type I cytokine receptor

Which cytokine receptor family is mainly used by the majority of cytokines and mainly signals through a JAK/STAT pathway?

Type I cytokine receptor

What is the primary function of the IL-2Rγc subunit in cytokine receptors?

Facilitating signal transduction for various interleukins

Which cytokine is associated with a JAK3 deficiency?

IL-2

Which cytokine is NOT primarily involved in angiogenesis?

CCL5 (RANTES)

Which cytokine primarily signals through seven transmembrane G-protein-coupled receptors?

CCL5 (RANTES)

What is the primary function of the VEGF-A cytokine?

Promotion of angiogenesis

What is the primary function of the CCL11 (eotaxin-1) chemokine?

Eosinophil chemotaxis

Which cytokine receptor family shares some receptor subunits with the receptors for IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21?

Type I cytokine receptor

Which statement about JAK3 and IL-2Rγc deficiencies is true?

A patient with a JAK3 deficiency would present with the same disease as a patient with an IL2RγC deficiency.

Which cytokine primarily signals through VEGFRs, which are tyrosine kinase receptors?

VEGF-A

Which cytokine is responsible for the initiation of the inflammatory response, induction of other proinflammatory cytokine synthesis and secretion, fever, and synthesis of acute-phase reactants by the liver?

IL-1β

Which cytokine is primarily associated with leukocyte proliferation, CD4 T lymphocyte differentiation into TH17 cell subset, and signals mainly through IL-6R?

IL-2

Which cytokine is involved in the activation of NK cells for the synthesis and release of IFN-γ, CD4 T lymphocyte differentiation into TH1 cell subset, and activation of Cytotoxic T Lymphocytes (CTLs)?

IL-12

Which cytokine is responsible for the proliferation of T and B lymphocytes, as well as NK cells, and signals mostly through common γ-chain receptors, but also through type I cytokine receptors?

IL-2

Which cytokine is associated with the activation of macrophage microbicidal functions (M1 macrophages), CD4 T lymphocyte differentiation into TH1 cell subset, and isotype-switching to IgG?

IFN-γ

Which cytokine is primarily involved in vasodilation, chemotaxis, endothelial activation, transendothelial migration, activation of neutrophils and macrophages, fever, and increased muscle and fat catabolism (cachexia)?

TNF-α

Which cytokine is responsible for the development and proliferation of NK cells and proliferation of T lymphocytes?

IL-15

Which cytokine signals mainly through type II cytokine receptors and is involved in the activation of macrophage microbicidal functions (M1 macrophages) and CD4 T lymphocyte differentiation into TH1 cell subset?

IFN-γ

Which cytokine is primarily associated with chemotaxis, endothelial activation, leukocyte integrin expression in inflammatory bed, and increased vascular permeability through disruption of adherens junctions?

TNF-α

Which cytokine is primarily involved in the proliferation and activation of eosinophils?

IL-5

What is the main function of TGF-β in CD4 T lymphocyte differentiation?

Differentiation into TH17 cell subset

Which chemokine is primarily responsible for chemotaxis of activated B cells, memory T cells, and immature dendritic cells in mucosa and skin?

CCL20

Which cytokine is mainly associated with the alternative activation of macrophages (M2 macrophages)?

IL-13

What is the primary function of IL-22 at the site of infection?

Increased barrier protection and defensin production

Which cytokine is mainly responsible for the proliferation of NK and T lymphocyte progenitors?

IL-7

Which chemokine is primarily involved in chemotaxis of monocytes, memory T lymphocytes, and NK cells?

CCL2

Which cytokine is mainly associated with hematopoiesis and immature cells?

IL-3

What is the primary function of platelet-activating factor (PAF)?

Involved in inflammation and thrombotic cascades

What is the primary function of IL-21?

B lymphocyte activation and proliferation

Which receptor primarily signals using the NF-kB signaling pathway and with crosstalk with Mitogen-Activated Protein Kinase (MAPK) signaling pathways?

IL-1 and IL-18 receptor

Which pathway is used by the vast majority of chemokines for signaling?

NF-kB signaling pathway

What is the primary function of the G-Protein Coupled Receptor involved in cytokine signaling regulation?

Phosphorylation of many protein substrates

Which cytokine primarily signals through seven transmembrane G-protein-coupled receptors?

TNF-α

Which transcription factor would fail to be activated in a patient with a NEMO (IKKγ) deficiency?

NF-κB (Correct answer)

Which TK is responsible for the phosphorylation of STATs?

JAKs (Correct answer)

What is the primary function of MyD88-related signaling?

Activating proinflammatory genes (Correct answer)

Which transcription factors are activated through the SAPK/JNK, ERK, and p38 MAPK pathways?

AP-1 (Correct answer)

What is the dichotomy in IL-1R signaling at the level of TAK1/TAB1-2/TRAF6 activation?

Activation of NF-κB and STAT transcription factors (Correct answer)

Which receptors primarily activate both NF-κB and IRF transcription factors?

TLR 3 (Correct answer)

What is the role of Toll-like receptor 4 in signaling pathways?

Activation of NF-κB and IRF transcription factors (Correct answer)

In MyD88-related signaling, what is the primary role of the MyD88 adaptor protein?

Activating proinflammatory genes (Correct answer)

Which signaling pathway is important for the initiation of inflammation and TCR/BCR signaling?

NF-κB pathway (Correct answer)

How do TLRs 3, 7, 8, and 9 differ from TLRs 1/2, 2/6, 4, and 5 in their signaling pathways?

Crosstalk with other transcription factors (Correct answer)

What is the primary effect of IL-1R and many TLRs signaling through the same pathways?

Activation of other signaling pathways

What is the key molecular pathway in the innate immune system responsible for initiating cellular response to pathogens?

MyD88-related signaling (Correct answer)

Which signaling pathway is the target of many pharmacological treatments and dysregulation of this pathway is key to the pathophysiology of many immune deficiencies?

JAK/STAT pathway

What is the primary function of the NF-kB pathway?

Triggering apoptosis through death domains

Which cytokine receptor family shares some receptor subunits with the receptors for IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21?

Type I cytokine receptors

Which cytokine primarily signals through seven transmembrane G-protein-coupled receptors?

IL-8

What is the term for a cytokine specialized in attracting cells, especially leukocytes?

Chemokine

What is the function of IL-21?

Proliferation and activation of eosinophils

The CCL11 (eotaxin-1) chemokine is primarily involved in:

Activation of macrophage microbicidal functions (M1 macrophages)

Which cytokine is known to signal through STAT1/STAT2 heterodimers?

IFN-γ

What type of signaling occurs when a membrane-bound cytokine interacts with its cognate receptor on the surface of a target cell?

Juxtacrine signaling

What is the primary effect of age on the function of components of the immune system?

Decreased function of innate and adaptive immune responses

Which cytokine is mainly associated with hematopoiesis and immature cells?

IL-7

In what specific context can tumor necrosis factor alpha (TNF-α) induce energy production through carbohydrate, protein, and fatty acid catabolism?

During inflammation

In the given example regarding lipolytic activation in adipocytes treated with proinflammatory cytokines, what kind of cytokine interaction(s) is(are) occurring?

Redundancy

Considering the functions of IL-1b, TNF-a, and IL-6, how can these cytokines be qualified?

Pleiotropic

What type of signaling is exemplified by IL-12 and IFN-g in the figure below?

Paracrine

Which cytokine would promote the production of new leukocytes following a bone marrow transplant in a 5-year-old boy with leukemia?

IL-3

A defect in the expression of which molecule most likely accounts for the rarity of granulocytes in the inflamed periodontium of the 5-year-old boy?

CXCL8

In a 25-year-old woman presenting with severe pain on the right side of the lower abdomen, nausea, and fever, the cytokines responsible for eliciting the fever are an example of what type of cytokine signaling?

Endocrine

Study Notes

  • Fusion sessions are online learning activities followed by a live session where participants translate content into practice.
  • Participants must complete learning content in Canvas before attending live sessions.
  • Recordings of fusion sessions will not be posted to encourage preparation and attendance.
  • The topic of the fusion session is Cytokines, Chemokines, & Cell Signaling in the field of Infectious Immune Diseases.
  • Cytokines are crucial elements of the immune system that direct the development and functions of various immune cells.
  • Cytokines and chemokines are essential for normal and pathological immunological processes, as well as the treatment of various conditions including inflammatory, infectious, autoimmune diseases, and others.
  • Major classes of cytokines include interleukins (IL), interferons (IFNs), and growth factors. Examples include IL-1, IL-2, IL-4, IL-6, IL-8, IFN-α, IFN-γ, and transforming growth factor-β (TGF-β).
  • Chemokines are a subclass of cytokines that primarily attract immune cells to sites of infection or injury. Classes include CC and CXC chemokines, with examples including RANTES, MIP-1α, IL-8, IP-10, and MCP-1.
  • Cytokines have unique properties such as pleiotropism (multifunctionality), redundancy, additivity, synergy, and antagonism.
  • Cytokine and chemokine receptors are crucial for the function of these signaling molecules. Examples include the IL-2, IL-4, IL-7, IL-15, and IL-21 receptors.
  • Signaling cascades for various receptors include those for type I and II cytokine receptors, TNF receptors, IL-1 receptors, and seven transmembrane G-protein-coupled receptors.
  • Topics covered in this fusion session include the development of the adaptive immune response, structure and function of various immune cells, cellular basis of the immune response, and immunologic diagnostics.
  • Understanding cytokines can be challenging due to the vast number of cytokines and their multifaceted functions. It's recommended to classify cytokines according to their general functions and learn their specific functions within context as the learning progresses.

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