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Questions and Answers
What does the term 'cytokine' derive from?
What does the term 'cytokine' derive from?
Cytokines only play a role in the adaptive immune system.
Cytokines only play a role in the adaptive immune system.
False (B)
Name one pro-inflammatory cytokine.
Name one pro-inflammatory cytokine.
IL-6
Cytokines signal via their receptors, which are ______ proteins.
Cytokines signal via their receptors, which are ______ proteins.
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Match the following cytokines with their effects:
Match the following cytokines with their effects:
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Which cytokine is known as an eosinophil growth factor?
Which cytokine is known as an eosinophil growth factor?
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IL-17 is associated with neutrophil mobilization.
IL-17 is associated with neutrophil mobilization.
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Identify two examples of diseases treated with cytokine therapeutics.
Identify two examples of diseases treated with cytokine therapeutics.
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Cytokines produced by _______ can have immunosuppressive effects.
Cytokines produced by _______ can have immunosuppressive effects.
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Which cytokine is known for activating T cells?
Which cytokine is known for activating T cells?
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Which interleukin is primarily responsible for the differentiation of T helper 17 (TH17) cells from naïve T cells?
Which interleukin is primarily responsible for the differentiation of T helper 17 (TH17) cells from naïve T cells?
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IL-1β is generally associated with the plasma membrane of the producing cell.
IL-1β is generally associated with the plasma membrane of the producing cell.
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What is the primary source of IL-1β production?
What is the primary source of IL-1β production?
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IL-1α is important for priming T cells during contact hypersensitivity and for the induction of high levels of serum IgE following immunization with __________.
IL-1α is important for priming T cells during contact hypersensitivity and for the induction of high levels of serum IgE following immunization with __________.
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Which cytokine is primarily produced by keratinocytes and endothelial cells?
Which cytokine is primarily produced by keratinocytes and endothelial cells?
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Dysregulation of IL-1 family members can lead to pathobiological diseases.
Dysregulation of IL-1 family members can lead to pathobiological diseases.
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Match the following interleukins with their primary function:
Match the following interleukins with their primary function:
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Which interleukin is notably involved in autoimmune and chronic inflammatory diseases?
Which interleukin is notably involved in autoimmune and chronic inflammatory diseases?
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What is one of the most frequent adverse events associated with Theralizumab?
What is one of the most frequent adverse events associated with Theralizumab?
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Cytokines have a long half-life, allowing for high efficacy in therapies.
Cytokines have a long half-life, allowing for high efficacy in therapies.
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Why are many immunotherapies administered at a late disease stage?
Why are many immunotherapies administered at a late disease stage?
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The immune response is activated by __________ cells in immunotherapy.
The immune response is activated by __________ cells in immunotherapy.
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Match the following cytokines with their primary roles:
Match the following cytokines with their primary roles:
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What is a limitation of systemic administration of cytokines?
What is a limitation of systemic administration of cytokines?
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Cytokines can be effectively used to treat many different types of diseases.
Cytokines can be effectively used to treat many different types of diseases.
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What negative effect can result from activated all T cells in therapy?
What negative effect can result from activated all T cells in therapy?
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Which of the following cytokines are produced in the inflamed joints of patients with rheumatoid arthritis?
Which of the following cytokines are produced in the inflamed joints of patients with rheumatoid arthritis?
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Anti-TNF therapies have shown no significant improvement in psoriasis patient plaques.
Anti-TNF therapies have shown no significant improvement in psoriasis patient plaques.
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What are the two types of TNF receptors mentioned in relation to psoriasis?
What are the two types of TNF receptors mentioned in relation to psoriasis?
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IL-2 is primarily secreted by _____________ T cells.
IL-2 is primarily secreted by _____________ T cells.
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Match the anti-TNF therapies with their types:
Match the anti-TNF therapies with their types:
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What is the main application of IL-2 therapy?
What is the main application of IL-2 therapy?
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Cytokine release syndrome can be triggered by multiple factors including infections and drugs.
Cytokine release syndrome can be triggered by multiple factors including infections and drugs.
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What is the approved treatment for metastatic melanoma and renal cell carcinoma mentioned?
What is the approved treatment for metastatic melanoma and renal cell carcinoma mentioned?
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In cardiovascular disease, TNF blockade hasn’t proved ____________ clinically beneficial.
In cardiovascular disease, TNF blockade hasn’t proved ____________ clinically beneficial.
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In the context of IL-2 therapy, repeated injections are necessary due to its ____________.
In the context of IL-2 therapy, repeated injections are necessary due to its ____________.
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Which of the following cytokines requires Caspase 1 processing to be fully activated?
Which of the following cytokines requires Caspase 1 processing to be fully activated?
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IL-33 is primarily associated with TH1 cytokine production.
IL-33 is primarily associated with TH1 cytokine production.
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What receptor does IL-33 primarily signal through?
What receptor does IL-33 primarily signal through?
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In autoimmune diseases like Systemic Lupus Erythematosus, there are increased amounts of IL-18 in the skin and _____ of patients.
In autoimmune diseases like Systemic Lupus Erythematosus, there are increased amounts of IL-18 in the skin and _____ of patients.
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Match the cytokines with their primary immune-related functions:
Match the cytokines with their primary immune-related functions:
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Which cytokine is involved in the maturation of B cells into antibody producing plasma cells?
Which cytokine is involved in the maturation of B cells into antibody producing plasma cells?
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Caspase 1 is not necessary for the activation of pro-IL-18.
Caspase 1 is not necessary for the activation of pro-IL-18.
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What is the role of soluble IL-18 binding protein (IL-18BP)?
What is the role of soluble IL-18 binding protein (IL-18BP)?
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IL-6 and IL-11 belong to the same _____ family.
IL-6 and IL-11 belong to the same _____ family.
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Match the following immune-mediated diseases with their associated cytokines:
Match the following immune-mediated diseases with their associated cytokines:
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What is a known effect of IL-6 in inflammatory diseases?
What is a known effect of IL-6 in inflammatory diseases?
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Soluble ST2 levels are decreased in asthmatics.
Soluble ST2 levels are decreased in asthmatics.
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In which immune-mediated disease is dysregulated IL-6 production commonly observed?
In which immune-mediated disease is dysregulated IL-6 production commonly observed?
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IL-18 serum concentrations are suggested to increase in proportion to _____ severity in Crohn's disease.
IL-18 serum concentrations are suggested to increase in proportion to _____ severity in Crohn's disease.
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Study Notes
Cytokine Therapeutics
- Cytokines are low molecular weight proteins (<30 kDa) secreted by cells of the innate and adaptive immune systems
- Cytokines are typically not stored, but are synthesized by new gene transcription upon cellular stimulation
- Cytokines mediate their effects by binding to specific receptors on the surface of target cells, affecting cell behavior
- Cytokines act as a means of communication between cells and tissues, mediating responses to external stimuli or tissue damage
- Cytokines can act in three different ways: autocrine (on cells producing them), paracrine (on nearby cells), and endocrine (on distant cells)
Lecture Objectives
- Understand what a cytokine is, its role, mechanisms of action, and traits
- Recognize cytokines of the innate and adaptive immune system
- Understand the role of cytokines in inflammation (pro- vs. anti-inflammatory)
- Describe effects of different cytokines in disease
- Know at least two examples of cytokine therapeutics used for disease treatment
Cytokine Biology
- Cytokines are chemical messengers
- Cytokines are crucial for immune system function
- Cytokine effects are pleiotropic (cytokine has many effects on different cell types)
- Cytokines act in a redundant manner (several cytokines may have the same effect)
Cytokines and Their Actions
- Cytokines can act via autocrine, paracrine, or endocrine mechanisms.
Cytokine Traits
- Many cytokines have different effects (activation, differentiation, proliferation) on multiple cell types (pleiotropy)
- Cytokines can be produced by various cell types and act on many different cell types
- Different cytokines can have similar effects on a cell type (redundancy)
- Combinations of cytokines can have a stronger effect than either cytokine alone (synergy)
- The effects of one cytokine can inhibit another (antagonism)
Cytokines and the Immune System
- Cytokines are produced in response to innate and adaptive immune system activation.
- Cytokine production is associated with type I interferon, interleukins (IL-) 1, 6, and tumor necrosis factor (TNF).
- Cytokines produced by the adaptive immune response include interferon-y, IL-2, 4, and 5.
- Other cytokines stimulate immature leukocyte growth and differentiation (IL-3, colony stimulating factors)
- Interleukins are a subset of cytokines.
Cytokines Affecting Many Organ Systems and Cell Types
- Cytokines affect various organ systems and different cell types throughout the body
- Cytokines influence cells in different parts of the body
- Cytokines can be produced by numerous cells and tissues, affecting cells in many tissues and organs.
Cytokines and Inflammation
- Inflammation involves responses initiated within hours of infection or injury
- Inflammation's effects include destruction of invading microorganisms, induction of blood clotting, and repair of injured tissue.
Cytokines Drive the Inflammatory Response
- Cytokines play a key role in amplifying inflammatory responses
- Cells release cytokines and chemokines following infection to trigger vasodilation, increased vascular permeability, and recruitment of inflammatory cells
- Cytokines stimulate the production of antimicrobial and antiviral proteins, and cause the killing of infected cells
Pro-inflammatory vs Anti-inflammatory Cytokines
- Pro-inflammatory cytokines stimulate an immune response to infection or injury.
- Anti-inflammatory cytokines control and limit the pro-inflammatory response to prevent its over-escalation and tissue damage.
Disturbing the Balance of Cytokine Production
- An excess of either pro-inflammatory or anti-inflammatory cytokines can lead to serious complications, such as sepsis or immunosuppression
- Sepsis is caused by an excessive pro-inflammatory response
- Immunosuppression is caused by an excessive anti-inflammatory response
Cascade Effects of Cytokines (Produced by Macrophages)
- Activated macrophages secrete a range of cytokines
- Cytokines produced by macrophages induce local and systemic effects, including inflammation, fever, and the production of acute-phase proteins.
Cascade Effects of Cytokines (Produced by T Cells)
- Activated T cells produce a range of cytokines
- Cytokines produced by T cells affect various cell types and contribute to immune regulation and inflammatory responses
Cytokine Signaling
- Cytokines signal via their receptors.
- Cytokine receptors are a part of families of receptor proteins
- This signaling involves binding of ligands (e.g., cytokines) to extracellular domains of receptors.
Cytokine Effects in Disease
- Diseases can result from dysregulation of cytokine production
- Cytokines are involved in various pathological conditions
Cytokines - IL-1 Family
- Comprised of 11 members
- Promote innate immune system cells' activity (e.g., neutrophils, eosinophils, basophils)
- Activate and reinforce T cell functions
- Help differentiate T helper 17 (TH17) cells from naïve T cells
Cytokines - IL-1a and IL-1β
- IL-1β is secreted and circulates systemically; IL-1α acts locally.
- Monocytes and macrophages produce IL-1β.
- Keratinocytes and endothelial cells express high levels of IL-1α.
Cytokines - IL-18 and IL-33
- IL-18 and IL-33 are involved in various immune responses
- These cytokines have crucial immunomodulatory functions
Cytokines - IL-6
- Member of the same family as IL-11
- Expressed by mononuclear phagocytes, T cells, B cells, fibroblasts, and endothelial cells
- Involved in hematopoiesis, B cell maturation, and T cell activation
IL-6 and Immune-Mediated Diseases
- Cytokine dysregulation plays a significant role in various diseases
- Elevated levels of IL-6 can be a predictor of disease activity in several contexts
IL-2
- Pleiotropic cytokine, initially identified as a T cell growth factor
- Produced by antigen-stimulated CD4+ T cells, CD8 T cells, NK cells, and activated DCs
- Plays a role in T cell differentiation and memory cell formation
IL-2 Therapy
- IL-2 is a key factor for Treg cell survival and maintenance
- Low-dose IL-2 is effective in various conditions
- The short half-life of IL-2 necessitates repeated injections
IL-2 Therapy in Cancer
- Approved treatment for metastatic melanoma and renal cell carcinoma (ALDESLEUKIN)
- Administered systemically
The Other Side of the Coin…
- Low-dose IL-2 therapy is an important approach to regulating immune responses in various disease states
- High-dose IL-2 therapy has safety concerns
Cytokine Release Syndrome
- Cytokine release syndrome is a systemic inflammatory response triggered by various factors
- The resulting cytokine storm often involves massive T cell stimulation, leading to serious adverse events.
A Long Way to Go…
- Limitations of cytokine therapies include short half-lives, efficacy, systemic administration requirements requiring repeated injections, and potential toxicities prompting further investigations into disease-specific treatments and strategies for improving outcomes
TNF-α
- Pro-inflammatory mediator with cytolytic and cytostatic effects on tumor cells.
- Linked with coagulation, insulin resistance, and endothelial function (pleiotropic effects)
TNF-α and Immune-Mediated Diseases
- Pro-inflammatory cytokine implicated in rheumatoid arthritis, psoriasis, and certain cardiovascular diseases.
- Anti-TNF therapies (e.g., Humira, Remicade, Enbrel, Simponi Aria, and Cimzia) are widely used for managing TNF-related conditions.
Anti-TNF Therapies
- Treatment strategies mainly for autoimmune diseases
- Various categories of therapies exist, including fully human monoclonal antibodies and fusion proteins
Key Points and Clinical Uses
- Many cytokines have specific roles in disease, but they are not always beneficial
- Cytokine therapeutics are an emerging approach to treat a variety of diseases, but further research is still needed to improve efficacy in clinical applications and find safer delivery methods.
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Description
Test your knowledge on cytokines and their role in the immune system. This quiz covers various aspects such as the definition, functions, and therapeutic applications of cytokines. Assess your understanding of pro-inflammatory cytokines, interleukins, and their effects on immune cells.
