Cytokine Definitions and Functions
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Questions and Answers

Which cytokine is primarily responsible for the survival and proliferation of T cells?

  • IL-4
  • IL-10
  • IL-2 (correct)
  • IFN-g

Which cells are primarily affected by TNF-b according to the roles of Th1 cells?

  • Neutrophils (correct)
  • Eosinophils
  • B cells
  • T cells

What is the biological effect of IL-5 on B cells?

  • Isotype-switching to IgA (correct)
  • Proliferation and activation
  • Inhibition of phagocytosis
  • Differentiation to TH1 class

What is a primary criterion for diagnosing an allergic disease?

<p>Correlation of clinical symptoms with allergen exposure (A)</p> Signup and view all the answers

What is the structure of receptors in the Type II Cytokine Receptor Family?

<p>Dimeric receptors (B)</p> Signup and view all the answers

Which of the following cytokines is involved in TH2 differentiation?

<p>IL-4 (B)</p> Signup and view all the answers

Which of the following laboratory tests specifically measure IgE antibodies related to allergies?

<p>Allergen-specific IgE immunoassay (A)</p> Signup and view all the answers

Which statement accurately describes the intracellular domain of the TNF Receptor Family?

<p>Contains death domains that bind to TRADDs (B)</p> Signup and view all the answers

How does in vitro testing for specific IgE compare to skin testing?

<p>In vitro testing has superior quantitative ability. (C)</p> Signup and view all the answers

What is a characteristic feature of the dimeric or trimeric receptors in the Type I cytokine receptor family?

<p>Has a membrane proximal WSXWS motif (B)</p> Signup and view all the answers

Which statement correctly differentiates between tryptase and histamine?

<p>Tryptase is released from activated mast cells with a longer half-life. (C)</p> Signup and view all the answers

Which cytokine plays a role in the inhibition of macrophage activation according to the roles of Th2 cells?

<p>IL-10 (C)</p> Signup and view all the answers

What characterizes the extracellular domain of G-Protein Coupled Receptors?

<p>It forms chemokine-binding domains within its loops (A)</p> Signup and view all the answers

Which response does INF-g NOT mediate?

<p>Recruitment of neutrophils (D)</p> Signup and view all the answers

What role does the food challenge play in allergic disease diagnosis?

<p>It identifies the specific allergen responsible for symptoms. (B)</p> Signup and view all the answers

Which type of hypersensitivity is primarily dependent on IgE and mast cells?

<p>Type I (B)</p> Signup and view all the answers

Which of the following classes of allergens includes substances commonly found in the environment?

<p>Inhalants (C)</p> Signup and view all the answers

What is the primary function of the immunoglobulin-like receptor family?

<p>Bind to IL-1 and IL-18 (C)</p> Signup and view all the answers

In the context of immune responses, what distinguishes a hypersensitivity reaction from a normal immune reaction?

<p>Hypersensitivity reactions cause tissue damage due to an uncontrolled or inappropriate immune response. (D)</p> Signup and view all the answers

What are the immune mediators primarily involved in Type II hypersensitivity reactions?

<p>IgM and IgG antibodies (D)</p> Signup and view all the answers

What is the primary clinical application of total IgE testing?

<p>To assess the dosage for anti-IgE therapy. (B)</p> Signup and view all the answers

Which of the following pathways does NOT get initiated by the binding of the TNF receptor-associated factors (TRAFs)?

<p>Caspase activation pathway (B)</p> Signup and view all the answers

What is a significant limitation of using total IgE levels in allergy diagnosis?

<p>Elevated total IgE does not confirm specific allergy diagnosis. (B)</p> Signup and view all the answers

What defines the transmembrane domain structure of the Type II Cytokine Receptor Family?

<p>Single-pass structure with hydrophobic residues predominating (B)</p> Signup and view all the answers

What is the primary characteristic of XLA (X-linked agammaglobulinemia)?

<p>B cell deficiency leading to profound hypogammaglobulinemia (D)</p> Signup and view all the answers

Which type of primary immunodeficiency (PID) has the highest prevalence?

<p>B cell (humoral) defects (D)</p> Signup and view all the answers

What role does laboratory testing play in the management of primary immunodeficiencies?

<p>It establishes whether recurrent infections are due to a PID. (C)</p> Signup and view all the answers

How is Selective IgA Deficiency characterized?

<p>B cell deficiency with associated autoimmune disorders (A)</p> Signup and view all the answers

Which of the following is a potential cause of secondary immunodeficiencies?

<p>Surgical procedures and trauma (A)</p> Signup and view all the answers

Which PID is known for its broad and heterogeneous clinical presentation in adults?

<p>CVID (Common Variable Immunodeficiency) (D)</p> Signup and view all the answers

What is a major contributing factor to the occurrence of inhibitory anti-IgA antibodies in Selective IgA Deficiency?

<p>Deletions in specific IgA genes (C)</p> Signup and view all the answers

In the classification of primary immunodeficiencies, which defect accounts for only 5% of cases?

<p>Complement deficiencies (A)</p> Signup and view all the answers

Which IgG subclass deficiency is most commonly associated with impaired polysaccharide responsiveness?

<p>IgG2 deficiency (D)</p> Signup and view all the answers

What is the primary characteristic of Wiskott-Aldrich Syndrome?

<p>Combined B and T cell abnormalities (D)</p> Signup and view all the answers

In DiGeorge Syndrome, which of the following conditions is NOT part of the classic presentation?

<p>Ataxia (C)</p> Signup and view all the answers

What condition is characterized by selective IgM deficiency alongside normal B cell functionality?

<p>Selective IgM deficiency (B)</p> Signup and view all the answers

Which group of individuals is most commonly affected by IgG3 subclass deficiency?

<p>Adults (C)</p> Signup and view all the answers

Which of the following diseases is associated with defective T-cell responses to Candida antigen?

<p>Chronic Mucocutaneous Candidiasis (B)</p> Signup and view all the answers

Which feature is NOT typically associated with Ataxia-Telangiectasia?

<p>Elevated IgM levels (C)</p> Signup and view all the answers

What is a common outcome of IgG subclass deficiency in individuals?

<p>Recurrent upper respiratory infections (D)</p> Signup and view all the answers

What is the primary cause of edema in Hereditary Angioedema?

<p>Dysfunctional C1 esterase inhibitor (A)</p> Signup and view all the answers

Which testing method is used to diagnose Chronic Granulomatous Disease?

<p>Measure superoxide production (A)</p> Signup and view all the answers

In Chediak-Higashi Syndrome, which of the following signs is most commonly associated with the disease?

<p>Enlarged cytoplasmic granules in granulocytes (D)</p> Signup and view all the answers

Which gene mutation is commonly associated with Hyper-IgE Syndrome?

<p>STAT3 gene (B)</p> Signup and view all the answers

What is a key laboratory finding in the diagnosis of DiGeorge syndrome?

<p>Chromosome 22q11.2 deletion (D)</p> Signup and view all the answers

What hormonal level is significantly elevated in patients with Hyper-IgE Syndrome?

<p>Serum IgE (D)</p> Signup and view all the answers

What does the Nitroblue Tetrazolium (NBT) Reduction Test assess in Chronic Granulomatous Disease?

<p>Oxidative metabolism (C)</p> Signup and view all the answers

In terms of genetic testing, which gene mutation is most frequently implicated in Chronic Granulomatous Disease?

<p>gp91phox gene (A)</p> Signup and view all the answers

Flashcards

Type II Cytokine Receptor Structure

Two subunits: a cytokine-binding subunit, and a signaling subunit. Has an extracellular domain with specific cysteine residues, a transmembrane domain similar to type I, and an intracellular domain.

TNF Receptor Structure

The TNF receptor family has a trimeric receptor structure(three parts) with extracellular cytokine-binding domains similar to other receptor types, and intracellular "death domains" that activate signaling pathways.

G-protein Coupled Receptor structure

A single polypeptide spanning the cell seven times, with extracellular loops for binding and intracellular loops for signaling through G-proteins.

Hypersensitivity Reaction

An immune response causing tissue damage, either uncontrolled or targeting inappropriate antigens.

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Type I Hypersensitivity

A rapid hypersensitivity reaction mediated by IgE and mast cells, an immediate response.

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Type II Hypersensitivity

Antibody-mediated hypersensitivity involving IgM and IgG antibodies.

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Type III Hypersensitivity

Immune complex-mediated hypersensitivity. Antigens and antibodies form complexes that deposit and cause inflammation.

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Type IV Hypersensitivity

T-cell mediated hypersensitivity involving CD4+ and CD8+ T cells that trigger cell-mediated tissue damage.

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Th1 cell role in immune system

Th1 cells produce cytokines like IFN-γ, activating B cells for IgG production, and stimulating T cells for isotype switching; they also recruit neutrophils for phagocytosis.

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Th2 cell role in immune system

Th2 cells regulate immune response by producing cytokines like IL-4, IL-5, IL-10, and TGF-β to activate B cells, macrophages, and eosinophils in different ways; promoting or inhibiting reactions.

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Cytokine function: IL-2

Stimulates T cell proliferation and survival, as well as activating NK cells and B cells.

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Cytokine function: IFN-γ

Induces B cell differentiation into Th1 cells and activates isotype switching to IgG. Important in cell mediated immunity.

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Cytokine function: TNF-β

Promotes neutrophil recruitment and activation of phagocytosis for immune defense

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Cytokine function: IL-4

Promotes differentiation of T cells towards Th2 cells and triggers an isotype switch of B cells to IgE.

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Cytokine function: IL-5

Stimulates the proliferation and activation of B cells and specifically promotes isotype switching to IgA antibodies

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IL-1, IL-18 receptor Family

Membrane-bound receptors with immunoglobulin-like domains, involved in intracellular signaling pathways that lead to activation and immune response.

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Allergic Disease Diagnostic Criteria

Diagnosis requires a compatible clinical history, identification of allergen-specific IgE, and demonstration of a clinical response after allergen exposure.

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Allergen Classes

Allergens are broadly categorized as inhalants, foods, drugs, insects, and occupational exposures.

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Total IgE Testing

Measures the overall level of IgE in the blood, used to detect and monitor certain allergic diseases and conditions, like allergic bronchopulmonary aspergillosis and hyper IgE syndrome.

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Allergen-specific IgE

Identifies IgE antibodies targeting specific allergens, crucial for diagnosing allergies to inhalants, foods, venom, and drugs.

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In Vivo Testing (Skin Testing)

Direct skin exposure to potential allergens. A method for identifying allergen-specific IgE, used for detecting allergies by looking for allergic reactions on the skin

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In Vitro IgE Testing

Laboratory testing of blood samples that identify allergen specific IgE. Measures allergen specific IgE in the blood, for testing allergies that cannot be done through skin tests.

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Histamine Testing

Measures histamine levels, a chemical released during allergic reactions, identifying the amount in bodily fluids, typically useful in acute allergic reactions.

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Tryptase Testing

Measures tryptase, an enzyme from mast cells, used to assess mast cell activation, which is important for inflammation and acute reactions but has a longer half-life than histamine.

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Primary Immunodeficiencies (PIDs) Classification

Broad categories of PIDs encompassing B cell, T cell, phagocytic, and complement defects.

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Secondary Immunodeficiencies Causes

Acquired immunodeficiencies caused by various factors like lymphoproliferative disorders, infections, surgeries, medications, and metabolic diseases.

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X-linked agammaglobulinemia (XLA)

A B cell deficiency caused by a defective Bruton's tyrosine kinase (Btk) gene, resulting in severely reduced/absent B cells and antibodies.

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Common Variable Immunodeficiency (CVID)

Common adult-onset B cell deficiency with a diverse presentation, often difficult to diagnose, with familial inheritance.

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Selective IgA Deficiency

A B cell deficiency characterized by low IgA levels (< 7 mg/dL), often causing recurrent infections and GI problems.

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Phagocytic Deficiencies

Immune system defects involving cells that engulf and destroy pathogens like PMNs (neutrophils) and monocytes.

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Complement Deficiencies

Immunodeficiency related to the complement system, which helps antibodies mark pathogens for destruction.

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Laboratory Testing in PIDs

Essential for diagnosing and managing PIDs, identifying specific defects, and evaluating associated complications, crucial for early intervention, and genetic counseling in families.

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IgG Subclass Deficiency

A B cell deficiency where specific types of IgG antibodies are low, even though total IgG may be normal. This leads to increased susceptibility to infections.

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DiGeorge Syndrome

A T cell deficiency caused by a genetic deletion, leading to a variety of immune and physical issues, and affects the thymus.

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Chronic Mucocutaneous Candidiasis (CMC)

A T cell deficiency that causes recurring yeast infections, particularly on the skin and mucous membranes.

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Wiskott-Aldrich Syndrome (WAS)

A combined B and T cell disorder impacting blood platelets, skin (eczema), and increasing risk of infection..

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Ataxia-Telangiectasia

A combined B and T cell deficiency, causing neurological abnormalities, vascular defects, and high cancer risk.

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22q11.2 Deletion

A genetic deletion associated with DiGeorge syndrome affecting numerous body systems, including immunologic functions.

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Immune Deficiency

A group of conditions characterized by an impaired ability to fight off infections due to the malfunctioning of the immune system.

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Hereditary Angioedema

A rare genetic disorder characterized by recurrent episodes of swelling, particularly in the face, extremities, and airway, due to a deficiency in the C1 esterase inhibitor protein.

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C1 Esterase Inhibitor

A protein that inhibits the activation of the complement system, specifically the C1 enzyme, preventing excessive inflammation.

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Chronic Granulomatous Disease (CGD)

A rare genetic disorder characterized by recurrent and severe infections caused by a defect in the NADPH oxidase enzyme, leading to impaired phagocyte function, resulting in an inability to kill certain bacteria.

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NADPH Oxidase

An enzyme that produces reactive oxygen species (ROS) in phagocytes, crucial for killing bacteria and other pathogens.

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Chediak-Higashi Syndrome

A rare, autosomal recessive disorder characterized by enlarged lysosomes in phagocytes, leading to impaired immune function, albinism, and susceptibility to infections.

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Hyper-IgE Syndrome (Job's Syndrome)

A rare genetic disorder characterized by recurrent infections due to defects in Th17 cells, leading to very high IgE levels, eczema, and other immune dysfunctions.

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Nitroblue Tetrazolium (NBT) Reduction Test

A diagnostic test for Chronic Granulomatous Disease, where the ability of neutrophils to reduce NBT is measured, indicating their capacity to produce superoxide radicals.

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Dihydrorhodamine (DHR) 123 Oxidation Test

A diagnostic test for Chronic Granulomatous Disease (CGD), measuring the ability of phagocytes to oxidize DHR 123, reflecting the functional capacity of the NADPH oxidase complex.

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Study Notes

Cytokine Definitions and Characteristics

  • Cytokines are soluble polypeptides produced by cells in response to infection or antigens.
  • They are crucial for cell-cell communication within the immune system.
  • Cytokine expression is tightly regulated.
  • Cytokines can act locally (autocrine, paracrine) or systemically (endocrine).
  • Cytokines can be pleiotropic (affect multiple cells with various functions) or redundant (multiple cytokines with similar functions).
  • Cytokine actions can be synergistic (combined effect greater than individual effects) or antagonistic (opposite effects).
  • Cytokines are not pre-formed and are rapidly secreted after being produced.
  • Cytokines have short half-lives.
  • Their ultimate effect is the transcription and translation of new proteins.

Cytokine Classes and Functions

  • Interleukins (ILs): Communicate between white blood cells (WBCs)
  • Interferons (IFNs): Broad pro-inflammatory cytokines
  • Tumor necrosis factor (TNF): Mediates immune response to bacteria
  • Colony-stimulating factors (CSFs): Mediate survival and differentiation of immune precursor cells
  • Transforming growth factors (TGFs): Inhibit proliferation and activation of WBCs
  • Chemokines: Regulate WBC migration

Cytokine Functions (Specific examples)

  • Th1 cytokines:
    • IL-2: Proliferation and survival of T cells and NK cells, proliferation of B cells
    • IFN-γ: Differentiation to TH1 class, isotype-switching to IgG, recruitment and activation of phagocytosis
    • TNF-β: Recruitment and activation of neutrophils

Cytokine and Chemokine Receptor Families

  • Immunoglobulin-like receptor family (IL-1, IL-18):
    • Extracellular immunoglobulin-like domain
    • Single-pass transmembrane domain
    • Intracellular domain with a Toll/IL-1 receptor (TIR) motif
  • Type I cytokine receptor family (IL-2, IL-5):
    • Dimeric or trimeric receptors with cytokine-binding and signaling subunits
    • Extracellular domain with conserved cysteine residue pairs
    • Transmembrane domain similar to immunoglobulin-like receptors
    • Intracellular domain
  • Type II cytokine receptor family (IFN-α, IL-10):
    • Dimeric receptors with cytokine-binding and signaling subunits
    • Similar extracellular and transmembrane domains, composed of hydrophobic residues

Cytokines Important to Innate Immunity, Adaptive Immunity, and Hematopoiesis

a) Innate immunity: -Major cell source: macrophages -Primary function: mediate inflammation. -Cellular target and biological effects:

b) Adaptive immunity: -Major cell source: T cells -Primary function: regulate lymphocyte proliferation and differentiation and activate effector cells. -Cellular target and biological effects:

c) Hematopoiesis: -Major cell source: BM stromal cells, fibroblasts, etc. -Primary function: promote development of mature leukocytes from myeloid and lymphoid progenitor cells. -Cellular target and biological effects:

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Description

This quiz explores the definitions, characteristics, and classes of cytokines, vital components of the immune system. You will learn about their roles, regulation, and the distinctions between different cytokine types such as interleukins and interferons.

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