Questions and Answers
Which cytokines are essential for class switching to IgG subtypes, IgA, and IgE?
What is a key structural difference between plasma cells and mature B-cells?
What role do memory B cells play in the immune response?
Which of the following correctly describes the antibody class IgE?
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Which mechanism of action involves antibodies coating pathogens to enhance their uptake by phagocytes?
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What role does CD21 play in B-cell activation?
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What happens to the antigen after it binds to the B-cell receptor (BCR)?
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Which molecules does a B-cell express more of after presenting its antigen?
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Which type of T-helper cell does a B-cell present its antigen to within germinal centers?
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What is the primary function of CD19 in B-cell activation?
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What occurs immediately after mast cells are recruited into tissue during an acute response?
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Which cytokines are released later in response to mast cell activation, depending on the stimulus?
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What happens to a mast cell when an antigen binds to IgE on its membrane?
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When mast cells are repeatedly degranulated, what chronic condition can develop?
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What role do mast cell factors play in tissue remodeling during an immune response?
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Which mediators are pre-synthesized and released instantly during mast cell activation?
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What function does histamine serve when released by mast cells?
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What is a potential outcome if mast cell activation is sufficiently strong?
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Which of the following is NOT a function of lipid mediators released by mast cells?
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What type of receptors do mast cells express that can also trigger degranulation?
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What is a defining characteristic of chronic inflammation?
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Which of the following conditions is associated with chronic inflammation?
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What is the consequence of visceral obesity in relation to chronic inflammation?
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What consequence does excessive lipid build-up in adipocytes primarily lead to?
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Which cells predominantly contribute to chronic inflammation?
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What role do alternatively activated macrophages play in inflammation?
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In autoimmune diseases, which immune response is primarily implicated?
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Which of the following best describes granulomatous inflammation?
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What is a primary effect of chronic inflammation on tissues?
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What type of exposure can lead to chronic inflammation other than persistent infections?
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What is the characteristic feature of Type I hypersensitivity reactions?
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Which type of hypersensitivity is primarily associated with the formation of immune complexes?
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In the context of hypersensitivity reactions, what does the early-phase response in Type I refer to?
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Which of the following best describes Type II hypersensitivity reactions?
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Which classification of hypersensitivity reactions is referred to as 'delayed reactions'?
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Study Notes
Cytokines for Class Switching
- TH1 cells secrete IFN-γ, inducing class switching to IgG subtypes.
- TGF-β stimulates class switching to IgA.
- TH2 cells release IL-4 and IL-5, promoting class switching to IgE while also driving significant IgM production.
Plasma Cells vs. Mature B-cells
- Plasma cells are larger than mature B-cells due to increased rough endoplasmic reticulum, which supports higher antibody production.
- Plasma cells primarily secrete antibodies, while mature B-cells express B-cell receptors (BCRs) on their surface for antigen recognition.
Memory B Cell Role
- Memory B cells allow for rapid and robust secondary immune responses upon re-exposure to antigens.
- They are long-lived, enabling quicker antibody production and higher affinity antibodies through previous affinity maturation.
Antibody Antimicrobial Mechanisms
- ADCC (Antibody-Dependent Cell-mediated Cytotoxicity): Antibodies bind to infected cells, attracting immune cells to destroy these targets.
- Opsonization: Antibodies coat pathogens, enhancing their uptake and destruction by phagocytes.
- Agglutination: Antibodies clump pathogens together, making them easier for immune cells to eliminate.
- Neutralization: Antibodies block pathogen entry into cells or inactivate toxins.
- Complement Activation/Cell Lysis: Antibodies trigger the complement system, leading to the formation of pores in pathogen membranes and cell lysis.
- Degranulation: Antibodies facilitate the release of granules from immune cells, contributing to inflammation and pathogen destruction.
Functions of Antibody Classes
- IgA: Provides mucosal immunity, primarily found in secretions (saliva, tears).
- IgD: Functions in B-cell activation; involved in respiratory tract secretions, present in low quantities.
- IgE: Mediates allergic responses; binds to allergens and triggers degranulation of mast cells and eosinophils.
- IgG: Most abundant antibody; provides long-term immunity and neutralizes pathogens.
- IgM: First antibody produced during the primary immune response; effective in agglutination and activating the complement system.
B-Cell Development Overview
- B cells originate from hematopoietic stem cells, progressing to common lymphoid progenitors under the influence of IL-7.
- B cells migrate into circulation as immature, naïve B cells, ready to present antigens.
B-Cell Activation Process
- Antigen binding to BCR is aided by co-receptors CD21, CD19, initiating survival and proliferation signals.
- Activated B cells upregulate co-stimulatory molecules (CD80/86, ICOSL, CD40), facilitating interaction with T helper cells (Tfh).
- Tfh cells produce cytokines, such as IL-21 and IL-4, driving B cell proliferation and antibody production.
Somatic Hypermutation and Class Switching
- Somatic hypermutation occurs in germinal centers, where B cells undergo high mutation rates in their antibody variable regions, enhancing affinity for specific antigens.
- B cells either continue with high-affinity antibodies or undergo apoptosis if low-affinity or self-reactive.
B-Cell Signaling Signals
- Successful B-cell activation requires antigen binding, co-stimulation from Tfh cells, and cytokine support, leading to class switching and affinity maturation.
Mast Cells – Function and Mediators
- Mast cells express Fc receptors for IgE, allowing binding of circulating IgE and serving as antigen-specific receptors.
- Antigen binding to IgE on mast cells triggers degranulation, releasing granule contents.
- Activation of mast cells can also occur via pattern recognition receptors (PRRs) like TLRs and NLRs, as well as complement receptors (C3a, C5a).
- Granule contents can be released instantly; lipid mediators (prostaglandins, leukotrienes) are synthesized as needed.
Mast Cells – Early Mediators
- Histamine: increases small vessel permeability, mucous secretion, vasodilation, and smooth muscle contraction.
- Heparin: involved in platelet activation and coagulation.
- Chemotactic Factors: attract eosinophils and neutrophils, as well as monocytes during repair processes.
- Prostaglandins and Leukotrienes: facilitate smooth muscle contraction and increased vascular permeability.
- Proteases: contribute to inflammation through degradation of type IV collagen and activation of coagulation.
- Cytokines: immediate release of IL-4 and TNF-α; later cytokines depend on the stimulus.
Mast Cells – Acute Response Integration
- Associated with Type I hypersensitivity responses, implicating immediate allergic reactions.
Organization of Mast Cell Activity
- Mast cells are recruited into tissues and become sensitized through increased expression of Fc receptors and granule production.
- Degranulation leads to acute responses, which manifest in conditions like atopic dermatitis and allergic rhinitis.
- Possible outcomes of repeated activation include tissue resolution, fibrosis, or chronic inflammation.
Epithelial Cells and Barrier Immunity – The Skin
- Keratinocytes form a waterproof barrier to prevent antigen and microbe entry, while secreting antimicrobial proteins like psoriasin and cathelicidins.
- Langerhans cells, found in the epidermis, sample the environment, present antigens via HLA-2, and migrate to lymph nodes.
The Skin – Immunological Aspects
- More lymphocytes, including all three types of innate lymphoid cells (ILCs) and resident macrophages, are found in the dermis.
- Filaggrins and tight junctions are crucial in preventing pathogen penetration into deeper skin layers.
Applied Barrier Immunology – Atopic Dermatitis
- Some atopic dermatitis cases may trigger Th17 responses instead of Th2, characterized by hyperkeratosis without increased IgE.
- Chronic Th2 responses can coexist with Th17 responses, complicating understanding.
- Langerhans cells facilitate Th2 polarization through interactions with naïve T cells, influenced by cytokines like TSLP.
Itch Mechanism in Atopic Dermatitis
- Itching exacerbates skin barrier damage, promoting moisture loss and increasing neuronal sprouting of pain/itch fibers.
- Histamine, TSLP, and Th2 cytokines contribute to the sensation of itch.
Upper Respiratory Tract Infection – Influenza
- Influenza binds respiratory epithelial cells and is endocytosed, initiating infection.
- Epithelial and dendritic cells detect influenza via TLR7 and RIG-like receptors, activating ILC1 and releasing pro-inflammatory cytokines.
- The early immune response includes NK cells targeting infected epithelial cells.
- A later response involves macrophage activation and Th1 polarization, leading to further immune activation and CD8+ T cell recruitment.
Type 1 Inflammation from Influenza Infection
- Type 1 inflammation expresses IL-23, promoting activation of ILC3 and Th17 cells, contributing to antimicrobial peptide secretion and neutrophil recruitment.
Chronic Inflammation Overview
- Chronic inflammation lasts for weeks to years, characterized by ongoing inflammation, tissue injury, and repair.
- It can arise from unresolved acute inflammation, autoimmune diseases, or sustained damage to tissues or organs.
Chronic Inflammation and Pathologies
- Common conditions associated with chronic inflammation include Alzheimer’s disease, atherosclerosis, obesity, and metabolic syndrome.
- Visceral obesity increases risks for diseases like type II diabetes, atherosclerosis, and cancer due to chronic inflammatory cytokine production.
Mechanisms of Chronic Inflammation
- Excessive lipid accumulation in adipocytes leads to reactive oxygen species (ROS) production and cytokine release (e.g., IL-6, TNF-alpha), contributing to insulin resistance.
- Chronic infections result in macrophage and lymphocyte predominance, leading to tissue replacement with fibrotic aspects that impair normal function.
Macrophage Role in Inflammation
- Macrophages transition from monocytes and can become classically activated (pro-inflammatory) or alternatively activated (repair-focused).
- Classically activated macrophages promote inflammation and destroy pathogens, while alternatively activated macrophages assist in tissue repair and regeneration.
Cytokine Roles
- Cytokines such as IL-1 and TNF-alpha are secreted by macrophages, enhancing inflammation and recruiting other immune cells.
- Macrophages also produce chemotactic factors guiding leukocyte migration to sites of injury.
Wound Healing Phases
- Initial hemostasis involves platelet activation, coagulation, and controlled blood flow to begin tissue repair through inflammation, proliferation, and remodeling.
Granuloma Formation
- Granulomas form as an immune response to difficult-to-eradicate pathogens or substances, creating a localized area of chronic inflammation.
- Such aggregates consist of macrophages, which can transform into epitheloid cells or giant cells, surrounded by lymphocytes.
Immune System Interaction
- Granuloma formation involves a cell-mediated immune response (Type IV hypersensitivity), recruiting macrophages and T-cells, leading to further inflammation.
- Conditions leading to granuloma formation include tuberculosis, leprosy, syphilis, sarcoidosis, and Crohn’s disease.
Fibrosis in Chronic Inflammation
- Persistent inflammation leads to fibrosis, replacing normal tissue with scar tissue, and can occur due to immune-mediated diseases or prolonged exposure to toxic agents.
Key Takeaways
- Understanding the mechanisms, consequences, and healing processes involved in chronic inflammation is crucial for addressing various diseases and injuries. Inflammation plays a complex role in both pathology and healing, requiring a balance between pro-inflammatory and anti-inflammatory responses for effective tissue repair.
Hypersensitivity Reactions Overview
- Hypersensitivity reactions are excessive or pathogenic immune responses to foreign or self-antigens.
- Classifications established in 1963 categorize hypersensitivity into four major types: Type I, Type II, Type III, and Type IV.
Types of Hypersensitivity
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Type I Hypersensitivity:
- IgE-mediated and also called immediate hypersensitivity.
- Involves rapid reactions, often resulting in conditions like anaphylaxis, asthma, and allergic rhinitis.
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Type II Hypersensitivity:
- Antibody-mediated cytotoxic responses, including IgG and IgM involvement.
- Associated with disorders causing immune destruction of RBCs, rheumatoid arthritis, and Graves' disease.
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Type III Hypersensitivity:
- Characterized by immune complex formation that leads to inflammation, often in blood vessels and joints.
- Conditions include lupus and certain vasculitis types.
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Type IV Hypersensitivity:
- T-cell mediated reactions with delayed responses.
- Different subtypes (IVa, IVb, IVc, IVd) involve varying Th cell responses and associated disorders like Type 1 diabetes, contact dermatitis, and rheumatoid arthritis.
Time Course of Symptoms
- Type I: Rapid onset; symptoms develop in minutes.
- Type II, III, IV: Subacute onset; symptoms may develop over days to weeks.
- Chronic Disorders: Type II to IV often have prolonged symptoms lasting months to years.
Type I Hypersensitivity Mechanisms
- Priming of mast cells with IgE and Th2 cytokines leads to rapid degranulation, causing immediate responses like edema and bronchoconstriction.
- Late-phase responses involve recruitment of eosinophils, resulting in prolonged inflammation and potential for severe complications like anaphylaxis.
Type II Hypersensitivity Mechanisms
- Antibodies bind to cell or matrix components, leading to inflammation and cell destruction.
- Mechanisms include complement activation, antibody-dependent cytotoxicity, and receptor activation causing idiosyncratic effects.
Type III Hypersensitivity Mechanisms
- Involves antigen-antibody complexes that induce inflammation at deposition sites, primarily in blood vessels or synovial membranes.
- Damage typically manifests as fibrinoid necrosis and can lead to occlusive vasculitis.
Type IV Hypersensitivity Characteristics
- Mechanisms vary significantly across disorders, with involvement of various T helper cell subtypes (Th1, Th2, Th17).
- Reactions develop over extended periods, except for acute cases triggered by toxins or contact allergens.
Importance of Antibodies and T-cells
- Type I heavily relies on IgE antibodies, Type II and III on IgG/IgM, while Type IV is primarily mediated by T-cells with less antibody involvement.
- The understanding of Th cell subtypes enhances clarity in pathology associated with hypersensitivity reactions.
Summary
- Hypersensitivity reactions are complex immune responses encompassing a variety of conditions that can be categorized by their mechanisms, timing, and specific immune components involved.
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Description
Explore the key cytokines involved in inducing class switching to different IgG subtypes, IgA, and IgE. Understand the structural and functional differences between plasma cells and mature B-cells, and learn about the important role memory B cells play in enhancing the secondary response to antigens. This quiz covers fundamental concepts in antibody mechanisms and B-cell immunology.
