BMS150 - Wk 3

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Questions and Answers

Which cytokines are essential for class switching to IgG subtypes, IgA, and IgE?

IL-1 and IFN-gamma

IL-6 and IL-8

IL-4 and IL-13 (correct)

IL-7 and IL-10

What is a key structural difference between plasma cells and mature B-cells?

Mature B-cells have a larger nucleus compared to plasma cells.

Mature B-cells have greater endoplasmic reticulum than plasma cells.

Plasma cells have a higher number of membrane-bound antibodies.

Plasma cells contain more cytoplasmic organelles for antibody production. (correct)

What role do memory B cells play in the immune response?

They store antibodies for long-term use.

They only function during the initial infection.

They promote the production of new antibodies.

They enhance the secondary response by recalling previously encountered antigens. (correct)

Which of the following correctly describes the antibody class IgE?

IgE plays a crucial role in allergic reactions and defense against parasites. Signup and view all the answers

Which mechanism of action involves antibodies coating pathogens to enhance their uptake by phagocytes?

Opsonization Signup and view all the answers

What role does CD21 play in B-cell activation?

It binds to an antigen bound to the complement component C3d. Signup and view all the answers

What happens to the antigen after it binds to the B-cell receptor (BCR)?

It is presented to T-helper cells. Signup and view all the answers

Which molecules does a B-cell express more of after presenting its antigen?

Co-stimulatory molecules Signup and view all the answers

Which type of T-helper cell does a B-cell present its antigen to within germinal centers?

TH2 cells Signup and view all the answers

What is the primary function of CD19 in B-cell activation?

To enhance the signal transduction process. Signup and view all the answers

What occurs immediately after mast cells are recruited into tissue during an acute response?

Increased expression of Fc receptors for IgE Signup and view all the answers

Which cytokines are released later in response to mast cell activation, depending on the stimulus?

IL-4, TGF-β, IL-6, and IL-18 Signup and view all the answers

What happens to a mast cell when an antigen binds to IgE on its membrane?

It triggers degranulation. Signup and view all the answers

When mast cells are repeatedly degranulated, what chronic condition can develop?

Chronic Type II inflammation Signup and view all the answers

What role do mast cell factors play in tissue remodeling during an immune response?

They release growth factors for repair or fibrosis Signup and view all the answers

Which mediators are pre-synthesized and released instantly during mast cell activation?

Proteases and heparin Signup and view all the answers

What function does histamine serve when released by mast cells?

Increases permeability of small vessels. Signup and view all the answers

What is a potential outcome if mast cell activation is sufficiently strong?

Mast cells can present antigens via HLA-2 Signup and view all the answers

Which of the following is NOT a function of lipid mediators released by mast cells?

Degradation of collagen Signup and view all the answers

What type of receptors do mast cells express that can also trigger degranulation?

Complement receptors and TLRs Signup and view all the answers

What is a defining characteristic of chronic inflammation?

It includes simultaneous inflammation and tissue repair. Signup and view all the answers

Which of the following conditions is associated with chronic inflammation?

Alzheimer disease Signup and view all the answers

What is the consequence of visceral obesity in relation to chronic inflammation?

It serves as a risk factor for multiple diseases. Signup and view all the answers

What consequence does excessive lipid build-up in adipocytes primarily lead to?

Decreased insulin sensitivity Signup and view all the answers

Which cells predominantly contribute to chronic inflammation?

Macrophages and lymphocytes Signup and view all the answers

What role do alternatively activated macrophages play in inflammation?

They aid in tissue repair and resolution of inflammation. Signup and view all the answers

In autoimmune diseases, which immune response is primarily implicated?

Adaptive immune response Signup and view all the answers

Which of the following best describes granulomatous inflammation?

It involves the formation of granulomas as part of a chronic inflammatory response. Signup and view all the answers

What is a primary effect of chronic inflammation on tissues?

Formation of fibrotic tissue Signup and view all the answers

What type of exposure can lead to chronic inflammation other than persistent infections?

Prolonged exposure to toxins Signup and view all the answers

What is the characteristic feature of Type I hypersensitivity reactions?

IgE-mediated immune response Signup and view all the answers

Which type of hypersensitivity is primarily associated with the formation of immune complexes?

Type III hypersensitivity Signup and view all the answers

In the context of hypersensitivity reactions, what does the early-phase response in Type I refer to?

Mast cell degranulation and histamine release Signup and view all the answers

Which of the following best describes Type II hypersensitivity reactions?

Caused by IgG and IgM antibodies binding to cell surface antigens Signup and view all the answers

Which classification of hypersensitivity reactions is referred to as 'delayed reactions'?

Type IV hypersensitivity Signup and view all the answers

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

Type I Hypersensitivity:
- IgE-mediated and also called immediate hypersensitivity.
- Involves rapid reactions, often resulting in conditions like anaphylaxis, asthma, and allergic rhinitis.
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.
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.
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.