Podcast
Questions and Answers
What is the primary mechanism used by antibodies in Type II hypersensitivity reactions to mediate cell damage?
What is the primary mechanism used by antibodies in Type II hypersensitivity reactions to mediate cell damage?
- Activation of the alternative complement pathway
- Antibody-dependent cellular cytotoxicity (ADCC) (correct)
- Direct cell apoptosis by T cells
- Phagocytosis by neutrophils
Which clinical example is associated with Type III hypersensitivity reactions?
Which clinical example is associated with Type III hypersensitivity reactions?
- Transfusion reactions
- Arthus reactions (correct)
- Erythroblastosis fetalis
- Contact dermatitis
What laboratory test is commonly used to diagnose Type IV hypersensitivity reactions?
What laboratory test is commonly used to diagnose Type IV hypersensitivity reactions?
- Patch test (correct)
- Complete blood count
- Coombs test
- ELISA
What is a key feature of granuloma formation in tuberculosis?
What is a key feature of granuloma formation in tuberculosis?
Which method is commonly used for tuberculosis skin testing?
Which method is commonly used for tuberculosis skin testing?
What is the primary immune response responsible for the formation of tubercules in tuberculosis infections?
What is the primary immune response responsible for the formation of tubercules in tuberculosis infections?
Which of the following accurately describes tubercules?
Which of the following accurately describes tubercules?
Which clinical manifestation is most indicative of primary pulmonary tuberculosis?
Which clinical manifestation is most indicative of primary pulmonary tuberculosis?
What is the primary function of macrophages in the context of tuberculosis infection?
What is the primary function of macrophages in the context of tuberculosis infection?
Which feature is NOT associated with Type IV hypersensitivity reactions?
Which feature is NOT associated with Type IV hypersensitivity reactions?
In the context of tuberculosis, what is the importance of granuloma formation?
In the context of tuberculosis, what is the importance of granuloma formation?
Which diagnostic method is commonly used for detecting tuberculosis?
Which diagnostic method is commonly used for detecting tuberculosis?
What does a chest x-ray reveal in a patient with active tuberculosis?
What does a chest x-ray reveal in a patient with active tuberculosis?
Which statement about Type IV hypersensitivity is true?
Which statement about Type IV hypersensitivity is true?
What is the significance of a histologic section showing tubercules in lung tissue?
What is the significance of a histologic section showing tubercules in lung tissue?
What does the Mantoux test specifically measure in the diagnosis of tuberculosis?
What does the Mantoux test specifically measure in the diagnosis of tuberculosis?
What is the typical time frame for the reaction to develop in contact dermatitis after exposure to an allergen?
What is the typical time frame for the reaction to develop in contact dermatitis after exposure to an allergen?
Which of the following is a feature of the IGRA test used for TB diagnosis?
Which of the following is a feature of the IGRA test used for TB diagnosis?
In granuloma formation associated with TB, what type of immune cells are primarily present?
In granuloma formation associated with TB, what type of immune cells are primarily present?
Which method is primarily used to diagnose Type IV hypersensitivity like contact dermatitis?
Which method is primarily used to diagnose Type IV hypersensitivity like contact dermatitis?
What is the time frame to observe skin induration after the Mantoux test injection?
What is the time frame to observe skin induration after the Mantoux test injection?
What defines a positive reaction in a patch test for contact dermatitis?
What defines a positive reaction in a patch test for contact dermatitis?
What is a common sensitizing allergen associated with contact dermatitis?
What is a common sensitizing allergen associated with contact dermatitis?
Which statement correctly describes the result of a positive tuberculin skin test?
Which statement correctly describes the result of a positive tuberculin skin test?
What type of hypersensitivity does the IGRA test primarily fall under?
What type of hypersensitivity does the IGRA test primarily fall under?
Which of the following substances is NOT typically associated with contact dermatitis?
Which of the following substances is NOT typically associated with contact dermatitis?
What type of hypersensitivity is primarily associated with contact dermatitis?
What type of hypersensitivity is primarily associated with contact dermatitis?
Which immune response is predominantly involved in the development of granulomas in tuberculosis infection?
Which immune response is predominantly involved in the development of granulomas in tuberculosis infection?
What is the primary component detected by the QuantiFERON-TB Gold assay?
What is the primary component detected by the QuantiFERON-TB Gold assay?
How long should the allergen-impregnated material be left on the skin during a patch test?
How long should the allergen-impregnated material be left on the skin during a patch test?
What type of skin reaction is characterized by vesicles at the site of contact in contact dermatitis?
What type of skin reaction is characterized by vesicles at the site of contact in contact dermatitis?
Which of these is a typical feature of Type IV hypersensitivity reactions?
Which of these is a typical feature of Type IV hypersensitivity reactions?
What is the role of haptens in causing contact dermatitis?
What is the role of haptens in causing contact dermatitis?
What is the primary characteristic of type III hypersensitivity?
What is the primary characteristic of type III hypersensitivity?
Which of the following is NOT commonly a treatment for type III hypersensitivity reactions?
Which of the following is NOT commonly a treatment for type III hypersensitivity reactions?
What is a common feature of type IV hypersensitivity reactions?
What is a common feature of type IV hypersensitivity reactions?
During the sensitization phase of type IV hypersensitivity, which cells primarily become activated?
During the sensitization phase of type IV hypersensitivity, which cells primarily become activated?
What cytokine is most often associated with the recruitment of macrophages in type IV hypersensitivity reactions?
What cytokine is most often associated with the recruitment of macrophages in type IV hypersensitivity reactions?
Which cellular components contribute to tissue destruction in the effector phase of type IV hypersensitivity?
Which cellular components contribute to tissue destruction in the effector phase of type IV hypersensitivity?
Granuloma formation in tuberculosis is primarily a result of prolonged activation of which immune cells?
Granuloma formation in tuberculosis is primarily a result of prolonged activation of which immune cells?
What is a common method for diagnosing tuberculosis?
What is a common method for diagnosing tuberculosis?
Which of the following components is typically present in the hapten-carrier complex in type IV hypersensitivity?
Which of the following components is typically present in the hapten-carrier complex in type IV hypersensitivity?
What immune response does the standard TB test assess?
What immune response does the standard TB test assess?
What type of hypersensitivity is demonstrated by the localized reaction observed in the 6-month-old after a DTaP booster?
What type of hypersensitivity is demonstrated by the localized reaction observed in the 6-month-old after a DTaP booster?
Is it true that food allergies cannot develop in patients with selective IgA deficiency?
Is it true that food allergies cannot develop in patients with selective IgA deficiency?
Which cytokine would be most effective at reducing the severity of poison ivy reactions?
Which cytokine would be most effective at reducing the severity of poison ivy reactions?
What characteristic feature is associated with Type III hypersensitivity reactions?
What characteristic feature is associated with Type III hypersensitivity reactions?
Which component is primarily responsible for the T cell-mediated response in tuberculosis infections?
Which component is primarily responsible for the T cell-mediated response in tuberculosis infections?
In the context of hypersensitivity reactions, which type is primarily mediated by IgE antibodies?
In the context of hypersensitivity reactions, which type is primarily mediated by IgE antibodies?
In a local reaction such as an Arthus reaction, what immune mechanism is primarily involved?
In a local reaction such as an Arthus reaction, what immune mechanism is primarily involved?
What is a common outcome of excessive TNF-α release in hypersensitivity reactions?
What is a common outcome of excessive TNF-α release in hypersensitivity reactions?
What role do plasma cells play in the immune response?
What role do plasma cells play in the immune response?
Which condition is associated with elevated serum IgE levels?
Which condition is associated with elevated serum IgE levels?
Which therapy is essential for treating systemic anaphylaxis but generally not for other Type I hypersensitivities?
Which therapy is essential for treating systemic anaphylaxis but generally not for other Type I hypersensitivities?
Which type of hypersensitivity reaction may lead to dermatitis?
Which type of hypersensitivity reaction may lead to dermatitis?
What is a common feature of Type II and Type III hypersensitivity reactions?
What is a common feature of Type II and Type III hypersensitivity reactions?
Which of the following best describes the immediate phase of a Type I hypersensitivity reaction?
Which of the following best describes the immediate phase of a Type I hypersensitivity reaction?
Which antibody isotype would likely be elevated in a patient experiencing allergic asthma?
Which antibody isotype would likely be elevated in a patient experiencing allergic asthma?
Drug-induced hemolytic anemia is an example of which type of hypersensitivity reaction?
Drug-induced hemolytic anemia is an example of which type of hypersensitivity reaction?
What condition involves the deposition of immune complexes leading to tissue damage?
What condition involves the deposition of immune complexes leading to tissue damage?
Which cells primarily mediate allergic reactions involving IgE production?
Which cells primarily mediate allergic reactions involving IgE production?
What type of hypersensitivity reaction is primarily associated with tissue damage initiated by the deposition of immune complexes?
What type of hypersensitivity reaction is primarily associated with tissue damage initiated by the deposition of immune complexes?
Study Notes
Type IV Hypersensitivity Reactions
- Mediated by TH1 cells (also known as TDTH cells), macrophages, and sometimes CTLs
- Allergen is commonly a microbial component, or a chemical, metal, or drug that complexes with proteins in the skin = hapten-carrier complex
- Initial exposure is often through direct contact with the allergen
- The reaction takes 24-72 hours to develop
- Two distinct phases:
- Sensitization phase: first exposure to the allergen leads to a primary immune response and development of memory T cells
- Effector phase: re-exposure to the allergen leads to activation of memory TH1 cells
Sensitization Phase
- Initial exposure to allergen is commonly by contact; processing and presentation of hapten-carrier complex by APCs
- Common allergens include metals, plastic/rubber, chemicals, soaps, herbicides, some infectious organisms…
- Activation and differentiation of helper T cells into TH1 cells and resulting in development of memory (sensitized) TH1 cells
- Can also involve activation of CD8 T cells
Effector Phase
- APC activation of memory (or sensitized) TH1 cells upon subsequent exposure to antigen
- Release of TH1 cytokines and chemokines to recruit and activate macrophages and neutrophils, resulting in inflammation
- Focus on IFN- and IL-8 (CXCL8)
- Recall: TH1 cells can also help activate CD8+ T cells
- Release of TH1 cytokines and chemokines to recruit and activate macrophages and neutrophils, resulting in inflammation
- Recruitment/activation of macrophages and neutrophils results in tissue destruction due to release of lytic enzymes and ROIs
- Effector CTLs can kill host cells
- Prolonged reactions can lead to granuloma formation
- Can occur in some persistent bacterial infections (e.g., Valley Fever & TB)
- Various other causes; chronic inflammatory component
Diagnostic Testing for TB
- In vivo testing: Intradermal tuberculin reaction (Mantoux test, PPD test)
- Clinically-induced skin reaction caused by intradermal injection of tuberculin (PPD) proteins
- Look for area of induration within 72 hrs
- Used to determine exposure to/infection with TB
- Clinically-induced skin reaction caused by intradermal injection of tuberculin (PPD) proteins
- In vitro testing: IFN- release assay (IGRA)
- Eg, QuantiFERON-TB Gold In-Tube (QFT assay)
- Designed to measure IFN- released by T cells in response to tuberculin or purified mycobacterial antigens
Clinical Manifestations/Examples
- Tubercule formation
- Infection with some organisms, such as M.tuberculosis (TB) can result in the formation of tubercules within the tissues
- Tubercules = granulomas formed due to infection with TB
- Enhanced Th1 + macrophage responses to contain and prevent dissemination of the organism
- Infection with some organisms, such as M.tuberculosis (TB) can result in the formation of tubercules within the tissues
- Contact dermatitis
- Sensitizing allergen (e.g., metals, chemicals, topical drugs, plant saps, soaps/fragrances, etc) is a hapten that complexes with proteins in the skin or mucosa
- Characterized by an eczematous, blistering reaction at the site of contact with the allergen after 48-72 hrs
Diagnostic Testing & Treatments
- In vivo test: Patch test
- An assay to determine the cause of a Type IV hypersensitivity (e.g., contact dermatitis)
- A small square of material (cotton, linen, paper) impregnated with the suspected allergen is applied to the skin for 24-48 hours
- The development of redness, edema, and formation of vesicles constitutes a positive test
- An assay to determine the cause of a Type IV hypersensitivity (e.g., contact dermatitis)
- Treatments will vary depending on the response and clinical manifestations, but often include:
- Corticosteroids
- Antibiotics (if infectious cause)
- Supportive care: IV fluids, NSAIDs, etc
Type II (Cytotoxic) Hypersensitivity
- Occurs through the production of IgM or IgG that binds to specific allergens located on cells
- Intrinsic cell surface components (e.g., blood group antigens)
- Extrinsic compounds adsorbed to the cell surface (e.g., some drugs)
- Some autoimmune diseases are classified as Type II hypersensitivities (e.g., MG, pemphigus)
- Two distinct phases:
- Sensitization phase: exposure to the antigen leads to IgM or IgG production
- Effector phase: re-exposure to the antigen allows allergen-specific IgM or IgG to bind, causing immune-mediated damage or blocks normal function of the cell/tissue (see next slide for details)
Type II: Effector Phase
- Mechanisms
- Antibody-dependent cellular cytotoxicity (ADCC)
- NK cells or macrophages killing antibody-coated targeted cells
- Complement-mediated lysis
- Activation of classical complement pathway to form membrane attack complexes (MAC) to kill target cells
- Antibody interference
- Antibodies can interfere with normal cellular functions when bound to a target cell
- Can be stimulatory or inhibitory
- This will be covered in more detail in the autoimmunities lectures
- Antibodies can interfere with normal cellular functions when bound to a target cell
- Antibody-dependent cellular cytotoxicity (ADCC)
Hypersensitivity Reactions
- Type I (Immediate Hypersensitivity) is mediated by IgE and mast cells.
- Type I symptoms result from mast cell degranulation.
- Type I can be treated with antihistamines, mast cell stabilizers and allergy shots.
- Type II (Cytotoxic Hypersensitivity) is mediated by IgG or IgM antibodies.
- Type II is involved in drug-induced hemolytic anemia.
- Type III (Immune Complex Hypersensitivity) is initiated by the deposition of small immune complexes.
- Type III leads to tissue damage, and can be identified by elevated serum complement levels.
- Type IV (Delayed-Type Hypersensitivity) is mediated by T cells.
- Type IV is responsible for contact dermatitis and the standard TB test.
Immediate Phase of Type I Hypersensitivity
- Vasodilation occurs during the immediate phase of a Type I hypersensitivity reaction.
- Increased mucus production occurs.
- Contraction of non-vascular smooth muscle occurs.
- Increased vascular permeability occurs.
Systemic Anaphylaxis
- Epinephrine is the most effective treatment for systemic anaphylaxis.
Conditions Mediated by Antibody Isotypes
- Atopic urticaria (hives) is mediated by IgE.
- Erythroblastosis fetalis is mediated by IgG.
- Transfusion reaction is mediated by IgG or IgM.
- Contact dermatitis is mediated by T cells.
- Serum sickness is mediated by IgG or IgM.
Conditions Mediated by Antibody Isotypes
- IgA deficiency does not affect IgE production, therefore food allergies can still develop.
Treatment of Poison Ivy
- IL-10 can be helpful in treating poison ivy, as it is an immunosuppressive cytokine.
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Description
Explore the mechanisms behind Type IV hypersensitivity reactions, mediated by TH1 cells and macrophages. This quiz covers the sensitization and effector phases, detailing allergen exposure, immune response development, and common allergens. Test your knowledge on this critical aspect of immunology.