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Questions and Answers
What type of cytokine is primarily associated with Th1 cells in the context of delayed-type hypersensitivity?
Which type of T cell is primarily involved in the mechanism of graft rejection?
In systemic lupus erythematosus, which antibodies are most commonly directed against cellular components?
What is the primary clinical manifestation site for systemic lupus erythematosus?
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Which immune cell type is critical for granuloma formation associated with CD4+ T cell activity?
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Which factor is NOT considered an essential element in the pathogenesis of autoimmune diseases?
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What type of T cell activities are associated with allergic reactions, particularly in Th2 mediated responses?
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Which of the following is a key feature of Th1 and Th2 T-cell balance in relation to autoimmune disorders?
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What is the female to male ratio for systemic lupus erythematosus incidence?
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Which of these ailments is NOT typically associated with Th1 cell activation?
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Which of the following cytokines promotes the differentiation of naïve T cells towards the Th1 lineage?
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Which type of hypersensitivity is mediated by CD8+ T cells during a viral infection?
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How does the body typically respond to chronic inflammation settings post antigen presentation?
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What is the primary characteristic of amyloid as defined in the content?
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Which type of amyloidosis is associated with chronic inflammation?
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What composition of proteins is primarily found in amyloid deposits?
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Under polarized light, amyloid stained with Congo Red exhibits what characteristic?
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Which type of amyloidosis is most commonly associated with renal involvement?
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What is the prognostic outcome for generalized amyloidosis?
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What type of amyloidosis is characterized by the presence of the A4 protein and associated with Alzheimer's disease?
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Which of the following proteins is chemically distinct and contributes to amyloid formation?
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What cellular component is mainly involved in the production of abnormal amyloid proteins?
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Which type of hypersensitivity is primarily mediated by IgE antibodies?
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What type of amyloidosis is associated with beta2 microglobulin in dialysis patients?
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What is the role of cytokines like IL-4 in Type I hypersensitivity?
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Which type of hypersensitivity involves the binding of antibodies to surface antigens on target cells?
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What is a common example of Type III hypersensitivity?
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In cell-mediated Type IV hypersensitivity, which cells are primarily responsible for the immune response?
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During anaphylaxis, which chemical mediator released by Mast cells primarily causes vasodilation and increased vascular permeability?
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Which of the following is NOT a primary mediator released by mast cells during Type I hypersensitivity?
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An example of autoimmune hemolytic anemia is an example of which type of hypersensitivity?
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The activation of complement in hypersensitivity reactions typically leads to what outcome?
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Which cytokine is produced in response to antigen signaling in a Type I hypersensitivity reaction?
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Which of the following conditions is primarily associated with Type IV hypersensitivity?
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What defines Type II hypersensitivity from other types?
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Which mediator is primarily involved in the late-phase response of Type I hypersensitivity?
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What role does eosinophil activation play in immediate hypersensitivity reactions?
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What is the defining characteristic of diffuse proliferative glomerulonephritis in systemic lupus erythematosus (SLE)?
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Which of the following clinical features is least associated with Sjögren syndrome?
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In systemic sclerosis, which antibody is most commonly associated with the diffuse form?
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Which type of immunodeficiency is characterized by a deficiency in both T and B cells and presents with early onset of severe infections?
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Which of the following conditions is associated with a high risk of developing malignant lymphoma?
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What is a distinguishing histological feature of nonbacterial verrucous endocarditis associated with SLE?
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Which deficiency in the complement system is specifically linked to increased susceptibility to neisserial infections?
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What is the common pathophysiological feature of renal allograft rejection?
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Which of these is NOT a common feature of AIDS?
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Which statement accurately describes a potential consequence of alcohol metabolism?
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What is a common presentation of DiGeorge syndrome?
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Which laboratory finding is typically seen in a patient with X-linked infantile agammaglobulinemia?
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In severe combined immunodeficiency disease (SCID), what typically leads to the pathology?
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Which is not considered a risk factor for Vibrio vulnificus infection?
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Study Notes
Immune System
- Innate immunity is the first line of defense against pathogens.
- Adaptive immunity is a more specific and targeted response, involving T cells and B cells.
- The innate and adaptive immune systems work together to protect the body from infection.
Cytokine Network
- Cytokines are signaling molecules that help to regulate the immune response.
- They are produced by a variety of cells, including macrophages, T cells, and B cells.
- They act on other cells to trigger a variety of responses, including inflammation, cell proliferation, and differentiation.
- Examples of cytokines include: IFNα, IFNβ, IFNγ, IL-1, IL-6, IL-10, IL-12, TNFα, TNFβ
Hypersensitivity Reactions
- Hypersensitivity reactions are exaggerated immune responses that can damage tissues.
- There are four types of hypersensitivity reactions.
Immediate (Type I) Hypersensitivity
- This is also known as anaphylactic hypersensitivity.
- IgE antibodies bind to mast cells and basophils.
- Upon re-exposure to the allergen, these antibodies crosslink, releasing histamine and other inflammatory mediators.
- Examples include systemic anaphylaxis, skin allergies, and food allergies.
Antibody-Mediated (Type II) Hypersensitivity
- This involves antibodies directed against cell surface antigens.
- Complement dependent cytotoxicity involves the activation of complement by antibodies bound to cell surfaces, leading to cell lysis.
- Antibody-dependent cellular cytotoxicity involves NK cells and cytotoxic T cells killing antibody-coated cells.
- Antibody-mediated cellular dysfunction involves antibodies interfering with normal cell function.
- Examples include Goodpasture syndrome, pernicious anemia, Graves’ disease, and myasthenia gravis.
Immune Complex-Mediated (Type III) Hypersensitivity
- Immune complexes form when antigens bind to antibodies.
- These complexes can deposit in tissues, triggering complement activation, inflammation, and tissue damage.
- Examples include serum sickness, systemic lupus erythematosus, and Arthus reactions.
Cell-Mediated (Type IV) Hypersensitivity
- This is a delayed hypersensitivity reaction mediated by T cells.
- The T cells become sensitized to an antigen.
- Upon re-exposure, the T cells release cytokines that attract macrophages and other inflammatory cells.
- Delayed type hypersensitivity is mediated by CD4+ T cells and usually involve MHC II antigens.
- T cell-mediated cytotoxicity is mediated by CD8+ T cells and usually involve MHC I antigens.
- Examples include contact dermatitis, tuberculosis infection, and graft rejection.
Asthma
- Asthma is a chronic inflammatory condition of the airways that results in airway obstruction, wheezing, and shortness of breath.
- A common trigger for asthma is allergens.
- Allergens cause mast cells to release mediators, including histamine and leukotrienes, causing bronchospasm, mucous secretion, and inflammation.
Delayed-type hypersensitivity
- Inflammation caused by CD4+ (helper) T cells and CD8+ (cytotoxic) T cells
- Antigen-presenting cells (APCs) present antigens to T cells
- CD4+ T cells release cytokines (TNF, IL-2, IFN-g) that lead to granuloma formation
- Granulomas are composed of macrophages, epithelial cells, giant cells, fibroblasts, and lymphocytes
Cell-mediated cytolysis
- Mediated by CD8+ cytotoxic T lymphocytes (CTLs)
- CTLs recognize and kill cells expressing specific antigens
- CTLs release cytotoxic molecules that cause cell death and tissue injury
- Examples: viral infections, graft rejection, tumor-associated antigens
Th1 and Th2 T-cell Balance
- Th1 cells: promote inflammation and cell-mediated immunity (e.g., rheumatoid arthritis, Crohn disease)
- Th2 cells: promote allergic reactions (e.g., asthma, allergies)
- Immune system balance between Th1 and Th2 influences the development of autoimmune and allergic diseases
Autoimmune Diseases
- Caused by failure of self-tolerance -- the immune system attacks its own tissues
- Triggered by genetic susceptibility, infections, inflammation
- Examples: systemic lupus erythematosus (SLE), Sjögren syndrome, scleroderma
Systemic Lupus Erythematosus (SLE)
- Affects females more than males
- Characterized by autoantibodies against various cellular components
- Clinical manifestations: skin rashes, joint pain, kidney problems, heart problems, etc.
Sjögren Syndrome
- Characterized by dry mouth and dry eyes
- Primarily affects females over 40 years of age
- Related to B-cell dysfunction and autoantibodies against ribonucleoproteins
Scleroderma (Progressive Systemic Sclerosis)
- Causes excessive fibrosis throughout the body
- Two main types: diffuse scleroderma (affects skin widely, rapid progression) and CREST syndrome (affects skin, esophagus, fingers, fingertips, and blood vessels)
Immunodeficiency Syndromes
- Divided into primary and acquired immunodeficiencies
- Primary immunodeficiencies: inherited, usually caused by genetic mutations, affect specific parts of the immune system
- Acquired immunodeficiencies: result from environmental factors, infections, and disease processes; acquired during a person’s lifetime
X-Linked Infantile Agammaglobulinemia
- Primary B cell deficiency
- Lack of immunoglobulins
- Increased susceptibility to bacterial infections
- Affects males due to X-linked inheritance
DiGeorge Syndrome
- Absence of thymus
- Deficient T cell function
- Increased susceptibility to fungal and viral infections
Severe Combined Immunodeficiency Disease (SCID)
- Affected individuals have a severe deficiency in both B cells and T cells
- Patients are highly susceptible to infections
- Common mutations involve genes responsible for ADenosine Deaminase (ADA) and the common gamma chain in cytokine receptors
- Treatment: bone marrow transplant, gene therapy
Wiskott-Aldrich Syndrome (WAS)
- X-linked recessive disorder
- Characterized by Thrombocytopenia, eczema, and recurrent infections
- Decreased serum IgM and depletion of T-cell dependent areas in lymph nodes
Complement System Disorders
- Inherited deficiencies affecting specific complement proteins or pathways
- Deficiencies in C3: recurrent bacterial infections and immune complex diseases
- Deficiencies in C5, C6, C7, and C8: recurrent meningococcal and gonococcal infections
- Deficiency of C1-INH: hereditary angioedema - causes edema at mucosal surfaces
Acquired Immunodeficiencies
- Resulting from various conditions including systemic diseases (diabetes, collagen vascular diseases), chronic alcohol use, transplantation, and immunosuppressive drugs
- Common consequence: increased susceptibility to infections
Renal Allograft Rejection
- Immune response targeting the donor kidney transplant
- Direct pathway: recipient's T cells recognize donor MHC molecules
- Indirect pathway: recipient APCs present donor antigens to recipient T cells
- Both pathways can lead to rejection of the graft
AIDS
- Characterized by a CD4+ cell count less than 200 cells per microliter
- AIDS is caused by the Human Immunodeficiency Virus (HIV)
- HIV targets CD4+ T cells, macrophages, and other immune cells
- Transmission: sexual contact, intravenous drug use, perinatal transmission, contaminated blood products
HIV Pathogenesis
- Primary infection: HIV spreads rapidly, causing acute symptoms
- Clinical latency: HIV replication is partially controlled, but the virus remains latent in immune cells
- AIDS: Extensive viral replication severely depletes CD4+ T cells, leading to immune dysfunction and opportunistic infections
Metabolic Consequences of Alcohol Metabolism
- Liver: Alcohol dehydrogenase and acetaldehyde dehydrogenase are key enzymes in alcohol metabolism.
- Increased NADH production: Alcohol metabolism generates excess NADH, inhibiting metabolic processes that require NAD+ (e.g., the Krebs cycle, beta-oxidation, gluconeogenesis)
- Immunosuppression of Neutrophils: Alcohol consumption impairs neutrophil function, contributing to susceptibility to infections.
Vibrio Vulnificus
- Risk Factors: Liver disease, chronic alcoholic use, diabetes, chronic renal disease, immunosuppressive medications
- Can cause severe skin infections and sepsis, especially those with compromised immune systems
AIDS Virus (HIV)
- HIV is composed of a lipid bilayer envelope, core proteins, and RNA genome
- Viral envelope: gp120 and gp41 glycoproteins
- Core proteins: p24 capsid, p17 matrix, p7 nucleocapsid
- Viral Enzymes: reverse transcriptase, protease, integrase
AIDS Virus Life Cycle
- Attachment: HIV gp120 binds to CD4 and chemokine receptors on host cells.
- Fusion: HIV gp41 mediates fusion of the viral envelope with the host cell membrane allowing the virus to enter the cell.
- Reverse transcription: HIV reverse transcriptase converts viral RNA into DNA.
- Integration: Proviral DNA integrates into the host cell genome.
- Transcription and Translation: Host cell machinery transcribes and translates HIV DNA into viral proteins and RNA.
- Assembly: Newly produced HIV proteins and RNA assemble into new viral particles.
- Budding: New viral particles bud from the host cell, acquiring a lipid envelope.
AIDS Virus Genome
- LTR (long terminal Repeat): contains regulatory elements for viral transcription
- Gag: encodes core proteins
- Pol: encodes viral enzymes (reverse transcriptase, protease, integrase)
- Env: encodes the viral envelope proteins (gp120, gp41)
- Vif: viral infectivity factor, helps overcome host defense mechanisms
- Vpu: promotes gp120 shedding and degradation, influences virion release
- Nef: negative effector, downregulates surface expression of CD4 and MHC I, enhances viral infectivity
Stages of HIV Disease
- Acute phase: Viral mononucleosis syndrome, seroconversion
- Chronic phase: Persistent generalized lymphadenopathy, minor opportunistic infections
Clinical Course of HIV Disease
- CD4+ T cell count decreases as the disease progresses
- Viral load increases during the early stage and later stage
- Opportunistic infections become more common as the immune system weakens
- Treatment: antiretroviral therapy can slow disease progression and extend survival
Monitoring HIV Infection
- Western blot: confirms the presence of HIV antibodies
- CD4+ T cell count: measures the number of CD4+ cells in the blood
- Viral load: measures the amount of HIV RNA in the blood
- Monitoring these parameters helps to assess disease progression and the effectiveness of treatment.
Viral Load
- Viral load refers to the amount of HIV in the blood.
- A high viral load indicates active HIV replication and a greater risk of transmitting HIV to others.
- A low viral load can help to prolong life and reduce the risk of opportunistic infections
Opportunistic Infections
- Opportunistic infections occur when a weakened immune system is unable to fight off infections that normally wouldn't cause serious illness.
- Common opportunistic infections for people with HIV include:
- Oral thrush
- Kaposi sarcoma
- Tuberculosis
- Herpes zoster
- Pneumocystis carinii pneumonia
- Dementia
- Toxoplasmosis
- Cryptococcosis
- Cryptosporidiosis
- Cytomegalovirus
- Mycobacterium avium complex
- Progressive multifocal leukoencephalopathy
Treatment
- Combination antiretroviral treatment (CART) is used to suppress HIV replication.
- Reverse transcriptase inhibitors are a type of antiretroviral medication that is commonly used in CART.
CMV Pneumonia
- It is an infection of the lungs caused by the cytomegalovirus (CMV).
- It primarily affects people with weakened immune systems like those with HIV/AIDS.
- Symptoms include fever, cough, shortness of breath, and chest pain.
- Treatment can be difficult and involves antiviral medications.
Pneumocystis Jiroveci Pneumonia
- It is a type of pneumonia caused by the fungus Pneumocystis jiroveci.
- It commonly affects people with weakened immune systems, particularly those with HIV/AIDS.
- Symptoms: shortness of breath, fever, dry cough, and chest pain
- Treatment involves anti-fungal medications such as trimethoprim-sulfamethoxazole (TMP-SMX).
Mycobacterium Avium Complex
- It is a type of bacteria that causes a serious infection, especially in individuals with weakened immune systems, such as people with HIV/AIDS.
- Symptoms: fever, night sweats, weight loss, fatigue, diarrhea, and abdominal pain.
- Treatment consists of a combination of antibiotics, often for extended periods.
Invasive Candida Esophagitis
- It is an infection of the esophagus caused by the fungus Candida.
- It can be a serious condition, especially in people with weakened immune systems.
- Symptoms: difficulty swallowing, pain when swallowing, and chest pain.
- Treatment involves anti-fungal medications.
Herpetic Simplex Esophagitis
- It is an infection of the esophagus caused by the herpes simplex virus (HSV).
- It can be a serious condition and involves a painful inflammation of the esophagus.
- Symptoms: pain during swallowing, difficulty swallowing, and chest pain.
- Treatment involves antiviral medications.
Neuropathology of HIV Disease
- It is the study of the neurological disorders associated with HIV infection.
- Includes a variety of neurological complications like:
- Cryptococcal meningitis
- Toxoplasmosis
- Progressive multifocal leukoencephalopathy
- Malignant B-cell lymphoma
- AIDS dementia
Cryptococcal Meningitis
- It is a serious infection of the brain and lining of the spinal cord caused by the fungus Cryptococcus.
- Symptoms include headache, fever, stiff neck, nausea, vomiting, and confusion.
- Treatment involves anti-fungal medications.
Toxoplasmosis
- It is a parasitic infection that can affect the brain and other organs.
- It is particularly problematic for people with weakened immune systems, especially those with HIV/AIDS.
- Symptoms: headache, fever, confusion, seizures, and vision problems.
- Treatment involves anti-parasitic medications.
HIV-associated Neoplasias
- Neoplasias are abnormal growths of new tissue, also known as tumors.
- Various tumors associated with HIV include:
- Hairy leukoplakia
- Kaposi sarcoma
- Malignant lymphoma
- Non-Hodgkin Lymphoma
- Hodgkin Lymphoma
- Parasite-Derived Cancer
Hairy Leukoplakia
- It is a common oral condition that appears as white, raised patches on the tongue.
- It is caused by the Epstein-Barr virus (EBV) and primarily affects people with HIV.
- It is usually harmless but can be a sign of weakened immunity.
Kaposi Sarcoma
- It is a type of cancer that affects the blood vessels and lymph vessels.
- It often appears as reddish-purple or brown lesions on the skin, but can affect internal organs.
- It is most common in people with HIV, but can occur in people with other conditions.
- It is caused by the Kaposi sarcoma-associated herpes virus (KSHV).
- Infection with HIV can lead to the reactivation of KSHV contributing to the proliferation of mesenchymal spindle cells and endothelial cells leading to KS.
Gastric AIDS-associated Non-Hodgkin Lymphoma
- It is a type of cancer that affects the lymph nodes in the stomach.
- It is commonly associated with HIV and usually involves B-cell lymphoma.
AIDS-associated Hodgkin Lymphoma
- It is a type of cancer that affects the lymph nodes, typically involving B-cell lymphoma.
- It is often associated with HIV infection.
Confirmation of Hymenolepis nana Infection
- It is a type of tapeworm infection that affects the digestive tract.
- It is more common in people with weakened immune systems.
- Confirmation of infection involves identifying the tapeworm eggs in stool samples or examining the tapeworm in the stool.
Amyloidosis
- It is a disorder characterized by the abnormal buildup of amyloid protein in various organs and tissues.
- Amyloid protein is made up of misfolded proteins, that can accumulate in the organs and tissues of the body.
- It can be classified as either primary or secondary
- Primary amyloidosis involves the abnormal production of amyloid protein. The cause of primary amyloidosis is unknown, but it is often linked to a condition called monoclonal gammopathy of undetermined significance (MGUS)
- Secondary amyloidosis results from chronic inflammation (e.g. rheumatoid arthritis).
- Amyloidosis is further classified as:
- Systemic amyloidosis affects multiple organs, such as the heart, kidneys, liver, spleen, and intestines.
- Localized amyloidosis affects only one organ or a few organs.
- Amyloidosis can be classified based on which type of protein forms the amyloid fibrils. The three main types are:
- AL amyloidosis: The amyloid protein is made of light chains.
- AA amyloidosis: The amyloid protein is made of serum amyloid A protein.
- ATTR amyloidosis: The amyloid protein is made of transthyretin (TTR) protein.
Cardiac Amyloidosis
- It is a type of amyloidosis that affects the heart.
- It can lead to heart failure.
- Symptoms include shortness of breath, fatigue, swelling in the feet and ankles, and arrhythmias
Clinical Course of Amyloidosis
- The kidneys are the most common organ affected by amyloidosis.
- The heart is the second most common organ affected by amyloidosis, and it can lead to restrictive cardiomyopathy.
- The liver, spleen, gastrointestinal tract, and endocrine glands can also be affected by amyloidosis.
- The prognosis for generalized amyloidosis is poor.
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