Immunopathology
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Questions and Answers

What type of cytokine is primarily associated with Th1 cells in the context of delayed-type hypersensitivity?

  • IL-4
  • IL-10
  • TGFβ
  • IFN-g (correct)
  • Which type of T cell is primarily involved in the mechanism of graft rejection?

  • CD4+ T cells
  • Th2 cells
  • Treg cells
  • CD8+ T cytotoxic cells (correct)
  • In systemic lupus erythematosus, which antibodies are most commonly directed against cellular components?

  • Both B and C (correct)
  • Anti-phospholipid antibodies
  • Anti-dsDNA antibodies
  • Anti-SM antibodies
  • What is the primary clinical manifestation site for systemic lupus erythematosus?

    <p>Skin, joints, kidneys, heart</p> Signup and view all the answers

    Which immune cell type is critical for granuloma formation associated with CD4+ T cell activity?

    <p>Macrophage</p> Signup and view all the answers

    Which factor is NOT considered an essential element in the pathogenesis of autoimmune diseases?

    <p>Presence of allografts</p> Signup and view all the answers

    What type of T cell activities are associated with allergic reactions, particularly in Th2 mediated responses?

    <p>Production of IL-4</p> Signup and view all the answers

    Which of the following is a key feature of Th1 and Th2 T-cell balance in relation to autoimmune disorders?

    <p>An imbalance can exacerbate autoimmune conditions</p> Signup and view all the answers

    What is the female to male ratio for systemic lupus erythematosus incidence?

    <p>10:1</p> Signup and view all the answers

    Which of these ailments is NOT typically associated with Th1 cell activation?

    <p>Asthma</p> Signup and view all the answers

    Which of the following cytokines promotes the differentiation of naïve T cells towards the Th1 lineage?

    <p>IL-12</p> Signup and view all the answers

    Which type of hypersensitivity is mediated by CD8+ T cells during a viral infection?

    <p>Type IV</p> Signup and view all the answers

    How does the body typically respond to chronic inflammation settings post antigen presentation?

    <p>Granuloma formation</p> Signup and view all the answers

    What is the primary characteristic of amyloid as defined in the content?

    <p>Amorphous, proteinaceous substance deposited extracellularly</p> Signup and view all the answers

    Which type of amyloidosis is associated with chronic inflammation?

    <p>Reactive (secondary) amyloidosis</p> Signup and view all the answers

    What composition of proteins is primarily found in amyloid deposits?

    <p>Fibrillary proteins and glycosaminoglycans</p> Signup and view all the answers

    Under polarized light, amyloid stained with Congo Red exhibits what characteristic?

    <p>Green birefringence</p> Signup and view all the answers

    Which type of amyloidosis is most commonly associated with renal involvement?

    <p>Primary amyloidosis</p> Signup and view all the answers

    What is the prognostic outcome for generalized amyloidosis?

    <p>Poor prognosis</p> Signup and view all the answers

    What type of amyloidosis is characterized by the presence of the A4 protein and associated with Alzheimer's disease?

    <p>Localized amyloidosis</p> Signup and view all the answers

    Which of the following proteins is chemically distinct and contributes to amyloid formation?

    <p>Transthyretin</p> Signup and view all the answers

    What cellular component is mainly involved in the production of abnormal amyloid proteins?

    <p>B-lymphocytes</p> Signup and view all the answers

    Which type of hypersensitivity is primarily mediated by IgE antibodies?

    <p>Type I Hypersensitivity</p> Signup and view all the answers

    What type of amyloidosis is associated with beta2 microglobulin in dialysis patients?

    <p>Hemodialysis associated amyloidosis</p> Signup and view all the answers

    What is the role of cytokines like IL-4 in Type I hypersensitivity?

    <p>Enhance eosinophil activation</p> Signup and view all the answers

    Which type of hypersensitivity involves the binding of antibodies to surface antigens on target cells?

    <p>Type II Hypersensitivity</p> Signup and view all the answers

    What is a common example of Type III hypersensitivity?

    <p>Serum sickness</p> Signup and view all the answers

    In cell-mediated Type IV hypersensitivity, which cells are primarily responsible for the immune response?

    <p>CD8+ T cells</p> Signup and view all the answers

    During anaphylaxis, which chemical mediator released by Mast cells primarily causes vasodilation and increased vascular permeability?

    <p>Histamine</p> Signup and view all the answers

    Which of the following is NOT a primary mediator released by mast cells during Type I hypersensitivity?

    <p>IgG</p> Signup and view all the answers

    An example of autoimmune hemolytic anemia is an example of which type of hypersensitivity?

    <p>Type II Hypersensitivity</p> Signup and view all the answers

    The activation of complement in hypersensitivity reactions typically leads to what outcome?

    <p>Inflammatory response</p> Signup and view all the answers

    Which cytokine is produced in response to antigen signaling in a Type I hypersensitivity reaction?

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

    Which of the following conditions is primarily associated with Type IV hypersensitivity?

    <p>Tuberculosis skin test</p> Signup and view all the answers

    What defines Type II hypersensitivity from other types?

    <p>Mediated by IgM and IgG</p> Signup and view all the answers

    Which mediator is primarily involved in the late-phase response of Type I hypersensitivity?

    <p>Prostaglandins</p> Signup and view all the answers

    What role does eosinophil activation play in immediate hypersensitivity reactions?

    <p>Amplifying inflammatory response</p> Signup and view all the answers

    What is the defining characteristic of diffuse proliferative glomerulonephritis in systemic lupus erythematosus (SLE)?

    <p>Presence of subepithelial immune complex deposits</p> Signup and view all the answers

    Which of the following clinical features is least associated with Sjögren syndrome?

    <p>Peripheral neuropathy</p> Signup and view all the answers

    In systemic sclerosis, which antibody is most commonly associated with the diffuse form?

    <p>Anti-DNA topoisomerase I antibody</p> Signup and view all the answers

    Which type of immunodeficiency is characterized by a deficiency in both T and B cells and presents with early onset of severe infections?

    <p>Severe Combined Immunodeficiency Disease</p> Signup and view all the answers

    Which of the following conditions is associated with a high risk of developing malignant lymphoma?

    <p>Sjögren syndrome</p> Signup and view all the answers

    What is a distinguishing histological feature of nonbacterial verrucous endocarditis associated with SLE?

    <p>Vegetations on the mitral valve</p> Signup and view all the answers

    Which deficiency in the complement system is specifically linked to increased susceptibility to neisserial infections?

    <p>Factor B deficiency</p> Signup and view all the answers

    What is the common pathophysiological feature of renal allograft rejection?

    <p>Infiltration of neutrophils and destruction of renal tubules</p> Signup and view all the answers

    Which of these is NOT a common feature of AIDS?

    <p>Eosinophilia</p> Signup and view all the answers

    Which statement accurately describes a potential consequence of alcohol metabolism?

    <p>Inhibition of gluconeogenesis due to increased NADH</p> Signup and view all the answers

    What is a common presentation of DiGeorge syndrome?

    <p>Tetany due to hypoparathyroidism</p> Signup and view all the answers

    Which laboratory finding is typically seen in a patient with X-linked infantile agammaglobulinemia?

    <p>Decreased levels of all immunoglobulin classes</p> Signup and view all the answers

    In severe combined immunodeficiency disease (SCID), what typically leads to the pathology?

    <p>Defects in lymphoid stem cells</p> Signup and view all the answers

    Which is not considered a risk factor for Vibrio vulnificus infection?

    <p>Advanced age over 50</p> Signup and view all the answers

    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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