Carcinogenesis and Immunopathology
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Which of the following is a type of carcinogen?

  • Polycyclic aromatic compounds (correct)
  • Chronic injury
  • Hormonal stimulation
  • Percival Pott

    • What is the definition of carcinogenesis?

  • The process of treating cancer
  • The process of diagnosing cancer
  • The process of initiation and promotion of cancer (correct)
  • The process of preventing cancer

    • Benign tumours can never undergo malignant change.

    False (B)

    Carcinogens can be viruses.

    <p>True (A)</p> Signup and view all the answers

    What is an example of a gross defect mutation?

    <p>Translocations or breaks in chromosome arms</p> Signup and view all the answers

    What is the name of the fungus that produces aflatoxin, a carcinogen, in starchy foods?

    <p>Aspergillus flavus</p> Signup and view all the answers

    The process of carcinogenesis involves changes in the ______________ of cells.

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

    The higher incidence of hepatocarcinoma in SE Asia compared to Australia is an example of an ______________ factor.

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

    What are the principle targets of genetic damage in carcinogenesis?

    <p>Normal regulatory genes (C)</p> Signup and view all the answers

    Which of the following is an example of a physical agent that can cause cancer?

    <p>Inert substances in body (A), Ionizing radiation (B), Trauma (C)</p> Signup and view all the answers

    Match the following types of mutations with their descriptions:

    <p>Point mutations = Substitutions, deletions, or insertion of a single base-pair of DNA Gross defects = Translocations or breaks in chromosome arms</p> Signup and view all the answers

    Cancer is more common with decreasing age.

    <p>False (B)</p> Signup and view all the answers

    Carcinogens only include chemicals and radiation.

    <p>False (B)</p> Signup and view all the answers

    Match the following extrinsic factors with their corresponding examples:

    <p>Chemical agents = Percival Pott's discovery of soot exposure and carcinoma of the scrotum Physical agents = Ionizing radiation Biological agents = Aspergillus flavus fungus producing aflatoxin</p> Signup and view all the answers

    What is the name of the carcinogen that was previously used in food products and is also known as 'Butter Yellow'?

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

    What do growth promoting proto-oncogenes normally code for?

    <p>Proteins involved in the control of normal cell growth and differentiation</p> Signup and view all the answers

    What is the primary effect of thyroid-stimulating antibodies (TSI) in Graves' disease?

    <p>Excessive secretion of thyroid hormones (T3, T4) (B)</p> Signup and view all the answers

    Myasthenia gravis is an example of Type III immune complex mediated hypersensitivity.

    <p>False (B)</p> Signup and view all the answers

    What is the primary site of involvement in Myasthenia gravis?

    <p>Ocular and facial muscles</p> Signup and view all the answers

    In Graves' disease, excessive secretion of thyroid hormones leads to ______________ and decreased weight.

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

    What is the outcome of immune complexes (Ag-Ab) formation in Type III immune complex mediated hypersensitivity?

    <p>Thrombosis, inflammation, tissue damage, and necrosis (D)</p> Signup and view all the answers

    Match the following diseases with their respective mechanisms:

    <p>Graves' disease = Antibody-mediated stimulation of thyroid hormone secretion Myasthenia gravis = Antibody-mediated blockade of acetylcholine receptors Rheumatoid arthritis = Immune complex-mediated inflammation</p> Signup and view all the answers

    Type II antibody-mediated hypersensitivity is characterized by the formation of immune complexes.

    <p>False (B)</p> Signup and view all the answers

    What is the primary effect of thyroid-stimulating antibodies (TSI) on thyroid follicular epithelium?

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

    What is the result of microthrombus formation and complement injury in Type III immune complex mediated hypersensitivity?

    <p>Tissue damage (B)</p> Signup and view all the answers

    Antibodies are involved in Type IV T cell mediated hypersensitivity.

    <p>False (B)</p> Signup and view all the answers

    What is the reaction that occurs in the skin in Type III immune complex mediated hypersensitivity?

    <p>Arthus phenomenon</p> Signup and view all the answers

    In Type III immune complex mediated hypersensitivity, immune complexes form in response to _______________________

    <p>horse-derived antitoxin</p> Signup and view all the answers

    What is the result of immune complex formation in glomerulonephritis?

    <p>Acute vasculitis, albuminuria, haematuria, and oedema (A)</p> Signup and view all the answers

    Match the following type of hypersensitivity with its characteristic:

    <p>Type III immune complex mediated hypersensitivity = Immune complexes lodge in vascular walls Type IV T cell mediated hypersensitivity = No antibodies involved Serum sickness = Formation of immune complexes (systemic) Glomerulonephritis = Immune complexes form, filtered by glomeruli of the kidney</p> Signup and view all the answers

    Renal failure may occur in glomerulonephritis.

    <p>True (A)</p> Signup and view all the answers

    What is the result of sensitized T-cells, killer cells, activated macrophages, and secretion of cytokines in Type IV T cell mediated hypersensitivity?

    <p>Tissue damage</p> Signup and view all the answers

    What is the normal function of tumour suppressor genes?

    <p>To discourage cell growth or temporarily halt cell division to carry out DNA repair (B)</p> Signup and view all the answers

    All tumours have the same genetic makeup.

    <p>False (B)</p> Signup and view all the answers

    What is the result of genetic alterations in key genes regulating growth?

    <p>Abnormal uncontrolled proliferation of cells (i.e. tumour cells develop with growth and survival advantages over normal cells)</p> Signup and view all the answers

    Trisomy 21, as seen in Down's Syndrome, predisposes to ___________________.

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

    What is an example of a racial and geographic factor in carcinogenesis?

    <p>Higher incidence of carcinoma of the breast in Australia compared to Japan (A)</p> Signup and view all the answers

    What is the Philadelphia chromosome associated with?

    <p>Chronic myeloid leukaemia</p> Signup and view all the answers

    Match the following genetic factors with their associated cancers:

    <p>Trisomy 21 = Leukaemia Philadelphia chromosome = Chronic myeloid leukaemia Autosomal dominant trait = Polyposis coli</p> Signup and view all the answers

    Carcinogens are the sole cause of cancer.

    <p>False (B)</p> Signup and view all the answers

    Study Notes

    Carcinogenesis

    • Carcinogenesis is the process of initiation and promotion of cancer
    • A carcinogen is any agent or substance that initiates cancer, e.g. chemicals, radiation, viruses
    • The process involves changes in the genome of cells, including mutations, over-expression of genes, or loss of activity of gene products
    • Mutations may be gross defects (e.g. translocations or breaks in chromosome arms) or a defect involving a single base-pair of DNA (e.g. point mutations, substitutions, deletions)

    Classes of Normal Regulatory Genes

    • Four classes of normal regulatory genes are the principle targets of genetic damage:
      • Growth promoting proto-oncogenes (normally code for proteins involved in the control of normal cell growth and differentiation)
      • Growth-inhibiting tumour suppressor genes (normally discourage cell growth, or temporarily halt cell division to carry out DNA repair)
      • Genes that regulate apoptosis (normally allow programmed cell death to occur, preventing further cell growth)
      • Genes involved in DNA repair (normally allow repair of DNA following damage/mutations by stimuli)

    Aetiology of Cancer

    • Tumours have a multifactorial aetiology in which carcinogens play only one part
    • Body factors (intrinsic factors) and environmental factors (extrinsic factors) both contribute to the causation of cancer
    • Genetic makeup, racial background, climactic conditions, environmental agents, and diet may all contribute to cancer development

    Intrinsic Factors

      1. Genetic factors:
      • Leukaemia, e.g. Trisomy 21 in Down's Syndrome
      • Chronic myeloid leukaemia, e.g. Philadelphia chromosome
      • Polyposis coli, an autosomal dominant trait where hundreds of benign tumours form on the colonic mucosa
      1. Racial and geographic factors:
      • Higher incidence of carcinoma of the breast in Australia compared to Japan
      • Higher incidence of hepatocarcinoma in SE Asia compared to Australia
      1. Immunological factors:
      • Patients with immunodeficiency (e.g. AIDS) have a higher incidence of some cancers (e.g. Kaposi's sarcoma, lymphoma)
      1. Sex and Hormonal Influences:
      • Hormonal stimulation can lead to some cancers, e.g. breast (oestrogen stimulation)
      1. Age:
      • Cancer is more common with increasing age, e.g. carcinoma of the colon
      1. Pre-existing Benign Neoplasms:
      • Benign tumours that are left untreated for long periods may undergo malignant change due to additional mutations, e.g. polyposis coli, adenomatous polyp

    Extrinsic Factors

      1. Chemical agents:
      • Percival Pott (1775) described the association between soot exposure and carcinoma of the scrotum in chimney sweeps
      • Polycyclic aromatic compounds are carcinogenic, e.g. 2-naphthylamine, 7,12-dimethylbenzanthracene (DMBA)
      1. Physical agents:
      • Ionizing radiation, e.g. UV light, X-rays, g-rays, products of radioactive decay
      • Trauma, e.g. chronic injury and tissue damage, not single episode of trauma
      • Inert substances in the body, e.g. plastic films, glass, fibres, methylcellulose, metal foils and wires, asbestos fibres
      1. Biological agents:
      • Parasites, e.g. Schistosoma spp cause a chronic infection of the bladder and predispose to carcinoma
      • Fungi and bacteria, e.g. Aspergillus flavus produces aflatoxin (carcinogen) in starchy foods, leading to primary hepatocarcinoma

    Types of Hypersensitivities

    • Type II Antibody Mediated Hypersensitivity:
      • Graves' disease (thyrotoxicosis), e.g. thyroid-stimulating Abs (TSI) bind to TSH receptor leading to excessive secretion of thyroid hormones and hyperplasia of thyroid follicular epithelium
      • Myasthenia gravis, e.g. Abs form against acetylcholine receptors of skeletal muscle cells, blocking action of acetylcholine, leading to fatigue, weakness of muscles, ocular, facial muscles involved early, ptosis, difficulty in speaking, chewing, swallowing
    • Type III Immune Complex Mediated Hypersensitivity:
      • Soluble antigen combines with specific Abs to form immune (Ag-Ab) complexes, which circulate around body and localize in walls of vessels, leading to thrombosis, inflammation, tissue damage, necrosis
      • Examples: serum sickness, glomerulonephritis
    • Type IV T Cell Mediated (Delayed) Hypersensitivity:
      • No antibodies involved, sensitized T-cells, killer cells, activated macrophages, and secretion of cytokines cause tissue damage
      • Examples: contact dermatitis, tuberculin reaction, Jones-Mote reaction

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