Carcinogenesis & Immunopathology
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Questions and Answers

Which of the following genes normally promote cell growth and mitosis?

  • Oncogenes (correct)
  • Genes that regulate apoptosis
  • Genes involved in DNA repair
  • Tumour suppressor genes

    • What is the result of genetic alterations in genes regulating cell growth and survival?

  • Abnormal uncontrolled proliferation of cells (correct)
  • Programmed cell death
  • Normal cell growth and division
  • Increased DNA repair

    • What is the term for the process by which normal cells develop abnormalities and are transformed into neoplastic cells?

  • Carcinogenesis (correct)
  • Apoptosis
  • Mitosis
  • Neoplasia (correct)

    • What is the term for the study of the causes of cancer?

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

    What is an example of an intrinsic factor that can contribute to the development of leukaemia?

    <p>Trisomy 21</p> Signup and view all the answers

    What is the term for the chromosome abnormality seen in 90% of cases of chronic myeloid leukaemia?

    <p>Philadelphia chromosome</p> Signup and view all the answers

    What is an example of an autosomal dominant trait that increases the risk of developing benign tumours?

    <p>Polyposis coli</p> Signup and view all the answers

    Why may two people exposed to the same carcinogen not develop the same cancer?

    <p>All of the above</p> Signup and view all the answers

    What is the process of initiation and promotion of cancer?

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

    What type of mutations may be involved in carcinogenesis?

    <p>Both gross defects and single base-pair defects</p> Signup and view all the answers

    What are the four classes of normal regulatory genes that are the principle targets of genetic damage?

    <p>Growth promoting proto-oncogenes, tumor suppressor genes, DNA repair genes, and apoptosis genes</p> Signup and view all the answers

    What is an example of a carcinogen?

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

    What is the result of over-expression of genes in carcinogenesis?

    <p>Uncontrolled cell growth</p> Signup and view all the answers

    What occurs in the genome of cells during carcinogenesis?

    <p>Changes in the genome of cells</p> Signup and view all the answers

    What is an example of a gross defect mutation?

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

    What is the normal function of growth promoting proto-oncogenes?

    <p>To promote cell growth and differentiation</p> Signup and view all the answers

    What is a characteristic of children with severe combined immunodeficiency?

    <p>Recurrent infections of various types</p> Signup and view all the answers

    What is a consequence of ageing on the immune system?

    <p>Decreased production of bone marrow stem cells</p> Signup and view all the answers

    Which of the following infections can depress immunity non-specifically?

    <p>All of the above</p> Signup and view all the answers

    What type of cancer can depress immunity?

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

    What is the purpose of immunosuppressive drugs?

    <p>To suppress the immune response during transplantation</p> Signup and view all the answers

    What is the effect of radiation on the immune system?

    <p>Depletes lymphocytes</p> Signup and view all the answers

    What is the primary target of HIV in the immune system?

    <p>CD4+ cells</p> Signup and view all the answers

    What is the year in which AIDS was first described?

    <p>1981</p> Signup and view all the answers

    Which of the following bacteria is associated with an increased risk of carcinoma of the stomach?

    <p>Helicobacter pylori</p> Signup and view all the answers

    Which of the following viruses is associated with the development of Kaposi's sarcoma?

    <p>Human Herpes Virus-8</p> Signup and view all the answers

    What is the primary defect in Bruton's disease?

    <p>Low/absent B-cells</p> Signup and view all the answers

    What is the primary defect in Di George syndrome?

    <p>Absent thymus/functional tissue</p> Signup and view all the answers

    Which of the following is a characteristic of immunodeficiency disorders?

    <p>Increased susceptibility to tumours</p> Signup and view all the answers

    Which of the following viruses is associated with the development of hepatocarcinoma?

    <p>Hepatitis B Virus</p> Signup and view all the answers

    What is the primary defect in Swiss-type syndrome?

    <p>Absent lymphocyte stem cells in bone marrow</p> Signup and view all the answers

    Which of the following is a characteristic of autoimmune diseases?

    <p>Inappropriate immune response</p> Signup and view all the answers

    What is the characteristic time frame for the development of a delayed hypersensitivity reaction?

    <p>24-48 hours after contact with an antigen</p> Signup and view all the answers

    What is the term for the immune response that leads to tissue damage and chronic inflammation in autoimmune diseases?

    <p>T cell-mediated immune response</p> Signup and view all the answers

    What is an example of an antigen that can trigger a delayed hypersensitivity reaction?

    <p>All of the above</p> Signup and view all the answers

    What is the result of an autoimmune response against tissues in the body?

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

    What is the type of hypersensitivity reaction that involves granuloma formation?

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

    What is the term for a reaction that occurs when a sensitized T cell encounters an antigen?

    <p>Delayed hypersensitivity reaction</p> Signup and view all the answers

    What is an example of organ-specific autoimmune disease?

    <p>Hashimoto's thyroiditis</p> Signup and view all the answers

    What is the term for substances that stimulate an immune response against the body's own tissues?

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

    What is the primary outcome of carcinogenesis?

    <p>The development of a cancer</p> Signup and view all the answers

    Which of the following types of mutations can occur in carcinogenesis?

    <p>Both gross defects and point mutations</p> Signup and view all the answers

    What is the normal function of growth promoting proto-oncogenes?

    <p>To promote cell growth and differentiation</p> Signup and view all the answers

    What is the target of genetic damage in carcinogenesis?

    <p>Four classes of normal regulatory genes</p> Signup and view all the answers

    What is the result of over-expression of genes in carcinogenesis?

    <p>Uncontrolled cell growth and division</p> Signup and view all the answers

    What is the consequence of changes in the genome of cells during carcinogenesis?

    <p>Uncontrolled cell growth and division</p> Signup and view all the answers

    What is an example of a carcinogen?

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

    What is the process of carcinogenesis?

    <p>The process of initiation and promotion of cancer</p> Signup and view all the answers

    What type of hypersensitivity reaction involves the formation of IgE antibodies?

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

    What is the result of the degranulation of mast cells in Type I immediate hypersensitivity?

    <p>Release of histamine and other mediators</p> Signup and view all the answers

    What is an example of an allergen that can cause anaphylaxis?

    <p>All of the above</p> Signup and view all the answers

    What type of hypersensitivity reaction is involved in Erythroblastosis foetalis?

    <p>Type II antibody mediated hypersensitivity</p> Signup and view all the answers

    What is the result of anaphylactic shock?

    <p>Intense bronchoconstriction and vasodilatation</p> Signup and view all the answers

    What is the term for the process by which IgE antibodies attach to the surface of mast cells?

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

    What is an example of an organ-specific autoimmune disease?

    <p>Hashimoto's thyroiditis</p> Signup and view all the answers

    What is the term for the study of the causes of allergy?

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

    Which of the following viruses is associated with the development of cervical cancer?

    <p>Human Papilloma Virus</p> Signup and view all the answers

    What is the result of an abnormality in immune system function?

    <p>All of the above</p> Signup and view all the answers

    What is the characteristic of Agammaglobulinaemia or Bruton's disease?

    <p>Low/absent B-cells</p> Signup and view all the answers

    Which of the following is a primary immunodeficiency disorder?

    <p>Congenital thymic aplasia</p> Signup and view all the answers

    What is the result of absent B-cells and T-cells in Combined immunodeficiency?

    <p>Increased susceptibility to viral and fungal infections</p> Signup and view all the answers

    Which of the following bacteria is associated with an increased risk of carcinoma of the stomach?

    <p>Helicobacter pylori</p> Signup and view all the answers

    What is the characteristic of Congenital thymic aplasia or Di George syndrome?

    <p>All of the above</p> Signup and view all the answers

    Which of the following viruses is associated with the development of Kaposi's sarcoma?

    <p>Human Herpes Virus-8</p> Signup and view all the answers

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

    <p>Excessive secretion of thyroid hormones</p> Signup and view all the answers

    What is the primary mechanism of tissue damage in Type III immune complex mediated hypersensitivity?

    <p>Formation of immune complexes and microthrombi</p> Signup and view all the answers

    What is the primary mechanism of antibody-mediated hypersensitivity in Myasthenia gravis?

    <p>Blocking of acetylcholine receptors</p> Signup and view all the answers

    What is the characteristic feature of Type II antibody-mediated hypersensitivity?

    <p>Antibody binding to cell receptors</p> Signup and view all the answers

    What is the main difference between Type III and Type IV hypersensitivity reactions?

    <p>Type III involves immune complexes, while Type IV involves T cells</p> Signup and view all the answers

    What is the typical outcome of glomerulonephritis following streptococcal infection in children?

    <p>Resolution usually occurs</p> Signup and view all the answers

    What is the outcome of antibody binding to TSH receptors in Graves' disease?

    <p>Hyperplasia of thyroid follicular epithelium</p> Signup and view all the answers

    What is the role of platelet aggregation in Type III hypersensitivity?

    <p>Formation of microthrombi</p> Signup and view all the answers

    What is the characteristic feature of Myasthenia gravis?

    <p>Fatigue and weakness of muscles</p> Signup and view all the answers

    What is the characteristic feature of serum sickness?

    <p>Systemic immune complex formation</p> Signup and view all the answers

    What is the consequence of immune complex formation in Type III hypersensitivity?

    <p>Thrombosis and inflammation</p> Signup and view all the answers

    What is the primary target of antibodies in Graves' disease?

    <p>Thyroid-stimulating hormone (TSH) receptor</p> Signup and view all the answers

    What is the consequence of immune complex formation in glomerulonephritis?

    <p>All of the above</p> Signup and view all the answers

    What is the primary mechanism of tissue damage in Type IV hypersensitivity?

    <p>Sensitized T cells, killer cells, and cytokines</p> Signup and view all the answers

    What is the primary effect of antibody binding to acetylcholine receptors in Myasthenia gravis?

    <p>Blockade of muscle contraction</p> Signup and view all the answers

    What is the characteristic of the Arthus phenomenon?

    <p>Reaction in the skin</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 can be gross defects (e.g. translocations or breaks in chromosome arms) or single base-pair defects (e.g. point mutations, substitutions, deletions)

    Four Classes of Normal Regulatory Genes

    • 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
    • Genetic alterations in these genes lead to abnormal uncontrolled proliferation of cells (i.e. tumour cells develop with growth and survival advantages over normal cells)

    Aetiology of Cancer

    • Tumours have a multifactorial aetiology in which carcinogens play only one part
    • Body factors (intrinsic factors) and environmental factors (extrinsic factors) contribute to the causation of cancer
    • Genetic makeup, racial background, climactic conditions, environmental agents, and diet may all contribute
    • Explains why two people exposed to the same single carcinogen may not develop the same cancer

    Intrinsic Factors

    • Genetic factors: e.g. leukaemia, trisomy 21 in Down's syndrome, Philadelphia chromosome in chronic myeloid leukaemia, polyposis coli
    • Racial and geographic factors: e.g. higher incidence of carcinoma of the breast in Australia compared to Japan
    • Biological agents: viruses, e.g. hepatitis B virus → hepatocarcinoma, human herpes virus-8 → Kaposi's sarcoma, Epstein-Barr virus → Burkitt's lymphoma, human papilloma virus → cervical cancer

    Immunopathology

    • Disorders due to an abnormality in immune system function
    • Subdivided into:
      • Immunodeficiencies (1° or 2°): inadequate immune response → increased susceptibility to infections and tumours
      • Hypersensitivities: excessive immune response → tissue damage
      • Autoimmune diseases: inappropriate immune response → tissue damage

    Primary Immunodeficiency

    • Present at birth due to genetic/congenital disorder
    • Examples:
      • Agammaglobulinaemia (Bruton's disease): X-linked disorder, low/absent B-cells, normal T-cell function, severe bacterial infections
      • Congenital thymic aplasia (Di George syndrome): developmental disorder, absent thymus/functional tissue, often no parathyroids, absent T-cells, near normal B-cell function, severe viral, fungal, and protozoal infections
      • Combined immunodeficiency (Swiss-type syndrome): developmental disorder, absent lymphocyte stem cells in bone marrow, absent B-cells and T-cells, overwhelming recurrent infections of various types

    Secondary Immunodeficiency

    • Due to:
      • Ageing:  production of bone marrow stem cells
      • Infections: depress immunity non-specifically
      • Neoplasms: depress immunity
      • Immunosuppressive drugs: specifically lower immunity
      • Radiation: lymphocyte depletion due to radiation therapy, nuclear blasts
    • Acquired Immune Deficiency Syndrome (AIDS): infection with the Human Immunodeficiency Virus (HIV), may be congenital or acquired, targets immune system and CNS, virus infects CD4+ cells

    Hypersensitivities

    • Type IV T cell mediated (delayed) hypersensitivity:
      • Tuberculin reaction (Mantoux test): +ve reaction > 72hrs
      • Contact dermatitis: due to nickel plated buckle, nickel plated stud, perfume, rubber soles
      • Mosquito bites, transplanted organ rejection
    • Autoimmune diseases:
      • Organ-specific diseases: autoantibodies form against tissue (glandular tissues/epithelia/blood cells) → tissue damage, chronic inflammation
      • Systemic autoimmune diseases: multiple organs affected, e.g. systemic lupus erythematosus

    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 can 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)

    Biological Carcinogens

    • Viruses are the only biological agents that can directly cause tumours
    • Examples of virus-induced cancers:
      • Hepatitis B Virus → Hepatocarcinoma
      • Human Herpes Virus-8 → Kaposi's sarcoma
      • Epstein Barr Virus → Burkitt's lymphoma
      • Human Papilloma Virus → Cervical cancer

    Immunopathology

    • Disorders due to an abnormality in immune system function
    • Subdivided into:
      • Immunodeficiencies (1° or 2°)
      • Hypersensitivities
      • Autoimmune diseases

    Primary Immunodeficiencies

    • Present at birth due to genetic/congenital disorder
    • Examples:
      • Agammaglobulinaemia (Bruton's disease)
        • X-linked disorder
        • Low/absent B-cells (↓ antibody production)
        • Normal T-cell function
      • Congenital thymic aplasia (Di George syndrome)
        • Developmental disorder → absent thymus/functional tissue
        • Often no parathyroids → hypocalcaemia
        • Absent T-cells, no cellular immunity
        • Near normal B-cell function
      • Combined immunodeficiency (Swiss-type syndrome)
        • Developmental disorder
        • Absent lymphocyte stem cells in bone marrow
        • Absent B-cells & T-cells

    Type I Immediate Hypersensitivity

    • Allergen → IgE Antibody → Sensitized mast cell
    • First exposure to allergen → no reaction
    • 2nd & subsequent encounters with allergen → degranulation of mast cells → release of mediators of anaphylaxis (histamine, serotonin, etc.) → anaphylaxis (local or generalised effects)
    • Examples:
      • Allergy to bee stings → blistering
      • Allergy to pollen → hay fever (allergic rhinitis)

    Type II Antibody Mediated Hypersensitivity

    • Due to IgG or IgM Abs causing direct cell damage & lysis
    • Examples:
      • Erythroblastosis foetalis (haemolytic disease of the newborn)
      • Incompatible ABO blood transfusion reactions
      • Graves' disease
      • Myasthenia gravis

    Type III Immune Complex Mediated Hypersensitivity

    • Soluble antigen combines with specific Abs to form immune (Ag-Ab) complexes
    • These 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

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