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Foundations in Microbiology
          Fifth Edition

                                        Talaro
                                     Chapter
                                       17

    Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Disorders in Immunity
        Chapter 17      2
Immunopathology
• Allergy, hypersensitivity – an exaggerated,
  misdirected expression of immune responses
• Involves the same types of immune reactions as
  those at work in protective immunities.
• Autoimmunity – abnormal responses to self Ag
• Immunodeficiency – deficiency or loss of
  immunity
• Cancer – results from a lack of surveillance
                                             3
4
5
Type I Hypersensitivity
• Atopy – any chronic local allergy such as
  hay fever or asthma
• Anaphylaxis – a systemic, often explosive
  reaction that involves airway obstruction
  and circulatory collapse



                                              6
Mechanism of Type I
• sensitizing dose – on first contact with allergen,
  specific B cells form IgE which attaches to mast
  cells and basophils
• provocative dose - subsequent exposure with the
  same allergen binds to the IgE-mast cell complex
• degranulation releases mediators with
  physiological effects such as vasodilation and
  bronchoconstriction
• symptoms are rash, itching, redness, increased
  mucous discharge, pain, swelling, and difficulty
  breathing
                                                       7
8
Role of Mast Cells & Basophils
• Mast cells are located in the connective tissue
  of virtually all organs; high conc. in lungs,
  skin, GI and genital tract
• Basophils circulate in blood, migrate into
  tissues
• each cell can bind 10,000-40,000 IgE
• cytoplasmic granules contain physiologically
  active cytokines, histamine, etc
• cells degranulate when stimulated by allergen9
Chemical mediators




                     10
11
Systemic Anaphylaxis
• Sudden respiratory and circulatory
  disruption that can be fatal in a few minutes
• Allergen and route are variable
• Bee stings, antibiotics or serum injection




                                              12
Strategies for circumventing allergic
                attacks




                                    13
Blocking Ab




              14
Type II Hypersensitivity
• Reactions that lyse foreign cells
• Involve antibodies, complement, leading to
  lysis of foreign cells
• Transfusion reactions
  – ABO blood groups
  – Rh factor – hemolytic disease of the newborn


                                                   15
16
17
18
19
Type III Hypersensitivity
• A large quantity of soluble foreign Ag
  stimulates Ab that produce small, soluble
  Ag-Ab complexes
• Immune complexes become trapped in
  tissues & incite a damaging inflammatory
  response
  – Arthus reaction – local reaction to series of
    injected Ag to same body site
  – Serum sickness – systemic disease resulting
    from repeated injections of foreign proteins
                                                    20
21
Autoimmunity
• In certain type I & II hypersensitivities, the immune
  system has lost tolerance to self molecules and
  forms autoantibodies and sensitized T cells against
  them.
• More common in females
• Disruption of function can be systemic or organic
  specific
   –   Systemic lupus erythematosus
   –   Rheumatoid arthritis
   –   Endocrine autoimmunities
   –   Myasthenia gravis
   –   Multiple sclerosis                            22
23
24
25
26
Type IV Hypersensitivity
• Cell-mediated
• A delayed response to Ag involving activation of
  and damage by T cells
• Delayed allergic response – skin response to
  allergens – tuberculin skin test, contact dermititis
  from plants, metals, cosmetics
• Graft rejection – reaction of cytotoxic T cells
  directed against foreign cells of a grafted tissue;
  involves recognition of foreign HLA

                                                         27
28
29
30
Immunodeficiency diseases
• Components of the immune response system are absent.
  Deficiencies involve B and T cells, phagocytes, and
  complement
   – Primary immunodeficiency – genetically based
     congenital lack of B-cell and/or T cell activity
   – B cell defect – agammaglobulinemia – patient lacks
     antibodies
   – T cell defect – thymus is missing or abnormal
   – Severe combined immunodeficiency - both limbs of
     lymphocyte system are missing or defective; no
     adaptive immune response
   – Secondary (acquired) immune deficiency – due to
     damage after birth (infections, drugs, radiation) AIDS
                                                        31
32
Cancer
• Overgrowth of abnormal tissue arises due to
  malfunction of immune surveillance
• Tumors may be benign (nonspreading) or
  malignant (a cancer) that spreads from tissue of
  origin to other sites
• Malignant tumors may be
   – carcinomas originate from epithelial tissue
   – sarcomas originate from embryonic connective tissue
• Cancers occur in nearly every cell type
                                                           33
Characteristics of cancerous growths

• Disorganized behavior and independence
  from surrounding normal tissues
• Permanent loss of cell differentiation
• Expression of special markers on their
  surface



                                           34
Interrelationship between genes and
               cancer
1. Cancer cell often have damaged chromosomes
2. A specific alteration in a gene can lead to cancer
3. Predisposition for some cancers is inherited
4. Rates of cancer are highest in individuals who
   cannot repair damaged DNA
5. Mutagenic agents cause cancer
6. Cells contain genes that can be transformed to
   cancer-causing oncogenes
7. Tumor-supressor genes exist in the normal
   genome                                            35
Mechanism of Cancer
• Some type of gene alteration turns a normal
  gene (proto-oncogene) that regulates the
  onset of mitosis into an oncogene
• The oncogene overrides normal mitotic
  controls and cause the cell to divide
  continuously
• Tumor suppressor genes may be missing or
  inactivated

                                            36
37
Role of viruses in cancer
• Some viruses carry oncogenes whose
  products cause transformation of host cells
  into cancer cells
• Viral genome may be inserted into
  regulatory sites
• Human papillomavirus cervical cancer
• Epstein-Barr virus – Burkitt’s lymphoma

                                                38
39
40
Function of immune system in
                cancer
• Cells with cancer-causing potential arise
  constantly in the body but the immune system
  normally discovers and destroys them
• Cell-mediated immunity, TC, NK & macrophages,
  antibodies
• Immune system fails in cancer
   – may not be immunogenic enough
   – may retain self-markers and not be targeted
• Maybe a slight or transient failure allows cancer to
  develop
                                                    41

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Immunopathology

  • 1. PowerPoint to accompany Foundations in Microbiology Fifth Edition Talaro Chapter 17 Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
  • 2. Disorders in Immunity Chapter 17 2
  • 3. Immunopathology • Allergy, hypersensitivity – an exaggerated, misdirected expression of immune responses • Involves the same types of immune reactions as those at work in protective immunities. • Autoimmunity – abnormal responses to self Ag • Immunodeficiency – deficiency or loss of immunity • Cancer – results from a lack of surveillance 3
  • 4. 4
  • 5. 5
  • 6. Type I Hypersensitivity • Atopy – any chronic local allergy such as hay fever or asthma • Anaphylaxis – a systemic, often explosive reaction that involves airway obstruction and circulatory collapse 6
  • 7. Mechanism of Type I • sensitizing dose – on first contact with allergen, specific B cells form IgE which attaches to mast cells and basophils • provocative dose - subsequent exposure with the same allergen binds to the IgE-mast cell complex • degranulation releases mediators with physiological effects such as vasodilation and bronchoconstriction • symptoms are rash, itching, redness, increased mucous discharge, pain, swelling, and difficulty breathing 7
  • 8. 8
  • 9. Role of Mast Cells & Basophils • Mast cells are located in the connective tissue of virtually all organs; high conc. in lungs, skin, GI and genital tract • Basophils circulate in blood, migrate into tissues • each cell can bind 10,000-40,000 IgE • cytoplasmic granules contain physiologically active cytokines, histamine, etc • cells degranulate when stimulated by allergen9
  • 11. 11
  • 12. Systemic Anaphylaxis • Sudden respiratory and circulatory disruption that can be fatal in a few minutes • Allergen and route are variable • Bee stings, antibiotics or serum injection 12
  • 13. Strategies for circumventing allergic attacks 13
  • 15. Type II Hypersensitivity • Reactions that lyse foreign cells • Involve antibodies, complement, leading to lysis of foreign cells • Transfusion reactions – ABO blood groups – Rh factor – hemolytic disease of the newborn 15
  • 16. 16
  • 17. 17
  • 18. 18
  • 19. 19
  • 20. Type III Hypersensitivity • A large quantity of soluble foreign Ag stimulates Ab that produce small, soluble Ag-Ab complexes • Immune complexes become trapped in tissues & incite a damaging inflammatory response – Arthus reaction – local reaction to series of injected Ag to same body site – Serum sickness – systemic disease resulting from repeated injections of foreign proteins 20
  • 21. 21
  • 22. Autoimmunity • In certain type I & II hypersensitivities, the immune system has lost tolerance to self molecules and forms autoantibodies and sensitized T cells against them. • More common in females • Disruption of function can be systemic or organic specific – Systemic lupus erythematosus – Rheumatoid arthritis – Endocrine autoimmunities – Myasthenia gravis – Multiple sclerosis 22
  • 23. 23
  • 24. 24
  • 25. 25
  • 26. 26
  • 27. Type IV Hypersensitivity • Cell-mediated • A delayed response to Ag involving activation of and damage by T cells • Delayed allergic response – skin response to allergens – tuberculin skin test, contact dermititis from plants, metals, cosmetics • Graft rejection – reaction of cytotoxic T cells directed against foreign cells of a grafted tissue; involves recognition of foreign HLA 27
  • 28. 28
  • 29. 29
  • 30. 30
  • 31. Immunodeficiency diseases • Components of the immune response system are absent. Deficiencies involve B and T cells, phagocytes, and complement – Primary immunodeficiency – genetically based congenital lack of B-cell and/or T cell activity – B cell defect – agammaglobulinemia – patient lacks antibodies – T cell defect – thymus is missing or abnormal – Severe combined immunodeficiency - both limbs of lymphocyte system are missing or defective; no adaptive immune response – Secondary (acquired) immune deficiency – due to damage after birth (infections, drugs, radiation) AIDS 31
  • 32. 32
  • 33. Cancer • Overgrowth of abnormal tissue arises due to malfunction of immune surveillance • Tumors may be benign (nonspreading) or malignant (a cancer) that spreads from tissue of origin to other sites • Malignant tumors may be – carcinomas originate from epithelial tissue – sarcomas originate from embryonic connective tissue • Cancers occur in nearly every cell type 33
  • 34. Characteristics of cancerous growths • Disorganized behavior and independence from surrounding normal tissues • Permanent loss of cell differentiation • Expression of special markers on their surface 34
  • 35. Interrelationship between genes and cancer 1. Cancer cell often have damaged chromosomes 2. A specific alteration in a gene can lead to cancer 3. Predisposition for some cancers is inherited 4. Rates of cancer are highest in individuals who cannot repair damaged DNA 5. Mutagenic agents cause cancer 6. Cells contain genes that can be transformed to cancer-causing oncogenes 7. Tumor-supressor genes exist in the normal genome 35
  • 36. Mechanism of Cancer • Some type of gene alteration turns a normal gene (proto-oncogene) that regulates the onset of mitosis into an oncogene • The oncogene overrides normal mitotic controls and cause the cell to divide continuously • Tumor suppressor genes may be missing or inactivated 36
  • 37. 37
  • 38. Role of viruses in cancer • Some viruses carry oncogenes whose products cause transformation of host cells into cancer cells • Viral genome may be inserted into regulatory sites • Human papillomavirus cervical cancer • Epstein-Barr virus – Burkitt’s lymphoma 38
  • 39. 39
  • 40. 40
  • 41. Function of immune system in cancer • Cells with cancer-causing potential arise constantly in the body but the immune system normally discovers and destroys them • Cell-mediated immunity, TC, NK & macrophages, antibodies • Immune system fails in cancer – may not be immunogenic enough – may retain self-markers and not be targeted • Maybe a slight or transient failure allows cancer to develop 41