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The immune response1


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Immunopathology lecture

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The immune response1

  1. 1. The Immune Response By Prof. Dr. Gamal El-Din Abd El-Hamid
  2. 2. 2ANATOMY OF THE IMMUNE SYSTEM  The immune system is localized in several parts of the body ◦ immune cells develop in the primary organs - bone marrow and thymus (yellow) ◦ immune responses occur in the
  3. 3. 3 PASSIVE IMMUNITY Antibodies (Y) are also found in breast milk. The antibodies received through passive immunity last only several weeks. While your immune system was developing, you were protected by immune defenses called antibodies. These antibodies traveled across the placenta from the maternal blood to the fetal blood.
  4. 4. IMMUNE DEFENSES Innate Immunity - invariant (generalized) - early, limited specificity - the first line of defense Adaptive Immunity - variable (custom) - later, highly specific - ‘‘remembers’’ infection
  5. 5.  Internal defenses v Innate, non-specific, immediate response (min/hrs) v Adaptive (Acquired) – attack a specific pathogen (antigen) Immune Defenses: Overview
  6. 6. Innate and Adaptive (Acquired) Immunity INNATE IMMUNITY Rapid responses to a broad range of microbes Adaptive IMMUNITY Slower responses to specific microbes External defenses Internal defenses Skin Mucous membranes Secretions Phagocytic cells Antimicrobial proteins Inflammatory response Natural killer cells Humoral response (antibodies) Cell-mediated response (cytotoxic lymphocytes) Invading microbes (pathogens)
  7. 7. Innate immunity ◦ Is present before any exposure to pathogens and is effective from the time of birth ◦ Involves nonspecific responses to pathogens
  8. 8. External Defenses I. Intact skin and mucous membranes ◦ Form physical barriers that prevents the entry of microorganisms and viruses .Certain cells of the mucous membranes produce mucus. A viscous fluid that traps microbes and other particles
  9. 9.  In the trachea, ciliated epithelial cells ◦ Sweep mucus and any entrapped microbes upward, preventing the microbes from entering the lungs
  10. 10. II. Secretions of the skin and mucous membranes ◦ Provide an environment that is often hostile to microbes ◦ Give the skin a pH between 3 and 5, which is acidic enough to prevent colonization of many microbes ◦ Also include proteins such as lysozyme, an enzyme that digests the cell walls of many bacteria
  11. 11. 11 Cellular response • Nonspecific - the same response works against many pathogens • This type of response is the same no matter how often it is triggered • The types of cells involved are macrophages, neutrophils, natural killer cells, and mast cells
  12. 12. Phagocytic Cells  Phagocytes attach to their prey via surface receptors and engulf them, forming a vacuole that fuses with a lysosome Pseudopodia surround microbes. 1 Microbes are engulfed into cell. 2 Vacuole containing microbes forms. 3 Vacuole and lysosome fuse. 4 Toxic compounds and lysosomal enzymes destroy microbes. 5 Microbial debris is released by exocytosis. 6 Microbes MACROPHAGE Vacuole Lysosome containing enzymes
  13. 13. Adaptive immunity (Acquired immunity) ◦ Develops only after exposure to inducing agents such as microbes, toxins, or other foreign substances ◦ Involves a very specific response to pathogens by lymphocytes.
  14. 14. Innate Immune System Adaptive Immune System Repeated infections Do Not improve resistance Improve resistance Cells PNLs, Macrophages, Mast cells NK cells Lymphocytes Soluble Factors C-reactive protein Interferon Complement Antibodies Cytokines
  15. 15.  It is a specific mechanism developing against particular types of irritants in order to: 1. Get rid of the irritant 2. Increase the ability of the body to overcome it on subsequent exposure .Steps in Immune defense ◦ Detect invader/foreign cells ◦ Communicate alarm & recruit immune cells ◦ Suppress or destroy invader Adaptive Immune Response
  16. 16.  Newly formed lymphocytes are all alike ◦ But they later develop into B cells or T cells, depending on where they continue their maturation Bone marrow Lymphoid stem cell B cell Blood, lymph, and lymphoid tissues (lymph nodes, spleen, and others) T cell Thymus
  17. 17. Lymphatic System: Overview of Immune Defense Organs & Cells  Bone marrow  Thymus  Lymph nodes  Spleen  Lymph vessels  Leukocytes (white blood cells – WBCs)
  18. 18. Lymphatic System
  19. 19. Cells of the immune system
  20. 20. T Lymphocytes: Cell Mediated Immunity T lymphocytes and NK cells
  21. 21. Antigen- binding sitesAntibody A Antigen Antibody B Antibody C Epitopes (antigenic determinants)  Antigen is any substance which when introduced in body can evoke an immune response.  It may be exogenous or endogenous  A lymphocyte actually recognizes and binds to just a small, accessible portion of the antigen called an epitope  The plasma membranes of both B cells and T cells have about 100,000 antigen receptor that all recognize the same epitope ANTIGEN
  22. 22.  MHC are molecules that mediate interactions of leukocytes  They bind processed foreign proteins (phagocytosed material)and present them on the cell surface to T-cells  MHC determines compatibility of donors for organ transplant as well as one's susceptibility to an autoimmune disease via crossreacting immunization.   They are two types: Class I antigns and Class II antigns Major Histocompatibility Complex (MHC) (Human Leukocyte Antigens – HLAs)
  23. 23. Infected cell Antigen fragment Class I MHC molecule T cell receptor (a) Cytotoxic T cell CD8+ A fragment of foreign protein (antigen) inside the cell associates with an MHC molecule and is transported to the cell surface. 1 The combination of MHC molecule and antigen is recognized by a T cell, alerting it to the infection. 2 1 2  Class I MHC molecules, found on almost all nucleated cells of the body ◦ Display peptide antigens to cytotoxic T cells
  24. 24. Cytotoxic T cell Perforin Granzymes CD8TCR Class I MHC molecule Target cell Peptide antigen Pore Released cytotoxic T cell Apoptotic target cell Cancer cell Cytotoxic T cell A specific cytotoxic T cell binds to a class I MHC–antigen complex on a target cell via its TCR with the aid of CD8. This interaction, along with cytokines from helper T cells, leads to the activation of the cytotoxic cell. 1 The activated T cell releases perforin molecules, which form pores in the target cell membrane, and proteolytic enzymes (granzymes), which enter the target cell by endocytosis. 2 The granzymes initiate apoptosis within the target cells, leading to fragmentation of the nucleus, release of small apoptotic bodies, and eventual cell death. The released cytotoxic T cell can attack other target cells. 3 1 2 3  The activated cytotoxic T cell ◦ Secretes proteins that destroy the infected target cell
  25. 25.  Class II MHC molecules, located mainly on dendritic cells, macrophages, and B cells ◦ Display antigens to helper T cells 1 2 Microbe Antigen- presenting cell Antigen fragment Class II MHC molecule T cell receptor Helper T cell CD4+ A fragment of foreign protein (antigen) inside the cell associates with an MHC molecule and is transported to the cell surface. 1 The combination of MHC molecule and antigen is recognized by a T cell, alerting it to the infection. 2 (b)
  26. 26. Helper T Cells: A Response to Nearly All Antigens  Helper T cells produce CD4, a surface protein ◦ That enhances their binding to class II MHC molecule–antigen complexes on antigen-presenting cells ◦ Activation of the helper T cell then occurs  Activated helper T cells ◦ Secrete several different cytokines that stimulate other lymphocytes
  27. 27. The role of helper T cells in acquired immunity After a dendritic cell engulfs and degrades a bacterium, it displays bacterial antigen fragments (peptides) complexed with a class II MHC molecule on the cell surface. A specific helper T cell binds to the displayed complex via its TCR with the aid of CD4. This interaction promotes secretion of cytokines by the dendritic cell. Proliferation of the T cell, stimulated by cytokines from both the dendritic cell and the T cell itself, gives rise to a clone of activated helper T cells (not shown), all with receptors for the same MHC–antigen complex. The cells in this clone secrete other cytokines that help activate B cells and cytotoxic T cells. Cell-mediated immunity (attack on infected cells) Humoral immunity (secretion of antibodies by plasma cells) Dendritic cell Dendritic cell Bacterium Peptide antigen Class II MHC molecule TCR CD4 Helper T cell Cytokines Cytotoxic T cell B cell 1 2 3 1 2 3
  28. 28. Infected cell Antigen fragment Class I MHC molecule T cell receptor (a) Cytotoxic T cell CD8+ A fragment of foreign protein (antigen) inside the cell associates with an MHC molecule and is transported to the cell surface. 1 The combination of MHC molecule and antigen is recognized by a T cell, alerting it to the infection. 2 Microbe Antigen- presenting cell Antigen fragment Class II MHC molecule T cell receptor Helper T cell CD4+ A fragment of foreign protein (antigen) inside the cell associates with an MHC molecule and is transported to the cell surface. 1 The combination of MHC molecule and antigen is recognized by a T cell, alerting it to the infection. 2 (b) The activated cytotoxic T cell Secretes proteins that destroy the infected target cell Proliferation of the T cel gives rise to a clone of activated helper T cells all with receptors for the same MHC–antigen complex.
  29. 29. Cytokines 1. TNF (Tumor Necrosis Factor) alpha: 1. Attraction and activation of macrophages 2. Granuloma formation
  30. 30. Interferon  1. Acts in a positive feedback signal activating T cells further 2. Activates Macrophages to be competent to contain bacteria 3. Regulates APC function 4. B cell differentiation
  31. 31. Interleukins (IL)  IL-12 § Produced by macrophages. § It stimulates differentiation of T-cells in TH1 pathway
  32. 32. CD4+ (Th1) T cell help to the infected macrophages T cell- Macrophage interaction can take several hours
  33. 33.  Acquired immunity includes two branches 1. Humoral immune response ◦.Involves the activation and clonal selection of B cells, resulting in the production and secretion of antibodies 2. Cell-mediated immune response ◦.Involves the activation and clonal selection of cytotoxic T cells
  34. 34. Humoral immune response Cell-mediated immune response First exposure to antigen Intact antigens Antigens engulfed and displayed by dendritic cells Antigens displayed by infected cells Activate Activate Activate Gives rise to Gives rise to Gives rise to B cell Helper T cell Cytotoxic T cell Plasma cells Memory B cells Active and memory helper T cells Memory cytotoxic T cells Active cytotoxic T cells Secrete antibodies that defend against pathogens and toxins in extracellular fluid Defend against infected cells, cancer cells, and transplanted tissues Secreted cytokines activate
  35. 35. Antibody Classes  The five major classes of antibodies, or immunoglobulins: ◦ They are produced by plasma cells ◦ They are γ globulins ◦ Differ in their distributions and functions within the body ◦ They are able to react specifically with Ag. that stimulate their
  36. 36. 1. Most abundant Ig class in blood; also presents in tissue fluids 2. Only Ig class that crosses placenta, thus conferring passive immunity on fetus 3. Promotes opsonization, neutralization, and agglutination of antigens 4. Less effective in complement activation than IgM IgG
  37. 37. 1. First Ig class produced after initial exposure to antigen; then its concentration in the blood declines 2. Promotes neutralization and agglutination of antigens 3. Very effective in complement activation IgM
  38. 38. 1. Present in secretions such as tears, saliva, mucus, and breast milk 2. Provides localized defense of mucous membranes by agglutination and neutralization of antigens IgA
  39. 39.  Triggers release of histamine and other chemicals from mast cells and basophils in allergic reactions IgE
  40. 40.  Presents primarily on surface of naive B cells that have not been exposed to antigens  Acts as antigen receptor in antigen-stimulated proliferation and differentiation of B cells. IgD
  41. 41. Antibody-mediated mechanisms of antigen disposal Binding of antibodies to antigens inactivates antigens by Viral neutralization (blocks binding to host) and opsonization (increases phagocytosis) Agglutination of antigen-bearing particles, such as microbes Precipitation of soluble antigens Activation of complement system and pore formation Bacterium Virus Bacteria Soluble antigens Foreign cell Complement proteins MAC Pore Enhances Phagocytosis Leads to Cell lysis Macrophage
  42. 42. Acquired Immunity: Antigen-Specific Responses Functions of antibodies
  43. 43.  It is a system of plasma proteins that exists in an inactive form and constitutes about 10% of serum globulins.  The proteins of the system form 2 inter-related enzyme cascades, termed The Classical and Alternative Pathways, providing 2 routes for cleavage of C3, the central event in the complement system The Complement System
  44. 44.  The proteins of the classical pathway are numbered C1 - C9. Most components are β globulin  The bulk of the plasma complement components are made in hepatic cells except C1 which is synthesized mainly in the epithelium of GIT and urogenital tracts
  45. 45.  Both classic and alternative pathways generate C3 convertase which converts C3 into C3b  The classic pathway represents an adaptive immune mechanism while the alternative pathway represents a non-specific innate immunity
  46. 46.  Complement activation is associated with the release of active mediators; the most important are C3a and C5a  Effects of C5a 1. Major chemotactic factor 2. Activation of PMNs 3. Increase of vascular permeability 4. Mast cell degranulation 5. Membrane attack complex (C6, 7,8, 9) helping in Effects of Complement Activation
  47. 47.  Hypersensitivity reactions are exaggerated (hypersensitive) responses to certain antigens called ALLERGENS ◦ They are classified into : • Type I (Anaphylactic) Reactions • Type II (Cytotoxic) Reactions • Type III (Immune Complex) Reactions Those associated with Humoral Antibodies • Type IV (Cell-Mediated) Reactions Those associated with Cell-mediated Immune Response
  48. 48.  In localized allergies such as § hay fever, § atopy, or § bronchial asthma Type I (Anaphylaxis, Atopy)
  49. 49.  The allergic response IgE antibodies produced in response to initial exposure to an allergen bind to receptors or mast cells. 1 On subsequent exposure to the same allergen, IgE molecules attached to a mast cell recog- nize and bind the allergen. 2 Degranulation of the cell, triggered by cross-linking of adjacent IgE molecules, releases histamine and other chemicals, leading to allergy symptoms. 3 1 2 3 Allergen IgE Histamine Granule Mast cell
  50. 50.  An acute allergic response sometimes leads to anaphylactic shock ◦ A whole-body, life-threatening reaction that can occur within seconds of exposure to an allergen
  52. 52. ◦ Involve activation of complement by IgG or IgM binding to an antigenic cell. ◦ The antigenic determinants may be: 1. Intrinsic to the cell membrane or matrix, or 2. Extrensic, such as a drug metabolite, that is adsorbed on a cell surface or matrix. ◦.In either case, the hypersensitivity reaction results from the binding of antibodies to normal or Type II (Cytotoxic) Reactions
  53. 53. Opsonization of cells by antibodies and complement components and ingestion by phagocytes. It occurs in Transfusion Reactions
  54. 54. ◦ Transfusion reactions:  ABO Blood group system: Type O is universal donor. Incompatible donor cells are lysed as they enter bloodstream.  Rh Blood Group System: 85% of population is Rh positive. Those who are Rh negative can be sensitized to destroy Rh positive blood cells.  Hemolytic disease of newborn: Fetal cells are destroyed by maternal anti- Rh antibodies that cross the placenta.
  55. 55. Table 43.1
  56. 56. Inflammation induced by antibody binding to Fc receptors of leukocytes and by complement breakdown products. It occurs in some forms of: Glomerulonephritis Vascular rejection in organ grafts, Acute rheumatic fever
  57. 57. Antireceptor antibodies disturb the normal function of receptors. In these examples, antibodies against the thyroid stimulating hormone (TSH) receptor activate thyroid cells in Graves disease, and acetylcholine (ACh) receptor antibodies impair neuromuscular transmission in myasthenia gravis.
  58. 58.  Antibody-mediated destruction of cells may occur by another process called antibody-dependent cellular cytotoxicity (ADCC).  This form of antibody-mediated cell injury Does Not involve fixation of complement but instead requires the cooperation of leukocytes (monocytes, neutrophils, eosinophils, and NK cells). Antibody-dependent cellular cytotoxicity (ADCC)
  59. 59. T Cell-Mediated Cytotoxicity  Sensitized CD8+ T cells kill antigen-bearing target cells. Such effector cells are called cytotoxic T lymphocytes (CTLs).  CTLs directed against cell surface histocompatibility antigens play an important role in graft rejection. They also play a role in resistance to virus infections
  60. 60. TYPE III HYPERSENSITIVITY (Immune Complex Reactions) ◦ Involves reactions against SOLUBLE antigens circulating in serum. ◦ Usually involve IgA antibodies. ◦ Antibody-Antigen immune complexes are deposited in organs, activate complement, and cause inflammatory damage. ◦ Two general types of antigens cause immune complex-mediated injury: (1) Exogenous, such as a foreign protein, a bacterium, or a virus; or (2) Self-components-endogenous antigens. This can be circulating antigens present in the blood or, more commonly, antigenic components of one's own cells and tissues.
  61. 61.  Examples:  SLE  Serum Sickness: Generalized disease caused by antibody produced to horse or bovine serum used in antitoxins. Aggregates of IgG activate complement.  Glomerulonephritis: membranous or post-streptococcal  Polyarteritis nodosa
  62. 62. ◦ Involve reactions by T memory cells.  First contact sensitizes person. Subsequent contacts elicit a reaction. ◦ Reactions are delayed by one or more days (delayed type hypersensitivity).  Delay is due to migration of macrophages and T cells to site of foreign antigens.  Examples are:  Contact dermatitis  Rheumatoid artheritis Type IV (Cell-Mediated) Reactions
  63. 63. Allergic Contact Dermatitis Reactions are frequently displayed on the skin: itching, redness, swelling, pain. Tuberculosis skin test Poison ivy Metals Latex in gloves and condoms
  65. 65.  Immune reactions against self-antigens causes damage to organs.  Loss of self-tolerance leads to production of antibodies or T cells that react against one’s own antigens.  Three types of autoimmune disorders: 1. Cytotoxic (Type II reactions) 2. Immune complex (Type III reactions) 3. Cell-mediated (Type IV reactions) Autoimmune Diseases
  66. 66. Involve antibody reactions to cell surface molecules, without cytotoxic destruction of cells. ◦ Grave’s Disease:  IgG Antibodies attach to receptors on thyroid gland and stimulate production of thyroid hormone.  Symptoms: Goiter (enlarged thyroid) and thyrotoxicosis. ◦ Myasthenia gravis:  Progressive muscle weakness. Antibodies block acetylcholine receptors at neuromuscular synapse. A. Type II (Cytotoxic) Autoimmune Reactions
  67. 67. ◦ Systemic Lupus Erythematosus:  Autoantibodies react against DNA, blood cells, neurons, and other tissues.  When cells die, immune complexes form and deposit under skin, joints, in kidneys, blood vessels, and central nervous system.  Inflammation interferes with normal function of these sites (arthritis, rash, kidney damage).  Most patients die from renal failure.  No cure. Symptoms treated with anti-inflammatory and immunosuppressive drugs. B. Type III (Immune Complex) Autoimmune Reactions
  68. 68. ◦Rheumatoid Arthritis: Cause unknown, but microbial mimicry may be involved. IgM autoantibodies (rheumatoid factors) against IgG form complexes in joint, leading to inflammation and cartilage damage. Often causes finger and joint deformities. No cure. Symptoms treated with anti- inflammatory (aspirin) and immunosuppressive drugs. Physical therapy keeps joints movable. Surgical replacement of joints may be necessary.
  69. 69. ◦ Insulin-dependent (Type I or Juvenile) Diabetes Mellitus: Insulin Dependent (Type I or Juvenile) Diabetes: Makes up 10% of diabetes cases. Characterized by insufficient insulin production due to immunological destruction by T cells of insulin- secreting cells of the pancreas. Usually develops before the age of 15. C. Type IV (Cell-Mediated) Autoimmune Reactions
  70. 70.  Immunodeficiencies can be divided into:  1) Primary immunodeficiency disorders, which are almost always genetically determined  2) Secondary immunodeficiency states, which may arise as complications of infections; malnutrition; aging; or side effects of immunosuppression, irradiation, or chemotherapy for cancer and other autoimmune diseases. Immunologic Deficiency Syndromes
  71. 71. Acquired Immunodeficiency Syndrome (AIDS)  AIDS is a disease caused by the retrovirus: Human Immunodeficiency Virus (HIV) and characterized by:  Profound immunosuppression that leads to opportunistic infections,  Secondary neoplasms, and  Neurologic manifestations. 
  72. 72. HIV and AIDS Acquired Immunodeficiency Syndrome • Disease caused by an infectious agent: A Retrovirus
  73. 73. HIV and AIDS The Cellular Picture In advanced disease: the loss of another cell type CD8+ cytotoxic killer cells Loss of one cell type throughout the course of the disease CD4+ T4 helper cells A fall in the CD4+ cells always precedes disease
  74. 74. • AIDS is therefore the end point of an infection that is continuous, progressive and pathogenic AIDS Definition • AIDS is the presence of one of 25 conditions indicative of severe immunosuppression OR • HIV infection in an individual with a CD4+ cell count of <200 cells per cubic mm of blood
  75. 75. Female sex partners of AIDS Not just in the Gay community Different ways of getting a similar syndrome • Blood transfusions • Intravenous drug use • Hemophilia (clotting factor) HIV and AIDS
  76. 76.  Mothers who are HIV infected can pass the virus on to their fetuses in utero or to infants via breast milk.  Infection is aided by the presence of other sexually transmitted diseases that can produce mucosal ulceration and inflammation.
  77. 77.  HIV infection is aided by Langerhans cells in mucosal epithelial surfaces which can become infected.
  78. 78.  When HIV infects a cell, it must use its reverse transcriptase enzyme to transcribe its RNA to host cell proviral DNA.  It is this proviral DNA that directs the cell to produce additional HIV virions which are released.
  79. 79. Types of HIV  HIV-1 is the most common type and is the infectious agent that has led to the worldwide AIDS epidemic. ØIt has a number of subtypes (A through H and O) which have differing geographic distributions but all produce AIDS similarly.  HIV-2 that is much less common and less virulent, but eventually produces clinical findings similar to HIV-1.
  80. 80. Acquired Immunodeficiency Syndrome (AIDS)  When the CD4 lymphocyte count drops below 200/microliter, then the stage of clinical AIDS has been reached. This is the point at which the characteristic opportunistic infections and neoplasms of AIDS appear.  The organ involvement of infections with AIDS represents the typical appearance of opportunistic infections in the immunocompromised host--that of an overwhelming infection--that makes treatment more difficult.
  81. 81.  Pneumocystis carinii is the most frequent opportunistic infection seen with AIDS.  It produces a pulmonary infection, called Pneumocystis carinii pneumonia (PCP), but rarely disseminates outside of lung. The most common clinical findings in patients with PCP are acute onset of fever, non- productive cough, and dyspnea. Pneumocystis carinii (jiroveci)
  82. 82.  Cytomegalovirus (CMV) is the most frequent disseminated opportunistic infection seen with AIDS.  It causes the most serious disease as pneumonia.  It can also cause serious disease in the brain and gastrointestinal tract. It is also a common cause for retinitis and blindness in persons with AIDS. Cytomegalovirus (CMV)
  83. 83.  Mycobacterial infections are frequently seen with AIDS. Mycobacterium tuberculosis has been increasing in frequency since the start of the AIDS epidemic.  The appearance of M tuberculosis with AIDS is similar to that of non-AIDS patients, with granulomatous pulmonary disease, though the infection may be more extensive or may be disseminated to other organs. Mycobacterium tuberculosis
  84. 84.  There are many types of fungi that can complicate the course of AIDS.  One of the most frequent (though uncommonly life- threatening) is Candida.  Oral candidiasis is often seen with HIV infection and may presage the progression to AIDS. Candida can occasionally produce invasive infections in esophagus, upper respiratory tract, and lung. Fungus Infection
  85. 85.  Toxoplasma gondii is a protozoan parasite that most often leads to infection of the brain with AIDS.  The lesions are usually multiple and Toxoplasma
  86. 86.  Herpes simplex virus infection with AIDS is most likely to involve the gastrointestinal tract, mainly the esophagus and the perianal region.  Herpes zoster infection of the skin can also occur prior to the onset of clinical AIDS. Herpes virus
  87. 87.  Cryptosporidium, Microsporidium, and Isospora are all capable of producing a voluminous watery diarrhea in patients with AIDS. Protozoal Infections
  88. 88. Malignant Neoplasms  Kaposi's sarcoma (KS) produces reddish purple patches, plaques, or nodules over the skin and can be diagnosed with skin biopsy.  Visceral organ involvement eventually occurs in 3/4 of patients with KS.  Malignant lymphomas seen with AIDS are typically of a high grade and extranodal, often in the brain. They are very aggressive and respond poorly to therapy.
  89. 89. Amyloidosis
  90. 90. Amyloidosis  A disease characterized by Extracellular Deposition of pathologic insoluble fibrillar proteins in organs and tissues.  Amyloid is especially deposited around the supporting fibers of blood vessels and basement membranes
  91. 91. Linear non branching aggregated fibrils with a diameter of 8-10nm Fibrillar nature and sheet configuration described by electron microscopy in 1959.
  92. 92. Amorphous homogenous, hyalin-like eosinophilic appearance of amyloid under light microscopy. Amyloid protein is either: a) Amyloidogenic itself or b) Can be modified to become amyloidogenic
  93. 93.  Detection: 1. Lugol’s iodine Deep brown color Blue color H2SO 4
  94. 94. 2) Methyl violet Red color
  95. 95. 3) Congo red Red orange color Apple Green Fluorescence Polarized light
  96. 96. 4) Thioflavin -T Strong Fluorescence Ultraviolet light
  97. 97. Distribution Systemic Primary (AL) Multiple Myeloma Plasmacytoma Some B-cell Lymphomas Secondary (AA) T.B. Lepromatous Leprosy Chronic Osteomyelitis Chronic suppurative lung diseases Localized β-amyloid Prealbumin Senile brain Medullary thyroid carcinoma
  98. 98. Effects Around blood vessels Increased Permeability Narrowing Pressure on adjacent cells Atrophy
  99. 99. v May present with rapid and progressive onset of CHF. v Characteristically, features of right sided CHF. v Concentrically thickened ventricles with normal-small cavity CARDIAC
  100. 100. RENAL  Nephrotic syndrome present in 30-50% at diagnosis.  Renal failure develops only rarely during course of the illness. Pale, waxy, and firm kidney
  101. 101. Effects Around blood vessels Increased Permeability Narrowing Pressure on adjacent cells Atrophy Proteinuria Degeneration of tubules Renal Failure
  102. 102. v Involvement of liver is common. v Hepatomegaly may be striking at presentation v Patients may present with severe intrahepatic cholestasis v Presence of jaundice is a bad prognostic factor Liver is enlarged, firm, and waxy HEPATIC
  103. 103.  Sago Spleen Deposit is limited to splenic follicles  Diffuse (Lardaceous) Spleen Deposit is present in the follicles and red pulp SPLENIC
  104. 104. v Atrophy of intestinal mucosa v The patient may present with: 1. Malabsorption 2. Diarrhea 3. Protein loss 4. Electrolyte imbalance The intestinal mucosa is pale and atrophic GIT