AIDS and Immune Disorders

  1. Hypersensitivities
    Antigenic response beyond what’s normal. Undesirable reaction produced by normal immune system.

    –4 types, types I - IV
  2. Autoimmunity
    Failure of organism to recognize own constituents as “self” resulting in immune response against own cells and tissues.
  3. Immune deficiency
    Immune system’s ability to fight infectious disease is compromised or absent.
  4. Hypersensitivity Type 1
    •Immediate, IgE-mediated; anaphylactic

    –Plasma cells secrete IgE & bind mast cells or basophils causing degranulation & release of histamine
  5. Hypersensitivity Type 2

    –Ag cause form. of IgM & IgG that bind & destroys target cell
  6. Hypersensitivity Type 3
    •Immune complex

    –Ab & Ag cause inflammation
  7. Hypersensitivity Type 4
    Cell mediated

    –Ag activate Tc that kill target cells

    2 - 3 days before you develop allergies

    delayed hypersensitivity

    t cells involved

    poison ivy
  8. 4 Types of Hypersensitivities
    • Type 1 Immediate, IgE-mediated; anaphylactic
    • Type 2 Cytotoxic
    • Type 3 Immune complex
    • Type 4 Cell mediated
  9. Type I – Immediate, IgE-mediated
    •Affects ~25% of the US population

    •Examples? PCN, asthma, hives

    •How does it develop? Reexposure to a specific type of antigen.
  10. Type I – Immediate, IgE-mediated 2
    •Symptoms? Breathing difficulty, shock, fever, asthma

    •Treatments? Epinephrine, antihistamines, corticosteroids
  11. Sensitization/IgE production (part 1)
    • 1. allergen particles enter mucous membrane
    • 2. they get carried to lymph nodes
    • 3. B cell recognizes allergen with help of T cell
    • 4. B cell proliferates into plasma cell
    • 5. Synthesize IgE
  12. Sensitization/IgE production (part 2)
    • 6. igE binds to mast cell surface receptors
    • 7. allergen attaches to igE on mast cells and triggers degranulation and release of allergic mediators
    • 8. distribution of mediators in bloodstream
    • 9. symptoms in various organs 
    •      - runny nose, hives, etc
  13. Type I Hypersensitivity
    •Mast cells – found in tissues

    •Basophils – found in blood

    - Release granules that contain:



  14. Histamine
    Dilates blood vessels and makes vessel walls abnormally permeable
  15. Leukotrines
    • Hormone that causes symptoms of hay fever
    • and asthma
  16. Prostaglandins
    –Functions in contraction & relaxation of smooth muscles, dilation & constriction of blood vessels, control of BP, & modulation of inflammation
  17. Localized Anaphylaxis
    associated with ingested Ag (food/pollen)

    •Examples: fish or plant pollen, dust mite feces.

    •Symptoms: Hives, systemic anaphylaxis or itchy eyes, sneezing.
  18. Systemic Anaphylaxis
    Individual sensitized to Ag exposed to it again

    •Examples: PCN sensitivity, peanuts, insect (bee sting)

    Symptoms: More sever, difficulty breathing, shock
  19. Treatment for Type I Hypersensitivies Allergy Shots 

    What is injected?
    Increasing dosages of antigen
  20. Treatment for Type I Hypersensitivies Allergy Shots 

    1. What is the goal of this therapy? 
    2. Why don’t you want the antigen to bind to ige?
    1. To produce igg instead of ige. 

    Why? Because if you are exposed to the antigen the igg will intercept. It will come in place and bind to the antigen before the antigen binds to ige. 

    • 2. It will cause degranulization and
    • therefore a hypersensitivity reaction.
  21. Type II 

    How does it develop
    Type II – Cytotoxic 

    Ab bind to Ag’s on patients own cell surfaces. Cells are recognized by APC causing B cell response where Ab’s are produced against foreign Ag.

    • Examples: Transfusion reactions, hemolytic dz
    • of newborn
  22. Type II – Cytotoxic 

    1. Symptoms
    2. Treatments
    1. lysis of RBC’s, severe anemia

    • 2. Passive immunization: RhoGAM,
    • transfusion. Anti-inflammatory & immunosuppressive
  23. Rh Incompatibility
    When a mother and her unborn baby carry different Rh protein factors. It is specifically caused when a mother is Rh-negative and her baby is Rh-positive. If a woman is Rh-negative and her baby is Rh-positive, then her body will determine the Rh-positive protein to be foreign. if blood cells from the baby cross into the mother’s bloodstream, the mothers immune system will make antibodies against the baby’s red blood cells. Once an Rh-negative mother’s body has made these antibodies her body will send these antibodies across the placenta to attack the baby’s red blood cells
  24. Type III
    Type III - Immune Complex

    How does it develop: Ag-Ab complexes deposited in organs. Cause inflammatory damage

    Examples: Glomerulonephritis, inflammatory damage to kidney glomeruli (site of blood filtration). Serum sickness. Lupus.
  25. Type III – Immune Complex 

    Symptoms: Chronic inflammation.

    Treatments: Steroids, prednisolone.
  26. Type IV
    Type IV - Cell Mediated, Delayed Hypersensitivity

    How does it develop: caused by T cells

    Examples: transplant rejection mediated by CTLs. TB test
  27. Type IV – Cell Mediated, Delayed Hypersensitivity

    •Symptoms: hypersensitivity of skin

    • •Treatments: immunosuppressive agents,
    • corticosteroids.
  28. Poison Ivy
    Type IV hypersensitivity
  29. HLA Reactions
    • HLA = human leukocyte antigen
    •      It’s a histocompatibility antigen the major histocompatibility antigen = MHC

    • human version of MHC
    • proteins classified as antigen

    body recognizes self or nonself
  30. HLA Reactions 2
    • •T cells recognize Ag + MHC
    •      –1-10% of T cells will recognize a foreign MHC molecule

    •Important for transplant rejection
  31. Autograft
    Tissue moved to different location within same individual
  32. Isograft
    Transplant between two identical individuals.
  33. Allograft
    Transplant from one person to another. Account for many human transplants: from cadavers, living related & unrelated donors.
  34. Xenograft
    Surgical graft of tissue from one species to an unlike species. 

    ie. Graft from baboon to human.
  35. Graft rejection
    Immune response that regards graft as foreign.
  36. How is graft rejection prevented?
    Cyclosporin, Tacrolimus – block T cell activation

    Sirolimus, mycophenolate mofetil – block proliferation of T & B cells

    Basiliximab & daclizumab – Abs that block IL-2
  37. Autoimmunity
    •Affects 5% of the developed world

    •Disproportionately affects women
  38. Autoimmunity 2
    •Loss of self tolerance

    • •Patients can have auto reactive T cells
    • and Abs
  39. Autoimmune reactions can be mediated by
    –Cytotoxic reactions

    –Immune complexes

    –Cell mediated hypersensitivities
  40. Type II (Cytotoxic) Hypersensitivity

    autoimmune diseases
    Grave’s disease

    Myasthenia Gravis
  41. Grave’s disease
    –Ab attach to thyroid stimulating to overproduced thyroid hormones. results in enlarged thyroid (goiter), bulging eyes.
  42. Myasthenia Gravis
    Ab coat acetylcholine receptors at nerve impulse/muscle junction. results in muscle weakness, respiratory arrest, death
  43. Type III (Immune Complex-Mediated) Hypersensitivity
    Systemic lupus erythematosus

    Rheumatoid Arthritis
  44. Congenital immunodeficiencies

    –How does it develop: Present at time of birth. Result of genetic defect.

    –Example: Di George’s syndrome
  45. Congenital immunodeficiencies 2
    –Symptoms: respiratory infections, chronic sinusitis, chronic bronchitis.

    –Treatment: depends on subtype
  46. Bubble Boy
    David Vetter
  47. Immunodeficiencies
    • 1.Congenital immunodeficiencies (primary)
    • 2.Acquired immunodeficiencies (secondary)
  48. Acquired immunodeficiencies

    • How does it develop: virus selectively
    • infects helper T cells.

    Examples: HIV
  49. Acquired immunodeficiencies 2
    –Symptoms: body vulnerable to life threatening infections & cancer. (Kaposi’s sarcoma).

    –Treatment: anti-viral or drugs to strengthen immune system.
  50. AIDS
    •Acquired Immunodeficiency Syndrome

    •Causative agent: HIV (human immunodeficiency virus)
  51. AIDS category A
    –asymptomatic or persistent lymphadenopathy
  52. AIDS category b
    –persistent infections with Candida albicans, may also have shingles, persistent diarrhea & fever
  53. AIDS category c
    –(clinical AIDS) Candida albicans infection of esophagus, bronchi & lungs; cytomegalovirus eye infection; TB; pneumocystis pneumonia; toxoplasmosis of the brain; Kaposi’s sarcoma
  54. AIDS 2
    •Less than 200 CD4+ T cells/ mm3

    •normal numbers are 800-1000 CD4+ T cells / mm3
  55. AIDS 3
    virus infects CD4+ T cells and macrophages. results in immunodeficiency

    –Secondary lymphoid tissue in the gut mucosa is destroyed 1st, early on in infection
  56. AIDS lifecycle
    •some virions remain in vacuoles inside the cell = latent virus

    •Provirus, viral DNA integrated into host chromosome and new viruses are released by budding
  57. AIDS lifecycle 2
    –Rapid immunogenic change allows it to evade the immune system; due to mutation rate of RT
  58. Latent HIV
    intact virion remains in a vacuole inside the cell
  59. Provirus HIV
    •viral DNA is integrated into the host’s DNA
  60. number of people worldwide infected with HIV
    35.9 - 44.3 million people worldwide are infected with HIV
  61. Epidemiology
    transmission via direct contact with bodily fluids (especially blood) – sexual contact, IV drug use, & perinatal contact
  62. Blood contains
    1,000-10,000 virions/ml
  63. Semen contains
    10-50 virions/ml
  64. Saliva contains
    < 1 virion/ml
  65. HIV can survive only
    ~6hrs. outside of a cell
  66. AIDS treatment
    (no cures)  anti-HIV drugs prolong life

    –HAART: highly active antiretroviral  therapy = 3+ drugs
  67. AIDS Prevention
    condom use, discouraging promiscuity, not sharing needles, screening of blood and organ donors
  68. AIDS - Obstacles to vaccine development
    –Virus clades differ greatly from 1 geographic area to another

    –Neutralizing Abs are exceedingly difficult to stimulate
  69. AIDS - Obstacles to vaccine development 2
    –Cells infected by HIV are often not recognized by the immune system and therefore not susceptible to CTL lysis

    –Provirus & latent viruses are immunologically invisible
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AIDS and Immune Disorders