Immuno Type II, III & IV Hypersen (15, 16)

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  1. Immuno 15
  2. Type ll Hypersensitivity (cytotoxic reactions)
    • abnormal antibody directed against a target organ causes destruction of the target cell/organ by complement mediated lysis or ADCC
    • complement mediated lysis: Ig attached to target cell, binds complement which punches holes in cell membrane, effectively killing the cell
    • ADCC: NK cell finds/attaches to the Fc portion of the antibody & kills cell by pumping into it perforin & granzyme
    • antibody (Ig) = 'guided missile' into target cell
  3. What other cells respond to antibody binding to a target cell?
    • neutrophils
    • when antibody binds to a target cell, neutrophils can ALSO bind to the antibodies & phagocytose said target cell
  4. Examples of Type II Hypersensitivity
    • Autoimmune hemolytic anemia
    • Autoimmune thrombocytopenia
    • Goodpastures syndrome
    • Hyperacute graft rejection
    • Anti-receptor antibody diseases (eg. Myasthenia gravis, Grave’s disease)
  5. How does antibody binding kill certain cells?
    • immune cells will recognize coated cells (or pathogens) using their Fc RECEPTORS, which bind to the Fc region of antibodies
    • engagement of a particular antibody with the Fc receptor on a particular cell triggers an effector function of that cell:
    • phagocytes: phagocytose
    • mast cells & neutrophils: degranulate
    • NK cells: release cytokines and cytotoxic molecules to destroy its target
  6. Autoimmune hemolytic anemia
    • autoantibodies are made against RBCs
    • RBCs are destroyed by activation of complement resulting in hemolysis or by macrophage phagocytosis
    • more common in women
  7. Autoimmune thrombocytopenia
    • autoantibodies are made against platelets
    • platelets bound with IgG are removed from the circulation by macrophages in the spleen and liver
    • symptoms = little red spots all over skin (purpuric spots) + bruising; low platelet count
  8. Goodpastures syndrome
    • autoantibodies are made against glomerular & alveolar basement membranes - made against same protein in both basement membranes
    • may affect kidneys AND lungs; clinical features include glomerulonephritis and hemoptysis (spitting up blood)
  9. Hyperacute graft rejection
    • pre-formed antibodies are made against antigens on transplanted tissue (graft)
    • activation of complement triggers the blood clotting cascade, leading to ischemia + loss of the graft within minutes to hours of transplantation
    • (also a type I hypersensitivity reaction - b/c immediate)
  10. Anti-receptor antibody diseases
    diseases where antibody is made against a receptor on the surface of a cell (eg. Myasthenia gravis & Grave’s disease)
  11. Myasthenia gravis
    • an autoantibody is made to the acetylcholine receptor (AChR) on muscle cells
    • said Ig binds to the receptor & BLOCKS binding of acetylcholine (an NT) --> as result there can be no muscle activation
    • additionally, the autoantibody induces complement activation, resulting in damage to the muscle end-plate detroying AChRs as the disease progresses; also the muscle cell itself phagocytoses the antibody-receptor complex, destroying AChRs
  12. Grave’s disease (Hyperthyroidism)
    • an autoantibody to the receptor for thyroid-stimulating hormone (TSH) on cells of the thyroid
    • its binding causes constant stimulation of the thyroid, & therefore unending overproduction of the thyroid hormones T3 & T4
    • cure: remove 3/4ths of thyroid
  13. Adison's disease
    an autoantibody is made against the adrenal gland
  14. Type lll Hypersensitivity (Immune-complex disease)
    • antigen-antibody immune complexes are trapped in the small vessels of the body, particularly in the skin, kidney, & joints
    • binding of complement to the Ig triggers an inflammatory reaction; the creation of C3a and C5a chemotactically attract neutrophils
    • neutrophils degranulate in the vessel wall releasing powerful lysosomal enzymes that serve to degrade the immune complex
    • however it simultaneously damages the vessel walls (vasculitis)
    • in the meantime as well, complement levels drop as they're being distracted by these immune complexes
  15. What types of animals CANNOT contract immune-complex diseases (type III hypersensitivity reactions)?
    animals with NO polymorphs (aka neutrophils)
  16. Systemic lupus erythematosus (SLE)
    • autoantibodies are made against your own DNA (antigen = DNA); called antinuclear antibodies (ANA)
    • immune complexes (antigen-antibody complexes) deposit in many tissues and affect many organ systems (skin, joints, serosal surfaces, kidneys, & CNS)
    • classic example of immune-complex disease
  17. Post-streptococcal glomerulonephritis
    • occurs after a person is infected by streptococcus bacteria [sore throat]
    • they make anti-streptococcal antibody, which combines with streptococcal antigen (immune complex) & gets stuck/deposits mainly in the glomerular capillary wall of the kidneys
  18. Serum Sickness
    • caused by antibodies made against contents of foreign serum from another animal (eg. a horse)
    • typically induced following therapy with large doses of foreign antibodies (eg. monoclonal mouse antibodies or horse serum antitoxins to cure snake bites)
    • immune complexes deposit in various tissues, especially in arteries, joints, & renal glomeruli
  19. Drug Reactions
    • when an antibody is made against a drug
    • they may combine with the drug forming immune complexes that can deposit in vessel walls producing vasculitis
    • *NOTE: penicillin & its derivatives may also cause acute allergic reactions (Type l), immune complex reactions (Type lll) OR delayed hypersensitivity reactions (Type lV)
  20. Localized Immune complex disease (Arthus Reaction)
    • a localized, not circulatory, type III hypersensitivity reaction
    • happens when antigen is introduced into an individual who already has pre-formed antibodies against that antigen
    • immune complexes at the site where antigen was introduced attract neutrophils & produce inflammation (after about 6-8 hours)
    • eg. tetanus booster or hypersensitivity pneumonitis (Farmer’s Lung or Bird Fancier's Disease)
  21. Tetanus Booster
    • when tetanus toxin is given in the form of a shot booster to a person who already has tetanus antibodies, the area of injection may get sore, red & inflamed as a result of immune complexes in the arm attracting neutrophils & such
    • example of Arthus reaction/localized immune complex disease/type II hypersensitivity reaction (6-8 hours to form)
  22. hypersensitivity pneumonitis
    • inflammation of the alveoli within the lung caused by a type III (immune complex) hypersensitivity reaction to inhaled organic dusts
    • an X-ray looks like there's a 'snow storm' in the lungs
    • eg. Farmer’s Lung, Bird Fancier's Disease
  23. Farmer’s Lung
    • occurs in farmers turning hay because organisms called actinomycetes are present in mouldy hay
    • repeated inhalation of these organisms stimulates systemic IgG antibody production
    • further inhalation produces immune complexes in the lung and an Arthus (localized) reaction
    • LATE there is infiltration by T-cells with cytokine production and further inflammation
    • *therefore this is a mixture of Type III and a Type IV hypersensitivity reactions
  24. Biopsying a region affected by Farmer's Lung or Bird Fancier's Disease what will you find?
    • Type III: antibody, antigen, polymorphs (neutrophils), complement AND
    • Type IV: T CELLS
  25. Immuno 16
  26. Delayed Hypersensitivity (Type IV)
    • delayed-type hypersensitivity (DTH) or Type IV reactions are mediated by T cells & activated macrophages
    • the mechanisms of DTH are the same as those for cell-mediated immunity however in delayed hypersensitivity, the result is tissue damage
    • T cells release inappropriately large amounts of cytokines in response to an antigen --> cytokines recruit & activate effector cells (mainly macrophages) which cause local tissue damage
  27. sensitization phase
    • similar to other hypersensitivity reactions, sensitization is REQUIRED to generate DTH
    • during sensitization, APCs (particularly dendritic cells) process the antigen and present it to TH1 cells
    • sensitization activates and expands the number of antigen-specific TH1 cells that can cause a DTH reaction if re-exposure to the antigen occurs
  28. effector phase
    • during the effector phase, T cells (antigen-specific TH1 cells) produce cytokines that recruit & activate macrophages + other inflammatory cells
    • accumulation of inflammatory cells causes local tissue damage
    • DTH reactions also involve CD8+ T cells which cause tissue damage via cell-mediated cytotoxicity
  29. contact dermatitis
    • skin inflammation that occurs when a foreign substance touches your skin causing irritation
    • example of delayed hypersensitivity
  30. foreign substances that might induce contact dermatitis:
    • urushiol in poison ivy
    • cosmetics
    • foreign chemicals
    • latex/rubber
    • metals (eg. nickel, zinc reacting with skin proteins) in jewelry
    • p-Phenyl diamine in hair dyes
    • Neomycin in topical ointments
  31. Characteristics of the Effector Phase
    • Cytokine and Chemokine Production
    • Endothelial Cell Activation
    • Macrophage Activation
    • Killing by Cytotoxic T Lymphocytes (CD8+)
  32. Cytokine and Chemokine Production
    • IL-2: promotes T cell proliferation
    • IFNγ: activates macrophages
    • IL-1 & TNF: upregulates adhesion molecules on endothelial cells
  33. Endothelial Cell Activation
    • endothelial cells undergo changes to facilitate infiltration of leukocytes into the site of inflammation
    • they increase their number of adhesion molecules on their surface
    • they change their shape to facilitate extravasation of leukocytes
    • they secrete IL-8, a chemokine which attractants leukocytes
  34. Macrophage Activation
    • INFγ + other T cell-derived cytokines stimulate new or increased gene transcription that up-regulates most macrophage functions
    • increased phagocytosis and killing
    • increased oxygen consumption
    • increased expression of surface molecules (MHC molecules, Fc receptors, + adhesion molecules)
    • increased secretion of monocyte/macrophage-derived cytokines (eg. IL-1, TNF, & IL-6)
  35. What purpose do macrophage-derived cytokines serve?
    • IL-1, TNF, & IL-6 increase the inflammatory response and may produce tissue destruction
    • LATER they contribute to fibrosis or scarring due to the fibrogenic effect of some cytokines
    • may also instigate granuloma formation (individual clusters/nodules of macrophages)
  36. Killing by Cytotoxic T Lymphocytes (CD8+)
    • is antigen-specific
    • requires cell contact
    • induces apoptosis of target cells by activating enzymes IN target cells that digest the cell’s own DNA, as well as the action of perforin & granzymes
  37. What surface molecules must interact to induce killing by Cytotoxic T Lymphocytes (CD8+ T cells)?
    • target --> T cell
    • LFA3 --> CD2
    • ICAM --> LFA1
    • MHC Class 1 --> CD8
  38. patch test
    • a commonly performed procedure used to identify the nature of the antigen causing contact dermatitis
    • a solution of the suspected antigen is spread on the skin and covered by an occlusive dressing
    • appearance of an area of induration & erythema within three days indicates sensitivity
  39. How LONG does it take for a delayed hypersensitivity reaction to occur?
    • 2-5 days
    • this is because memory cells have to be TURNED ON in order to elicit a reaction
    • why a patch test is usually read after ~48 hours
  40. forms of delayed hypersensitivity
    • tuberculin skin test
    • chronic infections (eg. Viral hepatitis)
    • chronic bacterial diseases (eg. TB, syphilis, leprosy)
    • chronic fungal infections (eg. Candidiasis)
    • parasitic diseases (eg. Leishmaniasis)
    • in many chronic conditions it is the immune response that causes the damage & disease manifestation
  41. Tuberculin Skin Test (Mantoux Reaction)
    • TB screening test that determines whether a person has been exposed to tuberculosis before; if positive 2-5 days later is a type of DTH reaction
    • tuberculosis protein purified protein derivative (PPD) is injected into the skin of an individual
    • if the person has had a previous cell-mediated immune response to M. tuberculosis, the site of injection becomes raised & red (erythema & induration) --> due to memory T cells reacting with/destroying the injected toxins
  42. What would a biopsy taken early in a Mantoux reaction reveal?
    primarily mononuclear cells of the monocyte-macrophage series along with a few lymphocytes
  43. In which type of reaction are Neutrophils a prominent feature?
    • Arthus, or immune complex reaction (type III)
    • they are NOT characteristic of a delayed hypersensitivity reaction (type IV)
  44. BCG
    • vaccine given to individuals born in other countries against tuberculosis
    • if given this vaccine, a person will have memory T-cells that can produce a positive tuberculin skin test
  45. Which infectious agents is CMI (cell-mediated immunity) crucial for protection?
    • 1. Intracellular Bacteria (tuberculosis)
    • 2. Large Viruses (pox & herpes)
    • 3. Fungi (candida albicans, pneumocystis)
    • 4. Parasites (toxoplasma)
    • these infections are what immunocompromised people get (HIV, transplant receivers)
    • [intense bacterial infection = lacking complement]
  46. Which autoimmune diseases are T cell mediated?!
    • Insulin-Dependent Diabetes Mellitus (IDDM)
    • Rheumatoid Arthritis
    • Multiple Sclerosis
    • Crohn’s Disease
    • Psoriasis
    • Celiac Disease
    • All of these diseases are primarily caused by T- cell attack
    • this may be followed by secondary auto-antibody production
  47. chronic inflammation
    • a form of inflammation that MAY follow acute inflammation OR may start as a low grade response to certain microorganisms, inanimate materials, or autoantigens
    • occurs when polymorphs of an acute inflammation response can't get rid of whatever is causing the inflammation, so lymphocytes & macrophages move into the site to try & take care of it --> chronic
    • present during Tuberculosis, Leprosy, Fungal infections, Silicosis, & Rheumatoid arthritis
  48. What type of cells are characteristic of chronic inflammation?
    • lymphocytes, macrophages, & plasma cells
    • there are NO polymorphs, antibody OR complement
    • what results is tissue destruction, fibrosis, & scar formation
  49. granuloma
    • when macrophages - in certain cases of chronic inflammation - collect in layers surrounding the problematical material (silica, or TB, etc)
    • and fuse, forming giant cells
    • structure = layers of macrophages surrounding a central core
  50. Why can't granulomas characteristic of tuberculosis destroy the phagocytized bacteria?
    because the bacteria somehow prevent lysosomes from fusing with the phagocytic vesicles

Card Set Information

Immuno Type II, III & IV Hypersen (15, 16)
2013-11-03 19:16:50

Exam 4
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