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

Exam 4
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