16. Hypersensitivity Reactions (III & IV) Flashcards
What causes Type III Hs?
large amounts of immune complexes that aren’t removed by normal mechanism
What are some examples of Type III Hypersensitivity disease?
Serum sickness, Farmer’s lung caused by inhalation of moldy hay
What are the hallmarks of DTH (Type IV)?
- Delayed time for reaction to develop
o 1-3 days - Purely cell-mediated rather than Ab mediated
- Recruitment of Macs (as opposed to neutrophils in type III reactions)
Basics of Type IV DTH
T helper cells encounter Ag, secrete cytokines that induce localized inflammatory reaction (delayed type hs), cytokines cause large influx of Macs which cause tissue damage
Immune complex =
Ab plus soluble Ag
Immune complexes can damage tissue. T or F?
TRUE
What type of response occurs if immune complex is deposited near site of Ag entry?
localized reaction
(Type III) What type of response occurs if complexes are formed in the blood?
reactions develop where deposited
(Type III) After immune complex is formed, what four steps occur:
- Immune complex activates complement
- Generation ofo anaphylatoxins (C3a, C4a, C5a)
- Recruit neutrophils and granule release
- Anaphylatoxins cause mast cell degranulation
Deposition of immune complexes can trigger
release of inflammatory mediators and vasoactive mediators including proteases which may damage connective tissues; clots may form as complexes activate platelets
Deposition of immune complexes in blood vessels causes
vasculitis
Deposition of immune complexes in kidneys causes
glomerulonephritis
Deposition of immune complexes in joints causes
arthritis
Arthus reactions are
localized Type III Hs reactions
Why is granuloma a double edged sword?
walls off organism in the infected tissue; macrophage lytic enzymes damage the body tissue
Explain skin testing for DTH reactions.
- To determine whether a person has been exposed to M. tuberculosis:
- PPD (bacterial cell wall protein) is injected intradermally
- Development of firm, red, swollen lesion @ 48-72 h indicates previous exposure
- Positive result indicates person has population of sensitized Th1 cells
Skin test for DTH reaction distinguishes whether exposure was to pathogenic for or to vaccination. T or F?
FALSE; skin test does not distinguish between exposure to pathogen for or to vaccination
Contact dermatitis is a Type IV Hs. T or F?
TRUE
How can sensitization occur?
if a reactive chemical compound binds to skin proteins
Type IV Hs can be induced by:
pharmaceuticals, cosmetics, industrial chemicals, metal ions, and more
What type of Hs can cause strong cell-mediated responses against skin cells, inducing blister-like lesions and rashes?
Type IV Hs (DTH)
Tolerance =
prevention of an immune response against self Ags
Central tolerance is the prevention of an immune response against self Ags by what mechanism?
deletion of lymphocytes before they mature; central tolerance limits development of autoreactive T and B cells
Where does tolerance occur?
generative lymphoid organs
Peripheral tolerance =
either renders self-reactive lymphocytes nonresponsive or actively generates inhibitive lymphocytes outside the bone marrow and thymus
Antigen sequestration
a means to protect self antigens from attack
What are some examples of antigen sequestration?
-anterior chamber and lens of eye lack lymphatic drainage
-blood brain barrier
-development of male reproductive cells
What does peripheral tolerance regulate?
autoreactive cells that made it into circulation
Name the 3 steps of peripheral tolerance.
- if T cells only receive “signal 1” they become anergic
- CTLA-4 expression on T cells (in lieu of CD28)
- Induction of T regulatory cells
T regulatory cells are
regulatory CD4+ T cells which can be generated in they thymus or in the periphery following Ag induction
Treg cells still engage Ag-MHC Class II complexes through TCR. T or F?
TRUE; but they downregulate responses when they do so
Name four mechanisms by which Tregs suppress.
- kill APCs and effector T cells by perforin and granzymes
- inhibit APC function via CTLA-4
- secrete immune inhibiting cytokines such as IL-10 and TGF-beta
- act like a sponge to absorb IL-2 so other T cells can’t get fully
Autoimmunity =
when the immune system turns on itself due to a lack of self tolerance
Some autoimmune diseases are mediated by direct cellular damage. Explain this four step process.
- lymphocytes or Abs bind to cell-membrane self Ags
- cellular lysis and/or inflammatory response
- damaged tissue replaced by scar tissue
- organ function declines
Hashimoto’s thyroiditis is most common in what population?
middle aged women
Hashimoto’s thyroiditis decreases the function of what?
thyroid function, leading to hypothyroidism
Explain the role of Ab in Hashimoto’s thyroiditis.
Auto Abs and Th1 cells produced are specific for thyroid Ags; Ab produced interferes with iodine uptake
Diseases characterized by induced DTH response in the thyroid.
Hashimoto’s Thyroiditis
Goiter
visual enlargement of the thyroid gland as a result of inflammation induced by DTH response in thyroid (intense WBC infiltration)
CTLA-4 expression only occurs on what type of cells?
activated T cells
CTLA-4 binding to _________________ inhibits T cells.
CD80/86
Mice lacking CTLA-4 show widespread _________________ disease.
autoimmune
