FMS Week 9 Flashcards
Immunology II
Describe the hypersensitivity associated with post-strep glomerulonephritis?
Generalized type III (serum sickness)
What leukocytes are associated with artheroclerosis?
macrophages
What are some of the issue with anti-tumor T-cells?
pretty well regulated by T-regs; also tumor evolution
Describe the hypersensitivity associated with myasthenia gravis:
type II; antibodies against acetylcholine receptors
What is the role of serotonin in type I hypersensitivity?
causes vasodilation (preformed in mast cells)
What are stable tissues?
normally inactive “queiescent” cells; replicate minimally, but can regenerate in response to injury
What leukocytes are associated with arthritis?
lymphocytes and macrophages
describe the role of PDGF in wound healing:
platelet-derived growth factor; comes from platelets, macrophages, and endothelial cells
stimulates growth, migration, and collagen synthesis in fibroblasts
what type of regenerative tissue are neurons?
permanent
What are hypertrophic scars?
excessive scarring about 4 weeks after injury; remains within wound borders
mostly type III collagen, organized, may regress spontaneously
What is the primary mechanism behind the anti-anaphylactic use of epinephrine?
vasoconstriction; reduces swelling
Describe the hypersensitivity associated with PPD testing:
type IV (delayed-type); memory T-cells recognize tuberculin, triggers Th1 response, redness and induration 24 to 72 hours later
What is granulation tissue?
“pre-scar tissue”; early healing stages (3 to5 days post injury)
collagen and new vessels, proliferating fibroblasts and some inflammatory cells
What is hypersensitivity?
an inappropriate (or exaggerated) immune response; resulting in a disease state
what type of regenerative tissue are the kidneys?
stable
What is the role of endothelial cells in inflammation?
express adhesion molecules for leukocytes (triggered by TNF-alpha and IL-1)
Proliferate to handle increased flow
Produce chemokines and stimulate angiogenesis
What are some of the issues with monoclonal antibodies as anti-tumor agents?
anti-mAb antibodies; also tumor evolution
Why are autoimmune diseases self perpetuating?
Self injured tissues produce more self-antigens, leading to growing autoimmune response
Describe the hypersensitivity associated with systemic lupus erythematosus?
Generalized type III (serum sickness); anti-DNA antibodies
what is a D-dimer?
Clinical test for inflammation; a degredation product of fibrin that indicates clot formation
What is PGD2?
Prostaglandin D2; causes bronchoconstriction and eosinophil infiltration
What is FOXP3?
a gene expressed in Treg cells that functions as a transcription factor for other immunosuppressive genes
What is lipoxygenase?
an enzyme involved in leukotriene synthesis from arachidonic acid
What is AIRE?
autoimmune regulator protein; drives the negative selection of T-cell self-antigen
Describe type IV hypersensitivity:
no antibodies; entirely cell-mediated (memory T-cells)
What are the mechanisms of type II hypersensitivity?
opsonization/phagocytosis, complement, physiologic responses (non-injury)
Why is copper deficiency associated with poor wound healing?
lysyl oxidase is a copper dependent enzyme involved in the cross-linking of collagen during scar maturation
What is atopy?
a genetic predisposition for localized hypersensitivity
what are the effects of FGF?
fibroblast chemotaxis, stimulates angiogenesis, stimulates extracellular matrix protein synthesis
Difference between adult and embryonic stem cells?
embryonic stem cells are undifferentiated
Why is vitamin C deficiency associated with poor wound healing?
necessary for collagen synthesis
What is the manifestation of Sjogren’s syndrome?
autoimmune damage to salivary and lacrimal glands
What are myofibroblasts?
fibroblasts with contractile proteins (similarities with smooth muscle);
contract wound, develop around day 5, lost by apoptosis as scar matures
What are the sources of FGFs?
macrophages, mast cells, endothelial cells
What is purulent exudate?
plasma with both active and dead neutrophils, fibrinogen, and necrotic parencymal cells. Associated with more severe infections
what type of regenerative tissue are hematopoietic stem cells?
labile
Describe the hypersensitivity associated with blood type mismatch:
type II; RBC lysis triggered by circulating IgG
manifestation of mutliple sclerosis
weakness, coordination and ocular problems, paralysis
Target antigen of multiple sclerosis
myelin sheath of CNS
What is type I hypersensitivity?
classic allergic response; inappropriately preformed IgE (instead of IgG) antibodies from primary exposure cause mast cells to attack antigens
What do Tregs do?
They “turn down” overall immune response
what are eicosanoids?
lipid derived immune signalling molecules from cell membranes
Describe the hypersensitivity associated with rheumatic fever:
type II; strep antibodies cross-react with cardiac myocytes
What are labile tissues?
tissues that are continuously dividing to replace lost cells
Target antigen of type 1 diabetes
glutamase decarboxylase, IA-2 phosphatase, insulin from beta-cells of pancreas
What is a granuloma?
an aggregation of lymphocytes and macrophages trying to contain an offending agent that is difficult to eradicate
What are the means of building peipheral B-Cell tolerance?
Anergy, follicular exclusion (leading to apoptosis), and induced apoptosis
what type of regenerative tissue is the pancreas?
stable
Describe the hypersensitivity associated with autoimmune hemolytic anemia:
type II; drugs (like methyldopa and penicillin) bind to RBCs prior to metabolism; or in mycoplasma pneumonia the disease creates antibodies against RBCs
What leukocytes are associated with pulmonary fibrosis?
macrophages and fibroblasts
What is the manifestation of Progressive Systemic Sclerosis?
skin thickening due to collagen deposition, fibrosis of internal organs
What are the symptoms of type I hypersensitivity?
urticaria, rhinitis, asthma, conjunctivitis, diarrhea (systemic anaphylaxis)
What is the role of platelets in inflammation?
contribute to blood clots
Release ROS to recruit additional platelets, fibroblast growth factors, serotonin for vasodilation, and anti-microbial peptides
How does desensitization work in type I hypersensitivity?
gradually increasing doses of allergen; response changes from IgE to IgG
What are the issues with CAR T-cells?
cytokine storm
What are DR2, DR3, DR4, and B27?
HLA genes that are associated with autoimmune diseases
Describe the hypersensitivity associated with rabies or tetanus antitoxin?
Generalized type III (serum sickness)
Describe the hypersensitivity associated with pemphigus vulgaris:
type II: antibodies against desmosomes in epidermis
What matrix proteins are secreted by fibroblasts?
initially collagen III and fibronectin, later collagen I
What are the 5 clinical signs of inflammation?
calor (heat), rubor (redness), tumor (swelling), dalor (pain), funtio lasea (loss of function)
What is LTC4?
Leukotriene C4; causes vasoconstriction and broncoconstriction
what type of regenerative tissue are cardiac myocytes?
permanent
What is LTB4?
leukotriene B4; causes neutrophil and eosinophil chemotaxis
What are the 3 steps of scar formation?
angiogenesis, fibroblast migration/activation, maturation over time
Why are Arthus reactions quicker than serum sickness reactions?
the antibodies are already formed from primary exposure in Arthus reactions
What is erythocyte sedimentation rate?
Clinical test for inflammation; fibrogenated RBCs aggregate and settle out fo suspension faster
What is the most common target of systemic autoimmune diseases?
DNA/RNA or associated proteins/enzymes (intracellular autoantibodies)
Describe the role of TGF-beta in wound healing:
transforming growth factor; released by platelets, T-cells, macrophages, endothelial cells, and others;
promotes collagen production, acts as an antiinflammatory by inhibiting lymphocytes
What are Curshmann spirals?
spirals of inspissated mucus most commonly found in asthma histology that are thought to be casts of small bronchioles
What is scar remodeling?
breakdown of type III collagens, crosslinking of collagen
key enzymes: metalloproteinase (zinc) and lysyl oxidase (copper)
What is the main cause of tissue damage by neutrophils?
reactive oxygen species
Describe type III hypersensitivity:
antibodies bind small antigens (usually IgG/IgM); large accumulation of these immune complexes in the tissues
manifestation of type 1 diabetes
hyperglycemia (dehydration, weight loss, nerve and vessel damage)
What is a type II hypersensitivity reaction?
Autoimmune response; IgG/IgM directed against tissue antigens
What is a serous effusion?
an accumulation of serum in a body cavity
What is keloid?
raised scars beyond borders of original wound
excessive healing/scarring; more common with dark skin; contains mixed collagen; disorganized
what are permanent tissues?
“terminally differentiated”; have almost no ability to proliferate or regenerate; damage leads to scar
what is an Arthus reaction?
type III hypersensitivity; localized accumulation in the tissue
What is the role of platelet activating factor in type I hypersensitivity?
bronchoconstriction
what is cyclooxygenase?
an enzyme involved in prostaglandin and thromboxane synthesis from arachidonic acid
What cytokine is key to type I hypersensitivity?
IL-4 (from Th2; important for class switching and IgE production)
Cellular infiltrates of acute and chronic inflammation:
Acute: mainly neutrophils
Chronic: mainly monocytes and lymphocytes
What does histamine cause physiologically?
vasodilation (warmth), venule permeability (swelling), smooth muscle contraction (bronchospasm)
Describe the hypersensitivity associated with multiple sclerosis?
type IV; cell mediated response to myelin basic protein (believed, not well understood)
manifestation of Graves disease
hyperthyroidism (weight loss, weakness, elevated heart rate)
What is a Creola body?
an aggregation of “benign” sloughed-off cells in the lungs; not exclusive to asthma
Difference in timeline of 2nd intention healing?
more inflammation, more granulation, more contraction, more scar tissue
Why is zinc deficiency associate with poor wound healing?
metalloproteinases contain zinc and are required for collagen breakdown in scar maturation
Target antigen of autoimmune hemolytic anemia
Rh and other antigens on RBC membranes
What is the significance of CTLA4 and PD-1?
Receptors on activated T-cells, one mechanism that allows for functional inactivation of self-reactive T-cells in the periphery
What is the timeline of 1st intention healing?
1st 24 hours: Inflammation, clot formation, neutrophil invasion (increased permeability)
3-7 days: macrophages replace neutrophils, fibroblasts, angiogeneis, myofibroblasts
Weeks: remodeling, metalloporoteinases
What is ECF-A?
eosinophil chemotactic factor of anaphylaxis; preformed in mast cells, attracts eosinophils
Target antigen of myasthenia gravis
acetylcholine receptor
What are the characteristics of bronchial remodelling in chronic asthma?
mucous plugging, goblet cell hyperplasia, epithelial injury, fibrosis of the basement membrane, increased vascularity, smooth muscle and mucous gland hypertrophy
What is the purpose of blood clotting in inflammatory process?
block access/contain to infectious agents
What pro-inflammatory cytokines are released by macrophages?
IL-6, TNF-alpha, IL-1-beta, IL-8 (CXCL8), IL-12
What is serum sickness?
a type III hypersensitivity; generalized accumulation
Describe the hypersensitivity associated with contact dermatitis?
Type IV (delayed-response cell-mediated)
Describe the hypersensitivity associated with polyarteritis nodosa?
Generalized type III (serum sickness); hep B antigens
manifestation of myasthenia gravis
intermittent muscle weakness, paralysis, vision and swallowing problems
What are the issues with blocking immunosuppresive mechanisms that protect tumors?
autoimmunity
Describe the hypersensitivity associated with Goodpasture syndrome:
type II; antibodies against type IV collagen, leading to nephritic syndrome and pulmonary hemorrhage
Describe the hypersensitivity associated with hypersensitivity pneumonitis?
Localized type III (arthus reaction); “farmers lung”, reaction to previously exposed environmental antigen
What are the means of “attack” in type II hypersensitivity?
phagocytosis, complement, ADCC
Describe late symptoms of Type I hypersensitivity:
around 6 hours later: influx of inflammatory cells, induration (cytokines > neutrophils/eosinophils)
What are Charcot-Leyden crystals?
“needle” shaped crystals associated with condesnsed granules from eosinophils in asthma and other allergic reactions
What is fibrosis?
scarring; occurs in cells without regenerative capability (normal or lost due to damage)
What is PGE2?
Prostaglandin E2; causes redness, edema, fever, and pain
What leukocytes are associated with chronic transplant rejection?
lymphocytes and cytokines
What are the effects of histamine release?
Swelling/inflammation, adrenaline, increased capillary permeability, bronchoconstriction, vessel dilation, elevated heartrate, blood clots, gastric acid secretion
What are FGFs?
fibroblast growth factors
What leukocytes are associated with asthma?
eosinophils and IgE
What is LTD4?
leukotriene D4; causes vasoconstriction and bronchoconstriction
What are the 2 characteristics of stem cell division?
self-renewal and asymmetric division (one mature daughter cell and one daughter stem cell)
Describe early symptoms of Type I hypersensitivity:
within minutes: edema, redness, itching (histamine, leukotrienes, and prostaglandins)
What is the mechanism behind Pernicious anemia?
Antibodies bind to intrinsic factor of gastric parietal cells and neutralize it, decreasing absorption of vitamin b12
what type of regenerative tissue is the liver?
stable
Describe first intention healing:
tissue surfaces are closed together, requires small amounts of tissue loss, primary mechanism is epithelial regeneration
minimal scar, minimal wound contraction
describe second intention healing:
large wounds, cannot approximate edges
significant scar formation
what type of regenerative tissue are most eipithelial cells?
labile
What are leukotrienes, prostaglandins and thromboxanes derived from?
Eicosanoids (arachidonic acid)
Target antigen of Graves disease
thyroid stimulating hormone receptor (in thyroid epithelial cells)
