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21 Cards in this Set
- Front
- Back
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Discuss repiratory epithelial cells and their role in host defense
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first innate defense mechanisms in the lungs; ciliated; they line inner lining of the lungs
between epithelial cells are goblet cells; produce copious amounts of mucous; when particulate matter enters lungs, they are trapped by mucous; rhythmic beating of ciliated epithelial cells expels organisms to exterior by cough ciliary epithelial cells produce antimicrobial peptide Beta-defensins, cationic peptides that bind to surface of bacterial cells and inactive them epithelial lining fluid contains B-defensins, glutathione (antioxidant), and IgA (secretory Ab); in infection, IgA Abs bind to cell surface of bacteria and prevents colonization of respiratory epithelial cells |
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Describe several microbes that are resistant to respiratory host defenses
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A. Bordetella pertussis-causes whooping cough in children; produces filamentous hemagglutinin that helps bacteria bind to respiratory epithelial cells and colonize lungs
B. Haemophilus influenzae-causes meningitis and sepsis in children; infection occurs by inhalation of aerosol particles; produces IgA proteases that degrade IgA so that it can colonize lungs encapsulated strains are invasive and can go to any part of body leading to meningitis and sepsis C. Mycoplasma pneumoniae-causes atypical pneumonia; tapering end of bacterium attaches to respiratory epithelial cells by cyoadhesins that facilitate attachment to scialic acid in epithelial cells this binding triggers host cells to produce reactive oxygen intermediates; not beneficial to host in killing pathogen because pathogen produces catalse that degrades them excess production of reactive oxygen intermediates will lead to damage of respiratory epithelial cells |
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Describe the role of alveolar macrophages in host defense
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derived from blood monocytes; efficient phagocytic cells; ingest microbes and kill them by different intracellular mechanisms
Macrophages recognize microbial infection using Pattern recognition receptors such as toll like receptor-4 (TLR-4), TLR-2 and complement receptors; once macrophages recognize infection they bind microbes and engulf them Phagocytosis occur through clatherin-coated pits; plasma membrane invaginates and ends of the membrane fuse to form vacuole (phagosome) that contains ingested organism; phagosome fuses w/ lysosomes in cytoplasm of phagocytes followed by degranulation or release of granules into phagosome Macrophages kill intracellular organism by either oxygen dependent or oxygen independent mechanisms Lactoferrin-sequesters iron; pathogens die due to iron starvation lipases and DNAases damage bacteria by acting on cells or DNA Macrophages play an important role in granulomatous response; also present antigens to T cells to initiate adaptive immunity |
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Describe oxygen dependent and oxygen independent mechanisms of macrophages
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A. oxygen dependent-perturbation of plasma membrane results in activation of NADPH oxidase that reduces oxygen to singlet superoxide; superoxide undergoes dismutation to form hydrogen peroxide; hydrogen peroxide inhibits growth of intracellular pathogens
macrophages can generate nitric oxide and reactive nitrogen intermediates that are efficient in controlling intracellular pathogens B. Oxygen independent-control of internalized pathogen by lysosomal enzymes and other antimicrobial peptides; lysozyme degrades peptidoglycan on surface of Gram positive bacteria |
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Describe the resistance to phagocytosis of some specific diseases
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A. Legionella-causes atypical pneumonia; cell mediated immunity plays important role in controlling infection
Inside macrophages, legionella completely alters phagosome by recruiting ribosomes onto membrane to resemble rough endoplasmic reticulum (RER) and don't fuse w/ ribosomes B. Mycobacterium tuberculosis-causes TB lives inside macrophages; M tb prevents maturation process (resembles early endosomes) and doesn't undergo acidification and fusion with lysosomes |
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Describe the role of neutrophils in immune response
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have short life and participate in innate immunity but can't present Ags so can't initiate adaptive immunity
induce pyogenic response and provide protection against S auerus and S pneumonia have multilobed nucleus; leave circulation to migrate to lungs in response to IL-8 (process called diapedesis) phagocytose the microbes and kill them intracellularly contain Primary (azurophilic) granules and secondary granules in cytoplasm; primary granules contain myeloperoxidase enzyme, lysozyme and alpa-defensins Myeolperoxidase enzyme catalyzes formation of hypochlorous acid (from H and Cl ions) and singlet O2; Hypochlorous inhibits growth of intracellular pathogens; singlet O2 derived from reaction b/t hypochlorous acid and hydrogen peroxide |
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Describe role of dendritic cells (DCs) in immune response
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have extended membrane filaments; both phagocytoses amd pinocytose; most efficient antigen presenting cells
In lungs, immature DCs phagocytose microbes and then differentiate into mature DCs; Mature DCs express co-stimulatory molecules and migrate from lungs to lymph nodes to sensitize naïve T cells CD4+T cells recognize processed protein Ags associated w/ MHC Class II molecules; CD8+T cells recognize MHC class I |
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Describe the role of natural killer cells (NK) in immune response
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not phagocytic but contribute to innate defenses against viral infection and cancer cells; express activating receptors (KAR) and killer inhibitory receptors (KIR) on cell surface
recognize target cells that express low levels of MHC class I molecules and lyse them by releasing antimicrobial peptides; viral infection downregulates expression of MHC Class I molecules on the cell surface of infected cells NK binds to target cells and releases perforin and granulysin; perforin creates pores on cell surface of bacteria and granlysin enters cells through pores and damages DNA of target cells |
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Describe role of CD8 cells in immune response
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recognize processed protein Ags on cell surface of DCs in association with MHC class I
During viral infection, viral proteins from the intracellular virus are processed inside proteasomes of DCs, then transported to rough endoplasmic reticulum (RER) by a transporter protein (TAP); Inside the RER Ag associates w/ MHC Class I molecules and is transported to cell surface of DCs for recognition by CD8+T cells CD8 T cells produce perforin and granulysin that kill target cells and the virus |
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Describe granulomatous response in the lungs
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M. tb infection originates in the lung; Inhaled droplets are phagocytosed by alveolar macrophages (first line of defense)
Innate immunity is often unsuccessful in controlling M. tb infection-->adaptive immunity kicks in macrophages release TNF-alpha that induces granuloma formation; Granuloma is a closed structure made up of monocytes, macrophages, giant cells and epithelioid cells; Giant cells are syncitial macrophages and are multi-nucleated cells Granuloma restricts and prevents spread of infection; absence of TNF-a inhibits granuloma formation leading to hematogenous spread Chemokines attract neutrophils, monocytes and lymphocytes to the site of granuloma; TH-1 subset of CD4+ T cells is critical for controlling infection; releases IL-2 (induces T cell expansion) and IFN-gamma |
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Describe the role of IFN-gamma (IFN-y) in the granulomatous response in the lungs
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essential for control of M tb infection; activates macrophages in several ways:
a. activate macrophages to produce increased levels of reactive O2 intermediates (superoxide, hydrogen peroxide, hydroxyl radicals and singlet O2); M. tb produces catalase that inactivates and degrades hydrogen peroxide b. promote fusion of phagosome w/ lysosomes-->inhibits growth of M tb c. activate expression of inducible nitric oxide synthase in macrophages-->catalyzes conversion of L-arginine to nitric oxide |
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Describe the pathogenesis of M tb
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M. tuberculosis infection originates in the lungs; infection begins when inhaled bacteria is engulfed by macrophages
90% of infected individuals have granuloma formation; granuloma gets converted to caseum; pH inside the caseum is low and O2 tension is low-->unfavorable environment for bacteria caseum often heals by fibrosis when there is deposition of type I and type III collagen although granuloma heals by fibrosis and there is growth inhibition of M. tb there is no guarantee that M. tb is killed; can remain dormant for decades inside granulom (latent tb) Individuals with LTBI are healthy, chest x-rays are normal, and aren't contagious Whenever immune system becomes weak due to aging, HIV-infection, immuno-suppressive drugs, or diabetes, dormant M. tb undergoes endogenous reactivation to cause active tb; reactivation usually occurs in upper lobe of lung which is more oxygenated; in 90% of individuals, infection does not lead to active disease In active disease, granuloma undergoes liquefaction; liquid caseum is similar to broth, allowing organisms to grow and multiply, leading to cavity formation; At this stage, patient is very contagious and large numbers of bacteria are released during cough |
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Describe sarcoidosis
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characterized by presence of granulomas (collections of inflammatory cells); disease is primarily of the lungs, but granulomas can also form in other parts of the body
granulomas disappear or become scar tissue; more common among Scandinavian descendents and African Americans |
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Describe hypersensitivity reactions
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condition where immune system is hyperactive and damages host cells
Type I-allergic reaction; fast reaction (occurs w/in minutes-hours); participating Ab belongs to class IgE and involves mast cells Type II and III-involves complement activation; participating antibodies are NOT Ig E Type II-Abs bind to cell surface Ags; occurs w/in hours-days Type III-induced by soluble Ag-Ab complex that occurs in serum; occurs w/in hours-days Type IV (delayed type)-cells that participate include macrophages and T cells; takes 2-4 days |
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Describe type I hypersensitivity reactions
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Allergic reaction (wheal and flare reaction)
To determine an allergy, allergens are injected in forearm; Previous exposure to allergens will result in secondary response Mast cells have IgE displayed on their cell surface and they react to allergen by undergoing degranulation and releasing histamine and heparin; Histamines enhance vascular permeability and cause smooth muscle contractions Allergic reaction manifested as redness and swelling indicates allergy Initial exposure to allergens result in IgE production by B cells; IgE binds to FcER1 (CD23) on mast cells |
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Describe type II hypersensitivity reactions
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Abs involved are either IgG or IgM (not IgE); Abs produced during immune response recognize and bind Ags
Ab/Ag complex activates complement proteins by “classical" pathway to cause inflammation at the site results in creation of defect on cell's surface-->breaking open of cell and cell death. |
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Describe Goodpasture's syndrome as an example of a type II hypersensitivity reaction
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subtype of Pulmonary renal syndrome (autoimmune syndrome of alveolar hemorrhage and glomerulonephritis) caused by circulating anti-glomerular basement membrane (anti-GBM) Abs
often develops in genetically susceptible people who smoke cigarettes major symptoms are hemoptysis and hematuria; confirmed by the presence of anti-GBM antibodies in blood or renal biopsy Prognosis good when treatment is begun before respiratory or renal failure |
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Describe the pathophysiology of Goodpasture's syndrome
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most often manifests as diffuse alveolar hemorrhage and glomerulonephritis together
Anti-GBM antibodies are directed against noncollagenous (NC-1) domain of α3 chain of type IV collagen (found in basement membranes of renal and pulmonary capillaries) genetically susceptible-HLA-DRw15, -DR4, and -DRB1 alleles Circulating anti-GBM Abs bind to basement membranes, fix complement, and trigger cell-mediated inflammatory response |
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Describe type IV hypersensitivity reactions
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This type of reaction is delayed (2-3 days); foreign substance is presented to T-cells
To test for previous M tb infection, mycobacterial Ags are injected in skin of forearm Ag presented by DCs and macrophages to memory T cells; Memory T cells proliferate and release cytokines that cause induration (>10mm indicates previous infection) |
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Describe hypersensitivity pneumonitis (extrinsic allergic alveolitis)
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inflammation around alveoli and bronchioles caused by allergic reaction to inhaled organic dusts (containing microorganisms or proteins) or chemicals
People develop fever, cough, chills, SOB w/in 4-8 hours of re-exposure to substances to which they are sensitized chest x-rays and tests of lung function determine if there's a problem; substance causing reaction can often be identified by blood test a. Farmer's lung-repeated inhalation of heat-loving bacteria in moldy hay b. Air conditioner lung-contaminated humidifiers or air conditioners circulate Ags capable of causing hypersensitivity reaction small number of people develop allergic reactions; small percentage of those suffer irreversible damage to lungs; generally, person must be exposed repeatedly over time before sensitivity and resultant disease develop repeated exposures result in Ab production and immune complex formation; circulating immune complexes cause complement activation resulting in pathogenesis T cells and macrophages respond to secondary exposure by undergoing granuloma formation leading to fibrosis |
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Describe idiopathic interstitial pneumonias
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non-infectious interstitial lung diseases that have no known cause and affect lungs similarly
6 types-idiopathic pulmonary fibrosis is most common and most severe (excessive fibrosis) Diagnosis requires chest x-rays, computed tomography, and lung tissue biopsy |
