Host Defense Flashcards
What are the general principles of Host Defense
Host Defense = Innate + adaptive immunity to eliminate microbes
Five Types: Extracellular/Intracellular bacteria, Fungi, viruses, parasites
Describe the most effective immune response to Extracellular bacteria
Innate:
–> Phagocytosis,
–> Alternative Complement pathway - bacterial cell wall components can activate complement to lyse or opsonize bacteria (doesn’t require antibody)
Adaptive:
–> Humoral immunity
** IgG opsonizes + toxin-specific antibodies neutralize
** IgM and IgG activate classical complement to lyse
describe how extracellular bacteria evade immunity
Polysaccharide capsule
- -> resist phagocytosis
- -> inhibit alternative pathway complement activation
Genetic variation of surface antigens:
–> one step ahead of antigen-specific antibodies
What are the deleterious effects of Extracellular bacteria of the immune response
Septic shock:
–> bacteria induce macrophages to release tumor necrosis factor and IL-1
Bacterial toxins = superantigens
- -> super antigens bind to class II MHC proteins on antigen presenting cells and to T cells, causing T cell activation
- -> Many T cells activated causes large amounts of cytokines which leads to septic shock-like conditions
Describe Rhematic fever
Cross-reactive antibodies induced by streptococcal M-protein causes binding to sarcolemma proteins in heart which leads to carditis
Describe Poststreptococcal glomerulonephritis
Infection with streptococci –> antibodies that form immune complexes with bacterial antigen –> lodge kidney –> nephritis
Define the general principles of intracellular bacteria
- -> survive/multiply in macrophages
- -> inaccessible to circulating antibodies
- -> strategies that allow them to thrive in phagocytic cells
Describe the innate response to Intracellular bacteria
innate:
- -> ineffective - bacteria not killed when ingested
- -> NKC activated by macrophage via IL-12 which causes NKC to produce IFN-gamma to activate macrophages
Describe the adaptive immunity to intracellular bacteria
DTH-like (type IV) reaction:
- -TH1 cells become activated → release interferon- → activated macrophages may eliminate bacteria
- -Organisms may persist in the body for extended periods of time
- -If so, activated macrophages may surround microbes to form a granuloma to prevent spread (walls off bacteria so it cannot spread
How do intracellular bacteria evade immunity
Mycobacterium –> inhibits fusion of phagosomes and lysosomes + may scavenge reactive oxygen intermediates to prevent bacterial killing
Listeria monocytogenes –> disrupts phagosome (escapes into cytosol)
–> CTL’s generated if the bacteria escape from phagosomes into cytosol or if bacterial antigens transported into cytosol (MHC Class II)
What are the deleterious effects of the intracellular bacteria
Granuloma formation may severely compromise tissue function:
–> devastating if infected tissue is the lungs
Define the general principles of virus immunity
Viruses - obligate intracellular microbes that pirate host cell’s machinery
–> many viruses lyse host cells
Describe the innate response to viruses
Type 1 IFN = alpha and beta interferons
- -> cause up regulate the expression of class I MHC
- -> activate NK cells
NK cells lyse virus-infected cells early in infections:
- -> Most viruses down regulate class I MHC expression
- -> released from normal state of inhibition by absence of class I MHC
- -> activity enhanced by interferons
Describe the adaptive immunity to viruses
Humoral immunity IMPORTANT EARLY IF ANTIBODIES PRESENT:
- -> prevent virus from binding to a target host cell
- -> opsonize virus to enhance phagocytosis
- -> Activate complement to lyse viral envelopes
CTL’s
- -> principle immune component during ESTABLISHED virus infections
- -> Virus antigen processed/presented on Class I MHC, therefore CTL’s are the form of immunity most effective against viruses
Describe how Viruses evade immunity.
Viruses can alter antigens in several mech.
- -> HIV = Error-prone reverse transcriptase causes point mutations and leads to antigenic variability
- -> Influenza reassortants produce antigenic alterations
- -> viruses prevent class I MHC expression
- -> HIV infects/kills CD4+ T cells, thereby preventing immune response
describe the deleterious effects of virus immune response
CTL’s may mediate pathologic lesions in some viral disease states:
- -> hepatitis B virus infection induces CTL response that destroys liver
- -> Some viruses express proteins with homology for host cell proteins.
Describe innate immunity response to Fungi
Neutrophils are the main mediators of innate immunity
- -> phagocytosis – lysosomal enzymes + reactive oxygen intermediates
- -> NEUTROPENIC individuals highly susceptible to fungal infections
Describe adaptive immunity response to fungi
Th1-mediated immunity = MOST IMPORTANT
- -> cryptococcus neoformans eliminated by CTL’s
- -> Granuloma formation
describe innate immunity response to parasites
Macrophages phagocytize protozoa –> many organisms resistant to killing (may even replicate)
Describe adaptive immunity response to parasites
Protozoa that survive within macrophages = CD4+ T lymphocytes –> interferon-gamma –> activates macrophages
Plasmodium –> Th1-mediated CTL’s (antibodies too, but not as effective)
Helminthic infestations (worms) –> IgE + eosinophils during ADCC (Th2 immunity)
describe the effector mechanisms used for optimal response
Antibody against intracellular bacteria would be INEFFECTIVE
CTL response against extracellular bacteria would be INEFFECTIVE
What are some of the negative consequences to immune response
Some tissue injury result from immune response:
–> overzealous immune response may result in injury to host tissue
