HDM TBL 11: Immune Response to Bacteria

intracellular bacteria

• mycobacterium tuberculosis

• listeria monocytogenes

• mycobacterium leprae

• brucella abortus

staphylococcus aureus

• extracellular, gram-positive cocci, grape-like clusters

• non-motile, facultative anaerobes

• part of normal flora of skin & nasopharynx

• → disease if barrier compromised

  • mild to lifethreatening [MRSA, VRSA]

LTA of S. aureus cell wall is bound by

TLR2 of macrophage

staphylococcus protein A

• inhibits phagocyte function by binding IgG to surface of organism via its Fc component so Fc cannot bind to surface of phagocytes

• inhibits humoral response by binding to surface IgM on B cells, crosslinking receptors

  • excessive signaling & apoptosis of B cells [similar to superantigen function]

Neisseria species

• gram-neg diplococci

• opportunistic pathogen

• in normal flora colonizing nasopharynx

• 2 imp pathogenic species

  • N. meningitidis

    • → meningococcemia & meningitis

    • transmits via resp droplets or close prolonged contact

  • N. gonorrhoeae

    • sexual transmission

    • infects urethra in men, cervix in women, eyes of newborn

Host immune function against s.aureus

• macrophages

• barrier

• neutrophils

• Th1 & Th17

• antibodies

  • IgG important opsonin

host immune functions against neisseria

• mucosal barrier

• complement system

  • MAC [C5-C9] esp imp!

• neutrophils

• antibodies

  • IgA at mucosal barriers

meningococcal meningitis

infection/inflamm of meninges around brain & spinal cord w/ CNS symptoms [headache, fever]

meningococcemia

• rare blood born infection where bacterial LOS induces inflamm cytokines IL-1, IL-6, TNF-alpha → sepsis & septic shock, including circulatory failure, multiorgan dysfunction, intravascular thrombosis

  • marked by purpura, petechiae, purpura fulminans, DIC, Waterhouse-Frederichsen Syndrome [acute adrenal gland failure from severe bleeding into gland]

mycobacterium tuberculosis

• facultative intracellular, non-toxin producing bacilli [rod-shaped]

• strongly acid-fast

  • long mycolic acid chains & complex LPS in cell wall

• slow-growing, can persist intracellulary for prolonged periods or lifelong

• cause TB - infect lung but other sites involved following reactivation in miliary TB

• strains w/ multidrug resistance have emerged

• 2 other species: M.avium, M. kansasii common in US

  • transmits airborne

• risk factors:

  • travel to south asia, sub-saharan africa, eastern europe, china

  • close contact

  • immunocompromised host

host immune function against TB

macrophages [granuloma formation], NK cells, Th1 cells, cytokines IL-12, IFN-gamma, TNF-alpha

AIDS & TB

TB leading cause of death in pple w/ AIDS

low CD4+ T cells → extreme susceptibility to opportunistic infections

primary TB infection

• persistent cough, fever, night sweats, unintentional weight loss, hemoptysis [coughing up blood-tinged sputum]

• granulomas in lungs seen on X ray

• Macrophages can’t totally degrade bacteria b/c sulfatides & ESX-1 inhibit phagolysosome formation, allowing bacteria to persist inside phagosome

Ranke complex

In TB, fibroblasts may surround granuloma, produce dense fibrotic/scar tissue, which may become calcified = Ranke complex