Lecture 16: Immune response to bacteria/fungi Flashcards
opportunistic pathogen
a bacterium, virus or other microorganism that can cause disease in animals w/ IMPAIRED immunity but not in healthy individuals
most E.coli strains are…
non-pathogen = harmless and frequent resident of mammalian microbe
ex: E.coli K12
what are common strains of pathogenic E.coli
- Enteropathogenic and Enterotoxigenic E.coli (EPEC and ETEC)
- can cause diarrheal diseases
- ETEC has multiple toxins
- EPEC has virulence factors for colonization of host
about how many bacterial cells are in the colon
10^12
pathogens cause direct damage to tissues by…
- killing host cells
- releasing toxins
how does the immune system respond to non-pathogens
- complement
- phagocytosis
- adaptive response to microbiota
how do pathogens evade immune response
- antigenic or phase variation
- antigenic drift
- molecular mimicry
- virulence factors
- capsule
- SIgA proteases
antigenic or phase variation
- ability of bacteria to change the expression of critical proteins on its surface
ex: differential expression of flagellin protein in salmonella
explain how Neisseria uses antigenic variation evade immune system
- pili function to attach to host cells
- made of protein call pilin that should be highly antigentic
- however it has 10-20 silent copies of pilS
what is antigenic drift
- natural mutations over time result in structural changes of proteins
what is molecular mimicry
- bacteria tries to make itself look like host cell so antibodies won’t be made against it
- ex: Campylobacter jejuni
explain the virulence factors used by Borrelia burgdorferi (Lyme disease)
- resists complement mediated phagocytosus by producing Osp proteins that binds complement protein factor H
- when C3b binds to factor H, it inactivates it
what are the main defenses against intracellular bacteria
- macrophage activation —> phagocytosis
- NK cells
activated NK cells secrete ______ to activate macrophages
INF-y
macrophages secrete _____ in response to ingested microorganisms that they cannot kill intracellularly
IL-12, which activates NK cells
IL-12 from phagocytes stimulates helper cells _____
Th1
Th1 response results in the secretion of ______ and the expression of ____ to activate macrophages
INF-y + expression of CD40L
how does a capsule help pathogens evade immune system
- prevents phagocytosis, esp. important for extracellular bacteria
what does SIgA protease do
cleaves IgA making it no longer able to bind to bacteria - bacteria is able to go through mucus and reach the epithelial cells
Fungal pathogens immune evasion tactics
- Biofilm - facilitates colonization, resists phagocytosis
- cell wall organization - masks antigens from immune system
- synthesis of structures that hinder immune system (fungal dimorphism, capsules)
- ability to obtain nutrients
- secretion of proteins that inactivate antimicrobial peptides
innate response to fungal pathogens
- neutrophils, macrophages, dendritic cells
- sentinel macrophages + DCs secrete PRRs that recognize fungal cell wall components
- neutrphils can phagocytose fungal cells, release ROIs, NETs, lysosomal enzymes
Adaptive response to fungal pathogens
- stimulated by cytokines from DC
- intracellular fungi -** Th1** + CTLs (Th1 activates macrophages)
- extracellular fungi - **Th17 **(stimulates inflammation and recuitment of neutrophils)
- antibodies -neutralization, opsonization, activation of complement, ADCC
Extracellular bacteria mechanisms of pathogenesis
- release of toxins
- endotoxins (LPS) - gram negative bacteria cell walls (causes activation of macrophages, release of cytokines, activates complement)
- Exotoxins - gram positive bacteria (stimulate cytokine release or are cytotoxic)
activated NK cells respond to intracellular bacteria in what 2 ways
- secreting INF-y to activate macrophages (increases production of ROS and lysosomal enzymes)
- directly killing infected cells if the bacterium caused a downregulation of MHC class I
CD8 (cytotoxic T cell) response to intracellular bacteria
- activated CTLs kill cells displaying bacterial antigens on class I MHC molecules
- CTLs kill infected cells via perforin and granzymes
role of antibodies against intracellular bacteria
- minor role
- binding to bacterial antigens displayed on the surface of infected cells can initiate ADCC
what intracellular bacteria escape phagosomes
- Listeria monocytogenes
- they poke holes in the phagosome so they can get out and replicate in the cytoplasm
what intracellular bacteria prevent phagosome-lysosome fusion
- Mycobacterium tuberculosis
what intracellular bacteria are resistant to lysosomal enzymes
- Corynebacterium pseudotuberculosis
Exotoxin that causes atrophic rhinitis in pigs
- *Bordatella brontisceptica
- Pasteruella multocida*
innate immune response to extracellular bacteria
- physical barriers (skin, mucosal membranes)
- antimicrobial peptides (lysozyme, defensins)
- If invasion of tissues occurs…
- Inflammation, activation of complement, phagocytosis
- Inflammation promoted by anaphylatoxins and pro-inflammatory cytokines
adaptive immune response to extracellular bacteria
- Antibodies are primary response - protective against bacterial cells and the proteins (toxins) they produce
Fungal pathogens mechanism of pathogenesis
* Persistence w/in phagocytes - survival or organisms within phagocytes leads to increased replication and potential spread
* Inflammation - results in tissue destruction
CTL cell activity - damages tissues
