Immune response against microbes Flashcards
General features of immune responses to microbes
responses always involve innate and adpative immunity
the immune system responds in distinct and specialized ways to different types of microbes to be most effective
microbes evade or resist the effector mechanisms of immunity
many microbes establish latent, or presistent, infections. The immuner esponse controls but does not eliminate the microbe and the microbe survives without propagating the infection
in many infections, tissue injury and disease may be caused by the host response rather than by the microbe itself
First line of defnse
mechanical barrier
secretions
commensal bacteria
low pH
physical mechanisms
second line of defnse
innate immunty: nonsepcific, macrophages, neutrophils, complement
adaptive immunty: antigen specific, lymphocytes (B and T cells) antibodies
Extracellular bacteria
extracellular bacteria may either induce inflammation or produce toxins
they are ony capable of replicating and surviving outside of host cells
Innate response, adaptive repsonses, bacterial toxins, evasion of immune responses, overreaction of immune response
Bacterial toxins
exotoxins: secreted by bacteria. neutralized by IgG and IgA
endotoxins: not secreted. LPS of cell wall
Extracellular bacteria evasion of immune response
bacterial capsules: external polysaccharide structure. prevent desiccation and resist phagocytosis
biofilms: prevents phagocytosis. increase tolerance to antibiotics. Pseudomonas
Extracellular bacteria evasion of immune system
antigenic variation
complement inhibtion
neutralization of reactive : catalase producing bacteria
protein A (staph) and protein G (strep): bind antibody and block opsonization and phagocytosis
overreaction to extracellular bacteria
abscess: collection of immune cells with a surrounding capsule
Septic shock
intracellular bacteria
surivive and replicate in host cells
they require cell mediated immunity to be eliminated as they are not able to be seen by antibodies and complement: innate response, adaptive response, evasion of immune response, overreaction of immune response.
Intracellular bacteria: innate immune response
phagocytes (DC/macrophages) become infected with intracellular bacteria
they release IL 12 which activate NK cells
NK cells then release IFN which activates phagocyte to kill the bacteria
Intracellular bacteria: adaptive immune response
innate immune response often fails to control intracellular infections
t cell mediate immunity is the primary protective response
CD4 cells (TH1) release IFN (activates phagocytes to kill bacteria)
TH1 cells have CD40L which activates phagocyte via CD40
CD8 cells kill infected cells
phagocyte activation
following IFN stimulation of infected phagocyte, microbes are eliminated by the fusion of hte phagosome and lysosome and exposure to reactive nitrogen intermediates (RNI) and reactive oxygen intermediates (ROI)
Intracellular bacteria evasion of immune system
escape from phagosomes
inhibition of phagosome and lysosome fusion
detoxification of RNI and ROI (catalse neutralized h202)
diminish phagosome’s ability to present antigens to CD4 T cells
overreaction to intracellular bacteria
granulom: collection of immune cells. Tuberculosis
promotes survival of bateria
Viruses
survive and replicate inside host cells
they require cell mediated immunity to be eliminated as they are not able to be seen by antibodies and complement
Viruses: innate immune response
host cell pattern recognition receptors (PRR) recognize viral pathogen associated molecular pattern (PAMPS)
infected cell produces cytokines (IFN a and B) which elicit antiviral properties in neighboring cells
NK cells recognize loss of MHC and kill infected cell
Virus: adaptive immune response
humoral response is effective when virus in outside of host cells
antibodies can neutralize virus and prevent its entry into cells
Viral evasion: antigenic drift vs shift
antigenic shift vs drift. anitgenic drift creates influenza viruses with slightly modified antigens, while antigenic shift generate viruses with entirely new antigens
viral evasion of immune system
code for anitbody receptors to block effector anitbody functions
inhibit IFN synthesis
produce soluble IFN receptors to block IFN function
mimic MHC molecuels, thus avoid being killed by NK cells (remember that NK cells kill cells that lack MHC)
Inhibit MHC I molecule expression, thus avoid CD8 cell recognition
decreases production of IL 12 (IL 12 stimulates IFN production by NK)
T cells and increases cytotoxic acitivity
viral latency EBV and herpes
Overreaction to virus: cirrhosis in hep B
HBV is not directly toxic to hepatocytes and people with imparied cellular immunity will have no inflammation
hepatocytes adre damaged by the immunological response
if the infection is not cleared, the insufficient immune response will continue and cause progressive liver damage.
Fungi
Can occur as yeast or mold (hypae)
Fungi: innate immune response
antibdoy opsonization
neutrophil and macrophage phagocytosis of yeast
pattern recognition receptors recognize pathogen associated molecules patterns
release of proinflammatory cytokines (IL12). Phagosome and lysosome fusion
neutrophils release NETS (neutrophil exracellular traps) for hyphae
Fungi adaptive immune response
T helper subsets are important
TH1 cells secrete IFN gamma and promote fungal clearance
TH17 cells recruits neutrophils
TH2 cells inhibit fungal clearance and have a role in allergic disease
T helper cell importance is seen in AIDS, where a lack of CD4 helper cells leads to increase susceptibility to fungal infections
Fungi evasion of immune response
stimulate production of Il 10 (inhibitory cytokine)
inhibit IL-12
inhibit phagolysosome
change cell wall composition: changing surface glycoproteins
Overreaction of fungi
granulomas
parasites
protozoa (one cell organisms)
helminths (multicellular worm)
parassite innate immune response
PRRS recognize PAMPs mobilizes and activates macrophages
antigen presentation and activation of adaptive immune system
rarely eliminates parasites, just slows the growth
parasites: adaptive immune response
antibodies neutralize the extracellular protozoa
CD8 t cells can kill infected cells directly
TH1 serete IFN and activate macrophages to kill intracellular protozoa
th2 cells are the primary response to helminth infections
Parasites adaptive imune response
IL13: cell turnover mucus
IL5: recruit eosinophils
IgE: regulates mast cells and enhance elimination
mast cells: inflammatory response. Mucus production. Muscle contraction.
Parasite evasion of immune system
antigenic variation
stage specific: different antigens see at different stages in the life cycle. COntinual alteration of antigens with replication
production of IL 10
prevention of lysosome and phagosome fusion
produce antioxidants to neutralize lysosome effects
overreaction to parasites
hepatosplenomeagly
increase in size and number of macrophages and engorgement of blood vessels
