Mechanisms of Host Defense Flashcards
what are the main two mediators of the innate immune system’s response to intracellular pathogens?
phagocytes and NK cells
DCs/MOs produce IL-X and IL-X that activates NK cells
IL-12 and IL-15
Innate immunity is mediated by NKs and MOs. What’s the relation?
They have a reciprocal amplifying effect using IL-12 and IFN-gamma
how long does the innate system operate until the adaptive system kicks in?
7 days
What happens if there is no subsequent adaptive response to an infection?
infection will not be destroyed
How CTLs kill infected cells
1) granule exocytosis
2) entry of granzymes
3) activation of caspaces
4) apoptosis of cell
Edogenous pathway
intracellularly PRODUCED peptides like viral proteins are degraded in cytoplasm by proteosome; these pieces are shunted into the ER through TAP proteins.
there they are loaded into MHC class I molecules and delivered to the surface
Exogenous pathway
extracellular pathogens are engulfed by phagosomes; inside phagosomes the peptides are loaded into MHC II molecules and delivered to surface
M. Tuberculosis
survive by preventing lysosomes from fusing with phagosomes
3 methods intracellular pathogens utilize to evade immune system
1) prevention of lysosome and phagosome fusing
2) suppression of oxidative enzymes and nitrogen species
3) disruption of phagosome membrane, escape into cytoplasm
Defenses against Viruses
Antibodies
Cytotoxic lymphocytes
Type I interferon (alpha/beta)
NK cells
How do IFN-alpha/beta prevent host infection?
IFN-alpha/beta initiate intracellular aniviral processes PKR16: 2’, 5’ oligoadenylate synthetase: RNase L18 produces antiviral stae
express molecules that enhance susceptibility to CTL mediated killing of class I MHC
so an ANTIVIRAL state of the cell and CTL mediated killing of the cell
cytotoxic mechanisms of NK cells
2 response types
Inhibitory receptor engaged: no killing
inhibitory receptor not engaged: killing
ADCC
IgG binds to FcyIIIR recepor on NK cell and releases mediators causing apoptosis
so Ab has to bind to infected cell, and NK binds to Ab
Viral strategies of evading immune detection
antigen variation
examples
HIV, rhinovirus, influenze
Viral strategies of evading immune detection
Inhibition of antigen processing
examples
Herpes simplex blocks TAP transporter in MHC 1
Cytomegalovirus removes MHC I from ER altogether
Viral strategies of evading immune detection
production of immunosuppressive cytokines
example
Epstein barr virus produces IL-10 lolololol
Viral strategies of evading immune detection
infection of immunocompetent cells
HIV
HIV
Main mechanisms against parasites
Mast cells, basophils, Eosinophils, Phagocytes, antibodies
TH2 cells activate a number of different cell types against parasites: what are they and what are the cytokines involved?
Eosinophil activation involves IL-4 and IL-5
B cell IgE production (which activates mast/basophils is stimulated by IL-4 and IL-6
MO activation stimulation
FcER1
mast cell receptor for IgE: multivalent cross links of IgE antibodies causes degranulation of preformed granules (histamine etc)
Fungi are detected by what PRRs?
TLRs and C-lectin-like receptors
b-glucan is detected by _____ on ____
dectin-1 on fungi
What are the main cytokines involved in fungal infection, what do they do and who releases them
IL-12: activation of T cells –> activation of MO
IL-17+IL-23–> Neutrophil and epithelia activation for enhanced antifungal response
What is Th2’s role in a fungal response?
It has none. Th2 involvement (Ab mediated) usually leads to further susceptibility of infection
what is Th1’s role in fungal response?
Th1 is absolutely critical for fungal for its clearance
Dectin-1
PRR for b-glucans on MOs (ONLY MOs)
b-glucans are mainly composed of glucose
dectin-1 is the main PRR against this epitope
signals NFkB signaling
