lecture 7 exam 2 Flashcards
major physiologic functions will
protect the host against microbial infections
bacteria, viruses, parasites, yeast
major physiology immune response to pathogens are
mediated by the combined effector mechanisms of innate and adaptive immunity
responds in distinct and specialized ways to different types of microbes
microbe survival and pathogenicity in a host are influenced by ability of microbe to evade or resist the effector mechanisms of immunity -> some pathogens require intervention to eradicate them
tissue injury and disease may be caused by the host response to microbe
responses to bacterial infection
innate
adaptive: Bcell/NK cell
adaptive: Tcell
innate immunity response to bacterial infectoin
complement system: alternate & lectin
natural antibodies
phagocytes: nitric oxide, myeloperoxidase, lysozyme, defensins
acute phase proteins: lactoferrin
adaptive Bcell/NK cell immunity response to bacterial infection
complement system: classical
antigen specific antibodies
ADCC: by NK and eosinophils
adaptive Tcell immunity response to bacterial infection
CD4+ Th1 IFNgamma secretion: activates macrophage!
CD8+ CTLs: killing cell infected w intracellular bacteria
CD4+ Th17 activation: IL17 secretion will recruit neutrophils, antimicrobial peptides
antibody responses to extracellular bacteria
neutralization
osponization and Fc receptor mediated phagocytosis (BCR)
phagocytosis of C3b coated bacteria (complement)
inflammation (complement)
lysis of microbe (complement
ex: salmonella, staphylococcus aureus, Ecoli
T cell response to extracellular bacteria
CD4+ helper cell releases:
- IL17, TNF -> inflammation
- IFNgamma -> macrophage activation = phagocytosis and bacteria killing
- various cytokines -> antibody response
synergistic antibacterial immune mechanisms
innate immunity: defensins, lysozymes, complement
antibody mediated immunity: antibodies
cell mediated immunity: T cells, activated macrophages
all these work together to kill bacteria
immunity to intracellular bacteria
initially the innate immune system has neutrophils (IL17) and macrophages (TNFgamma) and NK cells come to site and control infection through cytokines -> macrophages release IL12 to activate NK and NK release IFN gamma
as infection time goes on the TCells and macrophages work in adaptive immunity - T cells bind macrophage/APC w CD40L and release IFNgamme to activate macrophages for eradication of infection!
ex: brucella abortus, mycobacterium, ehrlichia canis
immunity to intracellular microbe
CTLs!
phagocytosed bacteria in vesicles and cytoplasm -> bind CD4+ Tcell which releases IFNgamma to activate macrophage to kill bacteria in phagolysosome and then CD8+ CTL will bind MHC1 + ag complex and kill the infected cell
ex: bacteria, virus, protozoa
CTL lysis of infected cell
intracellular bacteria, virus, protozoa w MHC1/Th1 CD8+
infected cells degrade intracellular pathogen into peptides
peptides are loaded into MHC1 and presented to CTLs which release their perforins and granzymes
CTL induce apoptosis and/or lysis of target bad cell through creating pore for granzymes to enter (CD95)
mechanisms of immune evasion by bacteria
immune pressure is what drives immune evasion
antigenic variation
inhibition of complement activation
resistance to phagocytosis
scavenging of ROS intermediates
resistance to complement/alternative pathway activation
neisseria gonorrhoeae, E Coli, salmonella evade immune system by
antigenic variation
many bacteria evade immune systems by
Inhibition of complement activation
pneumococcus evade immune systems by
resistance to phagocytosis
catalase + staphylococci evade immune systems by
scavenging of ROS intermediates
neisseria meningitides evade immune systems by
resistance to complement activation via sialic acid expression whihc inhibits C3 and C5 convertases
streptococcus evade immune systems by
resistnace to complement activation via M protein block C3 binding to organisms and C3b binding to complement receptors
mechanisms of immune evasion by bacteria
toxin production (LPS - cell destruction and shock)
disruption of phagosome membrane, escape into cytoplasm (listeria monocytogenes - hemolysin protein)
inactivation of ROS and NOS (mycobacterium leprae via phenolic glycolipid)
inhibition of phagolysosome formation (mycobacterium tuberculosis, legionella pneumophilia)
decrease MHC2 expression
super antigen production (S aureus toxin)
polysaccharide capsule (shield/shedding)
immune response against viruses
innate immunity
adaptive immunity
innate immunity response against virus
IFNalpha/beta (TYPE1 interferons - upregulate adenylate synthetase in macrophages) NK cells complement systems natural antibodies activated macrophages (IFNgamma)
adaptive immunity response against virus
virus specific antibodies & CTLs neutralizaiton opsonization complement (classical) ADCC NK cells
biological actions of IFNalpha/beta in innate immune response to virus
IFNa/b induces the expression of: adenylate synthetase in macrophages -> activates RNase L -> degrades viral RNA! inhibiting viral replication
NK cells adaptive immune response to virus
when inhibitory receptor engaged: NK cell NOT activated -> no cell killing
when inhibitory receptor no longer engaged: NK cell ACTIVATED -> kill target bad cell!
appear early in infections
kill some viral infected cells and tumor cells
secrete IFNgamma which activates macrophage!
adaptive immunity details for immune response against viruses
Bcell -> antibodies protect against infection
ADCC (low aff FcgammaR3) on NK responds to IgG on antibody coated target cell and kills - granzymes, FasL, perforins
CD8+ CTL binds infected cell and kills - eradication of established infeciton
latency: integration into host genome - oncogenes
lytic virus
antigenic variation evasion by virus
genetic recombination of differnet viruses among different organisms makes it harder to defend against
influenza, HIV, rhinovirus
inhibition of antigen processing and presenting evasion by virus
MHC down regulation - escapes surveillance/presentation
epitope mutation - antigenic variation/immune escape, reduced/failure of MHC loading
blockade of TAP transporter - herpes
removal of calss 1 from ER - cytomegalovirus
production of cytokine receptor homologs evasion by virus
vaccinia, poxviruses (IL1, IFNgamma), cytomegalovirus (chemokines)
prodcution of immunosuppressive cytokine evasion by virus
epstein barr (IL10)
infection of immunocompetent cells
HIV
Feline immunodeficiency virus evasion by virus
infects CD4+ T cells:
-slow destruction of adaptive immunity
-eventually allows other severe infections to develop and eventually lead to death
diagnosis: presence of antiFIV antibodies via western blot, ELISA, IFA
clinical symptoms: chronic inflammtion, infections, wgt loss and fever
prevention: vaccination - no longer efficient
immune response against fungi
innate
adaptive
ex: tinea (ringworm)
ringworm details
common fungal skin infection in animals and humans
failure of immune clearance leads to persistnet inflammation
treatment w antifungal
innate immunity response to fungi
activated macrophages & neutrophils: utilize PRR-PAMPS: phagocytosis!
PRR-PAMP interaction: inflammation, neutrophil recruitment (IL17)
complement system: lectin and alternate pathway
adaptive immunity response to fungi
cell mediated clearance: CD4+ Th1 and Th17 activate macrophages and neutrophils
injurious effect of immune response: granuloma and fivrosis (histoplasma capsulatum)
immune evasion by fungi
some fungal cells are too large to be phagocytosed
express complement and ROS inhibitors - complex glycan coat/carbohydrates
espcape from phagosome/alter phagolysosome: avoids destruction
cryptococcus neoformans: inhibits TNF & IL12 production and stimulates IL10 production -> inflammation
immune response to helminths
cell mediated clearance
eosinophil degranulation releases
cell mediated clearance immune response to helminths
activated CD4+ th2 cells induce: -mucosal eosinophil and mast cells -IgE production helminths are vulnerable to: -ADCC involving eosinophils, neutrophils & macrophages
eosinophil degranulation releases immune response to helminths
major basic protein (MBP) eosinophil cationic protein (ECP) eosinophil peroxidase (EP) eosinophil neurotoxin (EN) phospholipase D lysophospholipase all these are toxic to helminths!
