Microimmune Lecture 20 Study Notes
1. What happens when we are infected with a pathogen?
-wound healing induced, complement destruction (picked up by macrophages/DC in
-DC migrate to lymphnodes, phagocytosis, NK cells activated, cytokines and
-pathogens phagocytosed in lymphoid tissues
-adaptive immunity initiated by migrating DC
-infection cleared by specific antibodies, T cell-dependent macrophage activation
and cytotoxic T cells
2. What virus has coevolved successfully?
-infected 90% of all humans
-initial infection is in the GI tract and largely asymptomatic (infects us at very young
age; contaminated water or food)
-almost everybody has it but it doesn’t harm its host; good at spreading; live long
-pathology only in immunosuppressed patients
-non dangerous environmental bacteria/virus and converts it into a human
3. What virus has not coevolved successfully?
-infection is very rare, occurred in the 1970s
-highly lethal (50-100%) mortality
-person-to-person transmission is rare: this is because rapid death is caused;
otherwise the virus is easily spread
-persistent/latent infections do not occur
4. Discuss evolution of malaria/O type etc.
-malaria appeared 200mya when mammals appeared
-humans and chimps diverge from the same common ancestor
-human/chimp strain of malaria appeared 200mya
-we developed the o blood type after splitting from chimps – 5 mya
-o protects from malaria
-begin to see mutations protecting us against malaria in the areas where it is
endemic; as humans migrate out of Africa 80 000 ya
-malaria evolving in response to these changes
5. Discuss the evolution of HIV. -women/family in the sex trade frequently exposed to HIV but never got it
-they sequenced the MHC1 and MHC 11 alleles; found that MHC 11 were enriched
with alleles that were protected allowing them to survive
-the protective alleles were: HLA-A2 6802and HLA-DRB1*01
6. What were the first cases of HIV?
-oldest HIV-1 was in 1959
-suspected species “jumped” into humas in 1931 (HIV-1) and in 1940/1945 (HIV-2
7. What are the goals of a host pathogen?
-minimize loss of fitness
-select successful MHC haplotypes (get the right MHC to interact)
-selecting resistance genes
-“selection” of less-virulent pathogen strains
-host wants to survive and reproduce; selecting for pathogens that aren’t
8. What are the goals of a pathogen?
-maximize reproductive success
-host survival (at least until transmitted)
-modulation of virulence
9. To be a pathogen you must…
-be able to survive in the human b ody (pH, temperature etc)
-be able to avoid or modulate the immune response to allow your own survival
-most microorganisms are not pathogens
-most pathogens have immune-avoidance mechanisms
10.How does Borellia prevent opsonization?
-causes lyme disease
-coats itself in factor H
-inhibits complement deposition
-bound by exotoxin which binds factor H and turns it off
-factor H only binds to self proteins to regulate it; it is bound by an exotoxin which
will turn it off so that it can bind to the bacteria
11.How does Syphillis prevent opsonization?
-causes treponema -coats its surface with host proteins; thereby hiding itself and antigens/cell surface
from antibodies and complement
-non-specific binding to charged lipids in bacterial membrane (immune system
wont recognize it; only recognize self proteins)
12.How does streptococcus avoid the immune system?
-has two proteins A & G which bind to IgG on the Fc receptors
-this prevents opsonization, complementation and phagocytosis
13.What toxins shut down TLRs?
-Brucella, UTIs effectively shut down TLRs (common in a lot of bacteria)
-they contain TIR domains which bind to Myd88
-myd88 is important in the signaling cascade, by binding this it will prevent the
14.What does the virus pertussis do?
-pertussis (whooping cough) creates a toxin that will chemically modify the G alpha
-permanently off; can’t switch to GTP
-GPCRs are important to make chemokines (CXCL8) so that immune cells can get out
of the blood, without this pathway they won’t make it to the site
-GPCR is also important in production of superoxide (respiratory burst); so even if
the immune cells make it to the site; won’t be an effective way to kill it
15.What are other ways to disrupt phagocytosis?
-once the bacteria is internalized, pertussin avoids respiratory burst all together
-other bacteria such as brucella or staphylococcus express superoxide dismutase
which converts superoxide into hydrogen peroxide, but also expresses catalase
which converts that into hydrogen and water
-tuberculosis and leprosy will prevent fusion of granules/lysosomes to the
-chlamydia and legionelle will alter its membrane so they appear like some other
cell in the body (lipids) so nothing will fuse to it
-tuberculosis and leprosy can make it to the end where their phagosome is acidified;
but they can survive in this environment
16.What is killing immune cells?
-streptococcus and pseudomonas contain hemolysin and leukolysins
-these are pore-forming and lyse leukocytes
-best way to avoid immune system is to kill it (poke hole; contents spill out) 17.What is listeria?
-doesn’t slow growth when refrigerated
18.How does listeria get into our body?
-gain entry through the gut by cell extrusion
-go in through vili in the gut
-collect in divits; tight junctions supposed to block but the junction is being moved
to where its not supposed to be so it pops out of place; bacteria has entry to the
-listeria has two proteins InIA and InIB
-required to gain entry
-get a reorganization of junctions in order to extrude an epithelial cell
-results in a direct infection of the epithelia
20.What happens once it is inside?
-can go to the lymphatics and has access to resident immune cells
21.What happens during invasion of macrophages?
-goes to the macrophage by PRRs and gets taken up by the phagosome