ID: ch 17 and 18, fri 13th class

going through audio recorded lecture - all done

Six ways to avoid being killed by phagocytes

Talks and release, opsonization prevented (e.g. protein produced, which prevents interaction between opsonizing antibody and phagocyte), contact with phagocyte prevented (e.g. through a capsule), phagolysosome fusion inhibited (eg TB YUHH), escape into the cytoplasm (from the phagolysosome), resistance to killing (eg by producing antioxidants)

example of viral pathogen that evades TLR based innate defense & how they do it

Herpes - avoids ICP0 which tags immune proteins for degradation via the proteasome (tags them with ubiquitin), destroys IFN pathways - curbs virus response

example of bacterial pathogen that evades adaptive defense & some more details on the pathogen

salmonella - gram-, 2% of patients die, foodborne infection, bacteria hides in gallbladder with biofilm formation

strategies to evade adaptive defenses (4)

hiding places, mimicry, antigenic variation, immune interference

strategies to evade adaptive defenses: hiding places (2 + 1)

cyst: worm cyst in liver eg, or cytoplasm cyst by listeria monocytogenes
host genome: eg retroviral DNA integration

what is this image showing

cytoplasm as hiding place, cell to cell spread

strategies to evade adaptive defenses: mimicry more detail, 1 eg

not very effective, of host proteins, eg TB, risk of cross-reacting antibodies for host (eg step throat)

strategies to evade adaptive defenses: antigenic variation I example

influenza virus: genome has 8 ss RNA segments (separated), has 2 predominant surface proteins (haemaglutinin- attaches to sugars that project from the airway epithelium; Neuraminidase- cleaves bond between haemaglutinin and sialic acid (viral release));
4 types of influenza - A most relevant for humans and clinitiancs, and then H and N have diff variants; also can be low and high pathogenic avian influenza

most scary influenza variant rn

H5N1 avian flu (HPAI)

what organ system does influenza attack in birds vs mammals

mammals: respitatory tract
birds: gastrointestinal tract

antigenic shift vs antigenic drift

antigenic shift is a sudden major change, antigenic drift is a gradual process (usually a single mutation)

reasons for differences in death rate in avian flue SE asia vs US? (4)

surveillance bias (mild cases detected), different virus strains, different exposure intensity, earlier treatment

why does the H5N1 virus spread easily among birds but not humans?

H5 - binds to alpha 2,3linkage between sialic acid and galactose - deep in lungs, more deadly, spreads more difficult
H1 - eg seasonal virus, binds to alpha2,6 linkage - in upper respirator tract - much less fatal but easier spread

worries with H5N1 avaian virus

antigenic drift: and bind to 2,6 sialic acid-galactose
antigenic shift: mix of deadly avian virus and easily spreadable human virus- coinfection in one host and reassortment

what happens w/ influenza coinfection

the diff ss DNA strands - reassort and mix different fragments together, reassortment, sudden major change in properties

strategies to evade adaptive defenses: antigenic variation II descr.

gene switching, eg coat switching in parasite that causes sleeping sickness, through variant surface glycoproteins (VSG)

strategies to evade adaptive defenses: antigenic variation III descr.. eg

gene conversion, eg gonorrhoeae - their pili can change their shape - silent copy recombinded with expressed copy, changes it

strategies to evade adaptive defenses: immune interference I

Th1/Th2 balance - Th1 promote macrophages to become M1 (warmongers), Th2 promote macrophages to become M2 (peacekeepers)

strategies to evade adaptive defenses: immune interference II

suppression, eg HIV

strategies to evade adaptive defenses: immune interference III

modulators like superantigens (Sag) - forces MHCII and TCR apart - no recognition of antigen but huge stimulation of T cells, bind outside the conventional antigen-binding site

results of Sag

uncoordinated/ineffective immune response (20% vs 0.01%), cytokine storm, toxic shock syndrome, overwhelming inflammatory response

pathogen related to toxic shock syndrome

staphylococcus aureus - common if you have tampons in for too long, gram+ cocci

immune sensing in (intestinal) epithelia (4)

toll-like receptors, PRR in cytoplasm: cytosolic nucleotide binding domain and leucine rich repeat containing receptors (assemble inflammosomes- danger sensing proteins), nucelic acid receptors (eg RIG-I), can sense PAMPs and DAMPs

imflammosome more in depth

danger-sensing proteins, detect when cells become infected or damaged, become activated and bind tgt forming inflammosomes, cleave active proteins into their dormant form - dormanr forms can then create pores in cells - pyroptosis

how does toxic shock syndrome happen

outside-in signaling mechanism, cell lysis by alpha toxn, epithelium dissolves, cell death by pyroptosos

strategies to evade adaptive defenses: immune interference IV

persistent infections, latent to patent (eg TB!!)

pathology of infectious diseases (6)

endotoxin (pathogen antigens), exotoxin (released agent), inflammation, immune response, allergies, oncogenesis

endotoxin descr

fingerprint structural molecules of the pathogens, powerful activators of immune and inflammatory responses

4 hypersensitivities

IgE mediated: allergic/anaphylactic shock, IgG mediated cytoytoxic - autoimmune disease, Ab against skin, immune-complex mediated - inflammation around blood vessels, cell mediated eg nicket hypersensitivity - landerhans cells cause T cell inflammation

cancer and ID

6 possible ID, usually viruses, eg HPV - causes papilloma virus, vaccine greatly helps!!