HTHSCI 1DT3 Lecture Notes - Lecture 18: Interleukin 4, Affinity Maturation, Thymus
23 Jun 2018
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Role of immune system
Differences between innate and adaptive
Innate comprises number of barrier functions which prevent bacterial
translocation into body: skin, epi tight junctions in gut, competition of
commensal bacteria (competes for nutients and access to mucosa),
chemical bile, proteases, Hcl, mucus – iga and long-chain FAs.
Cellular and soluble component activation relies on recognition of pamps:
TLRs, NOD-like receptors, collectins, complement, scavenger receptors
TLRs – have extracellular leucine rich repeat motifs intracellular toll-il2R
domain involved in signal tranmission. Bind tir domain containg adaptors
like myd88, tirap and trif to transmit singals. Recognize pamps on
pathogens; localized to function 379 in endosomal compartment as
requires intracell gradaion before genetic material recognized KO
hayashi 2001 stop codon in tr 5 removes cellular domain decreasing
signaling ; tlr arg 677-trp. Hep c cleaving tlr 3 TRIF pathway kinases; heAg
inhibiting TLR 2 hepaotlogy 2007
NOD2 – role with TLR2/6 pro-inflamam mediator release form
macrophages and production of cryptodins and defensins from paneth
cells
Rig-1 = intracellular PRR which recognizes dsRNA MAVs IRF3 inf-
beta
So ns3/4a complete blockade of ifn beta production
Collectins
Innate effectors are: complement, interferon, defensins, proteases,
DNAases and RNases – present in skin
Defnsins- contain multiple cysteine-disuphilde bridges called hairpin like
structures – small cationic peptides which bind neg charges PL iabundant
in bact cell walls > human; forming pores
Complement: complex series of proteins and glycorpoteins mainly prod in
liver and monocytes and macrophages, triggered by enxyme cascade in
the lood producing a rapid highly ampl response. 3 pathways – draw y of
complement functions: opsonisation for pahgo, direct lysis, dealing of
immune complexes, promotion of inflammation, augmenting induction of
specific antibody
IFN: cytokines i.e. soluble mediators largely involved in antiviral defense.
Produced different types in response to different viruses: 3 types: type
one IFN alpha and beta innate phase, IFN-gamma produced aadapitve. IFN
actions. Activate JAK/STAT pathways to cause initaiotn of multiple
mechnisms:
Induce 2’5’ OAS to produce 2’5’ OAS from ATP this is an rnaseL that
cleaves viral RNA; induce protein kinase R which inhibits eif-2 inhibitng
trnalsaiton – NS£/4A and E2 HCV inhibit PKR function. induce adenosine
demainase changes viral proteins and induce MX proteins, small GTPases
which colimerise to trap viral component preventing tranlsaiton,
transport and assembly.
mutation on 21 e.g. G—t> confers protection from HCV chronicity found
in Japanese and replicated in Caucasians as improve s Mxa IFn sensitivity
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Document Summary
Innate comprises number of barrier functions which prevent bacterial translocation into body: skin, epi tight junctions in gut, competition of commensal bacteria (competes for nutients and access to mucosa), chemical bile, proteases, hcl, mucus iga and long-chain fas. Cellular and soluble component activation relies on recognition of pamps: Tlrs have extracellular leucine rich repeat motifs intracellular toll-il2r domain involved in signal tranmission. Bind tir domain containg adaptors like myd88, tirap and trif to transmit singals. Recognize pamps on pathogens; localized to function 379 in endosomal compartment as requires intracell gradaion before genetic material recognized ko hayashi 2001 stop codon in tr 5 removes cellular domain decreasing signaling ; tlr arg 677-trp. Hep c cleaving tlr 3 trif pathway kinases; heag inhibiting tlr 2 hepaotlogy 2007. Nod2 role with tlr2/6 pro-inflamam mediator release form macrophages and production of cryptodins and defensins from paneth cells. Rig-1 = intracellular prr which recognizes dsrna mavs irf3 inf- beta.
