2 - foreign activators Flashcards by Sylvie Wilson

‘non-self’

substance that originates from outside the body at birth

generally bug e..g polymer (>3000 daltons)

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examples of non-self molecules

microbes
allergens
foreign tissues

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tyes of immune failure

non-responsiveness

over-responsiveness

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examples of non-responsiveness of immune system

HIV

tumours

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examples of over-responsiveness of immune system

sepsis

auto-immunity

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features of innate immune system

fast
general
hours after exposure to infectious agent

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features of adaptive immune system

specific
powerful
delayed - days after exposure

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soluble receptors secreted from

cells

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soluble receptors found in

blood
plasma
lymph
mucosal secretions

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cell surface receptos found on

macrophages, neutrophils, lymphocytes and other somatic cells

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properties of innate receptors

encoded in germline
pre-coded to recognise foreign activators
finite number - limited diversity
recognise structures common to different microbes

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properties of adaptive receptors

take time to evolve
generated by gene recombination
massive diversity
recognise structures unique to different microbes

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specific examples of immune system failure

spanish flu - 1918

TGN1412 - withdrawn 2006

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spanish flu

1918-1920
most lethal flu outbreak ever recorded
20-40 million killed
20-30 year old heavily targeted (good immune systems)
over-activation of immune system led to increased production of cytokines

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TGN1412

drug
a mono-clonal antibody to CD28 on T cells
passed animal testing
clinical trials - intended to only mildy activate immune system
caused cytokine storms and organ failure in humans
withdrawn from development in 2006

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types of PAMPs

cell wall components
nucleic acid
conserved surface proteins
conserved stress proteins

examples of cell wall components - PAMPs

bacteria:

peptidoglycan
LPS

fungi:
- phospholipomannans

examples of nucleic acid -PAMPs

bacteria:
- CpG motif DNA

viruses:

ssRNA
Ds RNA

example of conserved surface proteins - PAMPs

bacteria:

- flagellin

examples of conserved stress proteins

bacteria:

- heat shock proteins

PPRs

soluble receptor examples

natural antibodies
complement
pentraxins
collectins
ficolins

PRRs

cell receptors examples

TLRs
NOD-like receptors
RIG-like receptors
C-type lectin-like receptors
scavenger receptors
N-formyl met-leu-phe receptors

Toll-like receptors - structure

extracelllular domain - horseshoe structure, important for recognition

intracellular domain - dimerisation of 2 domains essential for signallign

examples of homodimer TLRs

TLR9 - recognises CpG DNA

TLR5 - recognises flagellin

example of heterodimer TLR | what does it recognise

TLR7/8 - recognises ssRNA

what happens if there are too many TLRs

increased cytokine production increased production of TRanscription factors inflammatory cascde

describe TLR4 binding and signalling

TLR4 allows macrophage to recognise LPS LPS binding protein transports LPS to CD14 CD14 transports LPS to the TLR LPS detected by MD-2 TLR dimerisation signalling pathway initiated eg. NF-kappaB

LPS binding protein

accessory protein | transports LPS to CD14 receptor

CD14

cluster of differentiation gene receptor either soluble OR binds to cell-surface via glycosylphatidylinositol anchor transports LPS to TLR

MD-2

recognises LPS | forms complex with TLR4

what do antibodies recognise

recognise discrete epitopes on a protein antigen

antibdy recognition sites

at tips can evolve and change to recognise different molecules CDR

CDR

complementarity determining region part of variable chain of an antibody hyper-variable determine specific binding of the antibody

epsilon toxin

important in disease in lambs and livestock | - all now vaccinated against

antibodies and gene recombinaton

lots of antibodies produced by different genes | each has different specificty

where does b cell production occur

progenitor cells in bone marrow

clonal deletion

the process by which self-recognising b cells are eliminated in the bone marrow

Product of clonal deletion

only B cells that recognise foreign antigens are allowed to mature and produce antibodies