Basic immunology in 20 minutes

Joseph Barillari (this part)

John McPhie (cool applications stay tuned)
4 November 2004
acts and graphics unashamedly stolen !rom Jane"ay# $ravers# et al%
Immunobiology# &
th
ed%' (o!meyr% )*n +vervie" o! the ,mmune -ystem.'
orrest# (o!meyr% ),mmunology as in!ormation processing.'
Pillai# (endric/son# et al% (-$ 012 course notes%# 3i/ipedia%org# 4pl%nasa%gov# etc%
3hat is the immune system5

Biological mechanism !or identi!ying and

destroying pathogens "ithin a larger organism%

Pathogens6 agents that cause disease

Bacteria# viruses# !ungi# "orms# etc%

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3hy "ould a computer scientist
study the human immune system5

Massively parallel in!ormation processing

mechanism "ith &%2B users7

,ncredibly e!!ective e8ample o! a distributed

system built !rom diverse components "hich are
constantly being rene"ed%

May inspire better computer security systems

(stay tuned !or ne8t "ee/)# as it9s

adaptive can train sel! to react to ne" threats

error-tolerant small mista/es are not !atal

self-protecting protects itsel!

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:oadmap

Many introductions present ,- as a giant parts

list%

3e9ll brie!ly consider it as a set o! barriers# !rom

a pathogen9s perspective%

;isadvantage6 lots and lots and lots o! supporting

details omitted% *s/ <uestions%

*dvantages6 !ast# tailored to hobby=horse

concepts o! immunologically=inspired security%

Namely negative selection# costimulation#

combinatorial > 4unctional diversity# and somatic
hypermutation% (Don't as/ <uestions about this line% 3e9ll get to this%)
irst line o! de!ense
is the innate immune system%
($his "asn9t in (o!meyr%)
,nnate immunity
Skin
(think firewall)
-/in repels
nearly everything
Pathogens
(ubi<uitous)
?ery# very !e"
evade innate
immunity
Not to scale.
?ery !e"
penetrate s/in
Macrophage
ingests > destroys
most pathogens
(ard=coded detectors
!or common
pathogenic signatures%
:arely# nasty germs can evade
the innate immune system%
@nter adaptive immunity%
*daptive immunity
B cells secrete antibodies
to attac/ e8tracellular pathogens
(Most bacteria)
B
Bacterium
B
T cells destroy in!ected cells
to eradicate intracellular pathogens%
(-ome bacteria# all viruses)
T
T
T
?irus=in!ected cell
The colors of the receptors indicate specificity: each can bind to one specific
antigen. daptive immunity can only attac! targets that it has prepared for.
-uppose you9re a pathogen%
Aou9ve avoided the innate immune system%
-hould the adaptive immune system give you pause5
3hy "ould one o! these receptors be able to bind to you5
-uppose you9re ne"% *s=yet=unseen%
,mpossible# right5
$ cell development# brie!ly outlined
T
T
-el!=targeted $ cells are deleted (2 slides !rom no")
T
Breates $ cell
receptor by
sloppy gene
rearrangement%
(ne8t slide)
T
T
Prototype cell#
moves !rom
bone marro"
to thymus gland
T
T
Cse!ul# non=sel!=reactive
$ cells are released !rom the thymus
$ cell receptor ($B:) creation
?0
?4
?1
?2
?2
?D
?E
?&
?F
;0
;E
;2
;4
J0 J2 JE J4 J2 J&
(0) $B: G ? segment H ; segment
H J segment% Ienome contains
several di!!erent copies o! each%
Pic/ one !rom each set%
(Combinatorial diversity.)
?&
;4
J0
(2) Join the copies together using a
sloppy techni<ue that introduces
randomness into the 4unctions%
(Junctional diversity.)
?&
;4
J0
(E) ,! you get an in=!rame protein#
continue%
"rom a fe# do$en %to several do$en& segements for each category %'(D()*&
the human immune system creates over +,
++
different antibody receptors.
Jane"ay 0E&
$ cell re!inement
-andidate T cells are e.posed to most of the proteins in the human body.
"or presentation( proteins are chopped into fragments and displayed on
speciali$ed presentation molecules.
T
T
T
J o! sel! peptides bound
b
i
n
d
i
n
g

s
t
r
e
n
g
t
h
$ cells "ith moderate
binding strength
are retained%
$ cells that do not bind
to any presentation molecules
are allo"ed to die%
-trongly autoreactive
$ cells are /illed
(negative selection)
T
T
$ cells !rom
the green Kone
are approved
T
/ummary of the last three slides
Aour immune system
has a repritoire o! T cells
capable o! binding and destroying cells
that e8hibit almost any !oreign protein%
-uppose you9re a pathogen%
Aou9ve avoided the innate immune system%
-hould the adaptive immune system give you pause5
3hy "ould one o! these receptors be able to bind to you5
-uppose you9re ne"% *s=yet=unseen%
,mpossible# right5
Wrong!
,t is unli/ely that any
intracellular=pathogen=in!ected cell
"ill escape binding by a $ cell%
$he !irst binding "ill lead
to replication o! the bound $ cell
and (i! all goes "ell)
eventual clearance
o! the in!ection%
+L# so ,9m toast% But "hat happens i!
a $ cell binds a human cell5 ($hey9re
moderately autoreactive# right5)
3ill the human cell be lysed5
'ern 'irus
*ns"er6 Costimulation
$o be activated# a $ cell needs to see
both its !irst signal (the target antigen)
and a second )DANGER. signal%
T
-econd
(;*NI@:)
irst
T cell signal receptors
$he )DANGER.
signal is provided by
antigen presenting
cells "hen they detect
signs o! in!ection (cell
lysates# certain
cyto/ines# etc%)
,! you haven9t noticed# bold italic means important!
$ cells cannot be
activated "ithout a
)DANGER. signal% ,!
a $ cell receives its !irst
signal "ithout the
second# it may become
toleriKed to its target%
,9m an extracellular pathogen%
3hat should , e8pect5
Pierce Pathogen
Most pathogens are not sel!=a"are%
B cells improve themselves
via somatic hypermutation
B
*ctivation via
BM$ collaboration
B
B
B
Clonal expansion
Somatic
hypermutation
(random mutation
o! BB:)
B
B
;eleterious
mutations
B
*dvantageous mutations
increase secreted antibody
binding a!!inity