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The Immune System: Innate and Adaptive Defenses
Figure 21.1
Non-
specific
Specific
1st line
2nd line
Phagocytosis,
cells, chemicals
Inflammation
3rd line
B, T cells
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First Line of Defense: Surface Barriers
Skin, mucous membranes, and their secretions
Skin- Keratin:
Presents a physical barrier to most microorganisms
Is resistant to eak acids and bases, bacterialen!ymes, and to"ins
#ucosae pro$ide similar mechanical barriers
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First Line of Defense: hemica! Barriers
%pithelial membranes Skin acidity &p' of ( to )* inhibits bacterial groth
Sebum- chemicals to"ic to bacteria
Stomach mucosae-'+l, protein-digesting en!ymes
Sali$a lacrimal fluid contain lyso!yme, Ig
.igesti$e respiratory systems- #ucus ciliatrap e/ect bacteria
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Second Line of Defense: e!!s and hemica!s
Phagocytes
Natural killer &NK* cells
ntimicrobial proteins in blood and tissue fluid
Inflammatory response ¯ophages, mast cells, 0B+s,and chemicals*
Surface carbohydrates on pathogens ser$e as
antigens
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Second Line of Defense: "hagocytes
#acrophages, monocytes &in blood*, neutrophils
&blood tissues*, mast cells, eosinophils
1ree: ander thru tissue in search of cellular debris
1i"ed: Kupffer cells &li$er*
#icroglia &brain*
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$#%
Lysosome
&icro#e adheres to phagocyte.
"hagocyte forms pseudopods that
eventua!!y engu!f the partic!e.
"hagocytic vesic!e is
fused 'ith a !ysosome.
&icro#e in fused vesic!e
is (i!!ed and digested #y
!ysosoma! en)ymes 'ithin
the phago!ysosome* !eaving
a residua! #ody.
Indigesti#!e andresidua! materia!
is removed #y
e+ocytosis.
"hagocytic vesic!e
containing antigen
$phagosome%.
,esidua! #ody
Acid
hydro!ase
en)ymes
"hago!ysosome
-
2
1
/
Phagocytosis
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Second Line of Defense: 0atura! i!!er $0% e!!s
Nonspecific
2arge granular lymphocytes
Bind targets &recogni!e as 3non-self4*
Induce apoptosis of targets
2yse cancer cells, $irus-infected cells
5elease perforins, other cytolytic chemicals %nhance inflammation
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Second Line of Defense:Inf!ammation
Non-specific response to in/ury
Pre$ents the spread of damaging agents to nearby tissues
.isposes of cell debris and pathogens
Sets the stage for repair processes
'allmarks:
1. Red (rubor)
2. Hot (calor)
3. Swollen (tumor)
. Painful (dolor)
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To!!!i(e ,eceptors $TL,s%
#acrophages and cells lining the gastrointestinal
and respiratory tracts bear T25s
T25s recogni!e specific classes of infecting
microbes
cti$ated T25s trigger the release of cytokines
that promote inflammation
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Inf!ammatory ,esponse: "hagocytic
&o#i!i)ation
1our main phases: 2eukocytosis 6 neutrophils are released from the
bone marro in response to leukocytosis-inducingfactors released by in/ured cells
#argination 6 neutrophils cling to the alls ofcapillaries in the in/ured area
.iapedesis 6 neutrophils s7uee!e through capillary
alls and begin phagocytosis
+hemota"is 6 inflammatory chemicals attractneutrophils to the in/ury site
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0eutrophi!s enter #!ood
from #one marro'
3ndothe!ium
Basement mem#raneapi!!ary 'a!!
&argination
Diapedesis
"ositive
chemota+is
Inf!ammatory
chemica!s diffusing
from the inf!amed
site act as chemotactic
agents
1
2
-
Inf!ammatory ,esponse: "hagocytic &o#i!i)ation
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Second !ine of "efense# Inflammation
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4omeostatic Im#a!ance
Inflammation does not clear infection debris
bscess &Pus not cleared*
58: I .
9ranulomas 6 infectious granulomas such as tuberclescontaining Mycobacterium tuberculosis
5esistant to digestion by #acrophages
Infected macrophages ith fibrous capsule +an remain asymptomatic until immunocompromised
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Second Line of Defense:Antimicro#ia! "roteins
ttack microorganisms ;r inhibit reproduction
Interferon
+omplement proteins
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Second Line of Defense:Antimicro#ia! "roteins
Interferon $IF0%
I1N synthesi!ed by $irus infected cells I1N diffuses to nearby cells, stimulate synthesis of proteins
&PK5* that inhibit $iral replication
PK5 is nonspecific inhibits replication of all $iruses #any types of I1N from many different cell types
lpha I1N used:
s an anti$iral drug against hepatitis + $irus
To treat genital arts caused by the herpes $irus
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Interferon $IF0%
Figure 21./
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Second Line of Defense:Antimicro#ia! "roteins
omp!ement
proteins in blood in an inacti$e form
Proteins include +? through +@, factors B, ., and
P, and regulatory proteins Pro$ides a ma/or mechanism for destroying foreign
substances in the body
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Second Line of Defense: Antimicro#ia! "roteins
omp!ement
cascade of r"ns that amplifies inflammation,nonspecific specific immune responses
Kills bacteria, cells &punches holes in membranes*
+lassical Pathay acti$ates specific immunity by:
b binds pathogen
+? binds to g-b comple" lternate Pathay by: factors B, ., P surface
polysaccharides of microorganisms
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omp!ement "ath'ays
Figure 21.6
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Second Line of Defense: Antimicro#ia! "roteins5
reactive "rotein $,"%
Produced by li$er in response to: Infection
Inflammation
Csed as clinical marker to assess the abo$e
Binds to pathogens targets them for:
Phagocytosis
;psoni!ation
+omplement acti$ation
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Second Line of Defense: Fever
body temperature
In response to infection by microorganisms or
e"posure to antigens
#oderate fe$er ;K: 2i$er, spleen se7uester iron !inc from pathogens
metabolic rate speeds up tissue repair
Too high, denatures en!ymes
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Adaptive Defenses $Specific Immune ,esponse%
dapti$e immune system- functional system :
5ecogni!es antigens &anything foreign*
ntigen-specific, systemic, and has memory
cts to immobili!e, neutrali!e, or destroyforeign substances
mplifies inflammatory response andacti$ates complement
'umoral 6 antibody-mediated immunity
+ellular- cell-mediated immunity
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Specific Immune ,esponse : Antigens
Anything the body perceives as foreign; “non-self”
utoimmune diseases
Substances that stimulate an immune response
Pathogenicity or $irulence is defined as the degree
to hich a pathogen can %D.% the immuneresponse
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Specific Immune ,esponse : omp!ete Antigens
1unctional properties:
Immunogenicity 6 ability to stimulate proliferation
of specific lymphocytes and antibody production
5eacti$ity 6 ability to react ith acti$ated
lymphocytes and the antibodies released in
response to them
+omplete antigens- foreign protein, nucleic acid,
some lipids, and large polysaccharides
Csually large molecules
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Specific Immune ,esponse: 4aptens $Incomp!ete
Antigens%
Small moleculesE peptides, nucleotides, manyhormonesE
not immunogenic
are reacti$e hen attached to protein carriers
'apten > bodyAs protein F immune response as inallergies
'aptens in poison i$y, dander, some detergents,and cosmetics
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Specific Immune ,esponse : Antigenic Determinants
Immunogenic part of ag
ntibodies and acti$ated lymphocytes bind to
antigenic determinants
#ost antigens Fnumerous antigenic determinants : #obili!e se$eral different lymphocyte populations
1orm different kinds of antibodies against it
2arge, chemically simple molecules &eGgG, plastics*
ha$e little or no immunogenicity
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Specific Immune ,esponse : Antigenic Determinants
Figure 21.7
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Specific Immune ,esponse: &4 "roteins
#a/or 'istocompatibility +omple"- self antigens,
uni7ue to an indi$idual
+lass I #'+ 6 on all body cells
+lass II #'+ 6 on certain cells in$ol$ed in theimmune response
These are the markers that ill elicit graft re/ection transfusion r"ns
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Specific Immune ,esponse: e!!s of Adaptive Immune
System
?G B lymphocytes or B cells 6 humoral immunityE
ab production
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S$ecific Immune Res$onse# !ym$hocyte %aturation,ed #one
marro'
Bone marro'Thymus
Lymph nodes*
sp!een* and other
!ymphoid tissues
Immature
!ymphocytesircu!ation
in #!ood
Immunocompetent*
#ut sti!! naive*
!ymphocyte migrates
via #!ood
Activated
Immunocompetent
B and T ce!!s
recircu!ate in
#!ood and !ymph
9 Site of !ymphocyte originey:
9 Site of antigen cha!!enge*
activation* and fina!diff erentiation of B andT ce!!s
9 Site of deve!opment of immunocompetence as
B or T ce!!s5 primary!ymphoid organs
Lymphocytes destined
to #ecome T ce!!s
migrate to the thymus
and deve!op
immunocompetence
there. B ce!!s deve!op
immunocompetence
in red #one marro'.
After !eaving the thymus
or #one marro' as nave
immunocompetent ce!!s*
!ymphocytes ;seed< the
!ymph nodes* sp!een* and
other !ymphoid tissues
'here the antigencha!!enge occurs.
Antigenactivated
immunocompetent
!ymphocytes circu!ate
continuous!y in the
#!oodstream and !ymph
and throughout the
!ymphoid organs of
the #ody.
11
1
22
2
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T e!! Se!ection in the Thymus Immunocompetence
Figure 21.=
&olerance'
recogniesbinds* %H+
Immunocom$etence' hasonly mild r,n to %H+
after binding- 2
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B e!!s Immunocompetence
B cells become immunocompetent and self-tolerant
in bone marro
Some self-reacti$e B cells are inacti$ated &anergy*
hile others are killed
;ther B cells undergo receptor editing in hich
there is a rearrangement of their receptors
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Immunocompetent B or T ce!!s .isplay uni7ue receptors 6 responds to 3that4 antigen
Become immunocompetent before encounteringantigens they attack
re e"ported to secondary lymphoid tissue here
encounters ith antigens occur
#ature into fully functional antigen-acti$ated cells
upon binding ith their recogni!ed antigen
It is genes, not antigens, that determine hich
foreign substances our immune system ill
recogni!e and resist
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Antigen"resenting e!!s $A"s%
?G Phagocytose antigens 6 partially digest
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Adaptive Immunity: Summary
'umoral, +ellular
B T lymphocytes, P+s, and specific molecules
to identify and destroy nonself particles
Its response depends upon the ability of its cells to: 5ecogni!e foreign substances &antigens* by
binding to them
+ommunicate ith one another so that the holesystem mounts a response specific to those
antigens
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4umora! Immunity ,esponse
ntigen challenge 6 first encounter beteen an
antigen and a nai$e immunocompetent cell
In spleen or other lymphoid organ
B cell receptor binds ag, receptor-mediatedendocytosis of the cross-linked antigen-receptorcomple"es, T cell acti$ationinteraction
B cell forms clones of identical cells &clonal
selection* Specific b produced against specific ag
"rimary ,esponse Antigen
A ti #i di
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"!asma
ce!!s
Secretedanti#ody
mo!ecu!es
!one of ce!!s
identica! to
ancestra! ce!!s
Su#se?uent
cha!!enge #y
same antigen
&emory
B ce!!
&emory
B ce!!s
"!asma
ce!!s
Secreted
anti#ody
mo!ecu!es
Secondary ,esponse
$can #e years !ater%
$initia! encounter
'ith antigen%
Antigen #inding
to a receptor on a
specific B !ymphocyte
$B !ymphocytes 'ith
noncomp!ementary
receptors remain
inactive%
"ro!iferation to
form a c!oneB !ympho#!asts
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Fate of the !ones
Secreted antibodies:
Bind to free antigens
#ark the antigens for destruction by specific or
nonspecific mechanisms
+lones that do not become plasma cells become
memory cells that can mount an immediate
response to subse7uent e"posures of the same
antigen
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Immuno!ogica! &emory
Primary immune response 6 cellular differentiation
and proliferation, hich occurs on the firste"posure to a specific antigen
2ag period: ( to H days after antigen challenge
Peak le$els of plasma antibody are achie$ed in ?=
days
ntibody le$els then decline
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Immuno!ogica! &emory
Secondary immune response 6 re-e"posure to the
same antigenE amnestic response
Sensiti!ed memory cells respond ithin hours
ntibody le$els peak in < to ( days at much higher
le$els than in the primary response
ntibodies bind ith greater affinity, and their
le$els in the blood can remain high for eeks to
months
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"rimary and Secondary 4umora! ,esponses
Figure 21.11
Ig# Ig9
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Active 4umora! Immunity
B cells encounter antigens and produce antibodies
against them
Naturally ac7uired 6 response to a bacterial or $iral
infection
rtificially ac7uired 6 response to a $accine of
dead or attenuated pathogens
Daccines 6 spare us the symptoms of disease, and
their eakened antigens pro$ide antigenic
determinants that are immunogenic and reacti$e
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"assive 4umora! Immunity
.iffers from acti$e immunity in the antibody
source and the degree of protection B cells are not challenged by antigens
Immunological memory does not occur
Protection ends hen antigens naturally degrade inthe body
Naturally ac7uired 6 from the mother to her fetus
$ia the placenta
rtificially ac7uired 6 from the in/ection of serum,such as gamma globulin
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Types of Ac?uired Immunity