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Biotechnolo and Pharmacolo Course To ic 03
Le Van Dong MD., PhD
Deputy Head, Department of Immunology
Vietnam Military Medical University
[email protected]; [email protected]
EDUCATION
INDUSTRY/ TREATMENT
RESEARCH
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Aims
Know key properties of innateimmunity.
Know components made up the
innate immune system.
Understand mechanism(s) by
which the innate immunity use to
protect body.
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Innate immunity and adaptive
Abbas A. K and Lichtman A. H
Basic Immunology 3rd Ed Saunders 2011
First line of defense
Non-specific
Second line of defense
Highly specific with memory
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Pro erties of innate immunit
,
another generation.
ways presen an mme a e y reac
as the microbe enters the body.
Utilize the same mechnism to fight
different microbes (non-specific).
No memory, reaction is not stronger
after each encounterment.
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Components of innate
Epithelia (skin and mucous
.
Phagocytes, NK cell.Plasma proteins, including
complements.
Cytokines.
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Mechnisms of innate immunit
Physical barries of skin and mucous membrane.
Cellular mechanisms: .
Killing by NK cell.
Humoral mechanisms:Lysis by complements.
Cytokines
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Physical and chemical mechanisms
mucous membranes
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Roles of epithelia in innate immunity
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E ithelial Barriers COMMON PORTALS OF ENTRY BY
MICROBES:skin, GI tract, respiratory tract. These 3 portals are lined by continuous
epithelia. These cells also produce peptide
antibiotics. In addition, intraepithelial
l m hoc tes T cell linea e ex ress anti en
receptors of limited diversity common class is
T cells(have and chains which are similar
. Intraepithelial lymphocytesrecognize microbial
trying to breach epithelia.
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a appens w en e p ys ca
and chemical barriers arebreached?
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Cellular mechanismsLeukocyte Players of Innate Immune
Responses
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Cellular mechanisms
Pha oc tosis
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Deployment of phagocyte to the infection site
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How phagocyte get out of the blood
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How do phagocytes recognize microbes?
Mannose
receptorMac-1
Scavenger
receptor
Mannose
receptorMac-1
Scavenger
receptor CD14
Toll like receptor
C FcC Fc
These cell have surface receptor for microbes, that can bind to
.
These receptor recognise unique structure on microbe only (MP).
Receptors for C and Fc to cache C or Ab coated microbe
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Phagocytosis process
NO
Arginine
Inducible nitric
oxide synthaseROI
Oxidase
(INOS)
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How phagocyte capture microbe
Direct
capture with
C coated microbe
(opsonization by C)v a recep or
Y Antibody coated microbe(opsonization by antibody)
(via Fc receptor)
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NK cell kills target cells
ELIMINATING MICROBIAL RESERVOIR
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WhenNKcellkillsothercell?
AL
NO
R
ORMA
Abbas A. K and Lichtman A. H Basic Immunology 2nd Ed Saunders 2004
AB
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Activating and Inhibitory receptors
molecules on stressed cells (viruses, IC bacteria, DNAdamage, malignant transformation, tumour cells) tell NK
to kill.
INHIBITORY RECEPTORSspecific for class I MHCs tellno o .
Viruses have mechanisms which block expression of
.
CTLs but inhibits the inhibitory NK receptors. Thus,NK
cells are still activated and continue to eliminate
v rus- n ec e ce s.
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Injection
Cholaera
Cholaera serum
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+
Fresh serum
+
56 0C
serum Non-
injected
serum
Bordets experiment
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The complement system C
Collection of circulatin membrane associated roteins
(mainly proteolytic enzymes) C activation pathways:
Alternative pathway (innate) is triggered when complement
proteins are activated on microbial surfaces. Microbes dont have
re ulator roteins and cant control it.
Classical pathway(humoral adaptive) is triggered after Abs bind
to microbes and other Ags.
Lectin pathway (innate immunity) activated when mannose-binding lectin binds to terminal mannose residues on microbial
surface glycoproteins (activates proteins of the classical pathway
u s nna e .
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C pathways
Alternative pathway and
innate immunity; Classical
pathway belongs to
Abbas A. K and Lichtman A. HBasic Immunology 2nd Ed Saunders 2004
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Beginning steps
Abbas A. K and Lichtman A. HBasic Immunology 2nd Ed Saunders 2004
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Final steps
3 pathways have
different beginnings but
chare same late steps
and effector functions
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Biolo ical effects of C
pson za on: coa s m cro es,
promotes phagocytosis.
ys s o ac er a: orma on o apenetrates the cell membrane and causes
either l sis or microbial a o totic death.
Chemotaxic: some C fragments arechemoattractants for ha oc tes and
eventually other leukocytes (ie. C5a, C3a).
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ofC
ect
s
a
lef
logi
Bi
Abbas A. K and Lichtman A. H Basic Immunology 2nd Ed Saunders 2004
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C tokines of Innate Immunit
u - u y u y ,
act on leukocytes (though not all).
e pr nc pa source o cy o nes are
activated dendritic cells and macrophages.
mos pro uce n sma amoun s
bind withhigh affinityto target cells
can act distant from site of secretion
C t ki i
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Cytokines serve various
TNF, IL-1 recuit blood neutrophils and monocytes to
n ec on can a so pro uce rom us orma on,
reduced myocardial contractility, vascular dilation,leakiness andshock.
Septic shock can be produced by disseminated gram-
neg infections. One sees low blood pressure,coagulation, metabolic disturbance in septic shock, one
seeshigh TNF levels.
IL-12 produced by macs and dends in response to LPS,other microbial products.
IFN - produced by NK cells, T cells both innate and
adaptive.
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Macro ha e c tokines
Abbas A. K and Lichtman A. H Basic Immunology 2nd Ed Saunders 2004
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Other Plasma Proteins
-
opsonizes and activates complement
-
Circulating levels of many plasma proteins
response
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Notes
Extracellularbacteria and fungi combated byphagocytes, complement, acute phase
proteins
n race u ar ac er a an v ruses com a e
by phagocytes, dendritic cells, NK cells
with help fromcytokines
I t i it
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Innate immunity
immunity
Innate immune
responses generate
second signals
(together with antigens)
to activate B and Tlymphocytes.
This microbe-
signal requirementensures no response
to harmless
substances.
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2 signals regulation
signal 1) and moleculesproduced during the innate
immune response (signal 2)
function cooperatively to activate
anti en-s ecific l m hoc tes.
The requirement for microbe-
tri ered si nal 2 ensures that
the adaptive immune response isinduced by microbes and not by
.
Microbes stimulate DC and M to produce
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Microbes stimulate DC and M to produce
second signals that stimulate T
lymphocytes
.
These bind to receptors on nave T cells Ag +.
ALSO DC and M secrete IL-12which stimulates T cell
B lymphocytes recognize C3d on microbes from
alternative athwa
There is a receptor for C3don B cellwhich serves as
costimulator
These second signals not only stimulate
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g y
adaptive immunity but also guide the
response
Intracellular pathogens need to be
eliminated by T cells thus T cells are
s mu a e y -ce cos mu a ors on
dendritic cells and macrophages.
x race u ar pa ogens e. oo -
borne) need to stimulate B cells and
-
stimulators
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Review uestions
. w u y
recognize microbes?
2.How do different components of innate
immunity function to combat different
3.How do innate immune reactions
stimulate adaptive immune responses?
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