1.innate-adaptive b9
TRANSCRIPT
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Immune system -
why?
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The major types of pathogen
confronting the immune system
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Innateand
Adaptive
immunity
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Gastrointestinal,
respiratory and
Infection occur only when the pathogen can
colonize or cross through these barriers
These barriers are
permanently present.
They do not normally
increase in concentration or
respond to specific
pathogens.
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Cellular innate immunity:
Granulocytes(polymorphonuclear
leukocytes)
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Macrophages
are activated by
pathogens and
both engulf
them and initiateinflammatory
responses
Pattern recognition receptors (PRRs)
on phagocytic cells recognize and are
activated by pathogen-associated
molecular patterns (PAMPs)
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Cytokines are small proteins (~ 25 kDa) thatare released by various cells in the body,
usually in response to an activating stimulus,and they induce responses through binding to
specific receptors.
They can act in autocrine manner,affecting the behavior of the cell that
releases the cytokine, in a paracrine
manner, affecting the behavior of adjacencells and some cytokines are stable
enough to act in an endocrine manner,
affecting the behavior of distant cells.
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Infection triggers an inflammatory response
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leukocytes leave the blood and migrate to sites of infection in
a multistep process mediated through adhesive interactions
Selectins
Chemokines
Integrins
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Bactericidal agents produced or released by
phagocytes on the ingestion of microorganisms
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Mannose-
binding
lectinrecognizes
bacterial
surfaces bytheir
particular
spacing of
carbohydraeresidues
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Schematic overview of the
complement cascade
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The actions of the innateimmune systems are a
prerequisite for thedevelopment of the adaptive
immunity
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All the cellular
elements of
the bloodarise from
pluripotent
hematopoieticstem cells in
the bone
marrow
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Adaptive
immunity
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Clonal
selection
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1 lymphocyte=
1specificity
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A specific immune response,
such as the production of antibodies
or activation ofT cells against aparticular pathogen, is known as an
adaptive immune response,because it occurs during the life
time as an adaptation to infection
with that pathogen.
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The key difference between the innate
and adaptive immune systems is thatresistance to infection is not improved
by repeated infection in the innate
immune system. In contrast, theadaptive immune system will increase
the ferocity of its defense to a pathogen
with repeated infection.
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Fab
Fc
Fab
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Antibodies can participate in host defense in three main ways
FcR
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FcR
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The T-cell
receptor
resembles a
membrane-bound
Fab fragment
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TCR has
constant and
variable regionshomologous in
structure and
function to thoseof
immunoglobulins
(TCR has only a
membrane form)
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Tri-molecular interaction
MHC-Ag-TCR CD4
MHC-II
E
F
TCR
MHC-
MajorHistocompatibility complex
TCR- TCell Receptor
Ag- antigen
CD8
E F
MHC--I
TCR
Ag
Professional APC
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MHC-I molecules are expressed at
low level on the vast majority of our cells
RBCLiver
cell
MHC--I
Kidneycell
MHC-I
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MHC Class I
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CD8 T cells kill viral
infected and malignant
target cells by lythic
granules (granzyme and perforin)
and receptor-induced apoptosis
Fas Ligand
Fas
Target cell
CD8
EF
TCR
DNA fragmentation
Caspasses
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Nature reviews microbiology 3:59 (2005)
The missing
self hypothesis
Downregulation of
MHC class-I molecules
from the cell surface
by oncogenic
transformation
or virus infection
renders these cells
more susceptible
to attack by NK cells
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Professional
Antigen
PresentingCells (APCs)
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MHC Class II
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macrophages
B cells
DC
express MHC-IIand present antigen
to CD4 T cells
Professional APC
CD8
E F
MHC I
TCR
CD4
B cell
MHC II
CD4
MHC II
E F
TCR
Th di ib i f l h id i i h b d
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The distribution of lymphoid tissues in the body
Lymphatics drain
extracellular fluid (lymph)
from the peripheral tissues
into the thoracic duct
Primary
lymph nodes
peripheral
Lymph nodes