Download The objectives of this course

The objectives of this course
How can you produce an antiserum or
aantibody
t o y with
t the
t e desired
es e characteristics?
c a acte st cs?
Study the basics of the immune system, especially
the (humoral) immune response
How can you obtain the best possible result
with a ggiven antiserum/antibodyy in a given
g
application?
Study the basics of the antibody structure and the
mechanism of antibody-target interactions
Non-Adaptive versus Adaptive immunity
has low specificity
needs no induction time
has no memory
acts through anatomic
barriers (*)
serves in the early stage of
d f
defense
high specificity
takes several days to put in
place
h memory
has
acts through lymphocytes and
accessory cells
ll
serves in the later phase of
events
t
... but remember : the two collaborate!
(*) physiological barriers, endocytic and phagocytic barriers,
inflammatory barriers
The inflammatoryy response
p
tissue
dammage
bacteria
vasoactive &
chemotactic
h
i factors
f
serum proteins
phagocytic
cells migrate
exudate
serum p
proteins,
complement,
antibody, ...
capillary
p
y
The four capital signs of inflammation:
tumor, rubor, calor & dolor
Endocytosis (Phagocytosis and Pinocytosis):
it's like eating and drinking ...
Phagocytosis : the "eating"
eating of particulate matter by a cell
Pinocytosis: the "drinking" of extracellular fluid, containing
macromolecules
11
2
3
4
5
3 phagosome moves toward
lysosome
2 ingestion into phagosome 4 fusion of phagosome and
lysosome
1 attachment to pseudopodia
5 digestion &
elimination
The cells that do the work
bone marrow
pluripotent hematopoietic stem cell
bone marrow
common lymphoid progenitor
myeloid progenitor
y
megakaryocyte
g y y erythroblast
blood
ppolymorphonuclear
y
p
leucocytes
y
B-cell
T-cell
effector cells
plasma cell
activated
T-cell
basophil eosinophil neutrophil
?
monocyte
tissues
mast cell
macrophage
platelets
erythrocyte
Key players of the immune system :
the lymphocytes
Small lymphocytes are
inactive cells:
condensed chromatin
little cytoplasm
small size
no RER
B-cells
B
cells
antigen-recognition sites
T-cells
T
cells
antigen-recognition site
The "dogmas" of immunology
All the antigen-recognition sites of a particular lymphocyte are
identical: one cell - one antigen .
Each lymphocyte generates a unique receptor by rearranging its
receptor genes; there
there'ss literally millions of possibilities: "diversity".
diversity .
Lymphocytes recognizing ubiquitous self-antigens are eliminated
p
byy a pprocess called "clonal deletion",, leadingg to
duringg development
"self-tolerance".
A lymphocyte
y p y needs to meet its antigen
g before it can get
g activated
and start producing identical daughter cells, a process called "clonal
expansion". This ensures the specificity of the immune response.
Upon encounter of that antigen, some of these daughter cells will
survive, even after the antigen has been eliminated: these cells
(("memoryy cells")) are the basis of immunological
g memory.
y
Lymphocytes are "educated" in the central lymphoid organs
Initial receptor repertoire
Ubi it
Ubiquitous
self
lf antigens
ti
Self antigens bind to receptors on newly formed cells
Anti-self cells die (clonal deletion) leaving mature self-tolerant
epe o e
reperoire
B-cells in the Bursa of Fabricius (Bone marrow)
T-cells
cells in the Thymus
The clonal selection theory
Removal of potentially self-reactive immature lymphocytes by clonal deletion
Negative selection
self antigens
self antigens
Pool of mature naive
lymphocytes
foreign antigen
Proliferation of activated specific lymphocytes to form a
clone
Differentiation to effector
cells
Effector cells eliminate antigens
Differentiation into resting memory cells
Memory cells respond more efficiently
to antigen
P i i selection
Positive
l i
Lymphocytes
y p
y
at work ...
1) antigen-receptor binding
2) activation by nearby T-cell
T cell
B-lymphocyte
1) antigen-receptor binding
2) Co-stimulation by
antigen-presenting cell (APC)
antigen- presenting
cell
proliferation (clonal expansion) and
differentiation to effector function
T-lymphocyte
The Professional Antigen-Presenting Cells (APC)
B-lymphocyte
Macrophage
Dendritic cell
B cell activation by helper CD4 cells
B-cell
1) Antigen bound by B-cell
B cell
surface receptor
2) Antigen internalized and
degraded
g
to ppeptide
p
fragments
g
3) Fragments bind to MHC-II and
are transported to cell surface
4) Recognition by T Helper cell
and activation of B-cell
When the bugs invade ...
Virus infects macrophage
Bacterium
macrophage
infects
Viral proteins synthesized in
cytosol
Bacterium gets digested
into peptide fragments
Fragments of viral proteins
bound by MHC class I in ER
Bacterial fragments are
bound by MHC class II in
vesicles
Bound peptides presented at
cell surface by MHCclass I
Bound peptides presented
at cell surface by MHCclass
II
Cytotoxic T cell recognizes
this complex and kills the
infected cell
T helper cell recognizes this
complex and activates APC
T cell - APC interaction in close up
p
T Helper -cell
TCR
C
Cytotoxic
i T
T-cellll
TCR
CD4
peptide
MHC-II
peptide
CD8
MHC-I
APC
Nucleated cell
g
of the immune system
y
The organs
Naive lymphocytes
enter lymph nodes
f
from
blood
bl d
adenoid
tonsil
right subclavian
vein
lymph
y p
node
kidney
appendix
lymphatics
Lymphocytes and
lymph return to blood
via thoracic
h
dduct
left subclavian vein
thymus
thymus
heart
thoracic duct
spleen
Peyer's patch in
small intestine
large
intestine
bone
bone
marrow
marrow
lymph
node
infected
peripheral
tissue
Antigens from sites of
infection reach lymph nodes
via lymphatics
Meeting point : the lymph node
primary lymphoid
follicle
afferent lymphatic
vessel
paracortical area
(mostly T-cells)
secundary lymphoid
follicle (mostly B-cells)
cortex
medullary cords
(macrophages and
plasma cells
medullary sinus
artery
vein
efferent lymphatic
vessel
marginal
sinus
antigen
naive
lymphocytes
effector
lymphocytes