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Nonspecific (innate)
•Physical and chemical
agents
•Lysozyme
•Acute phase proteins Specific (adaptive)
•Complement system •Antibodies
•Cytokines (chemokines) (B lymphocytes)
•Phagocytes (granulocytes, •T lymphocytes
macrophages)
•Natural killer (NK) cells
•Dendritic cells
•Pattern recognition receptors
(PRR)
Major differences between innate
and acquired immunity (acc. to U.
Koedel & W Pfister 2005)
Innate immune Acquired immune
system system
• Immediate maximal • Lag time (3-4 days) between
response exposure and max.
• No immunological memory response
• Not antigen specific • Immunological memory
• Receptors: germ line • Antigen specific
encoded, • Receptors: generated
• In almost all multicellular somatically,
organisms, • Only in vertebrates,
• Recognition of conserved • Recognition of details of
molecular patterns, molecular structure,
• Perfect self/non-self • Imperfect self/non-self
discrimination discrimination,
• Only hundreds of different • Over 100 000 000 000
THE IMMUNE SYSTEM
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Regulation of
Hematopoiesis
• Hematopoiesis is a continuous
process that generally maintains a
steady state in which the production
of mature blood cells equals their
loss (principally from aging).
• The average erythrocyte has a life
span of 120 days before it is
phagocytosed abd digested by
macrophages in the spleen.
9
Programmed cell death
• Cells undergoing programmed cell death
often exhibit distinctive morphologic
changes, collectively referred to as
apoptosis.
11
Lymphoid cells
• Lymphocytes constitute 20% - 40%
of the body’s white blood cells and
99% of the cells in the lymph.
• There are approxiamately 1011
(range depending on body size and
age: ~1010 – 1012) lymphocytes in the
human body.
• The lymphocytes can be broadly
subdivided into three populations-B-
cells, T-cells and null cells-on the
basis of function and cell membrane
12
Lymphocytes
• Produce antibodies
• B-cells mature in bone marrow then
concentrate in lymph nodes and
spleen
• T-cells mature in thymus
• B and T cells mature then circulate in
the blood and lymph
• Circulation ensures they come into
contact with pathogens and each
other
B -Lymphocytes
• There are c.10 million different B-
lymphocytes, each of which make a
different antibody.
• The huge variety is caused by genes
coding for abs changing slightly
during development.
• There are a small group of clones of
each type of B-lymphocyte
B -Lymphocytes
• At the clone stage antibodies do not leave
the B-cells.
• The abs are embedded in the plasma
membrane of the cell and are
called antibody receptors.
• When the receptors in the membrane
recognise and antigen on the surface of
the pathogen the B-cell divides rapidly.
• The antigens are presented to the B-cells
by macrophages
B -Lymphocytes
B -Lymphocytes
• Some activated B cells PLASMA
CELLS these produce lots of
antibodies, < 1000/sec
• The antibodies travel to the blood,
lymph, lining of gut and lungs.
• The number of plasma cells goes
down after a few weeks
• Antibodies stay in the blood longer
but eventually their numbers go
down too.
B -Lymphocytes
• Some activated B cells MEMORY
CELLS.
• Memory cells divide rapidly as soon
as the antigen is reintroduced.
• There are many more memory cells
than there were clone cells.
• When the pathogen/infection infects
again it is destroyed before any
symptoms show.
Null Cells
Markers
Cells
http:www.coleypharma.com
Developmental Pathway of
DCs
Follicular DCs
• Do Not Express MHC II Molecules
• Found in Lymph Follicles (Rich in B
Cell)
• Express FcR For Antibodies and
Complement
• Ag-Ab Complex Shown To Last Very
Long (weeks to months)
45
46
47
48
Phagocytosis
Phagocytosis
• If cells are under attack they release
histamine.
• Histamine plus chemicals from pathogens
mean neutrophils are attracted to the site
of attack.
• Pathogens are attached to antibodies and
neutrophils have antibody receptors.
• Enodcytosis of neutrophil membrane
phagocytic vacuole.
• Lysosomes attach to phagocytic vacuole
pathogen digested by proteases
Organs of the immune
system
• A number of morphologically and
functionally diverse organs and tissues
have various functions in the development
of immune responses.
• These can be distinguished by function as
the primary and secondary lymphoid
organs.
• The thymus and bone marrow are the
primary(or central) lymphoid organs,
where maturation of lymphocytestakes
place. 52
• The lymph nodes, spleen, and various
mucosal-associated lymphoid tissues
(MALT) such as gut-associated
lymphoid tissue (GALT) are the
secondary (or peripheral) lymphoid
organs, which trap antigen and
provide sites for mature lymphocytes
to interact with that antigen.
53
Organs of the
immune
system
54
Thymus
• Structure
– Gross
• Bi-lobed
• Lies above heart
– Microscopic
• Capsular
• Lobules with outer cortex and inner
medulla
Thymus
• Function
– Takes in immature T cells and puts out
mature (immunocompetent) T cells
– Increased diversity of T cells
– T cell selection
Thymus
• T cell selection
– Based on MHC/Ag complex recognition
• Recognize MHC/Non self AG complexes
• Recognize MHC/Self Ag complexes
• Do not recognize MHC/Ag complexes
• Athymic condition
– Natural
– Other
Bone marrow
• Structure
– Microscopic
• Less well defined than thymus
• Role of stromal cells
• Function
– Hematopoiesis
– B cell maturation
– B cell selection
– Puts out mature, naive B cells
Lymph Nodes
• Structure
– Gross
• Bean-shaped structures
• Drains major segments of lymphatic
system
Lymph Nodes
• Structure
– Microscopic
• Major cell types
– Lymphocytes
– Macrophages
– Dendritic cells
• Cortex/paracortex/medulla
• Follicles
– Primary
– Secondary
Lymph Nodes
• Function
– 1st line of response to antigens
– Secondary follicle (Germinal center) is site of B
cell proliferation, mutation, differentiation
– Specificity is high
– >90% of B cells die through apoptosis
– After Ag stimualtion lymphocyte numbers up by
50X in efferent lymphatic vessel
– Lympadenopathy
Spleen
• Structure
– Gross
• Ovoid organ in upper left quadrant of abdomen
– Microscopic
• Compartmentalized
– Red pulp
– White pulp
• Periarticualr lymphoid sheath
– Site of Ag presentation
• Major cell types
– Lymphocytes
– Macrophages
– Dendritic cells
– RBCs
Spleen
• Function
– Filters out older RBCs
– Responds to Ag in circulatory system
– Produces activated B cells
• Splenectomy
Tonsils
• Follicular structure
• Contains lymphocytes, macrophages,
mast cells
• Germinal centers appear in response
to Ag
• Protective role in URI
Appendix