Download 1. seminar 2012

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CELLS AND MOLECULES
OF THE IMMUNE SYSTEM
WHAT IS THE FUNCTION OF THE
IMMUNE SYSTEM?
How does it need to function?
Is there room for failure?
Immunodeficiencies!!!
What about speed?
What about specificity?
What about flexibility?
What about functional overlap?
Immunitas = exemption, protection
Protection from / against what?
Self or non-self substances?
(What about the useful bacteria living together with us and what about
tumors in this modell?)
- „Danger model”:
(Matzinger P., The danger model: a renewed sense of self. Science. 2002
Apr 12;296(5566):301-5.)
- harmful self / harmless self
- harmful non-self / harmless non-self factors!
-
DANGER SIGNAL / NO DANGER SIGNAL
obligate pathogen (Mycobacterium tuberculosis)
facultative pathogen (Candida albicans, E. coli)
opportunistic pathogen (Pseudomonas aeruginosa)
VACCINATION IS A POWERFUL WEAPON AGAINST
PATHOGENS AND PREVENTS EPIDEMICS
Smallpox virus was declerad eradicated
In 1979 by WHO
THE TWO ARMS OF THE IMMUNE SYSTEM
Differentiation between harmless and harmful impacts
DETECTION OF STRESS AND DANGER SIGNALS
INNATE IMMUNITY
Differentiation between self and non-self structures
Antigen-specific recognition
ADAPTIVE IMMUNITY
Neutralization and elimination of foreign and harmful structures
EXECUTIVE FUNCTIONS
COORDINATED AND REGULATED ACTIONS
INNATE IMMUNITY
- immediate reaction
- not antigen-specific
- no memory
ADAPTIVE IMMUNITY
communication
- developes in several days
- specific
- has memory
Humoral immunity
Cellular immunity
The innate and the aquired arm of the immune
system works hand-in-hand to eliminate germs
Pathogens win the battle in the absence
of either the innate or the adaptive arm of immunity
INNATE IMMUNE MECHANISMS ESTABLISH A STATE OF
INFLAMMATION AT SITES OF INFECTION
How do innate cells recognize bacteria and various other pathogens?
Is the reaction specific?
Recognition of lipopolysaccharide by Toll-like
receptor 4 (TLR4)
THE SITES OF IMMUNE CELL PRODUCTION DURING
DEVELOPMENT
embryo:
yolk sac, liver, spleen
after birth:
red bone marrow
- epiphysis of cancellous long bones
- flat bones (sternum, ribs, vertebras, hip bone)
CONSTANT REGENERATION
FAST REGENERATION
INTENSE ADAPTATION
IMMUNOCOMPETENT CELLS DERIVE FROM
A COMMON HEMATOPOIETIC STEM CELL (HSC)
FUNCTIONALLY DIFFERENT CELLS OF
THE IMMUNE SYSTEM
Resting lymphocyte
NK cell
Plasma cell
Mast cell
Monocyte
Tissue dendritic cell
Macrophage
Lymph node dendritic cell
MONOCYTES
- origin: pluripotent cells of the bone marrow
myeloid progenitors
- size: 10-15um
- nucleus: bean-shaped
- localization: circulation
out of circulation: macrophage
TISSUE - VENTRICLE
MACROPHAGES
-
phagocytic cells
antigen presenting cells (APC)
main types (based on tissue localization):
a) microglia (brain)
b) Kuppfer-cells (liver)
c) histiocytes (connective tissue)
d) osteoclasts (bone)
e) alveolar macrophages (lung)
- function: in cellular and humoral immun response
DENDRITIC CELLS
-
origin: myeloid or lymphoid progenitors
-
localization: the immatured dendritic cell migrates from the
circulation into the tissues and upon pathogen uptake it
differentiates to mature dendritic cell and migrates to the
draining lymph nodes
-
antigen presenting cells (APC)
-
types :
a) myeloid DCs:
- Langerhans cells (mucosa, skin)
- intersticial DCs (liver, spleen, etc.)
b) lymphoid DCs: - thymic DCs
- plasmacytoid DCs (pDC)
Follicular DCs: stroma cells of the centrum germinativum of
lymph nodes
NEUTROPHIL GRANULOCYTES
- highest number in blood (68% of circulating leukocytes,
99% of circulating granulocytes)
- phagocyting cells
- does not present in healthy tissues
- tissue damage, migration, elimination of pathogens
(enzymes, reactive oxygen intermediers)
- main participants in acute inflammatory processes
BASOPHIL GRANULOCYTES
- 0.1 - 1.5% of circulating leukocytes
- large granules in the cytoplasm
- nucleus with 2 lobes
- mast cells, histamin, allergic reactions
- high affinity IgE receptors
- against parasites
EOSINOPHIL GRANULOCYTES
- against parasites
- 0.1 - 5% of leukocytes
- allergic reactions
MAST CELLS
- origin: pluripotent cells of the bone marrow
myeloid progenitors
- localization: absent from circulation
differentiate in tissues
especially around small vessels
- function: - upon activation they regulate the permeability of the vessels with
their secreted molecules
- native and adaptive immunity
- allergic reactions (cell surface FceRI receptors)
- main types:
a) mucosal
b) connective tissue
COMMON LYMPHOID PROGENITOR CELLS
B lymphocyte
(Bursa fabricii)
T lymphocyte
(thymus)
maturation:
begins in bone marrow
continues in bone marrow
continues in thymus
differentiation:
peripheral tissues
plasma cells
effector T cells
- cytotoxic T cell
- helper T cell
antigen recognition
without MHC molecules
only via cell surface
MHC molecules
B LYMPHOCYTES
origin: pluripotent cells of the bone marrow
lymphoid progenitors
maturation: bursa equivalent tissues
(embrionic liver, later bone marrow)
-localization: takes 5-10% of the circulating lymphocytes; migrate from the
bone marrow to the secondary lymphatic organs thorugh the circulation
- antigen presenting cells (APC)
- activation: with antigens, via interaction with macrophages or
T lymphocytes, lymphokines, cytokines
- upon activation they differentiate to plasma cells or memory B cells
PLASMA CELLS
-function: - antibody production
- humoral immun response
T LYMPHOCYTES
- origin: pluripotent cells of the bone marrow
lymphoid progenitors
- maturation: thymus
- localization: in the thymus the thymocytes mature into
immunocompetent T cells and they enter to the peripheral (secunder)
lymphoid organs as TCR expressing T lymphocytes
- antigen recognition only via MHC molecules on the surface of APCs
-types:
- T helper (CD4+)
- T cytotoxic (CD8+)
- T regulator (suppressor)
NK CELLS
(natural killer)
- origin: pluripotent cells of the bone marrow
lymphoid progenitors
- 5-10% in circulation
- bigger than lymphocytes
- several granules in their cytoplasm
- has no antigen binding receptors („null cells”)
- participants of native immunity
Professional phagocytic cells
macrophages
neutrophyl granulocytes
dendrtitic cells
the phagocytosed cells or molecules may modify
the functions of the cell
phagocytosis followed by enzymatic degradation
Professional antigen presenting cells
macrophages
B lymphocytes
dendritic cells
they express MHC II molecules
the protein degradation products (peptides) can be presented
to T lymphocytes by MHC molecules
WHITE BLOOD CELLS IN THE SMEAR OF HUMAN
PERIPHERAL BLOOD
neutrophil
granulocyte
eosinophil
granulocyte
MONOCYTE
neutrophil
granulocyte
LYMPHOCYTE
basophil
granulocyte
LYMPHOCYTE
DISTRIBUTION OF BLOOD CELLS
AND LYMPHOCYTE SUBTYPES
Percentage
WHITE BLOOD
CELLS
leukocytes
Cell number/L
4.8 – 10.8 x 109
neutrophil
granulocytes
40 – 74
1.9 – 8 x 109
eosinophil
granulocytes
0.1 – 5
0.01 – 0.6 x 109
basophil
granulocytes
0.l – 1.5
0.01 – 0.2 x 109
lymphocytes
19 – 41
0.9 – 4.4 x 109
monocytes
3.4 – 9
0.16 – 0.9 x 109
RED BLOOD
CELLS
erythrocytes
4.2 – 6.1 x 1012
PLATELETS
thrombocytes
150-400 x 109
LYMPHOID ORGANS
Primer lymphoid organs:
• bone marrow
• thymus
Secunder lymphoid organs:
•
•
•
•
lymph node
spleen
tonsils
MALT (Mucosal-Associated Lymphoid Tissue)
– GALT (Gut-Associated Lymphoid Tissue)
– BALT (Bronchus-Associated Lymphoid Tissue)
MOLECULES OF THE IMMUNE SYSTEM
Cell surface molecules:
•
markers (CD)
•
receptors (BCR, TCR, MHCI, MHCII, PRR, cytokine, etc.)
•
costimulatory molecules
•
adhesion molecules (integrins, selectins, mucins, etc.)
Soluble molecules:
•
cytokines
•
antibodies
•
complements
•
metabolites
RECOGNITION OF PATHOGENS BY
THE INNATE ARM OF THE IMMUNE SYSTEM
THE MAIN TYPES OF CELL SURFACE MOLECULES
PARTICIPATING IN ANTIGEN RECOGNITION AND THE
INTERACTION BETWEEN DENDRITIC CELLS AND T CELLS
SOLUBLE MOLECULES
In plasma and other fluids
plasma:
90% H2O
10% dry material:
90% organic material
10% inorganic material
organic material:
carbohydrate (glucose)
lipid (cholesterol, triglyceride, phospholipid, lecithin, fat)
protein (globulin, albumin, fibrinogen)
glycoprotein
hormon (gonadotropin, erythropoietin, thrombopoietin)
amino acids
vitamins
inorganic material:
minerals in ionic, water-soluble forms
BIOACTIVE MOLECULES, THEY INFLUENCE THE ACTIVITY AND
FUNCTION OF THE IMMUNE SYSTEM
cytokines
chemokines
monokines
interleukines
limphokines
Nomenclature is based mainly on the producing cell type