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Gábor Koncz -- [email protected]
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Book: understanding the Immune System
http://www.cancer.gov/cancertopics/understandingcancer/immunesystem/IMM
UNE.PDF
Oral EXAM
(4-5 time point)
About the slides
!!
obligatory
!
important
Only for who wants 4 or 5 marks
Without mark
0
Not neccessary
(even the teachers dont know it)
week
1st
2nd
3rd
4th
5th
6th
7th
8th
9th
10th
11th
12th
13th
14th
15th
Date
2014.02.12
Seminar 1
2014.02.19
Seminar 2
2014.02.26
Seminar 3
2014.03.05
Seminar 4
2014.03.12
Seminar 5
2014.03.19
Seminar 6
2014.03.26
Seminar 7
2014.04.02
Seminar 8
2014.04.09
Seminar 9
2014.04.16
Seminar 10
2014.04.23
Seminar 11
2014.04.30
Seminar 12
2014.05.07
Seminar 13
2014.05.14
Seminar 14
2014.05.21
Seminar 15
Topic
Tissues/organs of the immune system.
Immune cells. Innate and adaptive arms of the immune system.
Innate immune system; recognition and elimination of pathogens.
Antigen presentation.
Immunoglobulins; structure and functions.
B cells; activation and effector functions.
T cells; types and functions.
The collaborations between innate and adaptive immunity. Antibody types and
functions.
Memory. Passive and active immunization.
The organization of the immune system.
Hypersensitivity reactions.
Autoimmunity. Immunological aspects in geriatrics. Rheumatology.
Inflammation. Anti-inflammatory agents. Biological therapy.
Modulation of the immune system with diet and exercise.
Consultation.
!
Human body 1014 cells--- 1013 cells are human
90% microorganism - 10% human
In the intestine 500-1500(1-1,5kg), bacteria species
On the palm~100 species
In the active phase of the HIV 10billion viruses develop/day
Bacteria may divide in
every 20 minutes
Vírus
3 hours
Complex parasites
Huge amount, variation and variablility of pathogens
3 hours
How can we survive?
symbiosis/commensalism
competion (~50 species compose of 99% of bacteria)
Immune system
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
INNATE IMMUNITY
ADAPTIVE IMMUNITY
- nonspecific
- immediate reaction
- does not improve after exposure
- no memory
- highly specific
- developes in several days
- improves after exposure
- has memory
Humoral
Complement proteins
Cytokines
Acute phase proteins
Antimicrobial proteins
Antibodies
Cellular
Granulocytes
Monocytes/Macrophages
Natural Killer cells
Dendritic cells
Mast cells
CD4+ (helper) T cells
CD8+ (cytotoxic) T
cells
B cells
!!
All cells of the immunesystem originate in the bone marrow from stem
cells.
Following it T cells differentiate and mature in the thymus.
HSC – hematopoietic stem cells
•Self renewing
•Pluripotent
• Symmetric-asymmetric cell division
!
THE CELLS AND MOLECULES
OF THE IMMUNE SYSTEM
Leukocytes derive from a common progenitorthe pluripotent hematopoietic stem cell (HSC)
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 immature dendritic cell migrates from the
circulation into the tissues and upon pathogen uptake it
differentiates to a mature dendritic cell and migrates to the
draining lymph node
-
DCs are professional 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)
BASOPHIL GRANULOCYTES
-1% of circulating leukocytes
- large granules in the cytoplasm
- nucleus with 2 lobes
- mast cells, histamin, allergic reactions
- high affinity IgE receptors
- against parasites
!
NEUTROPHIL GRANULOCYTES
- highest number in blood (68% of circulationg leukocytes,
99% of circulating granulocytes)
- phagocyting cells
- They are not present in healthy tissues
- tissue damage, migration, elimination of pathogens
(enzymes, reactive oxygen intermediers)
- main participants in inflammatory processes
EOSINOPHIL GRANULOCYTES
- agains parasites
- 2-3% 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
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)
A n ti g e n
Antigen
-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
-function: - antibody production
- humoral immun response
n
e
tig
n
A
PLASMA CELLS
!
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
Tsejt
to the peripheral (secunder) lymphoid organs
as TCR expressing T lymphocytes
- antigen recognition only in MHC
-molecules on the surface of APCs
-types:
- T helper (CD4+)
- T cytotoxic (CD8+)
- T regulator (suppressor)
APC
NK CELLS
(natural killer)
- origin: pluripotent cells of the bone marrow
lymphoid progenitors
- bigger than lymphocytes
- several granules in their cytoplasm
- has no antigen binding receptors („null cells”)
- participants of native immunity
!
The localization of blood cells
NK cells
WHITE BLOOD CELLS IN THE SMEAR OF HUMAN
PERIPHERAL BLOOD
neutrophil
granulocyte
eosinophil
granulocyte
MONOCYTE
neutrophil
granulocyte
LYMPHOCYTE
basophil
granulocyte
LYMPHOCYTE
Relative abundance of leukocytes in peripheral blood
Cell type
Neutrophil
Lymphocytes
Eosinophil
Basophil
Monocyte
Proportion of
leukocytes (%)
40-75
20-50
1-6
<1
2-10
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
dendrtitic cells
they express MHCII molecules
the protein degradation products (peptides) can be presented
to T lymphocytes by MHC molecules
!!
Monocite /
macrofage
Recognition
Cell-cel
(APC)
Communi
cation
Soluble
effector
function
DC
Mast
cell
Granulocites
NK cell
B cell
T cell
Complement
THE TWO ARMS OF THE IMMUNE SYSTEM
Monocytes, Macrophages,
Monocytes, Macrophages,
Dendritic cells, Granulocytes, NK
Dendritic cells, Granulocytes, NK
cells and Complement components
cells and Complement components
B and T cells
!!
Cells of innate immune system:
!!
Macrophages:
Macrophages are constitutively present in tissues and recognize microbes that enter
these tissues and respond rapidly to these microbes. Initiate the immune response
•These cells are phagocytes (eliminate the pathogens)
•Activate the innate immune response (by secreted proteins, called cytokines)
•Activate the adaptive immune system. Macrophages serve as APCs that display
antigens to and activate T lymphocytes
•Dendritic cells
are constitutively present in tissues and recognize rapidly microbes that enter these
tissues. Initiate the immune response.
•They have phagocytic capabilities
migrate to lymph nodes, and display microbial antigens to T lymphocytes,professional
antigen presentimg cells (APC)
Neutrophil granulocytes
are phagocytes, the main function to eliminate the pathogens
Appear only in the circulation under normal condition
Main actors In inflammatory processes
How do immunocytes communicate:
Soluble mediators
Infection
CYTOKINES & CHEMOKINES
Phagocyte activation
Soluble proteinsproduced by cells.
They have strong effect on the
function of other cells. Bit similar to
hormones.
How do immunocytes communicate:
Cell-cell interaction
. Cell-cell communication takes place commonly in all the phases of the
immune response
Cell killing
CTL
Target cell
T
Y
Antigen presentation
B
T
Antibody production
Activation of accessory cells
Dendritic cell macrophage
General schema of receptor funtion
MOLECULES OF THE IMMUNE SYSTEM
Most important receptors of the imune system
•receptors (BCR, TCR, MHCI, MHCII, PRR, etc.)
Soluble molecules:
• cytokines
• antibodies
• complement components
Receptors responsible for the recogniton of pathogens in the immune system
Caracteristics of innate
PRR Pattern recognition
immune system,
receptors
macrophage, dendritic cells
Danger signal and
Pathogen recognition
mainly in the innate immun
system
B cells
BCR (B cell receptor)
T cells
TCR (T cell receptor)
All nucleated cells in
human
MHC (MHCI) Major
Histocompatibility
Complex
Antigen recognition of B
cell
Antigen recognition of T
cell
Do not recognise
pathogens, but present
intracellular peptides
required for T cell receptor
professional antigen
presenting cells:
macrophages, DC, B cells
MHCII
Do not recognise
pathogens, but present
extracellular peptides
required for T cell receptor
THE MOST IMPORTANT FEATURES OF CYTOKINES
 The most important mediators of indirect cell communication in the
immune system („hormones” of the immune system).
 Act in low concentrations.
Cytokines can affect in an autocrine way, in a paracrine way,
or in an endocrine way 
pleiotropic effect.
 Cytokines can act by synergistic or antagonistic ways to each other.
A given cell may by affected by many cytokines resulting in the
same effect  redundant effect.
-
The responsiveness of the given cell is based on the expression of
cytokine-specific receptors.
!
 Cytokines can be devided into sub-groups by origin and
functional properties.
Functional groups:
Inflammatory cytokines
Direct the development and maturation of immune cells
Direct activation and differentiation of immune cells
Categories of cytokines
hormons
cytokines
interleukins
chemokine
interferons
!!
LYMPHOID ORGANS
Primary lymphoid organs:
- Bone marrow
- Thymus
Secondary lymphoid organs:
- Spleen
- Lymphatic vessels
- Lymph nodes
- Adenoids and tonsils
- MALT (Mucosal Associated Lymphoid Tissue)
GALT (Gut Associated Lymphoid Tissue)
BALT (Bronchus Associated Lymphoid Tissue)
SALT (Skin Associated Lymphoid Tissue)
NALT (Nasal Associated Lymphoid Tissue)