Core Data:
Subject: Immunology, Subject code: AOIMM02T5
lectures: 40, seminars: 10, laboratory practices: 10
ECTS Credit: 4
Prerequisites of the course: Biochemistry II., Cell Biology.
Prerequisites of the Pathology II. course: Immunology and Pathology I.
Web: www.immunology.unideb.hu
Education matters please, contact: alanyi@med.unideb.hu ; racz.andrea@med.unideb.hu
Signature of the Lecture Book
Participation in the Seminars and the Practical Courses is obligatory. The
Department shall refuse to sign the students' Lecture book if they are absent from
more than two practices or seminars in a semester. Students can make up for a
missed seminar or practice with another group only within the same week.
Examination
Evaluation is based on a written exam during the first third of the exam period. We
offer three dates for 'A' exams (tests and essay questions) covering all the course
material inluding Basic Immunology and Immune Pathology lectures as well as
Seminars and Practical Courses. The minimum requirement for passing the exam is
51%. ‘B' exam consists of a written entry test and an oral exam.
Downloading immunology lectures, seminars and practices from
Web: immunology.unideb.hu
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BOOK:
Peter Parham: The Immune system
Abbas: Basic Immunology
koncz.gabor@med.unideb.hu
Louis Pasteur
1880 rabies, 1888 Pastuer Institute
1884 Ilya Mechnikoff
Phagocytosis
Immunization with attenuated pathogens
CELLULAR IMMUNOLOGY
Vaccination is a powerful weapon against pathogens
and prevent epidemics
Smallpox virus was declerad eradicated
In 1979 by WHO
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
Pathogens win the battle in the absence
of either the innate or the adaptive arm of immunity
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 model?)
- „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
facultative pathogen (Staphylococcus aureus)
Monocite /
macrofage
recognition
Cell-cel
(APC)
Communication
Soluble
effector
function
DC
Mast
cell
Granulocites
NK cell
B cell
T cell
Complement
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 as a first line of defence
Innate immune cells recognize frequently found
structures of pathogens,
these are not found in human cells!
Examples: duple strain RNA
bacterial cell wall components
bacterial flagellin….
Recognition is inevitable
!!
PAMPs- Pathogen associated molecular patters
Structures on pathogens recognized by the innate cells
Recognition of pathogens by the innate
arm of the immune system.
THE CELLS AND MOLECULES
OF THE IMMUNE SYSTEM
The innate and the aquired arm of the immune
system works hand-in-hand to eliminate germs
Immunocompetent cells derive from a common
hematopoietic stem 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 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)
Follicular DCs: stroma cells of the centrum germinativum of
lymph nodes
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)
-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 in MHC molecules on the surface of APCs
-types:
- T helper (CD4+)
- T cytotoxic (CD8+)
- T regulator (suppressor)
DISTRIBUTION OF MHC ALLELES IN THE HUMAN
POPULATION
381
Polymorphism (number of alleles)
Class I
185
657 alleles
91
A B C
317
Class II
492 alleles
89
19
20 45
2
a b a b a b
DR
DP
DQ
077-298-32------------------218-329-10
HLA-C
HLA-B
HLA-A
HLA-B
HLA-A
HLA-C
anyai
apai
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
ANTIGEN RECOGNITION BY T-CELLS REQUIRES
PEPTIDE ANTIGENS AND ANTIGEN PRESENTING CELLS
THAT EXPRESS MHC MOLECULES
T
Y
soluble Ag
Native
membrane Ag
Cell surface MHCpeptide complex
Peptide
antigen
Cell surface
peptides
No T-cell response
APC
T-cell response
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
erithrocytes
4.2 – 6.1 x 1012
PLATELETS
thrombocytes
150-400 x 109
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 MHC molecules
the protein degradation products (peptides) can be presented
to T lymphocytes by MHC molecules
THE TWO ARMS OF THE IMMUNE SYSTEM
Monocytes/Macrophages,
Dendritic cells,
Granulocytes
NK cells
(complement system)
B and T lymphocytes
INNATE IMMUNITY
- immediate reaction
- not antigen-specific
- no memory
ADAPTIVE IMMUNITY
communication
- developes in several days
- specific
- has memory
Humoral immunity
Cellular immunity
LYMPHOID ORGANS
Primary lymphoid organs:
- bone marrow
- thymus
Secondary lymphoid organs:
- lymph node
- spleen
- tonsills
- 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, etc.)
• costimulatory molecules
• adhesion molecules (integrins, selectins, mucins, etc.)
Soluble molecules:
• cytokines
• antibodies
• complement components
• metabolites
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 (ckolesterol, triglicerid, phospholipid, lecitin, fat)
protein (globulin, albumin, fibrinoggn)
glycoprotein
hormon (gonadotropin, erytropoetin, trombopoietin)
amino acids
vitamins
Minerals:
in ionic, water-soluble forms
BIOACTIVE MOLECULES, THEY INFLUENCE THE ACTIVITY AND
FUNCTION OF THE IMMUNE SYSTEM
Cathegories of cytokines
cytokines
interleukines
chemokines
monokines
lymphokines
Nomenclature is based mainly on the producing cell
type
THE SITES OF IMMUNE CELL PRODUCTION DURING
DEVELOPMENT
embryo: yolk sac, liver, spleen
after birth:
- epiphysis
- flat bones – red bone marrow
(sternum, ribs, vertebras, hip bone)
CONSTANT REGENERATION
FAST REGENERATION
INTENSE ADAPTATION
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?
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)