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Transcript
Materials for the lectures and seminars can be downloaded:
Web: www.immunology.unideb.hu
Downloads
Login: student
Password: download
List of books:
For the first test: Gogolak P., Koncz G. Short textbook of Basic Immunology
(uploaded to our website)
Parham, P. The Immune System, Fourth Edition
Abbul K. Abbas Basic Immunology, Fourth Edition
Raif Geha, Luigi Notarangelo: Case Studies in immunology
Requirements for Medicine Students
 Changing of the seminar group – week 1-3 with permission from the
Department
 Absences from the seminars:
• More than two absences from the seminars – Department will refuse to sign
the student’s Lecture book
• Possibility for make up (on the same week of the seminar, should be
communicated to both seminar teachers)
 Syllabus of the practices: (you can find in the curriculum)
 SCTs: week 5, 11, 15:
• 14th of October 2016. (Friday) 06:30 pm –
• 24th of November 2016. (Thursday) 06:30 pm –
• 21st of December 2016. (Wednesday) 5 pm -
 Tresholds:
• 1st SCT above 70%
• 2nd and 3rd SCT above 50% (average)
170 – 204: pass (2)
205 – 239: satisfactory (3)
240 – 269: good (4)
270 – 300: excellent (5)
Requirements for MSc in Molecular Biology
Molecular Immunology
 Lecture from week 1-10
 Seminars: no absences are allowed
• Time: week 4, 7, 9, 11 Wednesdays 8:00-10:00
• Place: LSB 2.209
 SCTs: week 5, 11:
• 14th of October 2016. (Friday) 06:30 pm –
• 24th of November 2016. (Thursday) 06:30 pm –
 Tresholds:
• 1st SCT above 70%
• 2nd SCT above 50%
120 – 139: pass (2)
140 – 159: satisfactory (3)
160 – 179: good (4)
180 – 200: excellent (5)
Education Office
Gabor Koncz, MSc., Ph.D (academic advisor)
Official hours:
• Tuesday: 2 – 4 pm
• Thursday: 10 – 12 pm
Place: LSB 2.209 (LifeScience Building 2nd wing 2nd floor)
Andrea Dajkane Racz (administrative manager)
Official hours:
• Monday - Friday: 9 – 12 am
Place: LSB 2.207 (LifeScience Building 2nd wing 2nd floor)
FcR
Affinity for Immunoglobulin
Cell Distribution
Function
High (Kd < 10-9 M);
binds IgG1 and IgG3,
can bind monomeric
IgG
Macrophages,
neutrophils; also
eosinophils
Phagocytosis;
activation of
phagocytes
FcγRIIA (CD32)
Low (Kd > 10-7 M)
Macrophages,
neutrophils;
eosinophils, platelets
Phagocytosis; cell
activation (inefficient)
FcγRIIB (CD32)
Low (Kd > 10-7 M)
B lymphocytes
Feedback inhibition of
B cells
FcγRIIC (CD32)
Low (Kd > 10-7 M)
Macrophages,
neutrophils, NK cells
Phagocytosis, cell
activation
FcγRIIIA (CD16)
Low (Kd > 10-6 M)
NK cells
Antibody-dependent
cell-mediated
cytotoxicity
FcγRIIIB (CD16)
Low (Kd > 10-6 M);
GPI-linked protein
Neutrophils
Phagocytosis
(inefficient)
FcΕRI
High (Kd > 10-10 M);
binds monomeric IgE
Mast cells, basophils,
eosinophils
Cell activation
(degranulation)
FcΕRII (CD23)
Low (Kd > 10-7 M)
B lymphocytes,
eosinophils,
Langerhans cells
Unknown
FcγRI (CD64)
You do not have to know any data
presented in the red boxes
doi:10.1038/nri3650
Ectopic expression of FOXP3 in naive mouse CD4+ T-cells confers suppressive activity and
induces the expression of Treg-associated signature molecules such as CD25, CTLA4 and
GITR. Expression of these receptors also correlates with FOXP3 expression
in human CD4+ T-cells.
FOXP3 has a key role in maintenance of self tolerance.
Exams:
Based on the slideshows of the lectures
Only data presented in the slides will be asked.
(Notes are part of the sildes!)
Gábor Koncz
[email protected]
In this lecture:
1. Administration
2. Why do we need immune system
3. Simple schema of the immune system
4. Definition of antigen, lexical data (5)
Do we need immune system?
GENERATION TIME OF PATHOGENS
PATHOGENS
Bacteria
Virus
3 hrs
Viruses
3 hrs
Diversity
Fast development
In the active phase of the HIV 10billion
viruses develop/day
parasites
Bacteria may divide in every 20 minutes
The human microbiome
HIV
Streptococus.
Lysteria
Andida albicans
S. aureus
Flu
Salmonella
Mycobacterium
tuberculosis
Pneumocystis carnii
Trypanosoma brucei
Schistosoma mansoni
We live in a potentially hostile world filled with infectious agents of diverse
size, shape, and composition which would very happily use us as „petri
dishes”…
How can we survive????
1. The interest of microbes
The human microbiome
Normal bacterial flora can be different in each person
Transplantation of bacteria?
Tightly regulated balance between commensal flora and the
immune system
2. The 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
INNATE IMMUNITY
- immediate reaction
- not antigen-specific
- no memory
ADAPTIVE IMMUNITY
- developes in several days
- specific
- has
memory
Neutralization and elimination of foreign and harmful structures
COORDINATED AND REGULATED ACTIONS
Both the innate and adaptive arms of immunity are required for
elimination of pathogens
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
OVERVIEW OF THE IMMUNE
SYSTEM
Monocytes/Macrophages
Dendritic cells
Granulocytes
Immune system
The simplest
Schema of the immune system
Innate immunity
Intracellular
pathogens
Extracellular
pathogens
Adaptive Immunity
T cells
B cells
The main functions of the immune system:
Recognition
Communication
Elimination (effector functions)
The simplest
Schema of the immune system
Innate immunity
Recognition
Intracellular
pathogens
Communication
Elimination
Extracellular
pathogens
Adaptive Immunity
T cells
B cells
What can be recognised by the immune system?
RECOGNITION OF THE IMMUNE SYSTEM
INNATE IMMUNITY
ADAPTIVE
IMMUNITY
Structures shared by
classes of microbes
Structural details of
specific microbial
molecules
WHAT CAN
(Pathogen-associated molecular
(Antigen)
patterns (PAMP))
CELLS
DIFFERENT MICROBES – BUT IDENTICALRECOGNIZE? DIFFERENT MICROBES – DISTINCT
MOLECULES!!!
STUCTURES!!!
Complex antigen:
Bacteri
a
Lipoproteins
Flagelli
n
„Carrier”
(no direct
interaction with
the antigenbinding site)
Peptidoglycans
LPS
Pattern Recognition
Receptors (PRR)
(non-antigen specific)
Epitope
s
RECEPTORS
TCR (on T cells) and BCR
(on B cells)
(antigen specific)
THE ANTIGEN
Definition and properties
Antigenic determinant (epitope)
Antigen recognition by B and T cells
DEFINITIONS
• ANTIGEN (Ag) - any substance, which is
specifically recognized by the mature immune
system of a given organism
Any chemical structure
Soluble or corpuscle
Simple or complex
Originated from the body or comes from outside
Genetically self or non-self
Natural or artificial
DEFINITIONS
• ANTIGENICITY– capability of an antigen to bind
specifically with certain product of the adaptive
immunity: TCR or BCR/antibody,
– immunogenicity - capability of an antigen to induce an
(adaptive) immune response,
– tolerogenicity - capability to induce immunological
tolerance, specific immune non-responsiveness
FACTORS INFLUENCING IMMUNOGENICITY I.
From the aspect of our body:
• Genetics (self/non-self)
– species (evolutionarily nonconserved molecules)
– individual differences (e.g. MHC polymorphism – see later)
• Age
– newborn – less reactive immune system
– elderly – no new naive lymphocytes
• Physiological condition (e.g. immunodeficiencies,
starvation)
FACTORS INFLUENCING IMMUNOGENICITY II.
From the aspect of the antigen:
• Physical-chemical properties of the Ag
–
–
–
–
size/complexity (bigger  more epitopes, role of carrier)
corpuscular (cell, colloid) or soluble
denatured or native (different epitopes!)
degradability (by APCs)
• Availability (crystalline proteins of the eye are not presented
to lymphocytes)
FACTORS INFLUENCING IMMUNOGENICITY III.
From the aspect of vaccination:
• Dose
• Route
– intradermal/subcutan > intravenous > oral > intranasal
(oral vaccine against polio virus!)
ANTIGENIC DETERMINANT (=EPITOPE)
Part of the antigen which
directly interacts with
the antigen-binding site
of a defined
immunoglobulin
(BCR / antibody)
or TCR
B cell epitope
T cell epitope
recognized by B cells
recognized by T cells
• proteins
polysaccharides
lipids
DNA
steroids
etc. (many artificial
molecules)
• proteins
(8-23 amino acids)
• cell or matrix associated
or soluble
• requires processing by
APC
Communication in the immune system
Cell-cell interaction
Soluble mediators
Soluble mediators:
Cytokines „hormons” of the immune system
citokinek
monokinek
interleukinek
kemokinek
limfokinek
interferonok
Elnevezés általában a termelő sejttípus alapján
Summary of lexical data:
1. balance between commensal flora and the immune system
2. balance between immunogenicity and tolerogenicity
3. Innate and adaptive immune response
4. Antigen
5. Epitope
immundef