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Overview of Immunology
Components
of IS
Functions
of IS
Organs and tissues
Cells
Antigen (Ag)
Pathology
of IR
Hypersensitivity
Applications
Prevention
Autoimmune disease
Molecules
－ Antibodies
Immune Responses
－ Complement
－ Cytokines
Immunodeficiency
Tumor
Control mechanisms
－ MHC
* IS: Immune system
IR: Immune response
Transplantation
rejection
Diagnosis
Therapy
Consequences of IR
Physiology
• Immunologic defense
• Immunologic homeostasis
Pathology
• Hypersensitivity
• Immunodificiency
• Autoimmune diseases
• Tumor immunology
• Immunologic surveillance
• Transplantation rejection
Overview of Immunology
Components of IS
Functions of IS
Pathology of IR
Organs and tissues
Hypersensitivity
Cells
Molecules
－ Antibodies
－ Complement
－ Cytokines
－ MHC molecules
* IS: Immune system
IR: Immune response
Antigen (Ag)
Immune Responses
Autoimmune disease
Immunodeficiency
Tumor immunology
Control mechanisms
Transplantation
Components of IS -- Organs and tissues
Questions:
1.Which organs belong to the immune system?
2. Describe the functions of bone marrow and thymus.
3. What are the functions of secondary lymphoid organs?
4. Terms: MALT—IS / Location / function
Components of IS -- Organs and tissues
Questions:
Describe the mature T cell properties in peripheral lymphoid
organs from the functions of thymus.
Functions of thymus: -- 4分
Positive selection
Negative selection
Mature T cell properties: -- 4分
Recognition: TCR / MHC + Ag(no-self)
Classification: CD4 / CD8
Primary Lymphoid Organs
(Central Lymphoid Organs)
— Bone Marrow
• Primary source of pluripotent stem cells
All haemopoietic cells
• Place for B cell maturation
—
Thymus
• Place for T cell maturation
Primary Lymphoid Organs-- Bone Marrow
• Cells of IS are produced from haemopoietic stem
cells (HSC) in BM.
• Stromal cells (epithelial cells, fibroblast,
macrophage) is required for the differentiation of a
particular lineage.
• Cytokines( CSF) produced from stromal cells
provide the local environment for the
hematopoiesis.
Primary Lymphoid Organs -- Thymus
• Large numbers of functionally antigen specific
T cells are matured in thymus.
• Each of T cells has only one specificity.
• T cells are selected using their receptors
( positive and negative selection)
Secondary Lymphoid Organs
Lymph nodes
Place of immune response to pathogen entering
the tissues
Spleen
Place of immune response to blood borne
infections
MALT
Place of immune response to mucosal surfaces
Lymph nodes
- Situated alone lymphatic vessels (p30)
- Filter of the lymph
- Contain T/B lymphocytes and phagocytes(p29)
- Place of immune response to pathogen
entering the tissues
Spleen
-- Situated on the left side of the body below the
diaphragm
-- Filter of the blood
-- Contain T/B lymphocytes and phagocytes
-- Place of immune response to pathogen
entering the blood
Overview of Immunology
Components of IS
Functions of IS
Pathology of IR
Organs and tissues
Hypersensitivity
Cells
Molecules
－ Antibodies
－ Complement
－ Cytokines
－ MHC molecules
* IS: Immune system
IR: Immune response
Antigen (Ag)
Immune Responses
Autoimmune disease
Immunodeficiency
Tumor immunology
Control mechanisms
Transplantation
Components of IS -- Cells
Questions:
1. Which cells belong to the immune system?
2. The functions of mononuclear phagocytes are….?
3. Try to explain the classification and function of
lymphocytes.
The cells of immune system recognize antigens
by their receptors, please explain how the cells of followings
recognize target antigens:
Macrophage: PRR
NK cell:
T cells:
TCR
B cells:
-- 2分
KIR/ KAR
-- 2分
-- 2分
BCR
-- 2分
4. Terms:
CD : Marker / identification by mAb / function
TCR : Location / structure / function
BCR : Location / structure / function
PRR : Location / functions
KIR : Location / functions
KAR : Location / functions
Cells of Immune System-Classification
— Mononuclear phagocyte system
• Monocyte
• Macrophage
• Dendritic Cells
— Granulocytes
• Neutrophils
• Basophils
• Eosinophils
— Lymphocytes
• T lymphocyte
• B lymphocyte
• NK (Natural killer cells)
Functions in Immune Response (IR)
Target
cells
MHC
CK
Th1
CKs
Tc
NK
Ag
DCs
MHC
CK
Th2
CKs
Ab
B
PMN
Complement
Mononuclear Phagocyte System
— Phagocytosis
— Antigen presentation
— Cytokine secretion
Lymphocytes
— T lymphocyte
— B lymphocyte
— Natural killer cells (NK)
TH1
TH2
Cellular immunity
Humoral immunity
Virus
Bacterium
IL-1
Infected
cells
BCR
Killing
Neutralizing
Perforin
Granzymes
TNFa/TNFb
Complement
activating
NK
Antibody
C3b
MAC
PMN
Lysis
ADCC
C3a/C5a
Mq
Phagocytosis
Functions of T cells
TH (CD4+CD3+)
 TH1: Help Tc and macrophages by secretion of
IFN/γ/IL-2
 TH2：Help B cells by secration of IL-4,
IL-5,IL-6
TC (CD8+CD3+)
 Killing of target cells by releasing perforin and
granzymes
Functions of B cells
 Antibody production
Antibody Production by B cell
Th2
NK
Granulocytes
— Neutrophils
— Basophils
— Eosinophils
Overview of Immunology
Components of IS
Functions of IS
Pathology of IR
Organs and tissues
Hypersensitivity
Cells
Molecules
－ Antibodies
－ Complement
－ Cytokines
－ MHC molecules
* IS: Immune system
IR: Immune response
Antigen (Ag)
Immune Responses
Autoimmune disease
Immunodeficiency
Tumor immunology
Control mechanisms
Transplantation
Components of IS -- Ab
1.Try to describe the biological function of antibodies.
2. Terms: mAb / Ab / ADCC
4. Terms: mAb / Ab / ADCC
mAb : Artificial / hybridoma / property / application
Ab: Generation cell / structure/ classes/ functions
ADCC: Ab / Fab-target / Fc-NK / cytotoxocity
How to understand the antibodies and complement
are the molecules that are involved in both physiological and
pathological consequences of immune response by using
examples.
Antibodies -- 4分: Physiological / Pathological
Complement -- 4分: Physiological / Pathological
Complementarity
determining region
(CDR)
Functions of Antibody
Role of Ab alone
Role of Ab in complement activation
Role of Ab with effector cells
1、Role of Ab alone
 To Neutralize virus and toxins and
blocks their biological activity (IgG).
 To inhibit microbes attachment to
mucosal epithelial cells (IgA).
2、Role of Ab in complement activation
To Activate the classical pathway of
complement to lysis of the Ag by binding
to Ag (IgG/ IgM).
3、Role of Ab with effectors cells
Macrophage and neutrophil:
Opsonization and phagocytosis of microbes (IgG)
NK cell and eosinophil:
Antibody-dependent cellular cytotoxicity(ADCC) (IgG)
Basophil and mast cell:
Type I hypersensitivity – allergy (IgE)
NK cells
FcrR
(CD16)
IgG
Sensitization against allergens
pollen
Result
– Vasodilatation,
– Vascular Leakiness,
– Smooth Muscle Contraction,
– Mucus Secretion.
Overview of Immunology
Components of IS
Functions of IS
Pathology of IR
Organs and tissues
Hypersensitivity
Cells
Molecules
－ Antibodies
－ Complement
－ Cytokines
－ MHC molecules
* IS: Immune system
IR: Immune response
Antigen (Ag)
Immune Responses
Autoimmune disease
Immunodeficiency
Tumor immunology
Control mechanisms
Transplantation
Components of IS -- Complement
1. Try to describe the pathways that are involved
in
activation of complement.
2. The functions of complement include ….
3. Term: MAC– activation of C / components /
function
Functions of complement
— Anaphylatoxins: C3a, C5a
— Chemotaxis: C5a
— Opsonization: C3b
— Lysis of the microbes:MAC
Overview of Immunology
Components of IS
Functions of IS
Pathology of IR
Organs and tissues
Hypersensitivity
Cells
Molecules
－ Antibodies
－ Complement
－ Cytokines
－ MHC molecules
* IS: Immune system
IR: Immune response
Antigen (Ag)
Immune Responses
Autoimmune disease
Immunodeficiency
Tumor immunology
Control mechanisms
Transplantation
Components of IS -- Cytokines
1. Try to explain how cytokines play their
functions in immune response?
2. The General characteristics of CKs are……
3. Terms: CKs – generation / functions
Cellular immunity
Humoral immunity
Virus
Bacterium
IL-1
Infected
cells
BCR
Killing
Neutralizing
Perforin
Granzymes
TNFa/TNFb
Complement
activating
NK
Antibody
C3b
MAC
PMN
Lysis
ADCC
C3a/C5a
Mq
Phagocytosis
General characteristics of CKs
Small molecules
Secreted by： ⑴ Immune Cells; ⑵ Related cells
- Autocrine
- Paracrine
- Endocrine
Bind with specific receptor
Effector :
- Pleiotropy
- Synergy
- Redundancy
- Antagonism
Overview of Immunology
Components of IS
Functions of IS
Pathology of IR
Organs and tissues
Hypersensitivity
Cells
Molecules
－ Antibodies
－ Complement
－ Cytokines
－ MHC molecules
* IS: Immune system
IR: Immune response
Antigen (Ag)
Immune Responses
Autoimmune disease
Immunodeficiency
Tumor immunology
Control mechanisms
Transplantation
Components of IS – MHC molecules
1. Describe the biological functions of MHC molecules.
2. Terms: MHC -- genes / classes / functions
HLA – Human MHC
Components of IS – MHC molecules
MHC molecules are the important
molecules in transplantation rejection, why ?
Transplantation rejection = Immune response
Ag : graft -- MHC -- 3分
IR: APC -- MHC
Direct pathway – 2.5分
Indirect pathway – 2.5分
Biological functions of MHC
— Immune Response
— Transplantation
— Related with diseases
T differentiation
Deletion
Medical Immunology
吉林大学基础医学院免疫学教研室
21
T differentiation
MHC in immune response
Target
cells
MHC
CK
Th1
CKs
Tc
Target
MHC
NK
Ag
APCs
MHC
CK
Th2
CKs
Ab
B
PMN
Complement
Ag presentation
MHC in immune response
Target
cells
MHC
CK
Th1
CKs
Tc
Target
MHC
NK
Ag
APCs
MHC
CK
Th2
CKs
Ab
B
PMN
Complement
Virus
infection
Immune
response
Immune
response
to graft to graft
graft
MHC
CK
graft
Th1
Recognition
CKs
Tc
Activation
NK
APC
Effects
MHC
CK
Th2
CKs
PMN
Medical Immunology
Rejection
Ab
B
DEPARTMENT OF IMMUNOLOGY
Complement
11
Overview of Immunology
Components of IS
Functions of IS
Pathology of IR
Organs and tissues
Hypersensitivity
Cells
Molecules
－ Antibodies
－ Complement
－ Cytokines
－ MHC molecules
* IS: Immune system
IR: Immune response
Antigen (Ag)
Immune Responses
Autoimmune disease
Immunodeficiency
Tumor immunology
Control mechanisms
Transplantation
Functions of IS -- Ag
1. Try to explain the biological meanings of antigens
that are related with medicine with 2 or 3 examples.
2. Terms: (1)Antigenic determinant
(2) Hapten;
(3) Adjuvant
(1)Antigenic determinant: Ag / specificity
(2) Hapten: property / carrier
(3) Adjuvant
Functions of IS – IR : innate immunity?
1. What kind of factors might be involved in innate immunity?
2. Terms:
O Opsonization – Ab -Fc / C-CR /
phagocytes/ target cells
PRR– location / functions
KIR – location / function
KAR – location / function
Natural immune response
( Innate Immunity)
— External defenses
— Cell effects
— Molecular effects
Mq/DCs
Phagocytosis
NK
KAR
NK
KIR
Functions of IS – IR : Adaptive immunity?
1. What kinds of factors determine the specificity of
immune response?
2. How could lymphocytes be activated?
3. Describe the biological effects of humoral and cellular
immune response.
4. Try to explain the relationship between the innate
immunity and adaptive immunity.
Immune Response(IR)
Target
cells
MHC
CK
Ag
Th1
CKs
Tc
NK
APC
MHC
CK
Th2
CKs
Ab
B
PMN
Complement
Adaptive Immune Response
(Acquired Immunity)
— Antigen presentation
— Antigen recognition
— Activation of cells
— Effects
Antigen presentation
— Types of APCs
●
●
●
Monocytes/Macrophage
Dendritic cells
B lymphocytes
— Pathways of antigen processing
●
●
Class I processing pathway
Class II processing pathway
Antigen Recognition
 T cell recognition of Ag
 B cell recognition of Ag
Adaptive Immune Response
(Acquired Immunity)
— Antigen presentation
— Antigen recognition
— Activation of cells
— Effects
Activation of Cells
— Signals
●
●
●
Antigen
Co-stimulators
Cytokines
— Signal transduction
Th-2
Adaptive Immune Response
(Acquired Immunity)
— Antigen presentation
— Antigen recognition
— Activation of cells
— Effects
Effects of adaptive immune response
Antibody response （ Humoral immunity ）
T cell response
（ Cellular immunity ）
Cellular immunity
Humoral immunity
Virus
Bacterium
IL-1
Infected
cells
BCR
Killing
Neutralizing
Perforin
Granzymes
TNFa/TNFb
Complement
activating
NK
Antibody
C3b
MAC
PMN
Lysis
ADCC
C3a/C5a
Mq
Phagocytosis
Functions of IS – Control mechanisms
How to understand the immune
response to a particular Ag could be
maintained in a proper level ?
Regulationofof Immune
Immune Response
Regulation
Responses
Regulation in immune system
Target
cells
MHC
CK
Ag
Th1
Tc
NK
Ts
APC
MHC
CK
Th2
-
CKs
Ab
B
PMN
Medical Immunology
+
CKs
DEPARTMENT OF IMMUNOLOGY
Complement
26
neuroendocrine
system
Overview of Immunology
Components of IS
Functions of IS
Pathology of IR
Organs and tissues
Hypersensitivity
Cells
Molecules
－ Antibodies
－ Complement
－ Cytokines
－ MHC molecules
* IS: Immune system
IR: Immune response
Antigen (Ag)
Immune Responses
Autoimmune disease
Immunodeficiency
Tumor immunology
Control mechanisms
Transplantation
Pathology of IR – Hypersensitivity
1. Describe the mechanisms of hypersensitivity.
2.
What kind of cells will be involved in type I
hypersensitivity
and how ?
3. Try to give some examples of diseases that are belong to
type II and type III hypersensitivity.
Type-I
Allergen
Pollen
Insect venoms
Animal dander
Fungi
Worms
Food
Drugs
Hypersensitivity
(Allergy)
Result
– Vasodilatation,
– Vascular Leakiness,
– Smooth Muscle Contraction,
– Mucus Secretion.
Type-II Hypersensitivity
(Ab-dependent Cytotoxic)
Complement
activation
Ag
+ Ab
NK
PMN
lysis
Killing
phagocytosis
Type-III
Hypersensitivity
(Immune Complex)
Type-III
Hypersensitivity
(Immune Complex)
Type IV hypersensitivity
(Delayed reaction)
Pathology of IR -- Autoimmune disease (AD)
1. Why does the immune system not attack self-tissue in
normal conditions?
2. How could the self–tissue become the targets of immune system ?
3. How are the tissue destroyed by immune system ?
4. Terms:
Self-tolerance : self-Ag / no response / specificity
Self-tolerance

Innate Immunity

Adaptive Immunity
-- Central tolerance
-- Peripheral tolerance
Self-tolerance – Innate Immunity
-1.
Cells：
Mononuclear phagocyte system
2. Granulocytes
3. Natural killer cells (NK)
-- Molecule:
Complement
Self-tolerance -- Adaptive Immunity

Central tolerance

Peripheral tolerance
Selection of T cells in thymus
Immune response to self – Self-Tolerance
Target
cells
MHC
CK
Th1
CKs
Tc
NK
Self
DCs
MHC
CK
Th2
CKs
Ab
B
PMN
Complement
3. How are the tissue destroyed by immune system ?
Antibody mediated (type Ⅱ)
Immune complex mediated (type III)
T-cell mediated (type IV)
Mechanisms
Complement
activation
Ag
+ Ab
NK
PMN
lysis
Killing
phagocytosis
Mechanism
Type IV hypersensitivity mediated AD
Pancreatic Beta cells
IDDM
Loss of insulin production
Brain cells
Multiple sclerosis (MS)
Demyelination of CNS,
Paralysis
Pathology of IR -- Tumor
1. How could the tumor cells escape the surveillance of
immune
system?
2. What kinds of mechanisms could the tumor cells be destroyed
by immune system?
3. Do you have any ideas about the strategies of
immunotherapy?
4. Term: TAA—tumor/ quantity
TSA – tumor/ quality
Cellular immunity !!
Humoral immunity !
shed
tumor-Ag
shed
tumor-Ag
IL-1
Tumor
cells
BCR
Killing
Perforin
Granzymes
TNFa/TNFb
NK
Complement
activating
Antibody
C3b
Lysis
ADCC
Mq
Phagocytosis
Mechanisms of tumor escape
•
Variation of tumor antigens
•
Co-stimulator decrease
•
Down-regulation of MHC expression
•
Immune suppression of tumor
•
Masking of tumor cell antigen
1. Variation of tumor antigens
2. Co-stimulator decrease
3. Down-regulation of MHC expression
4. Immune-suppression of tumor
Tumor cells
5. Masking of tumor cell antigen
Immunotheropy of tumors
non-specific
BCG, Corynegacterium parvum
Preentive
Preventive vaccines of tumor cells, cell
active
specific
extracts,purified or recombinant antigens,
or idiotypes
non-specific
LAK cells, cytokines
Antibodies alone or coupled to drugs,
passive
specific
pro-drugs, toxins or radioisotopes bispecific antibodies T, T
cells
cells
combined
LAK cells and bi-dpecific
antibody
specific
Pathology of IR -- Transplantation rejection
1. What is the reason of transplantation rejection?
2.Do you have any ideas about how to overcome the
rejection?
3. Terms: GVHR/ HVGR/ MLR(MLC)
4. Terms:
GVHR: Ag-recipient / IS -graft
HVGR: Ag – graft / IS - recipient
MLR(MLC): method / application
transplantation
Immune
response
Immune
response
to graft to graft
graft
MHC
CK
graft
Th1
Recognition
CKs
Tc
Activation
NK
APC
Effects
MHC
CK
Th2
CKs
PMN
Medical Immunology
Rejection
Ab
B
DEPARTMENT OF IMMUNOLOGY
Complement
11
Indirect and direct pathways
Indirect pathway
Grafted
cells
Direct pathway
Donor
Donor
Recipient
Tc
Tc
Grafted
cells
Th
APCs
APC
Th
Passenger leukocytes
Allo-reactive T cells
Medical Immunology
DEPARTMENT OF IMMUNOLOGY
Recipient
Medical Immunology
DEPARTMENT OF IMMUNOLOGY
14
Prevention of rejection
 Family grafting
 Tissue typing
 Cross-matching
 Immunosuppression
Family grafting
Twins
Homozygotes
a
c
a
c
Tissue typing
Cross-matching -1
(Tritium)
Suppress T cell activation
graft
MHC
CK
graft
Th1
CKs
Tc
NK
APC
MHC
CK
Th2
CKs
Ab
B
PMN
Complement
Pathology of IR -- Immunodificiency
Terms: AIDS – HIV-gp120/ CD4-T / IS / clinical
Overview of Immunology
Components of IS
Functions of IS
Pathology of IR
Organs and tissues
Hypersensitivity
Cells
Molecules
－ Antibodies
－ Complement
－ Cytokines
－ MHC molecules
* IS: Immune system
IR: Immune response
Antigen (Ag)
Immune Responses
Autoimmune disease
Immunodeficiency
Tumor immunology
Control mechanisms
Transplantation