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Overview of Immunology
Organs and tissues
Cells
Molecules
- Antibodies
- Complement
- Cytokines
- MHC
Components of IS
Functions of IS
Pathology of IR
* IS: Immune system IR: Immune response
Applications
Prevention
Diagnosis
Therapy
Antigen (Ag)
Immune Responses
Control mechanisms
Hypersensitivity
Autoimmune disease
Immunodeficiency
Tumor
Transplantation
rejection
Consequences of IR
Physiology
• Immunologic defense
• Immunologic homeostasis
• Immunologic surveillance
Pathology
• Hypersensitivity
• Immunodificiency
• Autoimmune diseases
• Tumor immunology
• Transplantation rejection
Overview of Immunology
Organs and tissues
Cells
Molecules - Antibodies - Complement - Cytokines
- MHC molecules
Antigen (Ag)
Immune Responses
Control mechanisms
Hypersensitivity
Autoimmune disease
Immunodeficiency
Tumor immunology
Transplantation
Components of IS Functions of IS Pathology of IR
* IS: Immune system IR: Immune response
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
— 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(Central Lymphoid Organs)
• 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-- Bone Marrow
• 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)
Primary Lymphoid Organs -- Thymus
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
Secondary Lymphoid Organs
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
Organs and tissues
Cells
Molecules - Antibodies - Complement - Cytokines
- MHC molecules
Antigen (Ag)
Immune Responses
Control mechanisms
Hypersensitivity
Autoimmune disease
Immunodeficiency
Tumor immunology
Transplantation
Components of IS Functions of IS Pathology of IR
* IS: Immune system IR: Immune response
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 -- 2 分NK cell: KIR/ KAR -- 2 分T cells: TCR -- 2 分B cells: BCR -- 2 分
4. Terms: CD : Marker / identification by mAb / functionTCR : Location / structure / functionBCR : Location / structure / functionPRR : Location / functions KIR : Location / functionsKAR : Location / functions
— Mononuclear phagocyte system
• Monocyte• Macrophage• Dendritic Cells
— Granulocytes
• Neutrophils• Basophils• Eosinophils
— Lymphocytes
• T lymphocyte• B lymphocyte• NK (Natural killer cells)
Cells of Immune System-Classification
AgAg DCs
Th1 Tc
B Ab
PMNPMN
NK
Th2
ComplementComplement
Functions in Immune Response (IR)
TargetTargetcellscells
MHCMHCCKCK
MHCMHCCKCK
CKsCKs
CKsCKs
— Phagocytosis
— Antigen presentation
— Cytokine secretion
Mononuclear Phagocyte SystemMononuclear Phagocyte System
Infected cells
Virus Bacterium
IL-1
PerforinGranzymesTNFa/TNFb
Killing
Cellular immunity
BCR
Antibody
Neutralizing
Complementactivating
NK ADCC
Mq
PhagocytosisMAC
PMN
Lysis
C3b
C3a/C5a
Humoral immunity
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 T cells
Overview of Immunology
Organs and tissues
Cells
Molecules - Antibodies - Complement - Cytokines
- MHC molecules
Antigen (Ag)
Immune Responses
Control mechanisms
Hypersensitivity
Autoimmune disease
Immunodeficiency
Tumor immunology
Transplantation
Components of IS Functions of IS Pathology of IR
* IS: Immune system IR: Immune response
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 / applicationArtificial / 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 -- 4Antibodies -- 4 分分 : Physiological / Pathological: Physiological / Pathological
Complement -- 4Complement -- 4 分分 : Physiological / Pathological: Physiological / Pathological
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)
ResultResult
– Vasodilatation,
– Vascular Leakiness,
– Smooth Muscle Contraction,
– Mucus Secretion.
Overview of Immunology
Organs and tissues
Cells
Molecules - Antibodies - Complement - Cytokines
- MHC molecules
Antigen (Ag)
Immune Responses
Control mechanisms
Hypersensitivity
Autoimmune disease
Immunodeficiency
Tumor immunology
Transplantation
Components of IS Functions of IS Pathology of IR
* IS: Immune system IR: Immune response
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
— Anaphylatoxins: C3a, C5a
— Chemotaxis: C5a
— Opsonization: C3b
— Lysis of the microbes:MAC
Functions of complement
Overview of Immunology
Organs and tissues
Cells
Molecules - Antibodies - Complement - Cytokines
- MHC molecules
Antigen (Ag)
Immune Responses
Control mechanisms
Hypersensitivity
Autoimmune disease
Immunodeficiency
Tumor immunology
Transplantation
Components of IS Functions of IS Pathology of IR
* IS: Immune system IR: Immune response
Components of IS -- Cytokines
1.1. Try to explain Try to explain how cytokines play their how cytokines play their
functions functions in immune response?in immune response?
2.2. The The General characteristics of CKs are…… are……
3. 3. Terms: Terms: CKs CKs – generation / functions – generation / functions
Infected cells
Virus Bacterium
IL-1
PerforinGranzymesTNFa/TNFb
Killing
Cellular immunity
BCR
Antibody
Neutralizing
Complementactivating
NK ADCC
Mq
PhagocytosisMAC
PMN
Lysis
C3b
C3a/C5a
Humoral immunity
General characteristics of CKs Small molecules Secreted by : ⑴ Immune Cells; Related cells⑵ - Autocrine - Paracrine - Endocrine Bind with specific receptor
Effector : - Pleiotropy - Synergy - Redundancy - Antagonism
Overview of Immunology
Organs and tissues
Cells
Molecules - Antibodies - Complement - Cytokines
- MHC molecules
Antigen (Ag)
Immune Responses
Control mechanisms
Hypersensitivity
Autoimmune disease
Immunodeficiency
Tumor immunology
Transplantation
Components of IS Functions of IS Pathology of IR
* IS: Immune system IR: Immune response
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
AgAg APCs
Th1 Tc
B Ab
PMNPMN
NK
Th2
ComplementComplement
MHC in immune response
TargetTargetcellscells
MHCMHCCKCK
MHCMHCCKCK
CKsCKs
CKsCKs
TargetTargetMHCMHC
AgAg APCs
Th1 Tc
B Ab
PMNPMN
NK
Th2
ComplementComplement
MHC in immune response
TargetTargetcellscells
MHCMHCCKCK
MHCMHCCKCK
CKsCKs
CKsCKs
TargetTargetMHCMHC
Medical Immunology DEPARTMENT OF IMMUNOLOGY 11
graftgraft APC
Th1 Tc
B Ab
PMNPMN
NK
Th2
ComplementComplement
Immune response to graft
graftgraft
MHCMHCCKCK
MHCMHCCKCK
CKsCKs
CKsCKs
Recognition
Activation
Effects
Rejection
Immune response to graft
Overview of Immunology
Organs and tissues
Cells
Molecules - Antibodies - Complement - Cytokines
- MHC molecules
Antigen (Ag)
Immune Responses
Control mechanisms
Hypersensitivity
Autoimmune disease
Immunodeficiency
Tumor immunology
Transplantation
Components of IS Functions of IS Pathology of IR
* IS: Immune system IR: Immune response
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
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 responseNatural immune response ( Innate Immunity)
— External defensesExternal defenses
— Cell effectsCell effects
— Molecular effectsMolecular effects
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.
AgAg APC
Th1 Tc
B Ab
PMNPMN
NK
Th2
ComplementComplement
Immune Response(IR)
TargetTargetcellscells
MHCMHCCKCK
MHCMHCCKCK
CKsCKs
CKsCKs
Adaptive Immune ResponseAdaptive Immune Response(Acquired Immunity)(Acquired Immunity)
— Antigen presentationAntigen presentation
— Antigen recognitionAntigen recognition
— Activation of cellsActivation of cells
— EffectsEffectsI
Antigen presentation
— Types of APCs
● Monocytes/Macrophage
● Dendritic cells
● B lymphocytes
— Pathways of antigen processing
● Class I processing pathway
● Class II processing pathway
Adaptive Immune ResponseAdaptive Immune Response(Acquired Immunity)(Acquired Immunity)
— Antigen presentationAntigen presentation
— Antigen recognitionAntigen recognition
— Activation of cellsActivation of cells
— EffectsEffectsI
Adaptive Immune ResponseAdaptive Immune Response(Acquired Immunity)(Acquired Immunity)
— Antigen presentationAntigen presentation
— Antigen recognitionAntigen recognition
— Activation of cellsActivation of cells
— EffectsEffectsI
Effects of adaptive immune response
Antibody response ( Humoral
immunity )
Antibody response ( Humoral
immunity ) T cell response ( Cellular
immunity )
T cell response ( Cellular
immunity )
Infected cells
Virus Bacterium
IL-1
PerforinGranzymesTNFa/TNFb
Killing
Cellular immunity
BCR
Antibody
Neutralizing
Complementactivating
NK ADCC
Mq
PhagocytosisMAC
PMN
Lysis
C3b
C3a/C5a
Humoral immunity
Functions of IS – Control mechanisms
How to understand the
immune response to a particular
Ag could be maintained in a
proper level ?
Regulation of Immune Response Regulation of Immune Responses
Medical Immunology DEPARTMENT OF IMMUNOLOGY 26
AgAg APC
Th1 Tc
B Ab
PMNPMN
NK
Th2
ComplementComplement
Regulation in immune system
TargetTargetcellscells
MHCMHCCKCK
MHCMHCCKCK
CKsCKs
CKsCKs
Ts
neuro-endocrine
system
+
-
Overview of Immunology
Organs and tissues
Cells
Molecules - Antibodies - Complement - Cytokines
- MHC molecules
Antigen (Ag)
Immune Responses
Control mechanisms
Hypersensitivity
Autoimmune disease
Immunodeficiency
Tumor immunology
Transplantation
Components of IS Functions of IS Pathology of IR
* IS: Immune system IR: Immune response
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 Hypersensitivity (Allergy)
Type-I Hypersensitivity (Allergy)
PollenInsect venomsAnimal danderFungiWormsFoodDrugs
Allergen
ResultResult
– Vasodilatation,
– Vascular Leakiness,
– Smooth Muscle Contraction,
– Mucus Secretion.
Type-II Hypersensitivity (Ab-dependent Cytotoxic)
Type-II Hypersensitivity (Ab-dependent Cytotoxic)
Complementactivation
NK
PMN
Ag + Ab
lysis
Killing
phagocytosis
Pathology of IR -- Autoimmune disease (AD)
1. Why does the immune system not attack self-tissue in 1. Why does the immune system not attack self-tissue in normal conditions? normal conditions?2. How could the self–tissue become the targets of immune 2. How could the self–tissue become the targets of immune
system ?system ?3. How are the tissue destroyed by immune system ?3. How are the tissue destroyed by immune system ?4. Terms:4. Terms:
Self-tolerance : self-Ag / no response / specificitySelf-tolerance : self-Ag / no response / specificity
Self-tolerance – Innate Immunity
-- Cells :1. Mononuclear phagocyte system
2. Granulocytes
3. Natural killer cells (NK)
-- Molecule:
Complement
DCs
Th1 Tc
B Ab
PMNPMN
NK
Th2
ComplementComplement
Immune response to self – Self-Tolerance
TargetTargetcellscells
MHCMHCCKCK
MHCMHCCKCK
CKsCKs
CKsCKs
SelfSelf
3. How are the tissue destroyed by immune system ?
Antibody mediated (type )Ⅱ
Immune complex mediated (type III)
T-cell mediated (type IV)
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
IL-1
PerforinGranzymesTNFa/TNFb
Killing
Cellular immunity !!
BCR
AntibodyComplementactivating
NK ADCC
Mq
PhagocytosisLysis
C3b
Humoral immunity !
Tumorcells
shedtumor-Ag
shedtumor-Ag
Mechanisms of tumor escape
• Variation of tumor antigens
• Co-stimulator decreaseCo-stimulator decrease
• Down-regulation of MHC expressionDown-regulation of MHC expression
• Immune suppression of tumorImmune suppression of tumor
• Masking of tumor cell antigenMasking of tumor cell antigen
3. Down-regulation of MHC expression3. Down-regulation of MHC expression3. Down-regulation of MHC expression3. Down-regulation of MHC expression
4. Immune-suppression of tumor4. Immune-suppression of tumor 4. Immune-suppression of tumor4. Immune-suppression of tumor
Tumor cellsTumor cells
5. Masking of tumor cell antigen5. Masking of tumor cell antigen5. Masking of tumor cell antigen5. Masking of tumor cell antigen
Pathology of IR -- Transplantation rejection
1. What is the reason of transplantation rejection?2.Do you have any ideas about how to overcome the transplantation
rejection?3. Terms: GVHR/ HVGR/ MLR(MLC)
4. Terms: GVHR: Ag-recipient / IS -graftHVGR: Ag – graft / IS - recipient MLR(MLC): method / application
Medical Immunology DEPARTMENT OF IMMUNOLOGY 11
graftgraft APC
Th1 Tc
B Ab
PMNPMN
NK
Th2
ComplementComplement
Immune response to graft
graftgraft
MHCMHCCKCK
MHCMHCCKCK
CKsCKs
CKsCKs
Recognition
Activation
Effects
Rejection
Immune response to graft
Medical Immunology DEPARTMENT OF IMMUNOLOGY 14
Indirect pathway
Graftedcells
Tc
Th
Recipient
Donor
APC
Medical Immunology DEPARTMENT OF IMMUNOLOGY 15
Direct pathway
Graftedcells
Tc
Th
Recipient
APCs
Donor
Allo-reactive T cellsPassenger leukocytes
Indirect and direct pathways
graftgraft APC
Th1 Tc
B Ab
PMNPMN
NK
Th2
ComplementComplement
Suppress T cell activation
graftgraft
MHCMHCCKCK
MHCMHCCKCK
CKsCKs
CKsCKs
Overview of Immunology
Organs and tissues
Cells
Molecules - Antibodies - Complement - Cytokines
- MHC molecules
Antigen (Ag)
Immune Responses
Control mechanisms
Hypersensitivity
Autoimmune disease
Immunodeficiency
Tumor immunology
Transplantation
Components of IS Functions of IS Pathology of IR
* IS: Immune system IR: Immune response