Overview of Immunology Organs and tissues Cells Molecules － Antibodies － Complement － Cytokines － MHC Components of IS Functions of IS Pathology of IR.

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


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


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


Organs and tissues

Cells


－ MHC molecules

Antigen (Ag)

Immune Responses

Control mechanisms

Hypersensitivity

Autoimmune disease

Immunodeficiency

Tumor immunology

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 -- 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

— T lymphocyte

— B lymphocyte

— Natural killer cells (NK)

Lymphocytes

TH1

TH2

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

Antibody production

Functions of B cells

Antibody Production by B cell

Th2

NK

— Neutrophils

— Basophils

— Eosinophils

GranulocytesGranulocytes


Organs and tissues

Cells


－ MHC molecules

Antigen (Ag)

Immune Responses

Control mechanisms

Hypersensitivity

Autoimmune disease

Immunodeficiency

Tumor immunology

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 / 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

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)

FcrR(CD16)

IgG

NK cells

Sensitization against allergensSensitization against allergens

pollen

ResultResult

– Vasodilatation,

– Vascular Leakiness,

– Smooth Muscle Contraction,

– Mucus Secretion.


Organs and tissues

Cells


－ MHC molecules

Antigen (Ag)

Immune Responses

Control mechanisms

Hypersensitivity

Autoimmune disease

Immunodeficiency

Tumor immunology

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

— Anaphylatoxins: C3a, C5a

— Chemotaxis: C5a

— Opsonization: C3b

— Lysis of the microbes:MAC

Functions of complement


Organs and tissues

Cells


－ MHC molecules

Antigen (Ag)

Immune Responses

Control mechanisms

Hypersensitivity

Autoimmune disease

Immunodeficiency

Tumor immunology

Transplantation



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


Killing

Cellular immunity

BCR

Antibody

Neutralizing


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


Organs and tissues

Cells


－ MHC molecules

Antigen (Ag)

Immune Responses

Control mechanisms

Hypersensitivity

Autoimmune disease

Immunodeficiency

Tumor immunology

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

Medical Immunology 吉林大学基础医学院免疫学教研室 21

Deletion

T differentiation

T differentiation

AgAg APCs

Th1 Tc

B Ab

PMNPMN

NK

Th2


MHC in immune response


MHCMHCCKCK

MHCMHCCKCK

CKsCKs

CKsCKs

TargetTargetMHCMHC

Ag presentation

AgAg APCs

Th1 Tc

B Ab

PMNPMN

NK

Th2


MHC in immune response


MHCMHCCKCK

MHCMHCCKCK

CKsCKs

CKsCKs

TargetTargetMHCMHC

Virus infection

Medical Immunology DEPARTMENT OF IMMUNOLOGY 11

graftgraft APC

Th1 Tc

B Ab

PMNPMN

NK

Th2


Immune response to graft

graftgraft

MHCMHCCKCK

MHCMHCCKCK

CKsCKs

CKsCKs

Recognition

Activation

Effects

Rejection



Organs and tissues

Cells


－ MHC molecules

Antigen (Ag)

Immune Responses

Control mechanisms

Hypersensitivity

Autoimmune disease

Immunodeficiency

Tumor immunology

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 responseNatural immune response ( Innate Immunity)

— External defensesExternal defenses

— Cell effectsCell effects

— Molecular effectsMolecular effects

Mq/DCs

Phagocytosis

NK NK

KAR 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.

AgAg APC

Th1 Tc

B Ab

PMNPMN

NK

Th2


Immune Response(IR)


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

Antigen Recognition

T cell recognition of Ag

B cell recognition of Ag





— EffectsEffectsI

Activation of Cells

— Signals

● Antigen

● Co-stimulators

● Cytokines

— Signal transduction

Th-2





— 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


Killing

Cellular immunity

BCR

Antibody

Neutralizing


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


AgAg APC

Th1 Tc

B Ab

PMNPMN

NK

Th2


Regulation in immune system


MHCMHCCKCK

MHCMHCCKCK

CKsCKs

CKsCKs

Ts

neuro-endocrine

system

+

-


Organs and tissues

Cells


－ MHC molecules

Antigen (Ag)

Immune Responses

Control mechanisms

Hypersensitivity

Autoimmune disease

Immunodeficiency

Tumor immunology

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 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

Type-III Hypersensitivity (Immune Complex)




Type IV hypersensitivity(Delayed reaction)

Type IV hypersensitivity(Delayed reaction)

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

Innate Immunity

Adaptive Immunity

-- Central tolerance

-- Peripheral tolerance

Self-tolerance

Self-tolerance – Innate Immunity

-- Cells ：1. Mononuclear phagocyte system

2. Granulocytes

3. Natural killer cells (NK)

-- Molecule:

Complement

Central tolerance

Peripheral tolerance

Self-tolerance -- Adaptive

Immunity

Selection of T cells in thymus

DCs

Th1 Tc

B Ab

PMNPMN

NK

Th2


Immune response to self – Self-Tolerance


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)

MechanismsMechanisms

Complementactivation

NK

PMN

Ag + Ab

lysis

Killing

phagocytosis

MechanismMechanism

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


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

1. Variation of tumor antigens1. Variation of tumor antigens

2. Co-stimulator decrease2. Co-stimulator decrease

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

Immunotheropy of tumors

Preventive

specific

, T cells

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


graftgraft APC

Th1 Tc

B Ab

PMNPMN

NK

Th2



graftgraft

MHCMHCCKCK

MHCMHCCKCK

CKsCKs

CKsCKs

Recognition

Activation

Effects

Rejection



Indirect pathway

Graftedcells

Tc

Th

Recipient

Donor

APC


Direct pathway

Graftedcells

Tc

Th

Recipient

APCs

Donor

Allo-reactive T cellsPassenger leukocytes

Indirect and direct pathways

Prevention of rejection

Family grafting

Tissue typing

Cross-matching

Immunosuppressio

n

Family grafting

a c a c

TwinsHomozygotes

Tissue typing

Cross-matching -1

(Tritium)

graftgraft APC

Th1 Tc

B Ab

PMNPMN

NK

Th2


Suppress T cell activation

graftgraft

MHCMHCCKCK

MHCMHCCKCK

CKsCKs

CKsCKs

Pathology of IR -- Immunodificiency

Terms: AIDS – HIV-gp120/ CD4-T / IS / clinical


Organs and tissues

Cells


－ MHC molecules

Antigen (Ag)

Immune Responses

Control mechanisms

Hypersensitivity

Autoimmune disease

Immunodeficiency

Tumor immunology

Transplantation



Overview of Immunology Organs and tissues Cells Molecules － Antibodies － Complement － Cytokines － MHC Components of IS Functions of IS Pathology of IR.

Documents

cells of immune system

immune system ir

cells questions

immune responsecomponents

stromal cells epithelial

antigen specific t cells

functions of thymus

peripheral lymphoid