Overview of Immunology Organs and tissues Cells Molecules Components of IS Functions of IS Pathology of IR * IS: Immune system IR: Immune response Applications.

Overview of Immunology

Organs and tissues

Cells

Molecules

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

Cells of Immune System

— Mononuclear phagocyte system

— Granulocytes

— Lymphocytes

MonocyteMonocyte

MacrophageMacrophage

Dendritic Cells Dendritic Cells

NeutrophilsNeutrophils

BasophilsBasophils

EosinophilsEosinophils

T lymphocyteT lymphocyte

B lymphocyteB lymphocyte

NK (Natural killer cells)NK (Natural killer cells)

Cells of the innate immune system

Mononuclear phagocytes

Granulocytes

NK cells

Cells of the adaptive immune systemT lymphocytes

B lymphocytes

Cells of Immune System

Cell surface molecules expressed on various cell types in the immune system as markers:

• Lineage marker (e.g. CD3 on T cells)

• Maturation marker (e.g. CD4 / CD8 on T cells)

• Activation marker (e.g. CD25 on T cells)

Numbers of CD: CD1 – CD247

Cluster Differentiation(CD) System

One cell can express more than one different

CDs:

e.g. T cells: CD2, CD3, CD4 or CD8, CD28……

B cells: CD19, CD20, CD21, CD79……

Different cells can express same CD:

e.g. CD69 could be expressed on activated leukocytes:

T cells, B cells, NK cells, nuetrophils, basophils

Cluster Differentiation(CD) Molecules

Mononuclear phagocytes

Granulocytes

NK cells

Cells of the innate immune system

— Functions

— Markers (Receptors)

Mononuclear PhagocytesMononuclear Phagocytes

AgAg DCs

Th1 Tc

B Ab

PMNPMN

NK

Th2

ComplementComplement

Functions in Immune Response (IR)

TargetTargetcellscells

MHCMHCCKCK

MHCMHCCKCK

CKsCKs

CKsCKs

Maturation Maturation

Cells of Mononuclear Phagocytes System

— Phagocytosis

— Antigen presentation

— Cytokine secretion

Mononuclear Phagocyte SystemMononuclear Phagocyte System

AgAg DCs

Th1 Tc

B Ab

PMNPMN

NK

Th2

ComplementComplement

Functions in Immune Response (IR)

TargetTargetcellscells

MHCMHCCKCK

MHCMHCCKCK

CKsCKs

CKsCKs

Mq/DCs

Phagocytosis

PAMP: pathogen-associated molecule pattern

PRR

Recognition Receptors: PRR

Recognition and killing of phagocytes

By pattern recognition receptors(PRR)

Mannose receptors: mannose

CD14 : LPS

Scavenger receptors : carbohydrates /lipids

Toll like receptors (TLRs): PAMP

(lipid-

protein 、 LPS、 RNA、 DNA)

See:9-1

AgAg DCs

Th1 Tc

B Ab

PMNPMN

NK

Th2

ComplementComplement

Immune Response (IR)

TargetTargetcellscells

MHCMHCCKCK

MHCMHCCKCK

CKsCKs

CKsCKs

AgAg DCs

Th1 Tc

B Ab

PMNPMN

NK

Th2

ComplementComplement

Immune Response (IR)

TargetTargetcellscells

MHCMHCCKCK

MHCMHCCKCK

CKsCKs

CKsCKs

— Pattern recognition receptors(PRR): Recognition

— Fc receptor (FcR, CD16): Opsonisation

— Complement receptor (CR): Opsonisation

PhagocytosisPhagocytosis

— Phagocytosis

— Antigen presentation

— Cytokine secretion

Mononuclear Phagocyte SystemMononuclear Phagocyte System

AgAg DCs

Th1 Tc

B Ab

PMNPMN

NK

Th2

ComplementComplement

Immune Response (IR)

TargetTargetcellscells

MHCMHCCKCK

MHCMHCCKCK

CKsCKs

CKsCKs

Antigen Presentation

See:8-2Antigen presenting cells (APC)

Antigen that is presented on the APC could be recognized by T cell

Antigen Presentation Recognized by T cellsAntigen Presentation

See:8-2

Mononuclear phagocytes

Granulocytes

NK cells

Cells of the innate immune system

— Neutrophils

— Basophils

— Eosinophils

GranulocytesGranulocytes

AgAg DCs

Th1 Tc

B Ab

PMNPMN

NK

Th2

ComplementComplement

Functions in Immune Response (IR)

TargetTargetcellscells

MHCMHCCKCK

MHCMHCCKCK

CKsCKs

CKsCKs

— Majority of white blood cells

— Contain: lysozyme, antibiotic peptides

—Main function: phagocytosis

— Chemotaxis: C5a

— Opsonization: Ab and C3b

Neutrophils (Polymorphonuclear cells PMNs)Neutrophils (Polymorphonuclear cells PMNs)

— Neutrophils

— Basophils (Mast cells)

— Eosinophils

GranulocytesGranulocytes

— Localization:• Basophils － circulation

• Mast cells － tissues

— Granule contents: Mediators

• Histamine

• Leukotrienes

— Functions:• Attract: Leukocytes － acute inflammatory

response

• Allergy

Basophils and Mast cells

Mediators: allergyMediators: allergy

– Vasodilatation,

– Vascular permeability increase,

– Smooth muscle contraction,

– Mucous secretion.

Respiratory tractRespiratory tract

allergic rhinitis

Respiratory tractRespiratory tract

The lungs

asthma

The skin

Urticaria (hives)

— Present in circulation:

— Granule contents:• Peroxides/toxin

• Histaminase et al

— Functions:• Parasites killing

• Anti-inflammatory and allergy regulation

Eosinophils

Mononuclear phagocyte

Granulocytes

NK (Natural killer cells)

Cells of the innate immune system

-- Functions

-- Markers

Natural Killer cells (NK cells)

AgAg DCs

Th1 Tc

B Ab

PMNPMN

NK

Th2

ComplementComplement

Immune Response (IR)

TargetTargetcellscells

MHCMHCCKCK

MHCMHCCKCK

CKsCKs

CKsCKs

NK NK

KAR KIR

NK

Ab

CD16

NK

IL-2

LAK

Lymphokine activated killer cell

1. KAR : (Killer activating receptors):

Induce killing of the infected cells.

2. KIR: (Killer inhibitory receptor):

Prevent NK from killing the normal cells.

3. CD16: Mediate ADCC (see:Ab)

4. IL-2R: Bind to IL-2 and become lymphokine activated killer cells ( LAK) (see:CK)

Markers and functions of NK cells

Cells of the innate immune system

Mononuclear phagocytes

Granulocytes

NK (Natural killer cells)

Cells of the adaptive immune systemT lymphocyte

B lymphocyte

Cells of Immune System

AgAg DCs

Th1 Tc

B Ab

PMNPMN

NK

Th2

ComplementComplement

Immune Response (IR)

TargetTargetcellscells

MHCMHCCKCK

MHCMHCCKCK

CKsCKs

CKsCKs

— T

lymphocyte

— B

lymphocyte

Cells of the adaptive immune system

Classes

Functions

Markers

T Lymphocyte

TH: T help cells (CD4+CD3+) TH1

TH2

TC: T cytotoxic cells, CTL (CD8+CD3+)

Classes of T cells

AgAg DCs

Th1 Tc

B Ab

PMNPMN

NK

Th2

ComplementComplement

TargetTargetcellscells

MHCMHCCKCK

MHCMHCCKCK

CKsCKs

CKsCKs

Functions of T cells ？

— Recognition

— Activation

— Function

Functions of T cells

Recognition

• Composed of or chains （ 5-10% ） • Recognize Ag peptide /MHC complex

specifically;

• Mediates T cell activation.

TCR

TCR + CD3:

• Composed of γ 、 δ 、 ε and ζ chains;

• Mediates T cell activation signal into cells;

• Specific marker of T cells.

CD3

MHC I

MHC II

— CD4• On T helper cells• Ligand to MHC class Ⅱ molecules

— CD8

• On T cytoxic cells• Ligand to MHC class Ⅰ molecules

TCR -- MHC+ peptide

CD4 -- MHC class II

TCR -- MHC + peptide

CD8 -- MHC class I

— Antigen recognition

— Co-stimulations

— Cytokines

Activations of T cells

AgAg DCs

Th1 Tc

B Ab

PMNPMN

NK

Th2

ComplementComplement

TargetTargetcellscells

MHCMHCCKCK

MHCMHCCKCK

CKsCKs

CKsCKs

Functions of T cells ？

TH (CD4+CD3+) TH1: Help Tc and macrophages by secration of

IFNγ/IL-2.

TH2 ： Help B cells by secretion of IL-4, IL-5,IL-6.

TC (CD8+CD3+) Killing of target cells by releasing perforin and

granzymes

Functions of T cells

TC Cells (CTL)

Release of lytic granules containing perforin and granzymes

which enter the target cells

Mechanisms of cytotoxicity

Death of target cells

See: 8-1

— Functions

— Markers

B Lymphocyte

— Resognition

— Activation

— Functions

Functions of B cell

Th2

BCR + CD79BCR

Recognition of B cells

BCR ( B cell receptor):1) Cell surface of Ig ( IgM and IgD)

2) Specific binding with antigen

CD79

Mediate B cell activation

CD19/CD201 ） Co-receptors for B cell activation2 ） Specific marker of B cells

Markers of B cells

Th2

AgAg APCs

Th1 Tc

B Ab

PMNPMN

NK

Th2

ComplementComplement

Immune Response (IR)

TargetTargetcellscells

MHCMHCCKCK

MHCMHCCKCK

CKsCKs

CKsCKs

Th2

Function of B cells

BCR and TCR

BCR

MHC

• Site of maturation:

• MHC requirement for recognition:

• Markers:

• Functions

Characteristics of B and T cells

Innate immunity Adaptive immunity

Components chemical barrier

PhagocytesNK cells

T and B cells

Cytokines

Complement

Antibodies

Characteristics Receptors: Limited diversity Broad specificity Recognize many related molecules

Receptors: Very large diversity Very narrow specificity Recognize a particular epitopes

Immediate response Slow response

No memory Memory

Occurs in all metazoans Occurs in vertebrates only

Mq/DCs

Phagocytosis

PAMP: pathogen-associated molecule pattern

PRR

Recognition Receptors: PRR

NK NK

KAR KIR

Th2

AgAg DCs

Th1 Tc

B Ab

PMNPMN

NK

Th2

ComplementComplement

TargetTargetcellscells

MHCMHCCKCK

MHCMHCCKCK

CKsCKs

CKsCKs

Crosstalk between Innate and Adaptive Immunity

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.

4. Terms:

CD : Markers / functions

TCR : Location / structure / function

BCR : Location / structure / function

PRR : Location / functions

KIR : Location / functions

KAR : Location / functions

Questions: