Overview of Immunology Organs and tissues Cells Molecules Components of IS Functions of IS Pathology...

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


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


Granulocytes

NK cells


— 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




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


Immune Response (IR)


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




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


Granulocytes

NK cells


— Neutrophils

— Basophils

— Eosinophils

GranulocytesGranulocytes

AgAg DCs

Th1 Tc

B Ab

PMNPMN

NK

Th2




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)


-- Functions

-- Markers

Natural Killer cells (NK cells)

AgAg DCs

Th1 Tc

B Ab

PMNPMN

NK

Th2




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



Granulocytes

NK (Natural killer cells)

Cells of the adaptive immune systemT lymphocyte

B lymphocyte


AgAg DCs

Th1 Tc

B Ab

PMNPMN

NK

Th2




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



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



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

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

AgAg APCs

Th1 Tc

B Ab

PMNPMN

NK

Th2




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

AgAg DCs

Th1 Tc

B Ab

PMNPMN

NK

Th2



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:

Overview of Immunology Organs and tissues Cells Molecules Components of IS Functions of IS Pathology...

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