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

Cells of the innate immune system Mononuclear phagocytes Granulocytes NK cells Cells of the adaptive immune system T 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 Phagocytes

Ag DCs Th1 Tc B Ab PMN NK Th2 Complement Functions in Immune Response (IR) Targetcells MHCCK MHCCK CKs CKs

Maturation

Cells of Mononuclear Phagocytes System

— Phagocytosis — Antigen presentation — Cytokine secretion Mononuclear Phagocyte System

Ag DCs Th1 Tc B Ab PMN NK Th2 Complement Functions in Immune Response (IR) Targetcells MHCCK MHCCK CKs CKs

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

Ag DCs Th1 Tc B Ab PMN NK Th2 Complement Immune Response (IR) Targetcells MHCCK MHCCK CKs CKs

Ag DCs Th1 Tc B Ab PMN NK Th2 Complement Immune Response (IR) Targetcells MHCCK MHCCK CKs CKs

— Pattern recognition receptors(PRR): Recognition — Fc receptor (FcR, CD16): Opsonisation — Complement receptor (CR): Opsonisation Phagocytosis

— Phagocytosis — Antigen presentation — Cytokine secretion Mononuclear Phagocyte System

Ag DCs Th1 Tc B Ab PMN NK Th2 Complement Immune Response (IR) Targetcells MHCCK MHCCK CKs CKs

See:8-2 Antigen presenting cells (APC)

Antigen that is presented on the APC could be recognized by T cell Recognized by T cells Antigen Presentation See:8-2

 Mononuclear phagocytes  Granulocytes  NK cells Cells of the innate immune system

— Neutrophils — Basophils — Eosinophils Granulocytes

Ag DCs Th1 Tc B Ab PMN NK Th2 Complement Functions in Immune Response (IR) Targetcells MHCCK MHCCK CKs CKs

— Majority of white blood cells — Contain: lysozyme, antibiotic peptides —Main function: phagocytosis — Chemotaxis: C5a — Opsonization: Ab and C3b Neutrophils (Polymorphonuclear cells PMNs)

— Neutrophils — Basophils (Mast cells) — Eosinophils Granulocytes

— Localization: Basophils － circulation Mast cells － tissues — Granule contents: Mediators Histamine Leukotrienes — Functions: Attract: Leukocytes － acute inflammatory response Allergy Basophils and Mast cells

Mediators: allergy – Vasodilatation, – Vascular permeability increase, – Smooth muscle contraction, – Mucous secretion.

Respiratory tract allergic rhinitis

Respiratory 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)

Ag DCs Th1 Tc B Ab PMN NK Th2 Complement Immune Response (IR) Targetcells MHCCK MHCCK CKs CKs

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 system T lymphocyte B lymphocyte Cells of Immune System

Ag DCs Th1 Tc B Ab PMN NK Th2 Complement Immune Response (IR) Targetcells MHCCK MHCCK CKs CKs

— T lymphocyte — B lymphocyte Cells of the adaptive immune system

 Classes  Functions  Markers T Lymphocyte

TH: T help cells (CD4 + CD3 + ) ¹TH1 ¹TH2 TC: T cytotoxic cells, CTL (CD8 + CD3 + ) Classes of T cells

Ag DCs Th1 Tc B Ab PMN NK Th2 Complement Targetcells MHCCK MHCCK CKs CKs 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

Ag DCs Th1 Tc B Ab PMN NK Th2 Complement Targetcells MHCCK MHCCK CKs CKs Functions of T cells ？

TH (CD4 + CD3 + ) ¹TH1: Help Tc and macrophages by secration of IFNγ/IL-2. ¹TH2 ： Help B cells by secretion of IL-4, IL-5,IL-6. TC (CD8 + CD3 + ) ¹Killing 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 + CD79 BCR 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/CD20 1 ） Co-receptors for B cell activation 2 ） Specific marker of B cells Markers of B cells

Th2

Ag APCs Th1 Tc B Ab PMN NK Th2 Complement Immune Response (IR) Targetcells MHCCK MHCCK CKs CKs

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 immunityAdaptive immunity Components chemical barrier Phagocytes NK 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 responseSlow response No memoryMemory Occurs in all metazoansOccurs in vertebrates only

Mq/DCs Phagocytosis PAMP: pathogen-associated molecule pattern PRR Recognition Receptors: PRR

NK KAR KIR

Th2

Ag DCs Th1 Tc B Ab PMN NK Th2 Complement Targetcells MHCCK MHCCK CKs CKs 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: