Design of immune system

Immune system Self/non-self recognition The state of protection from infectious disease 自我非我 Memory Acceptance vs rejection 疫苗 Innate immunityAdaptive immunity

Colonize the host Find a nutritionally compatible niche in the host’s body Avoid, subvert, or circumvent the host’s innate and adaptive immune responses Replicate, using host resources Exit and spread to a new host Antigen (Ag) Establishment of infection

Innate immunity Physical barrier Biochemical barrier Phagocytes Inflammation

Inflammation (cells, soluble mediators) Innate immunity

Complement Inflammation Phagocytes Induction of adaptive immunity

Phagocytes Innate immunity Recognition of PAMPs by pattern recognition receptors

Adaptive immunity Humoral immunity Cell-mediated immunity (CMI) B cells: Antibody T cells

Immune recognition Innate (non-specific) immunity Adaptive (specific) immunity Pattern recognition receptors Epitope recognition receptors

Innate immunity Adaptive immunity

Part I Part III Part II Cells Organs & tissues Functions Antibody response T cell response

Cells Organs & tissues Functions Part I

WBC Myeloid cells Lymphoid cells Granulocytes Macrophages/ Dendritic cells TB CD4 CD8 NK Immune cells (Natural killer cells) (Tc)(Th) (DC) Adaptive immunity Innate immunity

Granulocytes Neutrophils Eosinophils Basophils Mast cells 顆粒性白血球 嗜中性白血球 嗜酸性白血球 嗜鹼性白血球 肥大細胞 (Degranulation)

Ag Innate Adaptive ExtracellularPhagocytes B cells Intracellular NK CD8 Tc cells (Altered self) Cytotoxicity CD4 Th Humoral response Cell-mediated immunity (CMI) 1 2 Function of immune cells Ag elimination is based on Ag location DC

Adaptive immunity NKPhagocytes Intracellular Extracellular Humoral immunity CMI Th1Th2

Infected cells Intracellular Ag Innate immunity Altered self

Lymphocytes Ag-specific receptor Adaptive immunity Epitope recognition receptors

Lymphoid organs and tissues Primary (Central) Bone marrow Thymus Secondary (Peripheral) Lymph nodes Spleen Peyer’s patches

Immune design Adaptive immunity Lymph nodes

Lymph node distribution in the body

Route Antigen-presenting cells (APC) Inflammation

DC T

1. Antigen specificity 2. Diversity 3. Immunological memory 4. Self tolerance Adaptive immunity

Design of immune system Ag-specific recognition Pattern recognition

Clonal selection ★ Low frequency Immune diversity Adaptive immunity Primary (Central) Secondary (Peripheral) B cell development and humoral immunity Specificity

Adaptive immunity Clonal expansion & differentiation

Memory response Adaptive immunity

Antibody response Part II

Antibody structure

Antibody structure Effector function Fab Fc Fab: Ag-binding fragment Fc: constant Effector function: complement, FcR

Antibody structure Epitope

Antibody isotype IgM IgG IgA Fc

Five classes of antibody Effector function

IgM Natural antibody

 C4b C1s 

Five classes of antibody Effector function

Opsonization: Enhanced phagocytosis by mediators (opsonin) FcR 調理作用

Antigen-antibody interaction Immune complex

IgA transport

IgE

Ab is a mediator to activate downstream immune pathways

Memory response IgM IgG C’

Class switching

Neutralizing (Blocking) Binding FcR Complement activation Function of antibody

T cell responsePart III CD4 Th B cells CD8 Tc Costimulation (Signal 2) Ag specific recognition (Signal 1) Cytokine (Signal 3) Humoral immunity CMI

T cell Receptor (TCR) Ag specific recognition (Signal 1)

Antigen-presenting cells (APC) T cell recognition & activation

APC T-DC interaction MHC: antigen presentation Ag specific recognition (Signal 1)

T cell recognition: MHC restriction CD8CD4

Co-receptor: CD4 & CD8

MHC HLA: Human leukocyte antigen Epitope

MHC 內 APC

Ag processing & presentation to CD4 T 外

Ag processing & presentation to CD8 T 內

T cell activation & expansion Costimulation (Signal 2) Clonal expansion

Th cell differentiation IL12 IL4

內 Cytokine (Signal 3) in T cell differentiation 1 Cytokine: Effector function Interferon 

CD4 Th B cells CD8 Tc Costimulation (Signal 2) Ag specific recognition (Signal 1) Cytokine (Signal 3) Humoral immunity CMI 1 2

APC 2 Costimulation

Innate immunity Adaptive Immunity (Humoral, CMI)

Adaptive immunity Clonal expansion & differentiation

1. Antigen specificity 2. Diversity 3. Immunological memory 4. Self tolerance Adaptive immunity

Tolerance

Host-pathogen relationship Persistent infection Immune evasion Persistence