Immune system The state of protection from infectious disease Self/non-self recognition 自我 非我 Acceptance vs rejection Memory 疫苗 2
Microbes Commensal Microbes 共生菌 Normal flora: usually confined to certain areas of the body, including the skin, mouth, large intestine, and vagina
Pathogens Primary pathogens causing overt disease in most healthy people Establishment of infection
Establishment of infection Colonize the host Antigen (Ag) Find a nutritionally compatible niche in the host s body Replicate, using host resources Avoid, subvert, or circumvent the host s innate and adaptive immune responses Exit and spread to a new host
Design of immune system
The growth of pathogen: Survival of host (not killing the host too quickly) Adaptive immunity Innate immunity
Immunity Innate immunity Adaptive immunity Humoral immunity B cells: Antibody Cell-mediated immunity (CMI) T cells
Immune recognition Innate (non-specific) immunity Adaptive (specific) immunity
Innate immunity Physical barrier Biochemical barrier Phagocytes Inflammation Immune cells
Physical & biochemical barrier 皮脂 Defensin Small intestine
Biochemical barrier The complement system A large and complex group of proteins Proenzymes / Zymogens Inactive form in plasma Activation of complement Proteolytic cleavage Removal of an inhibitory fragment Exposure of the active site 12
Biochemical barrier Complement producers Liver hepatocytes Blood monocytes Tissue macrophages GI epithelial cells 13
Biochemical barrier Complement
Complement Pore formation and lysis
abg C4b C1s a
Innate immunity Physical barrier Biochemical barrier Phagocytes Inflammation Immune cells
Complement Inflammation Phagocytes Induction of adaptive immunity
Innate immunity Phagocytes: phagocytosis 吞噬細胞 吞噬作用 調理作用 granules
Innate immunity ( 發炎反應 ) Inflammation (cells, soluble mediators)
Design of immune system
Part I Cells Organs & tissues Functions Part II Antibody response Part III T cell response
Part I Cells Organs & tissues Functions
Immune cells Innate immunity Adaptive immunity WBC Myeloid cells Lymphoid cells Macrophages/ Dendritic cells (DC) Granulocytes B T CD4 CD8 (Th) (Tc) NK (Natural killer cells)
Immunity Innate immunity Adaptive immunity Humoral immunity Cell-mediated immunity (CMI)
Extracellular Ag Altered self Intracellular Ag Colony
Function of immune cells Ag elimination is based on Ag location Humoral response Ag Innate Adaptive Extracellular Phagocytes 2 B cells CD4 Th Intracellular NK 1 CD8 Tc cells (Altered self) Cytotoxicity Cell-mediated immunity (CMI)
Phagocytes Extracellular NK Intracellular Adaptive immunity CMI Humoral immunity
Extracellular Ag Innate immunity Phagocytes: chemotaxis & phagocytosis RBC Ag recognition
Innate immunity Pattern recognition
Phagocytes Innate immunity Recognition of Conserved Features of Pathogens
Intracellular Ag Innate immunity Infected cells Altered self
Adaptive immunity Lymphocytes Ag-specific receptor
Lymphoid organs and tissues Primary (Central) Bone marrow Thymus Secondary (Peripheral) Lymph nodes Spleen Peyer s patches
Immune design Adaptive immunity
Lymph node distribution in the body
Lymph node DC HEV T
Inflammation Route Antigen-presenting cells (APC)
DC T
Adaptive immunity 1. Antigen specificity 2. Diversity 3. Immunological memory 4. Self tolerance
Design of immune system Pattern recognition Ag-specific recognition
Adaptive immunity B cell development and humoral immunity Primary (Central) Immune diversity Low frequency Specificity Secondary (Peripheral) Clonal selection
B
Adaptive immunity Clonal expansion & differentiation
Adaptive immunity Memory response
Part II Antibody response
Antibody structure
Fab Fc Antibody structure Effector function
Antibody structure Epitope
Antigen-antibody interaction Immune complex
Effector function Five classes of antibody
Ab is a mediator to activate downstream immune pathways
IgM
Memory response IgG IgM C
Effector function Five classes of antibody
Opsonization: Enhanced phagocytosis by mediators (opsonin) IgG
Effector function Five classes of antibody
IgE
IgA transport
Function of antibody Binding FcR Complement activation Neutralizing (Blocking)
Part III T cell response CD4 Th Ag specific recognition (Signal 1) Costimulation (Signal 2) Cytokine (Signal 3) B cells CD8 Tc cells
Ag specific recognition (Signal 1) T cell Receptor (TCR)
T cell recognition & activation Antigen-presenting cells (APC)
T-DC interaction APC
T cell recognition: MHC restriction
MHC HLA: Human leukocyte antigen
MHC 內 APC
Ag processing & presentation to CD4 T 外
Ag processing & presentation to CD8 T 內
Co-receptor: CD4 & CD8
T cell activation & expansion Costimulation (Signal 2)
Th cell differentiation
Cytokine (Signal 3) in T cell differentiation Cytokine: Effector function 1 Costimulation 內
Costimulation APC 2
Innate immunity Adaptive Immunity (Humoral, CMI)
Infectious diseases Public health measures Medical intervention: Anti-microbial drugs, Vaccination, etc.
Persistent infection Host-pathogen relationship Immune evasion Persistence
Type of interaction between microbes and immune responses in microbial pathogenesis Disease Immunopathology Pathogens colonize asymptomatically in hosts with normal immune responses