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Design of immune system

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

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

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Innate immunity Physical barrier Biochemical barrier Phagocytes Inflammation

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Inflammation (cells, soluble mediators) Innate immunity

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Complement Inflammation Phagocytes Induction of adaptive immunity

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Phagocytes Innate immunity Recognition of PAMPs by pattern recognition receptors

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

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

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Innate immunity Adaptive immunity

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

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Cells Organs & tissues Functions Part I

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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

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Granulocytes Neutrophils Eosinophils Basophils Mast cells (Degranulation)

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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

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Adaptive immunity NKPhagocytes Intracellular Extracellular Humoral immunity CMI Th1Th2

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Infected cells Intracellular Ag Innate immunity Altered self

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Lymphocytes Ag-specific receptor Adaptive immunity Epitope recognition receptors

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

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Immune design Adaptive immunity Lymph nodes

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Lymph node distribution in the body

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Route Antigen-presenting cells (APC) Inflammation

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DC T

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

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Design of immune system Ag-specific recognition Pattern recognition

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

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Adaptive immunity Clonal expansion & differentiation

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Memory response Adaptive immunity

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Antibody response Part II

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Antibody structure

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

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Antibody structure Epitope

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Antibody isotype IgM IgG IgA Fc

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Five classes of antibody Effector function

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IgM Natural antibody

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C4b C1s

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Five classes of antibody Effector function

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Opsonization: Enhanced phagocytosis by mediators (opsonin) FcR

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Antigen-antibody interaction Immune complex

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IgA transport

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IgE

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Ab is a mediator to activate downstream immune pathways

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Memory response IgM IgG C

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Class switching

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Neutralizing (Blocking) Binding FcR Complement activation Function of antibody

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

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

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

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

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T cell recognition: MHC restriction CD8CD4

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Co-receptor: CD4 & CD8

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MHC HLA: Human leukocyte antigen Epitope

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MHC APC

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Ag processing & presentation to CD4 T

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Ag processing & presentation to CD8 T

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

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Th cell differentiation IL12 IL4

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

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

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APC 2 Costimulation

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Innate immunity Adaptive Immunity (Humoral, CMI)

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Adaptive immunity Clonal expansion & differentiation

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

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Tolerance

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Host-pathogen relationship Persistent infection Immune evasion Persistence