ORGANIZATION OF THE IMMUNE SYSTEM different cell types diffuse communication network between cells ‚signal transduction’ and inhibition similarity to the nervous system communication: – direct cell-cell interaction (binding molecules) – indirect: via soluble molecules (cytokines) pathogen recognitiondirect communicationindirect communication

- nonspecific - immediate reaction - does not improve - no memory - highly specific - develops in several days - improves after exposure - has memory IMMUNE SYSTEM Innate / Natural Acquired / Adaptive Cellular Granulocytes Monocytes/Macrophages Natural Killer cells Dendritic cells Mast cells T cells B cells Plasma cells Humoral Complement proteins Cytokines Acute phase proteins Antimicrobial proteins Antibodies

Leukocytes derive from a common progenitor- the pluripotent hematopoietic stem cell (HSC)

COMMON LYMPHOID PROGENITOR CELLS B lymphocyteT lymphocyte (Bursa fabricii) (Thymus) maturation: begins in bone marrow continues in bone marrow continues in thymus differentiation: peripheral tissues (SLO) plasma cells effector T cells: cytotoxic T cell helper T cell antigen recognition can recognize native antigens require processing (degradation) and cell- or matrix-bound or solublepresentation (via MHC molecules) of antigen

The localization of blood cells

WHITE BLOOD CELLS IN THE SMEAR OF HUMAN PERIPHERAL BLOOD LYMPHOCYTE LYMPHOCYTE MONOCYTE neutrophil granulocyte basophil granulocyte neutrophil granulocyte eosinophil granulocyte

Relative abundance of leukocytes in peripheral blood Cell typeProportion of leukocytes (%) Neutrophil Lymphocytes Eosinophil Basophil Monocyte <1 2-10

Professional phagocytic cells macrophages neutrophyl granulocytes dendritic cells the phagocytosed cells or molecules may modify the functions of the cell phagocytosis followed by enzymatic degradation Professional antigen presenting cells macrophages B lymphocytes dendritic cells they express MHCII molecules the protein degradation products (peptides) can be presented to T lymphocytes by MHC molecules

Innate immunity: always present (ready to attack); many pathogenic microbes have evolved to resist innate immunity Adaptive immunity: stimulated by exposure to microbe; more potent !

SENSINGRECOGNITION SIGNALING RESPONSE INNATE IMMUNITY CellsReceptors Signaling pathways Cell-Cell collaboration Effector functions DEFENSE SYSTEMS ADAPTIVE IMMUNITY SENSINGRECOGNITION SIGNALING RESPONSE

General schema of receptor function receptor + ligand conformational change activation of messengers activation of transcription factors alteration of gene expression

IMPORTANT CELL SURFACE MOLECULES Cell typeCell surface moleculeFunction Cells of innate immunity (e.g. macrophage, dendritic cell) PRRs (Pattern recognition receptors) Sensing ‚Danger signals’ (presence of pathogens or tissue damage) B cellsBCR (B cell receptor)Antigen recognition of B cell T cellsTCR (T cell receptor)Antigen recognition of T cell All nucleated human cells MHC I (MHC = Major Histocompatibility Complex) present intracellular peptides required for cytotoxic T cell (Tc) receptor Professional antigen presenting cells (APCs): Mf, DC, B MHC IIpresent extracellular peptides required for helper T cell (Th) receptor

hormones cytokines chemokines interleukines interferons CYTOKINES

INTERLEUKINES (IL-1, IL-2, IL-4, IL-6, IL-10, IL-12, TNFα) control functions of leukocytes communication between leukocytes CHEMOKINES (IL-8, CCL21) inducing migration (chemotaxis) increasing adhesion activating leukocytes TYPE I INTERFERONS (IFNα, IFNβ) parts of innate immunity act against viral infections producers: infected cells, plazmacitoid DCs TYPE II INTERFERON (IFNγ) main activators of macrophages producers: Th1, CD8+, NK cells CYTOKINES

Primary lymphoid organs : - Bone marrow - Thymus Secondary lymphoid organs (SLO): - Spleen - Lymphatic vessels - Lymph nodes - Adenoids and tonsils - MALT (Mucosal Associated Lymphoid Tissue) GALT (Gut Associated Lymphoid Tissue) BALT (Bronchus Associated Lymphoid Tissue) SALT (Skin Associated Lymphoid Tissue) NALT (Nasal Associated Lymphoid Tissue) LYMPHOID ORGANS