Cells of the Immune System and Antigen Recognition Jennifer Nyland, PhD Office: Bldg#1, Room B10 Phone: 733-1586 Email: jnyland@uscmed.sc.edu

Teaching objectives To review the role of immune cells in protection from different types of pathogens To discuss the types of cells involved in immune responses To describe the nature of specificity in adaptive immune responses To understand the role of lymphocyte recirculation in immune responses

Overview of the immune system Purpose: Protection from pathogens Intracellular (viruses, some bacteria and parasites) Extracellular (most bacteria, fungi, and parasites) Eliminate modified or altered “self” Cancer or transformed cells Sites of action: Extracellular Intracellular

Overview- extracellular pathogens Ab are primary defense Neutralization Opsonization Complement activation

Overview- intracellular pathogens Cell-mediated responses are primary defense Ab are ineffective Two scenarios: Pathogen in cytosol Cytotoxic T cell (CD8) Pathogen in vesicles Th1 (CD4) releases cytokines Activates macrophages

Cells of the immune system Myeloid cells Granulocytic Eosinophils Basophils Neutrophils Monocytic Dendritic cells Kupffer cells Macrophages Lymphoid cells T cells Cytotoxic cells Suppressor cells Helper cells B cells Plasma cells NK cells

Development of the immune system NK cell Stem cell Macrophage Lymphoid progenitor Myeloid T cell B cell Plasma Cell Granulocyte Monocyte Mast cell Dendritic cell

Cells of the immune system Lymphocyte (T, B, NK) Eosinophil Plasma cell Basophil Granular Agranular (35% in circulation) Monocyte Neutrophil Dendritic cell

Phagocytosis and Intracellular killing Neutrophils and Macrophages

Phagocytes – neutrophils (PMNs) Characteristic nucleus, cytoplasm Granules CD66 membrane marker protein Neutrophil Geimsa stain Source: www.dpd.cdc.gov

Characteristics of neutrophil granules Primary granules Secondary granules Azurophilic; young neutrophils Specific for mature neutrophils Contain: cationic proteins, lysozyme, defensins, elastase and Lysozyme, NADPH oxidase components and myeloperoxidase Lactoferrin and B12-binding protein

Phagocytes – macrophages Characteristic nucleus lysosomes CD14 membrane marker protein Macrophage Source: Dr. Peter Darben, Queensland University of Technology, used with permission

Non-specific killer cells NK cells Eosinophils

Natural killer (NK) cells Also known as large granular lymphocytes (LGL) Kill virus-infected or transformed cells Identified by the CD56+/CD16+/CD3- Activated by IL-2 and IFN-γ to become LAK cells

Eosinophils Characteristic bi-lobed nucleus Cytoplasmic granules, stain with acidic dyes (eosin) Major basic protein (MBP) Potent toxin for helminths Kill parasitic worms Source: Bristol Biomedical Image Archive, used with permission

Mast cells Characteristic cytoplasmic granules Responsible for burst release of preformed cytokines, chemokines, histamine Role in immunity against parasites Source: Wikimedia

Cells of the immune system: innate Phagocytes Monocytes/macrophages PMNs/neutrophils NK cells Basophils and mast cells Eosinophils Platelets

Cells of the immune system: APC Cells that link the innate and adaptive arms Antigen presenting cells (APCs) Heterogenous population with role in innate immunity and activation of Th cells Rich in MHC class II molecules (lec 11-12) Examples Dendritic cells Macrophages B cells Others (Mast cells)

Cells of adaptive immune response T cells and B cells

Cells of the immune system: adaptive Lymphocytes B cells Plasma cells (Ab producing) T cells Cytotoxic (CTL) Helper (Th) Th1 Th2 Th17 T-reg

Major distinguishing markers B cell CTL T-helper Antigen R BCR (surface Ig) TCR CD3 -- + CD4 CD8 CD19/ CD20 CD40

Specificity of adaptive immune response T cell TCR Resides with Ag R on T and B cells TCR and BCR – both specific for only ONE antigenic determinant TCR is monovalent BCR is divalent Ag B cell BCR Ag Ag

Specificity of adaptive immune response Each B and T cell has receptor that is unique for a particular antigenic determinant on Ag Vast array of different AgR in both T and B cell populations How are the receptors generated? Instructionist hypothesis Does not account for self vs non-self Clonal selection hypothesis AgR pre-formed on B and T cells and Ag selects the clones with the correct receptor

Four principles of clonal selection Hθ Each lymphocyte has a SINGLE type of AgR Interaction between foreign molecule and AgR with high affinity leads to activation Differentiated effector cell derived from activated lymphocyte with have the same AgR as parental lymphocyte (clones) Lymphocytes bearing AgR for self molecules are deleted early in lymphoid development and are absent from repertoire

Specificity of adaptive immune response Clonal selection Hθ can explain many features of immune response Specificity Signal required for activation Lag in adaptive immune response Discrimination between self and non-self

Development of the immune system NK cell Stem cell Macrophage Lymphoid progenitor Myeloid T cell B cell Plasma Cell Granulocyte Monocyte Mast cell Dendritic cell Bone Marrow Thymus Tissues 2° Lymphoid

Lymphocyte recirculation Relatively few lymphocytes with a specific AgR 1/10,000 to 1/100,000 Chances for successful encounter enhanced by circulating lymphocytes 1-2% recirculate every hour

Lymphocyte recirculation T cell B cell Monocyte DC APC Bone marrow Thymus Tissues Virgin lymphocytes Spleen and lymph nodes Primed lymphocytes Lymphocytes enter 2° lymphoid organs via high endothelial venules (HEVs) Ag is transported to lymph nodes via APC Upon activation, lymphocytes travel to tissues

Lymphocyte recirculation T cell B cell Monocyte DC APC Bone marrow Thymus Tissues Virgin lymphocytes Spleen and lymph nodes Primed lymphocytes After activation, new receptors (homing R ) are expressed to direct to tissues R on lymphocytes recognize CAMs on endothelial cells Chemokines at infection help attract activated lymphocytes