Cells of the Immune System and Antigen Recognition

Cells of the Immune System and Antigen Recognition Jennifer Nyland, Ph. D Office: Bldg#1, Room B 10 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 (CD 8) • Pathogen in vesicles – Th 1 (CD 4) releases cytokines – Activates macrophages

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

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

Cells of the immune system Eosinophil Lymphocyte (T, B, NK) 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 • CD 66 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 Contain: Lysozyme, NADPH oxidase components and myeloperoxidase Lactoferrin and B 12 -binding protein

Phagocytes – macrophages Macrophage Source: Dr. Peter Darben, Queensland University of Technology, used with permission • Characteristic nucleus • lysosomes • CD 14 membrane marker protein

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 CD 56+/CD 16+/CD 3 • 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 Source: Bristol Biomedical Image Archive, used with permission • Kill parasitic worms

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

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) – – Th 1 Th 2 Th 17 T-reg

Major distinguishing markers Marker B cell CTL T-helper Antigen R BCR (surface Ig) TCR CD 3 -- + + CD 4 -- -- + CD 8 -- + -- CD 19/ CD 20 + -- -- CD 40 + -- --

Specificity of adaptive immune response • 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 T cell TCR Ag Ag B cell BCR 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 Ag. R 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 • Ag. R pre-formed on B and T cells and Ag selects the clones with the correct receptor

Four principles of clonal selection Hθ 1. Each lymphocyte has a SINGLE type of Ag. R 2. Interaction between foreign molecule and Ag. R with high affinity leads to activation 3. Differentiated effector cell derived from activated lymphocyte with have the same Ag. R as parental lymphocyte (clones) 4. Lymphocytes bearing Ag. R 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 Bone Marrow Tissues Thymus Stem cell Granulocyte T cell Myeloid progenitor Lymphoid progenitor NK cell Mast cell B cell Monocyte 2° Lymphoid Macrophage Dendritic cell Plasma Cell

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

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

Lymphocyte recirculation • 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 Bone marrow Thymus T cell B cell Virgin lymphocytes B cell Primed lymphocytes B cell Monocyte B cell Spleen and lymph nodes T cell DC APC Tissues