Cells of the Immune System and Antigen Recognition

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

2. 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

3. 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

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

5. 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

6. Cells of the immune system

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

8. Phagocytosis and Intracellular killing Neutrophils and Macrophages

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

10. Characteristics of neutrophil granules

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

12. Non-specific killer cells NK cells Eosinophils

13. 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

14. 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

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

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

17. 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)

18. Cells of adaptive immune response T cells and B cells

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

20. Major distinguishing markers

21. Specificity of adaptive immune response Ag Ag Ag • 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 TCR T cell BCR B cell

22. 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

23. 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

24. 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

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

26. 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

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

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