1. Cells of the Immune System and Antigen Recognition
Jennifer Nyland, PhD
Office: Bldg#1, Room B10
Phone:

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
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

7. 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

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

9. Phagocytosis and Intracellular killing
Neutrophils and Macrophages

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

11. 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

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

13. Non-specific killer cells
NK cells
Eosinophils

14. 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

15. 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

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

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

18. 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)

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

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

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

22. 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

23. 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

24. 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

25. 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

26. 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

27. 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

28. 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

29. 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