Overview of immune cells

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

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

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

9. Phagocytosis and
Intracellular killing
Neutrophils and Macrophages

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

11. 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 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
Marker B cell CTL T-helper
Antigen R BCR (surface Ig) TCR TCR
CD3 -- + +
CD4 -- -- +
CD8 -- + --
CD19/ CD20 + -- --
CD40 + -- --

22. 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
B cell
BCR

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
1. Each lymphocyte has a SINGLE type of AgR
2. Interaction between foreign molecule and
AgR with high affinity leads to activation
3. Differentiated effector cell derived from
activated lymphocyte with have the same
AgR as parental lymphocyte (clones)
4. 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
progenitor
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
• Lymphocytes
enter 2°
lymphoid organs
via high
endothelial
venules (HEVs)
• Ag is transported
to lymph nodes
via APC
• Upon activation,
lymphocytes
travel to tissues
T cell B cell
Monocyte
DC
APC
T cell
T cell B cell
B cell
B cell
T cell
Bone marrow
Thymus
Tissues
Virgin
lymphocytes
Spleen and lymph nodes
Primed lymphocytes

29. 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
T cell B cell
Monocyte
DC
APC
T cell
T cell B cell
B cell
B cell
T cell
Bone marrow
Thymus
Tissues
Virgin
lymphocytes
Spleen and lymph nodes
Primed lymphocytes