Download Cells of the Immune System and Antigen Recognition Jennifer Nyland, PhD

Cells of the Immune System and
Antigen Recognition
Jennifer Nyland, PhD
Office: Bldg#1, Room B10
Phone: 733-1586
Email: [email protected]
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
Immune system
Myeloid cells
Lymphoid cells
Granulocytic
Monocytic
T cells
Neutrophils
Macrophages
Helper cells
Basophils
Kupffer cells
Suppressor cells
Eosinophils
Dendritic cells
Cytotoxic cells
B 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
• 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
Contain:
Lysozyme,
NADPH oxidase components and
myeloperoxidase
Lactoferrin and B12-binding protein
Phagocytes – macrophages
Macrophage
Source: Dr. Peter Darben, Queensland
University of Technology, used with permission
• Characteristic nucleus
• lysosomes
• CD14 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
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
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)
–
–
–
–
Th1
Th2
Th17
T-reg
Major distinguishing markers
Marker
B cell
CTL
T-helper
Antigen R
BCR (surface Ig)
TCR
TCR
CD3
--
+
+
CD4
--
--
+
CD8
--
+
--
CD19/ CD20
+
--
--
CD40
+
--
--
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
B cell
TCR
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 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
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
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 AgR
– 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
T cell
B cell
B cell
DC
T cell
Virgin
lymphocytes
B cell
Spleen and lymph nodes
Primed lymphocytes
T cell
B cell
Monocyte
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
T cell
B cell
B cell
DC
T cell
Virgin
lymphocytes
B cell
Spleen and lymph nodes
Primed lymphocytes
T cell
B cell
Monocyte
APC
Tissues