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Cells of the Immune System and Antigen
Recognition
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
Development of the immune system
NK cell
Stem cell
Macrophage
Lymphoidprogenitor
Myeloidprogenitor
T cell
B cell
Plasma Cell
Granulocyte
Monocyte
Mast cell
Dendritic cell
Phagocytosis and Intracellular killing
Neutrophils and Macrophages
Phagocytes – neutrophils (PMNs)
• Characteristic nucleus, cytoplasm• Granules• CD66 membrane marker
protein
Geimsa stainSource: www.dpd.cdc.gov
Neutrophil
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
• Characteristic nucleus• lysosomes• CD14 membrane marker
proteinMacrophage
Source: Dr. Peter Darben, QueenslandUniversity of Technology, used with permission
Non-specific killer cellsNK 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
• Kill parasitic worms
Source: Bristol Biomedical Image Archive,used with permission
Mast cells
• Characteristic cytoplasmic granules• Responsible for burst release of
preformed cytokines, chemokines, histamine• Role in immunity against
parasites
Source:
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 cellTCR Ag
B cellBCR
Ag
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 AgR2. Interaction between foreign molecule and AgR with high affinity
leads to activation3. 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
NK cell
Stem cell
Macrophage
Lymphoidprogenitor
Myeloidprogenitor
T cell
B cell
Plasma Cell
Granulocyte
Monocyte
Mast cell
Dendritic cell
Bone Marrow ThymusTissues
2° Lymphoid
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
T cell B cellMonocyteDC
APC
T cell
T cell B cell
B cell
B cellT cell
Bone marrow
Thymus
Tissues
Virginlymphocytes
Spleen and lymph nodes
Primed lymphocytes
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 cellMonocyteDC
APC
T cell
T cell B cell
B cell
B cellT cell
Bone marrow
Thymus
Tissues
Virginlymphocytes
Spleen and lymph nodes
Primed lymphocytes
