Cells of the Immune System and Antigen Recognition

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Cells of the Immune System and Antigen Recognition

• Jennifer Nyland, PhD
• Office Bldg1, Room B10
• Phone [phone]
• Email jnyland_at_uscmed.sc.edu

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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

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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

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Overview- extracellular pathogens

• Ab are primary defense
• Neutralization
• Opsonization
• Complement activation

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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

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Cells of the immune system
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Development of the immune system
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Cells of the immune system
Lymphocyte (T, B, NK)
Eosinophil
Plasma cell
Basophil
Granular
Agranular (35 in circulation)
Monocyte
Neutrophil
Dendritic cell
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Phagocytosis and Intracellular killing

• Neutrophils and Macrophages

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Phagocytes neutrophils (PMNs)

• Characteristic nucleus, cytoplasm
• Granules
• CD66 membrane marker protein

Neutrophil
Geimsa stain Source www.dpd.cdc.gov
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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

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Phagocytes macrophages

• Characteristic nucleus
• lysosomes
• CD14 membrane marker protein

Macrophage
Source Dr. Peter Darben, QueenslandUniversity
of Technology, used with permission
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Non-specific killer cells

• NK cells
• Eosinophils

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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-? to become LAK cells

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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
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Mast cells

• Characteristic cytoplasmic granules
• Responsible for burst release of preformed
  cytokines, chemokines, histamine
• Role in immunity against parasites

Source
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Cells of the immune system innate

• Phagocytes
• Monocytes/macrophages
• PMNs/neutrophils
• NK cells
• Basophils and mast cells
• Eosinophils
• Platelets

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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)

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Cells of adaptive immune response

• T cells and B cells

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Cells of the immune system adaptive

• Lymphocytes
• B cells
• Plasma cells (Ab producing)
• T cells
• Cytotoxic (CTL)
• Helper (Th)
• Th1
• Th2
• Th17
• T-reg

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

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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

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Four principles of clonal selection H?

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

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Specificity of adaptive immune response

• Clonal selection H? can explain many features of
  immune response
• Specificity
• Signal required for activation
• Lag in adaptive immune response
• Discrimination between self and non-self

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Development of the immune system
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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

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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

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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