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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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
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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
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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?

• 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

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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