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Cells of the Immune System and Antigen Recognition

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... R on T and B cells ... Each B and T cell has receptor that is unique for a particular antigenic ... Lag in adaptive immune response. Discrimination between ... – PowerPoint PPT presentation

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Title: Cells of the Immune System and Antigen Recognition


1
Cells of the Immune System and Antigen Recognition
  • Jennifer Nyland, PhD
  • Office Bldg1, Room B10
  • Phone 733-1586
  • Email jnyland_at_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
7
Development of the immune system
8
Phagocytosis and Intracellular killing
  • Neutrophils and Macrophages

9
Phagocytes neutrophils (PMNs)
  • Characteristic nucleus, cytoplasm
  • Granules
  • CD66 membrane marker protein

Neutrophil
Geimsa stain Source www.dpd.cdc.gov
10
Characteristics of neutrophil granules
11
Phagocytes macrophages
  • Characteristic nucleus
  • lysosomes
  • CD14 membrane marker protein

Macrophage
Source Dr. Peter Darben, QueenslandUniversity
of Technology, used with permission
12
Non-specific killer cells
  • NK cells
  • Eosinophils

13
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

14
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
15
Mast cells
  • Characteristic cytoplasmic granules
  • Responsible for burst release of preformed
    cytokines, chemokines, histamine
  • Role in immunity against parasites

Source
16
Cells of the immune system innate
  • Phagocytes
  • Monocytes/macrophages
  • PMNs/neutrophils
  • NK cells
  • Basophils and mast cells
  • Eosinophils
  • Platelets

17
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)

18
Cells of adaptive immune response
  • T cells and B cells

19
Cells of the immune system adaptive
  • Lymphocytes
  • B cells
  • Plasma cells (Ab producing)
  • T cells
  • Cytotoxic (CTL)
  • Helper (Th)
  • Th1
  • Th2
  • Th17
  • T-reg

20
Major distinguishing markers
21
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

22
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

23
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

24
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

25
Development of the immune system
26
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

27
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

28
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
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