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Cells of the Immune System

With Prof. Peter J. Delves

S2031231 STUDENT, s2031231@siswa.um.edu.my


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Learning Objectives

• Recognize the two pathways of


hematopoiesis

• Outline the function of the different cell types


associated with innate and adaptive
immunity

• Identify the microbicidal mechanisms of


phagocytic cells

S2031231 STUDENT, s2031231@siswa.um.edu.my


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Hematopoiesis

Erythrocytes

Myeloid pathway Platelets

Cells of innate immune


response

Lymphoid pathway Cells of adaptive


immune response
Self-renewing,
multipotent,
Natural Killer cells
hematopoietic
(mostly innate) and
stem cell in
other innate
bone marrow
lymphoid cells

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Innate Immune Response

Neutrophil (together with eosinophils and Phagocytosis


basophils are polymorphonuclear granulocytes)

Monocyte and macrophage Phagocytosis

Dendritic cell Activation of T-cells

Follicular dendritic cell Activation of B-cells

Production of inflammatory
Eosinophil, basophil and mast cell
mediators

Natural Killer (NK) cell and other NK cell killing of infected cells.
innate lymphoid cells (ILCs) Diverse functions of ILCs

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Innate Immune Response

Neutrophil (together with eosinophils and Phagocytosis


basophils are polymorphonuclear granulocytes)

Monocyte and macrophage Phagocytosis

Dendritic cell Activation of T-cells

Neutrophils together with eosinophils and basophils


Follicular dendritic cell are polymorphonuclear granulocytes.
Activation of B-cells

Production of inflammatory
Eosinophil, basophil and mast cell
mediators

Natural Killer (NK) cell and other NK cell killing of infected cells.
innate lymphoid cells (ILCs) Diverse functions of ILCs

S2031231 STUDENT, s2031231@siswa.um.edu.my


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The Phagocytic Cells

Neutrophils are short-lived cells


that leave blood and enter tissues.

Monocytes leave blood to


develop into relatively long-lived
macrophages.

S2031231 STUDENT, s2031231@siswa.um.edu.my


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The Phagocytic Cells

The neutrophil and monocyte


bind to the blood vessel
endothelium using adhesion
molecules, and are attracted to
the site of the infection by a
concentration gradient of
chemotactic factors.

S2031231 STUDENT, s2031231@siswa.um.edu.my


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The Phagocytic Cells

• The phagocytic cells use pattern recognition


receptors (PRR) to recognize pathogen-
associated molecular patterns (PAMPs).
CR
• The pathogen can also become coated with
substances (opsonins) that are additionally
recognized by the phagocytic cells.

• Complement

• Antibody
CR

S2031231 STUDENT, s2031231@siswa.um.edu.my


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The Phagocytic Cells

• The phagocytic cells use pattern recognition


receptors (PRR) to recognize pathogen-
associated molecular patterns (PAMPs).

• The pathogen can also become coated with


substances (opsonins) that are additionally
recognized by the phagocytic cells.

• Complement

• Antibody

S2031231 STUDENT, s2031231@siswa.um.edu.my


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The Phagocytic Cells

• The phagocytic cells use pattern recognition


receptors (PRR) to recognize pathogen-
associated molecular patterns (PAMPs).
FcR
• The pathogen can also become coated with
substances (opsonins) that are additionally
recognized by the phagocytic cells.

• Complement

• Antibody
FcR

S2031231 STUDENT, s2031231@siswa.um.edu.my


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The Phagocytic Cells

• The phagocytic cells use pattern recognition


receptors (PRR) to recognize pathogen-
associated molecular patterns (PAMPs).

• The pathogen can also become coated with


substances (opsonins) that are additionally
recognized by the phagocytic cells.

• Complement

• Antibody

S2031231 STUDENT, s2031231@siswa.um.edu.my


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The Phagocytic Cells

Once engulfed by the phagocytic cell, the


pathogen is destroyed using reactive oxygen
intermediates generated by a respiratory burst,
and by a number of non-oxygen-dependent
killing mechanisms

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The Phagocytic Cells

PRR

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Microbicidal Activity of Phagocytic Cells

Oxygen-dependent Oxygen-independent

O2- (superoxide) Lysozyme – cleaves peptidoglycan

1O Defensins – forms channels in bacterial


2 (singlet oxygen)
membranes
.OH (hydroxyl radical) Lactoferrin – chelates iron

H2O2 (hydrogen peroxide) Proteases – e.g. elastase

HOCl (hypochlorite)

NO (nitric oxide)

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Microbicidal Activity of Phagocytic Cells

Oxygen-dependent Oxygen-independent

O2- (superoxide) Lysozyme - cleaves peptidoglycan

1O Defensins - forms channels in bacterial


2 (singlet oxygen)
membranes
.OH (hydroxyl radical)
In addition, neutrophils canLactoferrin - chelates
extrude their iron
DNA and
granule contents to produce neutrophil extracellular
H2O2 (hydrogen peroxide)
traps (NETs) containing Proteases
lyzozyme,- e.g. elastase
elastase,
defensins, etc.
HOCl (hypochlorite)

NO (nitric oxide)

S2031231 STUDENT, s2031231@siswa.um.edu.my


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Dendritic Cells

Dendritic cells Follicular dendritic cells

Derived from hematopoietic stem cells Derived from mesenchymal stem cells

Only present in germinal centers of


Present throughout the body
secondary lymphoid tissues

Initially phagocytic Never phagocytic

Possess MHC class II and costimulatory Lack MHC class II and costimulatory
(e.g. B7) molecules molecules
Do not activate helper T-cells, but specialised
Activate helper T-cells
to show antigen to B-cells

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Production of Inflammatory Mediators

Eosinophil Basophil Mast cell

Present in mucosal and


Present in blood and tissues Present in blood
connective tissues

Releases histamine, Releases histamine,


Characteristically releases
prostaglandins prostaglandins
major basic protein
and leukotrienes and leukotrienes

S2031231 STUDENT, s2031231@siswa.um.edu.my


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Innate Lymphoid Cells

One type of ILC, the Natural Killer cell,


induces apoptotic cell death in infected cells
using:

• Fas/FasL pathway

• Granzyme/Perforin pathway

Other types of ILCs have functions similar to


the helper T-cells and regulatory T-cells of the
adaptive response.

S2031231 STUDENT, s2031231@siswa.um.edu.my


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Cells of the Adaptive Immune Response

Help activate macrophages,


Helper T-cell
cytotoxic T-cells and B-cells

Suppress other cells of the


Regulatory T-cell
immune response

Cytotoxic T-cell Kill infected cells

B-cell and plasma cell Produce antibodies

S2031231 STUDENT, s2031231@siswa.um.edu.my


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Learning Outcomes

 The two pathways of hematopoiesis

 The function of the different cell types


associated with innate and adaptive
immunity

 The microbicidal mechanisms of phagocytic


cells

S2031231 STUDENT, s2031231@siswa.um.edu.my


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