Revision of basic immunology: Innate vs. adaptive immunity, University of Portsmouth

Learning Objectives

On completion of this session you should be able to

1. Define key terms in immunology.
2. Explain the importance of the immune system, distinguishing
   between innate and adaptive immunity.
3. Describe the cellular basis of immunity, including different
   immune cells and the lymphatic system.
4. Understand the principles of humoral-mediated immunity.

Key Terms in Immunology

1. Immunology: Study of immunity (the response of the immune
   system to infection)
2. Immunity: Ability of the host to protect itself against foreign
   organisms
3. Immune response: A reaction of the body in response to the
   presence of a foreign substance (i.e. antigens)
4. Antigens: Molecules from a pathogen or foreign organism that
   provoke a specific immune response

Homeostasis and the Immune System

1. Pathogens invade organisms because they are
   seeking
   · Source of food or water
   · Protection
   · Site for reproduction
2. Defense systems are evolved to get rid of the
   invading organisms

Inflammation and Immune Response

Our immune response includes innate
and adaptive responses

Pathogens
(microorganisms
and viruses)

Innate Immunity

All animals
·Recognition of traits
shared by broad ranges
of pathogens, using a
small set of receptors

Barrier defenses:
Skin
Mucous membranes
Secretions
·Rapid response
Internal defenses:
Phagocytic cells
Antimicrobial proteins
Inflammatory response
Natural killer cells

Adaptive Immunity

Only vertebrates
·Recognition of traits
specific to particular
pathogens, using a vast
array of receptors
·Slower response
Humoral response:
Antibodies defend against
infection in body fluids.
Cell-mediated response:
Cytotoxic lymphocytes defend
against infection in body cells.

First line of defence
Second line of defence
Third line of defence

Effector Mechanism

1. Processes by which pathogens are destroyed a
   nd cleared from the body
2. Can be both cell-mediated and humoral in
   origin
3. Cell-mediated - effector function is performed
   by a cell e.g. cytotoxic T cells (Tc), phagocyte,
   natural killer (NK) cell
4. Humoral - effector function is mediated by
   soluble molecules e.g. complement, antibodies

Cellular Basis of Immunity

1. Immune cells:
   1. Mononuclear phagocytes - monocytes and macrophages
   2. Dendritic cells - Langerhans, Interdigitating and Follicular
   3. Granulocytes - * neutrophils, eosinophils, basophils - help
   fight off infection
   4. Lymphocytes - B and T cells, NK cells

Mononuclear Phagocytes

1. Long lived phagocytic cells
2. Key initiators of inflammation
3. Involved in phagocytosis or intracellular
   killing of microorganisms
4. Can initiate an adaptive response
5. Found in blood (monocytes) and tissues
   (macrophages)

Phagocytosis Process

1 Microbe adheres to phagocyte
2 Phagocyte forms pseudopods that
eventually engulf the particle
Phagocytic vesicle
containing antigen
(phagosome)
Lysosome
3 Phagocytic vesicle is
fused with a lysosome
Phagolysosome
Acid
hydrolase
enzymes
4 Microbe in fused vesicle
is killed and digested by
lysosomal enzymes within
the phagolysosome, leaving
a residual body
- Residual body
5 Indigestible and
residual material
is removed by
exocytosis
(a)
(b)
Copyright 2004 Pearson Education, Inc., publishing as Benjamin Cummings.

Monocytes Characteristics

1. Comprise up to 10% of circulating WBCs
2. Motile and highly adherent upon phagocytic activity
3. During haematopoiesis in the bone marrow, monocyte progenitor cells
   differentiate into promonocytes, which leave the bone marrow and enter
   the blood, where they further differentiate into mature monocytes
4. Monocytes circulate in the bloodstream for about 8 hours, during which
   they enlarge; then migrate into the tissues and differentiate into
   macrophages and dendritic cells (Antigen presenting cells)

Macrophages Functions

1. Terminally differentiated, long-lived monocytes residing in tissues
2. Like monocytes, macrophages are motile and highly adherent upon
   phagocytic activity
3. Serve different functions in different tissues
   · Phagocytosis, Adaptive immunity, Muscle regeneration, Limb regeneration, Wound
   healing, Iron homeostasis - maintain constant concentrations of iron in the brain
   internal environment
4. Named according to their tissues location
   · Alveolar macrophages - lung
   . Histocytes - connective tissues
   . Kupffer cells - liver
   · Mesangial cells - kidney
   · Microglial cells - brain
   · Osteoclasts - bone
   I

Dendritic Cells Overview

1. Arises from hematopoietic stem cells via different pathways
   and in different locations
2. Antigen presenting cells: Acquire antigen by phagocytosis
   and display them to T cells
3. Langerhans cells: immature cells primarily found in skin and
   mucosal tissues

Dendritic Cells Types

1. Accessory cells - 2 types
   (a) Interdigitating dendritic cells
   · Mediate T cell activation and differentiation
   · Found in periphery and lymphatic tissues
   (b) Follicular dendritic cells
   · Unrelated to the above
   · Mediate B cell activation and differentiation
   · Restricted to lymphatic tissues

Granulocytes Overview

1. Contain cytoplasmic granules
2. Also called polymorphonuclear leukocytes (PMN, PML,
   PMNL)
3. Produced via granulopoiesis in bone marrow
4. Based on cellular morphology, cytoplasmic staining
   characteristics, granulocytes are classified as
   (a) Neutrophils
   (b) Eosinophils
   (c) Basophils

Neutrophils Characteristics

1. Most abundant myeloid cell type, comprising 40-70% of total
   WBCs
2. Multilobed nucleus and a granulated cytoplasm
3. Produced by haematopoiesis in the bone marrow that are
   released into the peripheral blood and circulate for 7-10
   hours before migrating into the tissues, where they have a
   life span of only a few days
4. Mobile and highly phagocytic

Neutrophils Role

1. Major role in anti-bacterial response: ingest, kill, digest
   microbial pathogens
2. Contain multiple antimicrobial agents, such as lysozyme
   (peptidoglycan degradation), hydrogen peroxide and
   lactoferrin (iron chelator)
3. Neutrophils dying at the site of infection contribute to
   the formation of the whitish exudate called Pus

Eosinophils Functions

1. Comprise about 1-3% of total WBCs
2. Bi-lobed nucleus and acidophilic granules
3. Granules contain major basic protein
4. Produced by haematopoiesis in the bone marrow and
   migrating into the tissues
5. Mobile and phagocytotic
6. Mediate anti-parasitic response and type I hypersensitivity
   reactions (allergy)

Basophils and Mast Cells

1. Comprise less than 1% of total WBCs
2. Single lobed nucleus and heavily granulated cytoplasm
3. Non-phagocytic
4. Support mast cell function in tissues, mediate Type I
   hypersensitivity reactions
5. Mast cells - cytoplasmic granules that contains histamine,
   play an important role in allergic response

Lymphocytes Subdivisions

1. Constitutes 20-40% of WBCs and 99% of cells in lymph
2. Continually circulate in the blood and lymph and are capable of
   migrating into tissue space and lymphoid organs
3. Subdivided into 3 classes
   (a) B-lymphocytes
   (b) T-lymphocytes
   (c) Natural killer cells (NK cells)

B-lymphocytes Role

1. Small cells, thin rim of cytoplasm
2. Mature in bone marrow
3. Differentiate into plasma cells to secrete antibodies
4. Mediate humoral arm of adaptive immune response
5. B cells interact with T-helper cells which proliferate and switch to
   different sub-populations
6. Plasma cells are terminally differentiated cells, many die in 1 or 2 weeks

Immunoglobulin Classes

lgM
pentamer
lgG
monomer
Secretory IgA
dimer
IgE
monomer
IgD
monomer
Secretory component
Heavy chains
u
Y
0
ε
δ
Number of
antigen
binding sites
10
2
4
2
2
Molecular weight
(Daltons)
900,000
150,000
385,000
200,000
180,000
Percentage of
total antibody in
serum
6%
80%
13%
0.002%
1%
Crosses placenta
no
yes
no
no
no
Fixes complement
yes
yes
no
no
no
Fc binds to
phagocytes
mast cells and
basophils
Function
Main antibody of primary
responses, best at fixing
complement; the monomer
form of IgM serves as the
B cell receptor
Main blood antibody of
secondary responses,
neutralizes toxins,
opsonization
Secreted into mucus,
tears, saliva, colostrum
Antibody of
allergy and
antiparasitic
activity
B cell
receptor

T-lymphocytes and Sub-populations

1. Morphologically identical to B cells
2. Produced in bone marrow and mature in thymus
3. Mediated cell-mediated arm of adaptive response
4. Several sub-population exist: T helper cells (CD4), cytotoxic T cells
   (CD8) and Natural killer T cells (NKTs)
5. B and T cells form memory cells

Natural Killer Cells

1. Larger rim of cytoplasm
2. Cytotoxic cells that kill tumour and virus infected cells
3. Constitute 5-10% of lymphocytes
4. Do not have membrane receptors for antigen but has NK cell receptors
5. Kill by releasing small cytoplasmic granule of proteins (perforin and
   granzyme) -> cause host cells to die by apoptosis

Lymphatic System Overview

1. Immune system consists of immune cells
   that continuously circulate between blood
   and lymphoid organs
2. Lymphatic system consists of lymphoid
   tissues and organs and circulating clear
   fluid called lymph
3. Site of initiation of adaptive immune
   response

Lymphoid Organs

1. Lymphoid organs are either primary
   (central) or secondary (peripheral)
2. Primary lymphoid organs:
   . Major sites of lymphocyte development
   i.e. thymus and BM
3. Secondary lymphoid organs:
   · Spleen, lymph nodes, mucosal-
   associated lymphoid tissues (MALT)
   including tonsils and Peyer's patches

Fig 1. The lymphoid organs in adults
Primary lymphoid organs
Secondary lymphoid organs
Neck (cervical)
lymph nodes
Thymus
Armpit (axillary)
lymph nodes
Spleen
Peyer's patches
Red bone
marrow
Groin (inguinal)
lymph node