Chapter One: Overview of the Immune System

Immunology
- is a science that examines the structure and function of the
immune system
– Study of the components and function of the immune
system

Immune System
– Molecules, cells, tissues and organs which provide non-
specific and specific protection against
• Microorganisms
• Microbial toxins
• Tumor cells
 Cont’d

“Immunity”
 All the mechanisms used by the body as
protection against environmental agents that
are foreign to the body.

2 major functions -
• protects against infection
• causes inflammation
 Cont’d

 Immunity can be
• natural or artificial
• innate or acquired=adaptive
• either active or passive.
 Cont’d

 Active natural (contact with infection):

• develops slowly, is long term, and antigen specific.
 Active artificial (immunization):
• develops slowly, lasts for several years, and is specific to the
antigen for which the immunization was given.
 Cont’d

 Passive natural (trans placental = mother to child):

• develops immediately, is temporary, and affects all antigens to
which the mother has immunity.
 Passive artificial (injection of gamma globulin):
• develops immediately, is temporary, and affects all antigens
to which the donor has immunity.
 PRINCIPAL FUNCTION OF THE IMMUNE SYSTEM

 To protect humans from pathogenic microorganisms

• Pathogenic microorganisms (Pathogens)

– Microorganisms capable of causing infection and/or disease

• Infection
– Ability of pathogen to enter host, multiply and stimulate an
immune response/disease

• Disease
– Clinical manifestations associated with infection
 Innate Mechanisms (Innate immunity)
• Inborn immune system that identify and eliminating
pathogens that might cause infection.
– First line of defense
– Non-specific
– cannot divide or reproduce on their own, but are the
products of multipotent hematopoietic stem cells present
in the bone marrow
– -eg.Natural killer cells, mast cells, eosinophils, basophils;
and the phagocytic cells including macrophages,
neutrophils and dendritic cells
 Responses of the innate immune system
• Phagocytosis – phagocytic cells engulf, or eat, pathogens or
particles.
• Inflammation is irritation stimulated by chemical factors
released by injured cells and serves to establish a physical
barrier against the spread of infection, and to promote
healing of any damaged tissue following the clearance of
pathogens.
• Complement system is biochemical cascade that attacks the
surfaces of foreign cells which triggers a rapid killing response
of pathogens by antibodies.
 Cont’d

 Adaptive immunity
• a high degree of specificity as well as “memory.”

• Formed within five or six days after the initial exposure to that
antigen

• Second line of defense

ORIGIN OF CELLS OF THE IMMUNE SYSTEM

• Derived from common progenitor cell in bone

marrow
– Pluripotent hematopoietic stem cell
• Progenitor Stem Cells
– Erythroid lineage
• Erythrocytes and Megakaryocytes
– Myeloid lineage
• Monocyte/macrophage, dendritic cells, PMN’s, mast cells
– Lymphoid lineage
• Small and large lymphocytes
CELLS OF INNATE AND ADAPTIVE IMMUNITY

• Myeloid Lineage
– Neutrophil
• Principal phagocytic cell of innate immunity
– Eosinophil
• Principal defender against parasites
– Basophil
• Functions similar to eosinophils and mast cells
– Referred to as
• Polymorphonuclear leukocytes (PMN’s)
– Nuclei are multilobed (2 to 5)
• Granulocytes
– Cytoplasmic granules
CELLS OF INNATE AND ADAPTIVE IMMUNITY

• Myeloid lineage
– Monocytes
• Leukocytes with bean shaped or brain-like convoluted
nuclei
• Circulate in blood with half life of 8 hours
• Precursors of tissue macrophages
– Macrophages
• Mononuclear phagocytic cells in tissue
• Derive from blood monocytes
• Participate in innate and adaptive immunity
CELLS OF INNATE AND ADAPTIVE IMMUNITY

• Myeloid lineage
– Dendritic cells
• Cells with dendriform (star shaped) morphology
• Interdigitating reticular cells (synonym)
• Capture and present antigens to T lymphocytes
– Mast cells
• Located in mucous membrane and connective tissue
throughout body
• Major effector cell in allergy
• Modulation of initial immune response
Cont’d
• Lymphoid Lineage
– Large lymphocytes (large granular lymphocytes)
• Natural killer (NK) cells (CD16, CD56)
• Innate immunity to viruses and other intracellular
pathogens
• Participate in antibody-dependent cell-mediated
cytotoxicity (ADCC)
– Small lymphocytes
• B cells (CD19)
• T cells (CD3, CD4 or CD8)
• Adaptive immunity
– Lymphocytes refers to small lymphocytes
 Discovery of Acquired Immunity
 In 1798, an English physician
named Edward Jenner carried
out
an experiment that marks the
beginning of the study of
immunology. 1749-1823

 The discovery of acquired

immunity is credited to
Edward Jenner.
 Cont’d

I. Introduction
 Smallpox: a disease caused by a virus
(variola). Killed more than 400,000
Europeans annually during 18th C;
a third cause of all blindness.
 Observation:
o People who didn’t die from such life-
threatening disease were subsequently
more resistant to the disease than were
people who had not been exposed to it.
o The milkmaids who had caught
“cowpox” rarely caught “smallpox”
 Hypothesis: Exposure to cowpox
provides protection against a deadly
disease smallpox
 Cont’d

II. Study design (Material & Methods)

 Study subjects were humans
 Pus from a lesion of a milkmaid who had cowpox
 Inoculated a boy with the pus (wait for some weeks)
 Then, deliberately exposed the boy to smallpox
III. Results
 The exposure failed to cause the disease smallpox
 The boy was protected from smallpox
IV. Discussion
 Not fully discussed in those days (he did not know about the virus,
immunity)
 Smallpox and cowpox are caused by two slightly different but basically
similar viruses.
 Patients with the cowpox virus mounted a defense that was also effective
against a later infection of the smallpox
 Cont’d

V. Conclusions and Recommendations

 Patients with a mild form of pox (cowpox) could be protected
from a deadly disease smallpox.
 It is possible to protect people from smallpox by exposing
them to cowpox
 Further studies were recommended to investigate the causative
agent and the mechanism how the already exposed people
become resistant to the disease.
 Based on his findings, It is already known that :
o Exposure to a harmless microbe (or weekend microbe) in
order to confer resistance to a dangerous one is called
vaccination (vacca means cow)
o Smallpox had been globally eradicated in 1980’s through
vaccination program.
 1.3. Organs and Cells of the Immune System
• Lymphoid tissues and organs
– Primary
• Development and maturation of lymphocytes
• Bone Marrow (B cells) and thymus gland (T cells)
– Secondary
• Mature lymphocytes meet pathogens
• Spleen, adenoids, tonsils, appendix, lymph nodes, Peyer’s
patches, mucosa-associated lymphoid tissue (MALT)

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Organs of the immune cont…

• Lymph
–Fluid and cells in lymphatic vessels

• Lymphatic vessels
–Collect and return interstitial fluid to blood
–Transport immune cells throughout body
–Transport lipid from intestine to blood

• Lymph nodes

• Kidney shaped organs at intervals along lymphatic vessels

 These structures are collectively referred to as the lymphoid system.
 The lymphatic system is a network running throughout the body, consisting of fluid called
lymph, tubes or vessels that transport the lymph, and other organs that contain ‘lymphoid’
tissue.
 Afferent lymphatic vessels: carry lymph to the lymph node
 Efferent lymphatic vessels: carry lymph away from the lymph node

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Primary lymphoid organs (PLOs)
 Bone marrow:

 Gives rise to all of the lymphoid cells that migrate to

the thymus and mature into T cells, as well as to the
major population of B cells.
 B cells differentiate and mature in the bone marrow.
 Bone marrow is composed of hematopoietic cells of
various lineages and maturity, packed between fat cells,
thin bands of bony tissue (trabeculae), collagen fibers,
fibroblasts and dendritic cells.
 Comparable to Bursa (Bursa of Fabricius)
in birds
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Primary lymphoid cont…
 Thymus
 A lymphocyte-rich, bi-lobed, encapsulated organ located
behind the sternum, above & in front of the heart.
 The site of T cell differentiation and maturation.
 The term ‘T cell’ means thymus-derived cell and is used to
describe mature T cells.
 The activity of the thymus is maximal in the fetus and in
early childhood and then undergoes weaken at puberty
although never totally disappearing.
 It is composed of cortical and medullary epithelial cells,
stromal cells, interdigitating cells and macrophages.
 These ‘accessory’ cells are important in the differentiation of
the immigrating T cell precursors prior to their migration into
the secondary lymphoid tissues.
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Primary lymphoid cont…

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 Each lobe is separated into lobules by fibrous septa
 Each lobule consists of two compartments, the cortex
and medulla
 The cortex makes up 85-90 % of the thymus and 90-
95 % of the cells in the thymus are found in the
cortex
 The medulla is less closely packed with thymocytes
than the cortex and contains structures of tightly
packed epithelial cells called Hassall’s corpuscles.
 Thymocytes in cortex are immature and
progressively differentiate into T cells.
 These cells migrate to the medulla where further
maturation occurs, then they excite as mature T cells
into the blood stream.
 Secondary lymphoid organs (SLOs)
 Once lymphocytes are mature, they leave the PLOs
and are now capable of responding to antigens.
 Antigens and lymphocytes will encounter each other
in the SLOs.
 Have two major functions: highly efficient in
trapping and concentrating foreign substances and are
the main sites of production of antibodies and
induction of T-cells (Immune response).
 Immune responses generated in the secondary
lymphoid tissues when lymphocytes interact with
antigens and accessory cells.
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 Secondary lymphoid cont…

 Lymph nodes
 Are small, highly organized, encapsulated, bean-shaped organs.
 Distributed throughout the body (armpit, groin, neck, stomach etc.)
 Involves in collecting the extracellular fluid (lymph) from the tissue
and returning it to the blood
 The afferent lymphatic vessels which drain fluid from the tissue
also carry antigens from sites of infection to the lymph nodes.
 The efferent lymphatic vessels pass from each lymph node to more
central chains of nodes and eventually to the thoracic duct where
the lymph re-enters the blood stream.
 Subdivided into a cortex and medulla and made up of largely of
lymphocytes and accessory cells.
 The cortex is compartmentalized into B and T cell areas.
 They are important centers for initiation and development of
immune responses.
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Secondary lymphoid cont…

 The cortical region contains primary lymphoid follicles

 Following antigenic stimulation, these structures enlarge to
form secondary lymphoid follicles with germinal centers
that contain dense population of lymphocytes (B cells) that
are undergoing mitosis.
 The deep cortical area (para-cortical region) contains T
cells and dendritic cells.
 The lymph nodes:
o Act as junction b/n the lymphatic and circulatory system
o Provide a site for phagocytosis and antibody production
o Support the induction, proliferation and differentiation of
lymphocytes.

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The structure of a lymph node

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Secondary lymphoid cont…

 Spleen
 The largest of the SLOs; major organ in which antibodies
are produced
 Composed of white pulp, rich in lymphoid cells, and red
pulp which contains many sinuses, erythrocytes and
macrophages.
 50% of spleen cells are B-cells, 30 -40 % are T- cells
 The white pulp is divided into an inner region called the
periarteriolar lymphoid sheath which contains mostly T
cells & a surrounding B cell corona.
 Filter and concentrate pathogens
 Clearing of aged, defected and died cells
 Site for phagocytosis and antibody production
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The structure of spleen
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Secondary lymphoid cont…

 Mucosa associated lymphoid tissues (MALT)

• Primary portals of entry for pathogens
– Respiratory tract
– Gastrointestinal tract

– Bronchial-associated lymphoid tissue (BALT)

– Gut-associated lymphoid tissues (GALT)
• Tonsils, adenoids, appendix, Peyer’s patches in the small intestine.

o Includes the adenoids, tonsils, appendix and the specialized structures called
Peyer’s patches
o Collect antigens from the epithelial surface of GIT
o Similar aggregates of lymphocytes protect the respiratory epithelium:
bronchial-associated lymphoid tissues (BALT).

• Pathogens are directly transferred across mucosa by “M” cells35

 Hematopoiesis: Development of blood cells
 Hematopoiesis is the process of blood cell formation and
maturation of immature precursor cells into mature blood cells. 
 A single type of stem cell gives rise to all the mature blood
cells in the body.
 This stem cell is called the pluripotential (pluripotent) stem
cell that are present in the bone marrow.
 Bone marrow has a vascular compartment and an extravascular
compartment. 
 The vascular compartment is supplied by a nutrient artery
 Hematopoiesis takes place in the extravascular compartment. 
 The extravascular compartment consists of a stroma of reticular
connective tissue and a parenchyma of developing blood cells,
macrophages and fat cells.
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 The high activity of the bone marrow is demonstrated by its
daily output of mature blood cells:
o2.5 billion erythrocytes,
o2.5 billion platelets,
o50-100 billion granulocytes.
o3.5 billion lymphocytes and monocytes
 The pluripotent stem cells multiply to produce more
pluripotent stem cells, thus ensuring the steady and lasting
supply of stem cells (self-renewal). 
 Some of the pluripotent stem cells divided to produce two
more specialized types of stem cells (differentiation):
oA lymphoid progenitor which gives rise to T and B lymphocytes
oA myeloid progenitor which gives rise to granulocytes
(leukocytes), erythrocytes and megakaryocytes.  
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Hematopoietic stem cells produce cells in blood and lymph
 Monocytes: Macrophage precursors
 Origin: bone marrow
 Larger and scarcer than lymphocytes
 Identifiable in blood smears by their lack of granules and a large,
horseshoe-
shaped nucleus
 Present in blood circulation for short (24hr)
 Function: to become macrophages
 Leave the bloodstream, they enter the connective tissues to become
macrophages
 Macrophages: Irregular shaped, large (‘big eaters’) cells
 Function : phagocytise pathogens & unwanted particulate matter,
produce cytokines, that are required for the inflammatory and40
Neutrophils:
 Origin and maturation: Bone marrow
 Function: Phagocytosis and killing of microorganisms
 Where: in blood circulation
 Sites of function: infection sites
 Short life span (4 days)
 Known by such names as polymorphonuclear Leukocytes (PMN)
 has small cytoplasmic granules and a complex, multilobed
nucleus (segmented nucleus)
 Their granules become lysosomes, capable of enzymatically
digesting pathogens. 41
Eosinophils: worm (parasite) killers
 Origin: bone marrow
 Characterized by a dumbbell-shaped nucleus and large,
prominent, red (eosinophilic) granules
 Common in the bloodstream than neutrophils.
 Function: killing of antibody-coated parasites through release of
killing mix (cytotoxic granules)
 Effector machinery: cytotoxic granules, cytokines and chemokines
 Perform their function in connective tissue

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Basophils: relatives of mast cells and eosinophils
 Origin : bone marrow
 the rarest of all granulocytes found in blood
 Function: important effector cells in allergic disorders and
immune responses to parasites
 A large cell filled with prominent blue (basophilic) granules
 It is generally thought that they leave the bloodstream, enter the
connective tissues, and become mast cells.
 Sensor: IgE receptor
 Effector machinery: cytotoxic granules, cytokines and
chemokines (histamine, heparin).
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Mast cells: parasite killers
 Origin : bone marrow
 Function: to kill parasites
 Sensor: IgE receptor
 Effector machinery: cytotoxic granules, cytokines and
chemokines (histamine, heparin)
 Found in connective tissues
 Mast cells degranulate and discharge their contents, which is not
only seem to cause capillaries to become leaky but also appear to
impede blood clot formation.
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 T -lymphocytes: master regulators of the immune system
 Origin: Bone marrow
 Maturation: Thymus
 Differentiation to effector cells in secondary lymphoid tissues
 Antigen receptors (TCR)
 Function: regulates humoral and cell-mediated immune
responses (cytotoxic T cells, helper T-cells, Memory T cells)
 Mechanisms: cytokines, cytotoxic granules.

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 B lymphocytes: antibody producers
 Origin and maturation: Bone marrow
 Differentiation to plasma B cells in secondary lymphoid tissues
 Antigen receptors: BCR (cell surface immunoglobulins).
 Function: Production of antibodies (IgM, IgE, IgA, and IgG)
 Regulated by T cells

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B lymphocytes

Antigens+ T cell help

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NK cells: natural killers
 Origin : Bone marrow
 Looks lymphocytes
 Antigen receptors: No

 Function: Kill tumor and virus-infected cells

 Effector machinery (weapons): perforins and granzymes

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Proportion of blood cells in peripheral blood circulation
Figure 1-12

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