Immunology

Shimelis Teshome (BSc MLS)

 Definitions
• Immune system = cells, tissues, and molecules that
mediate resistance to infections
• Immunology = study of structure and function of the
immune system
• Immunity = resistance of a host to pathogens and their
toxic effects
• Immune response = collective and coordinated
response to the introduction of foreign substances in an
individual mediated by the cells and molecules of the
immune system
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 Overview of the immune system

 We are constantly being exposed to infectious

agents
 In most cases, we are able to resist these
infections.
 It is our immune system that enables us to
resist infections.
 Immunity:- The state of protection from
infectious disease

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 Organs of the Immune System

•They can be distinguished by function as the primary and secondary

lymphoid organs

Primary (central) lymphoid organs:- where maturation of lymphocytes

takes place.
»Bone marrow
»Thymus
»Secondary
secondary lymphoid organs:- trap antigen and provide sites for mature
lymphocytes to interact with that antigen
»Lymph nodes
»Spleen
»Payer’s patches
»Appendix
»Lymphatic vessels
»Tonsils and adenoids
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 Hematopoiesis

– Embryonic yolk sac during the first weeks of

development
– Fetal liver and then to the spleen:- 3rd -7th months
of gestation.
– By birth bone marrow is the main site of
hematopoisis

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 Hematopoiesis

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 Cells of the Immune System

•Lymphocytes
– T-lymphocytes
– B-Lymphocytes, plasma cells
– natural killer lymphocytes
•Monocytes, Macrophage
•Granulocytes
– neutrophils
– eosinophils
– basophils

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 Cells of the Immune System

• Lymphocytes are the central cells of the immune system and

responsible for
– Adaptive immunity (diversity, specificity, memory, and self/nonself
recognition)

• The other types of white blood cells play important roles

– engulfing and destroying microorganisms
– presenting antigens, and

– secreting cytokines

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 Lymphocytes

• Lymphocytes constitute 20%–40% of the

body’s white blood cells and 99% of the cells
in the lymph
• Lymphocytes continually circulate in the
blood and lymph, tissue spaces and lymphoid
organs
• Populations (T cells, B cells, and natural
killer cells)

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 T-lymphocytes

• The effector cells of the T-cell lineage include the

cytokine-secreting T helper cell (TH cell) and the T
cytotoxic lymphocyte (TC cell).
• Some of the progeny of B and T lymphoblasts
differentiate into memory cells.
– The persistence of this memory cells is responsible for
life-long immunity to many pathogens.
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 B-Lymphocytes, plasma cells
• The proliferation and maturation.

• Mature B cells are definitively distinguished from other

lymphocytes by their synthesis and display of membrane-
bound immunoglobulin (antibody)
• All clonal progeny from a given B cell secrete antibody
molecules with the same antigen-binding specificity.
• Plasma cells are terminally differentiated cells, and many die
in 1 or 2 weeks.

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 natural killer lymphocytes
• Play an important role in host defense both against tumor cells and
against cells infected with some viruses.
• Constitute 5%–10% of lymphocytes in human peripheral blood

• Do not express the membrane molecules and receptors that distinguish

T- and B-cell lineages.
• NK cell employs NK cell receptors to distinguish
– abnormalities, notably a reduction in the display of class I MHC molecules and

– the unusual profile of surface antigens displayed by some tumor cells and cells
infected by some viruses

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 Monocytes, Macrophage
• Monocytes circulate in the bloodstream for
about 8 h, during which they enlarge; they
then migrate into the tissues and differentiate
into specific tissue macrophages
• This tissue specific monocyte is called
macrophage.

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 Monocytes, Macrophage
• Differentiation of a monocyte into a tissue
macrophage involves a number of changes:
– The cell enlarges 5- to 10 fold
– its intracellular organelles increase in both
number and complexity
– acquires increased phagocytic ability,
– Produces higher levels of hydrolytic enzymes,
and begins to secrete a variety of soluble factors.

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 Monocytes, Macrophage
• Macrophages are dispersed throughout the body.
– Fixed macrophages and motile/free or wandering,
macrophages.

• Are named according to their tissue location:

– Alveolar macrophages in the lung
– Histiocytes in connective tissues
– Kupffer cells in the liver
– Mesangial cells in the kidney

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 Granulocytic Cells

• Classified as neutrophils, eosinophils, and basophils on the basis of

cellular morphology and cytoplasmic staining characteristics
• Neutrophils, which constitute 50%–70% of the circulating white blood
cells, are much more numerous than eosinophils (1%–3%) or basophils
(1%).
 NEUTROPHILS
• They are the first to arrive at a site of inflammation.
• The resulting transient increase in the number of circulating
neutrophils, called leukocytosis, is used medically as an indication of
infection.

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 Granulocytic Cells
 EOSINOPHILS
• They play a role in the defense against
parasitic organisms
• The secreted contents of eosinophilic granules
may damage the parasite membrane.
 BASOPHILS
• Basophils are nonphagocytic granulocytes that
function by releasing pharmacologically active
substances from their cytoplasmic granules.
• These substances play a major role in certain
allergic responses.

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 Components of Immunity

Immune system

Adaptive
Innate (nonspecific) (specific)
1st line of defense 2nd line of defense

Cellular components Humoral components Cellular components Humoral components

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 Innate Immunity

Lysozymes

1. Components Mucus
a. Biochemical (physiologic
barriers) Cilia: trachea
• enzymes, C’, etc.
Sebaceous glands
• secretions
• pH Skin
b. Physical (anatomic barriers)
• Skin Acid in
stomach
• Mucous membrane
• cilia Commensal
c. Cells organisms in
gut & vagina
• Phagocytes, NK

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The Response of the Innate immune system

1. Non-inflammatory reaction: (body’s static

defenses) skin, gastric pH, lysozyme in tears,
saliva, mucous
2. Local inflammation: promotes migration of
phagocytes and plasma protein into infected
tissues
The phagocytes respond to surface structures
present in large groups of microorganisms
(peptidogcan, mannose)
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 Anatomical barriers- mechanical
System/Organ Cell type Mechanism
Skin Squamous Physical barrier
epithelium Desquamation
Mucous membranes Non-ciliated
epithelium (e.g. GI Peristalsis
tract)
Ciliated epithelium Mucociliary elevator
(e.g. respiratory
tract)
Flushing action of
Epithelium (e.g. tears, saliva, mucus,
nasopharynx) urine

Skin, the cough reflex, sneezing, mucus, associated cilia

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 Anatomical barriers- chemical
System/Organ Component Mechanism
Skin Sweat Antimicrobial fatty
acids
Mucous HCl (parietal cells), tears Low pH
membranes & saliva Lysozyme &
phospholipase A
Defensins (respiratory & Antimicrobial
GI tract)

Surfactants (lung) Opsonin

Chemical influences:
acidity (pH 5.6) of sweat, sebaceous glands, vagina (pH 5) and stomach (pH 1),
enzymes present in the skin and stomach, tears
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 Anatomical barriers- biological
System/Organ Component Mechanism
Skin and mucous Normal flora Antimicrobial substances
membranes (GI) (metabolic products like fatty
acids, bacteriocins, etc.)
Competition for nutrients and
colonization
Non-specifically stimulating
the immune system

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 Humoral components
Component Mechanism
Complement Lysis of bateria and some viruses
Opsonin
Increase in vascular permeability
Recruitment and activation of phagocytic
cells
Coagulation system Increase vascular permeability
Recruitment of phagocytic cells
B-lysin from platelets – a cationic
detergent
Lactoferrin and Compete with bacteria for iron
transferrin
Lysozyme Breaks down bacterial cells walls
Cytokines Various effects

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 Complement
• A series of serum proteins that are involved in inflammation
• Are normally present
• 9 are activated in the classical pathway by antibody
• Others are activated by foreign substances and are in the
alternative pathway
• Functions:
– opsonization, chemotaxis, lysis of cells

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 Overview of main components and effector actions of complement

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 Phagocytosis and Intracellular killing
• Three phagocytic cells:
– Macrophages,
– Neutrophils,
– immature DCs
• Can recognize, ingest and destroy pathogens
without the aid of the adaptive immune system
• Attracted by chemotaxins
– Complement components
– Coagulation cascade proteins
– Bacterial and viral products
– Mast cell, lymphocyte, macrophage,
neutrophil products

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 Cellular components
Cell Mechanism
Neutrophils Phagocytosis and intracellular killing
Inflammation and tissue damage
Macrophages Phagocytosis and intracellular killing
Extracellular killing of infected or altered
self targets
Tissue repair (by phagocytosis of cellular
debris, release of growth factors and
stimulation of fibroblasts to form a scar)
Antigen presentation for specific immune
response
NK Killing of virus-infected and altered self
targets
Eosinophils Killing of certain parasites

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Innate response to virus infection and altered
self
• Infected or altered self
(transformed) cell down regulated
NK cell
MHC
• NK does not receive inhibitory
signal NK R
Inhibitory R
• Signals kill infected cell
No MHC

Infected/transformed cell

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Innate response to extracellular
microorganisms (parasites)
• Activated eosinophils release granule
components
– Major basic protein
• Major component of granules
Eosinophil – Eosinophil peroxidase
• Cationic hemoprotein
– Eosinophil cationic protein
• ribonuclease

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 Natural and adaptive immune mechanisms
Humoral
Cellular

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 Adaptive and Innate - Interactions
Infectious Innate Immunity No
Exposure holds Disease

Innate Immunity
Fails
Adaptive Immunity
Specific memory

Disease

Adaptive Second Infectious

Recovery Exposure
Immune system
Same organism 33
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