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2 marks for class participation

1 - 2 marks for seminar

The rest for exam

Fundamentals of Immunology

What is Immunology ?
History of Immunology
Immunity
The Immune System

What is Immunology ?
:
The term derives from the Latin word immunitas, or
immunity.
In Roman times meant public officials could be
exempt (or protected) from legal prosecution while
they were in office.
Since Roman times it has come to mean the
protection of the body against infectious agents, as
well.

What is Immunology ?
Immunology involves the study of our body's
defenses against infectious diseases, i.e the study of
our bodys immune system.
The study of immunology covers many fields,
particularly cell biology, biochemistry, microbiology,
virology, genetics and medicine. It is an exciting
field of study, both today and certainly into the
distant future.

History of Immunology
430 BC - Thucydides (Greece) observes
immunity to the plague.
15th Century First attempts at
immunization in Turkey : Turks injected
pustular material into the vein of the
person desiring immunity to smallpox.
Lady Montague (wife of the British
ambassador to Turkey) introduced this
technique to the western world.

History of Immunology
1798 Edward Jenner (England) used
cowpox inoculum to immunize against
smallpox.

1880 Pasteur :Father of immunology.

Attenuation by ageing of microbes
Growing microbes at a temperature other
than at the temperature normal for
pathogenesis
and by drying.

Cholera organism, Anthrax bacillus and

rabies virus

Immunity
Immunity is the ability of the body to :
Resist invasion by foreign organisms

Eliminate those organisms (once they enter the

body)
Neutralize and eliminate potentially damaging
agents produced by those organisms, and
(in its more advanced development) survey the body
for rogue elements of the body itself, such as cancer
cells

Pathogens and the Immune System

The tissues and fluids of the human body are much
like a warm culture flask filled with a nutrient-rich
solution.
Therefore, it may be surprising that the interior of the
body--including blood, muscles, bones, and organs--is
generally sterile.
If not, microbes would simply degrade our tissues,
just as they readily decompose the carcass of a dead
animal.

The Immune System

Few systems in nature are as complicated as the

human immune system.

It exists apart from, and works in concert with, every

other system in the body.

When it works, people stay healthy. When it
malfunctions, terrible things happen.

The Immune System

Immune System

Innate
(Nonspecific)
1o line of defense

Cellular Components

Humoral Components

Adaptive
(Specific)
o
2 line of defense
Protects/re-exposure

Cellular Components

Humoral Components

The Immune System

Immune System

Innate
(Nonspecific)
1o line of defense

Innate Immunity
The innate, non-specific, immune defenses come into
play:
Fairly quickly
Whether or not there has been a prior exposure to the
offending agent.

The simplest way to avoid infection by

microorganisms is to prevent their gaining access to

the body.
A well-built fortress with a surrounding moat

Innate Immunity
Anatomical barriers
Mechanical factors
Chemical factors
Biological factors

Innate Immunity Mechanical Factors

An intact skin :
Almost impermeable to most infectious agents.
In addition : low pH from the lactic acid in sweat makes the
surface inhospitable.

Mucus on mucous membranes helps wash away

microbes
In some cases via active propulsion such as via the lungs
mucocilliary escalator.

Innate Immunity Chemical Barriers

System or Organ
Skin

Component
Sweat

Mucous Membranes HCl (parietal cells)

Tears and saliva

Mechanism
Anti-microbial fatty
acids

Low pH
Lysozyme and
phospholipase A

Defensins (respiratory & GI Antimicrobial

tract)
Sufactants (lung)

Innate Immunity Biological Barriers

System or Organ

Skin and mucous

membranes

Component

Normal flora

Mechanism

Antimicrobial
substances
Competition for
nutrients and
colonization

The Immune System

Immune System

Innate
(Nonspecific)
1o line of defense

Humoral Components

Innate Immunity - Humoral components

American Medical Dictionary Definition :
The component of the immune response involving the
transformation of B cells into plasma cells that produce and

secrete antibodies to a specific antigen

The correct definition :

Humoral : Of or Related to Humor
Humor : any fluid or juice of an animal or plant

Innate Immunity - Humoral components

Humoral components
Complement
Coagulation system
Cytokines

Innate Immunity - Humoral components

The Complement System
The complement system found in the blood of
mammals is :
Complex
Multicomponent (composed of about 26 proteins)
Acts as a cascade
The "complement cascade" is

Constitutive and non-specific

It must be activated in order to function.

Innate Immunity - Humoral components

The Complement System
The functions of complement proteins include:
Making bacteria more susceptible to phagocytosis

(opsonization)
Directly lysing some bacteria and foreign cells
Producing chemotactic substances

Innate Immunity - Humoral components

The Complement System

Opsonization signals
phagocytes to engulf
materials including
bacterial cells.

C3b serves as
an Opsonin.

C3b binds to all cells but is actively

removed from body cells.

Innate Immunity - Humoral

components
Humoral components
Complement
Cytokines
Interferons
, ,

Interleuknis
E.g. IL 1, IL 2, IL 6, IL 12

TNF (Tumour Necrosis Factor) : Rheumatoid

Arthritis, Autoimmune diseases

Coagulation system

Cytokines - Interferon

Cytokines - Interleukins
The IL 1, IL 6, IL 12 act by :
Activating the monocytes-macrophages and NK cells
Allowing the activation of the mechanisms responsible for
the elevation of the body temperature.

Reducing the capability of replication of the pathogen.

Cytokines - TNF
Tumor necrosis factor (TNF a) is the main trigger of

the inflammatory response.

It has an effect on the local blood vessels
It increases vascular permeability, which leads to the
accumulation of fluid as well as the accumulation of
immunoglobulins, complement and other blood proteins

in the tissue.

The Immune System

Immune System

Innate
(Nonspecific)
1o line of defense

Humoral Components

Cellular Components

Innate Immunity
Cellular Components

Cells of the Immune System

(Innate & Acquired)
All derive from the bone marrow
Two main lineages derive from the bone
marrow hematopoietic stem cells:

Myeloid lineage :
Monocytes, Macrophages, Dendritic cells,
Megakaryocytes, Granulocytes

Lymphoid lineage :
T cells, B cells, Natural Killer (NK) cells

Leukocytes (White Blood Cells)

Phagocytic Leukocytes

Eosinophils are involved

in allergic responses,
inflammation, and
release of Histamine;
Histamine is released by
Basophils.
Phagocytes

Innate Immunity Neutrophils

Innate Immunity Neutrophils

Primary Innate Immunity Effector Cells
Size : 12 15 m
Characteristic nucleus (Multi-lobe)
Abundant storage Granules (3 stages)
Grow to full maturity in bone marrow (~
60% marrow hematopoietic activity)

Released into blood where they die by

apoptosis after an average 12 hours. If
activated and enter tissue, survive for
1-2 days.
Cell surface receptors for
chemotactants, e.g. IL-8, IFN-gamma,
and C5a.

50 bn circulating in an adult, ~ 70% of

leukocytes
~ 10^11 (100 bn ) produced daily.
Terminally differentiated, i.e. do not
replicate.

Monocytes --> Macrophages

Innate Immunity - Monocyte

Macrophages
Macophage - Greek : Big Eater
Relatively large (12 - 20 m)
Characteristic nucleus (kidneyshaped)
Substantial supply of lysosomes
1-6% nucleated blood cells

After release circulate for ~1 day and

then settle in a tissue
Can digest more than 100 bacteria
before they finally die due to their
own digestive compounds
Found in nearly all tissues/organs
(Distinct morphological features : eg.
Osteoblasts in bones)

Phagocytosis - Initiation
Attachment via
Receptors:
IgG Fc
Complement
Toll-like

Phagocytosis

Attachment
Pseudopod extension
Phagosome formation
Granule fusion
Phagolysosome formation

Major cytokines
secreted by
activated
macrophages
in response to
bacteria

The Immune System

Immune System

Innate
(Nonspecific)
1o line of defense

Humoral Components

Cellular Components

Adaptive
(Specific)
o
2 line of defense
Protects/re-exposure

Adaptive (Specific) Immunity

Matures throughout life, developing the effective
response against specific invaders as each is
encountered.
Has memory

A greatly enhanced response to reexposure.

The Immune System

Immune System

Innate
(Nonspecific)
1o line of defense

Humoral Components

Cellular Components

Adaptive
(Specific)
o
2 line of defense
Protects/re-exposure

Cellular Components

Lymphocytes Development

Lymphocytes Development
B-Lymphocyte development entirely in bone

marrow.
T-Lymphocytes develop from immature

precursors (cells) that leave the bone marrow

and develop into mature T-lymphocytes in
Thymus.

Lymphocytes Development
Mature lymphocytes emerging from bone
marrow or thymus are in quiescent or resting
state :
They are mitotically inactive
They can NOT carry out immunological functions

When dispersed into the bloodstream, these

nave lymphocytes migrate efficiently into
various secondary lymphoid organs.

Nave

Lymphocytes Development
Secondary lymphoid organs maximize
encounters between lymphocytes and foreign
substances. Most immune responses launched
from these sites.
Nave lymphocytes have short life span.
If activated / stimulated by receiving signal
indicating presence of foreign substance or
pathogen
Undegoes several successive rounds of cell
division over several days.

Lymphocytes Activation
Lymphocyte activation
leads to both cell division
and differentiation.
At each cell division,
individual cells can cease
dividing and become
Memory (M) or Effector
(E) cells.

Lymphocytes Differentiation
Memory cells
Following activation and cell division, some progeny

cells revert to the resting state to become Memory

Lymphocytes.
Memory lymphocytes resemble nave cells but :
Are specific to an antigen
Can survive for many years.

Lymphocytes Differentiation
Memory cells
Memory lymphocytes make up a large proportion of
the immune system cells.
Like nave cells, memory lymphocytes can undergo
further cycles of activation and cell division.

Lymphocytes Differentiation
Effector cells
The other progeny of an activated nave
lymphocyte differentiate into effector cells.
Effector cells survive for only a few days.
During their short life-span they carry out
specific defensive activities against foreign

invaders.

Organs and Tissues of the Immune

System
PRIMARY ORGANS:
(lymphocyte production
and differentiation)

BONE MARROW: B LYMPHOCYTE

THYMUS: T LYMPHOCYTE

SYSTEMIC:

SECONDARY
ORGANS: (capture and
processing of antigens)
MUCOSAS:

LYMPH NODES
SPLEEN

GROUPED:
TONSILS
PEYER'S PATCHES
ISOLATED:
FOLLICLES

Organs and Tissues of the Immune System

Lymphocyte Recirculation
Nave lymphocytes
enter lymph nodes
from the blood circulation

Lymphocytes return
to blood
via the thoracic duct

Antigens from infected area

go to lymph nodes
via the lymphatic system

B-Lymphoctyes

B-Lymphocytes

B-Lymphocytes
109 B-lymphocytes generated daily.

The defining feature of B-cells : Their ability to

synthesize proteins called Immunoglobulins.

(No other cells produces these).

Immunoglobulins : An extremely diverse family
of proteins.

B-Lymphocytes
Mature B-cells can express immunoglobulins in
two different forms:
In resting (nave or memory) B-lymphocytes,
Immunoglobulins :
Expressed only on the cell surface.
Act as receptors for specific antigens.

B-Lymphocytes
Each resting lymphocyte may express tens of

thousands of membrane immunoglobulins on its

surface.
The effector cells (called plasma cells) are uniquely
speciallized to secret large amounts of
immunoglobulin proteins into their surrounding fluids.

Life Cycle of B cells Four

phases
Tens of billions each day

Primary
lymphoid tissue

Secondary
lymphoid tissue

B-Lymphocytes & 2 Organs

T-Lymphoctyes

T-(Thymus-dependent)
lymphocytes

T Lymphocytes
Receptors
T-cells do NOT express immunoglobulins
They detect presence of foreign substances by
means of T-cell recepetors (TCR).
TCR : A heterogeneous class of membrane
proteins.

T Lymphocytes
Receptors
TCRs closely related to immunoglobulins :
The ability to detect specific small molecular
ligands (antigens).
Unlike immunoglobulins NOT secreted.

T Lymphocytes
How they work
Unlike B-cells, can only detect a foreign
substance if it is :
first cleaved into small peptides,
then displayed on the surface of a host cell, called
Antigen Presenting Cell (APC) .

Certain cell types specially-adapted for this

purpose : Macrophages, B-lymphocytes and
Dendritic Cells .

T Lymphocytes
How they work
Have many long, spidery-like cytoplasmic
projections : dendrites

Their shape and other properties make them

extremely adept at antigen presentation at T-cell
activation

Most important APCs.

Professional APCs

Leukocyte Migration and

Localization