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Immunology part 1
Immunology refers to the study of the immune system of organisms and the processes
the host employs in order to maintain homeostasis of its internal environment, when it is “under
attack” by foreign substances/toxins/cells which come either from its internal or external
environment
...

During the long course of evolution, more advanced organisms have developed various
mechanisms which serve to protect them from anything that isn’t identified as intrinsic, or its
own
...
The cells and molecules which are responsible for protection make up the
immune system, and their coordinated activity as a response to threats make up the immune
response
...
Due to this, the need to have some sort of defense mechanism is
absolutely necessary in order to survive
...
It must differentiate between its
own cells and tissue and foreign threats
...

There are two types of immunity:
1
...
Specific immunity (adaptive) – with two components:
a
...

b
...

Both types are components of an integrated immune response in which numerous cells and
molecules function as a cooperative unit
...
Usually, initial contact with a pathogen results in the manifestation

of disease symptoms
...

The functions of both of these immune types are:
1
...
Homeostasis – degradation and removal of dead or damaged cells
...
Surveillance – detection of abnormal cells (most changes occur on cell surfaces)
...
D
...

Middle East – the technique of variolation (the intradermal application of powdered
scabs) became widespread, and eventually became introduced in England, but never
became popular
...

Edward Jenner (1798) – as a student, noticed that milkmaids, who had been infected
with cowpox, were seemingly immune to smallpox
...
Observed cell-mediated
immunity
...

o Germ Theory of Disease – states that microorganisms, pathogens, lead to the
occurrence of disease
...

Roux and Yersin (1885) – described the first toxin, which was isolated from Bacillus
tuberculosis, which was later used by Emil Adolf von Behring and Kitasato to inoculate
animals, who in turn produced an antitoxin, which had a neutralizing effect on the toxin
...

Paul Ehrlich – Humoral Theory of Antibody Function
...

Elie Metchnikoff – The Cellular Theory
...


•

Durham and von Gruber (1896) – agglutination of bacteria cells under the influence of
antiserum
...
It is present in the body as soon as an individual is born, and acts to protect against all
pathogens
...
However, this response is non-specific – it is able to differentiate between foreign
material and the body’s own tissue, and protects against all antigens equally
...
This type of immunity does not result in
immunological memory, as is the case with specific immunity
...
The response is non-specific
in that mechanisms recognize sequences of carbohydrates in bacterial cell walls, but not specific
functional groups
...
The innate response is activated before the adaptive
immune response
...
It consists of the lymphatic organs and tissue, as
well as numerous types of immune cells and chemical mediators
which circulate throughout the body
...


Any foreign substance or toxin
which enters the organism and
results in an immune response
(mainly the production of
antibodies)
...


The main components of the innate immune system:
•
•
•
•

Mechanical barriers – do not allow the penetration of microorganisms → removed from
skin surfaces
...

Circulating cells – carry out phagocytosis and/or produce chemical mediators
...


Mechanical barriers
The most usual places of entry for microorganisms include damaged skin, the
gastrointestinal tract and the lungs
...
The skin and mucous membranes, which lines
body cavities and covers internal organs, are efficient in clearing these surfaces of
microorganisms – via tear fluid, saliva, urine, etc
...
Coughing and sneezing also help to eliminate
pathogens/foreign particles
...

The largest and most efficient physical barrier is the skin
...
Cells located in the
skin include keratinocytes, Langerhans cells (LC), intraepithelial T cells
...

Epidermal Langerhans cells are immature dendritic cells which are able to form
nets and phagocytize antigens which enter via the skin
...


Chemical mediators (secretory molecules)
Chemical mediators participate in the innate immune response, but also have a role in the
adaptive immune response
...
Lysozyme – an enzyme that is found in the secretions of lacrymal glands, nasal mucus,
and gastric secretions
...

2
...

3
...

They also stimulate leukocyte attraction and phagocytosis
...
One cell has the ability to produce different kinds of
cytokines
...
In some cases, they
can be produced in greater amounts, and thus have an endocrine effect
...

Active macrophages produce the following cytokines:
1
...
IL-1 (interleukin 1)
3
...
They attract leukocytes to
the zone of inflammation
...
Some products
attract phagocytes, and others have the opposite effect, which allows for the
differentiation between positive and negative chemotaxis (most of the mentioned
products result in positive chemotaxis)
...
IL-2 – stimulate the production of IFN- (activate macrophages)
a
...
CSF (Colony-stimulating factors) – produced by cells located in bone marrow and T
lymphocytes
...

Interleukins are produced by macrophages and lymphocytes mainly
...
They stimulate the synthesis of B lymphocytes and block some vital functions of
target cells
...

Secretory molecule
Mediators on cell surfaces and in body
cavities

•
•
•

Description
Lysozyme – in tears, saliva, mucus in
nose and in sweat → cell lysis
Sebum
Hydrochloric acid -both sebum and
HCl are acidic and kill microorganisms

•

Histamine

Interferons (IFNs)

Complement system (complement cascade)

Mucus – contains microorganisms due
to texture/consistency
Produced by mastocytes, basophils and
thrombocytes
...
Protection
against viral infections
...
They
do not protect the infected cell, but rather
bind to surrounding, uninfected cells, and
stimulate the production of antiviral proteins
which then prevent viral replication
...

Plasma proteins which cause:
- An increase in the permeability of
blood vessels
- Stimulates release of histamine
- Stimulates cell lysis
- Attracts neutrophils, eosinophils,
monocytes, and macrophages
- Some proteins bind to bacterial cell
walls → lysis
- Some bind to bacterial cells and
facilitate phagocytosis
25 circulating proteins (named from C1 to C9)
which are produced in hepatocytes, by
macrophages, and epithelial cells of the
gastrointestinal system
...
They become active in a
cascade reaction, which ultimately leads to
the activation of C5 convertase → lysis of
pathogenic cells
...


Prostaglandins

Leukotrienes

Pyrogens

Lipids produced by mastocytes
...

- Prolong the duration of smooth
muscle contractions (especially
bronchioles)
- Increase blood vessel permeability
- Attract neutrophils and eosinophils
Released from neutrophils, monocytes
...
Phagocytic cells
a
...
Monocytes
c
...
Helper cells
a
...
K cells (Killer cells)
c
...
Eosinophils
e
...
Mastocytes

All are capable of ameboid movement, which allows for diapedesis to areas of inflammation
...
All phagocytic cells have receptors on their membranes ,
which usually react with/bind to carbohydrates, such as those found in bacterial cell walls
(lipopolysaccharides)
...


They make up around 55-70 % of immune
cells in the periphery circulation, and have a
diameter of 12-15 micrometers
...
Neutrophils are
able to survive in anaerobic tissue (a characteristic of
inflamed and necrotic tissue), where they can
successfully destroy and remove dead cells, and this
is a very important adaptation
...


They possess two types of granules:
1
...

2
...

Usually, their lifespan is approximately 6 hours in the circulation, and around 1-4 days in
connective tissue
...
In order for a healthy balance to be maintained, around 100 billion neutrophils must be
produced daily
...
Together with
monocytes and macrophages, they are named the “professional” phagocytes
...
When they
bind to a solid substrate, for example collagen, they become capable of ameboid movement, and
extend pseudopods which allows them to search for antigen
...
They bind to neutrophil-adhesion molecules (integrin
receptors) and move through capillary cell walls, and this allows for quick and efficient
movement to areas of inflammation
...
The activation of receptors on neutrophils induces:
→ Increased motor activity of the cell
→ Exocytosis of active compounds

→ An abrupt increase in oxygen uptake and the production of oxygen free radicals called
the “respiratory burst” – the activation of NADPH oxidase leads to the production of
superoxide, which is subsequently broken down to hydrogen peroxide, which is
converted to hypochlorous acid by the enzyme myeloperoxidase
...

In the acute phase of infection, neutrophils are one of the primary responders and first to
migrate towards the area of infection
...
Alongside eosinophils and basophils, neutrophils are
termed polymorphonuclear cells – all have a nucleus with multiple lobes
...
Neutrophils
release cytokines, and this process induces an amplification in the immune response because it
results in the recruitment and mobilization of other immune cells
...
Phagocytosis
2
...
Formation of neutrophil extracellular traps (NETs) – composed of DNA and serine
proteases
...
In this way, they act as a physical barrier
...
This is the process of engulfment of foreign particles by immunoglobulins, most
prominently IgG antibodies, and some proteins of the complement system, such as C3b)
...
Phagocytes
bind using their Fcg fragments/receptors
...

Following the process of ingestion, a phagosome is formed, which contains enzymes and free
radicals, all which act to break down the ingested pathogen
...
During their time in the
circulation, they are termed monocytes
...
Nuclei contain 1-2 nucleoli
...
Well-developed granulated endoplasmic reticulum
2
...
Well-developed Golgi apparatus which serves to condense material found in the
cytoplasmic granules
Monocytes stay in the circulation for approximately 72 hours,
after which they relocate to different types of tissue, where
they undergo important changes:
•
•

Increase in size
Increase in number of lysozomes and mitochondria

These characteristics allow for
more efficient phagocytosis
than neutrophils, and for
monocytes to morph into
macrophages
...
Their longevity in different tissue has not been
specifically confirmed, but it is approximated that they are able to live from several months to
even a few years, unlike neutrophils, which are shorter-lived
...

They activate lymphokines, produced by T lymphocytes
...
They phagocytize microorganisms, much like neutrophils,
but are much more efficient in this process
...

Type of macrophage
Langerhans dendritic cells
Histiocytes

Microglial cells
Kupffer cells
Macrophages and antigenpresenting cells (APC)
Pulmonary alveolar
macrophages
M cells
Sinusoidal and dendritic cells

Tissue
Dermis and hypodermis of
the skin
Bone marrow, blood, skin,
liver, lymph glands, spleen,
lungs
Brain (CNS)
Liver
Lymphoid organs
Lungs
Submucosa of
gastrointestinal system
Spleen

Macrophages secrete over 100 bioactive substances and play a significant role in the
amplification of the immune response
...

Their role as antigen-presenting cells (APC) – antigens which are “unknown” (foreign particles,
pathogens) to the adaptive immune system are processed and presented on cell surfaces in

forms which are recognizable to other immune cells
...

All phagocytic cells function similarly
...

1
...
Lysozyme
b
...
Hydrolytic enzymes
d
...
Cathepsin
2
...
Require the process of halogenation of bacterial proteins (a process catalyzed by
the enzyme myeloperoxidase)
...
Hydrogen peroxide (H2O2) and other free reactive radicals
3
...
O2, OH-, H2O2
b
...
These cells
are larger than B and T lymphocytes, have a greater amount of cytoplasm and have CD16 and
CD56 surface markers
...
They respond fast in response to viral infections as
well as in the presence of tumor cells
...


These cells are similar to NK cells, but are more efficient
...
They respond to lymphokines, especially IL-2,
and lead to the lysis of tumor cells (which may be resistant to NK cells)
...


The nuclei within these cells contain two lobes
...
These granules contain a crystalline core, called the inertum, which

contains the major basic protein (MBP), which serves to destroy parasitic helminths
...
Eosinophils exhibit a cytotoxic effect
on parasites surrounded by IgE antibodies
...
Their main role is
in parasitic infections, as well as allergic reactions
...
In tissue,
eosinophils are located under the epithelium of the skin, in the gastrointestinal system, as well as
the uterus and vagina
...
5-1
%
...
They have somewhat kidney-shaped
nucleus, which has two lobes usually
...
These granules contain heparin, which causes them to become a dark
purple color following the Giemsa staining method
...

T lymphocytes secrete a histamine-releasing factor which activates basophils and other
inflammatory mediators essential in hypersensitivity reactions (HR)
...

▪
▪

Basophilia – high basophil count
...


Mast cells are particularly numerous in connective tissue
...
Cytoplasmic
granules contain cytokines, interleukins, leukotrienes,prostaglandins, histamine and heparin
...
All of these functions and characteristics
allow mast cells to function as integrators and immune amplificators
...
In addition, they release TNF-alpha in
response to the presence of bacterial products
...
They have a role in allergic reactions, anaphylaxis
protection against pathogenic microorganisms, and wound healing
...
For example, wounded tissue or
bacterial cells produce various chemical mediators such as histamine, prostaglandins,
leukotrienes, proteins of the complement system, as well as kinins
...

Process
Vasodilation

Chemotactic attraction of
phagocytes
Increased vascular
permeability

Effect
Increased blood flow +
movement of immune
phagocytes to infected region
Large numbers of phagocytes
are “drawn” to area where
they are needed
Allows fibrinogen and the
complement system proteins
to enter affected tissue from
blood stream

Notes (additional
information)

Fibrinogen (inactive form) is
converted to the active form
fibrin which acts in stopping
the further spread of
infection → isolates infected
area
...

Chemical mediators and phagocytic attraction continues until the pathogenic cells are destroyed
...
Damaged tissue is remodeled by numerous chymases and tryptases
...


Local inflammation
•
•

•
•
•

Occurs in a specific region
...

The occurrence of pain is a result of swelling and the presence of chemical mediators on
pain receptors
...


Systemic inflammation
•
•

Affects more than one region of the body
...

▪ A fever promotes the activity of the immune system by:
• Stimulating phagocytosis
• Inhibiting the growth of some microorganisms



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