The Innate Immune System

Innate Immune
System

External Internal
defenses defenses

By Dr. Anna Sukiasyan

Main functions of the Innate Immune System

1. Initial response to microbes: Prevents controls and

eliminates infection. All invertebrates only have an
innate immune system.

2. Eliminate of damaged cells and initiate tissue repair.

3. Stimulates the adaptive immune system and

influences the type of adaptive immune response that
develops in response to infection and damage.
 Innate (Non-Specific) Immunity
1. Physiologic Barriers
– pH (stomach)
– Temperature (fever)
– Soluble Factors (interferons, lysozyme)

2. Phagocytic Barriers
– Specialized Cells Perform Most Of Phagocytosis
(macrophages, neutrophils)
 Innate (Non-Specific) Immunity
3. Inflammatory Barriers
– Vasodilation
– Cappillary permeability
– Leukocyte Infiltration
Innate immunity
Mast cells and basophils are innate cell types that, when activated,
secrete histamine, which can be an important inflammatory mediator
produced in response to initial tissue damage as a result of infection. Mast
cells are tissue resident (e.g. in mucosal tissues) whilst basophils are found
in the blood. In particular, they play a key role in the so-called allergic
response.

Innate immunity comprises both cellular and humoral (‘in solution’)

elements. The cellular elements are represented notably by phagocytes
(specifically neutrophils and macrophages) that can respond to signs of
infection (i.e. inflammation) in the tissues and home-in on infective
bacteria before neutralising and engulfing them (‘phagocytosis’).
Recognition of microorganisms by the innate system occurs via
characteristic pathogen-associated molecular patterns (PAMPs) on
microbial surfaces, and an important family of innate receptors called
pattern-recognition receptors (PRRs) are responsible for this (notably
including Toll-like receptors [TLRs]).
Innate immunity

The natural killer (NK) cell is another important innate cell that is able
to detect and target intracellular infection of body cells by viruses.

A further specialised innate cell is the eosinophil that plays a particular

role in targeting larger infective organisms, such as parasitic worms.

The complement system represents the humoral arm of innate

immunity, and consists of a number of proteins (found in solution in
the blood) that can interact directly, or indirectly, with infective
bacteria (through different activation pathways). Inflammation, as a
result of infection, allows plasma, containing complement proteins, to
enter infected tissues.
Innate immune system
External defenses
 Anatomical Barriers - Mechanical Factors

Skin

Mucociliary escalator
Flushing action of (responsible for movement of mucus
up and out of the respiratory tract)
saliva, tears, urine
Anatomical Barriers – Chemical factors
Hydrochloric acid in Lysozyme in tears /saliva
Antimicrobial stomach
Peptides in sweat
 Anatomical Barriers – Biological factors

Normal flora – microbes

in many parts of the body.

Normal flora –
competes with pathogens
for nutrients and space.
Innate immune system
internal defenses
Cells of the Innate Immune System

Phagocytes: neutrophils, macrophages,

Granulocytes: eosinophils, basophils,
neutrophil
Others: dendritic cells (DCs)
Lymphocytes
Natural killer cells (NK)
Innate lymphoid cells (ILCs)

Platelets
The main phagocytes are neutrophils and macrophages.
Neutrophils circulate in the blood and the macrophages reside in
tissues. There are many other types of phagocytic cells in the
liver, brain etc…

Neutrophil Macrophage
% in blood Most numerous WBCs Few
↑ in acute infection
Size Small Large and
mononuclear
Life Few hours Days
 White blood cells (WBCs)
Macrophages

B-lymphocytes

T-lymphocytes

Natural killer(NK) cells

Mast cells
 Neutrophils in innate immune response

• Most abundant WBCs (~50-60%)

• Efficient phagocytes

• WBCs (eg. Neutrophils) – find, eat

and digest microbes- as a process
of Phagocytosis
Neutrophils are phagocytic leukocytes that comprise the first line
of host immune response against invading pathogens. They are
also important effector cells during tissue injury-induced
inflammation. Neutrophils have a high potency and efficacy to
sense and eradicate microbial infections.

Infections and their associated inflammatory mechanisms are

accompanied by a rapid influx of neutrophils from the peripheral
blood to the inflammatory site. There they engage and kill
microorganisms and clear infections via a number of different
mechanisms including chemotaxis, phagocytosis and the
production and liberation of cytokines.
Primary Function of Neutrophils
Monocytes

• Monocytes (~5% of WBCs)

• Migrate into the tissues and become Macrophages

Monocytes are a crucial component of the innate immune system.

A monocyte is a type of white blood cell that differentiates into populations of
macrophages and dendritic cells to regulate cellular homeostasis, especially in the
setting of infection and inflammation .Monocytes have two distinct roles; they
regularly patrol the body for microbial cells and orchestrate an immune response in
times of infection and inflammation.
Monocytes have toll-like receptors on their surfaces that interact with PAMPS
(pathogen-associated molecular patterns) found on invading microbial cells. In
response to such stimuli, monocytes migrate from the bone marrow into the blood
circulation and infiltrate tissues within 12 to 24 hours.
Macrophages
Macrophages are specialised cells
involved in the detection,
phagocytosis and destruction of
pathogenic organisms. They are a
diverse phenotype of professional
phagocytic cells derived from bone-
marrow precursors and parent
monocytes in the peripheral blood.
They migrate to and circulate within
almost every tissue, patrolling for
pathogens or eliminating dead cells.

Macrophages also produce reactive

oxygen species, such as nitric oxide,
that can kill phagocytosed bacteria.
 Dendritic cells
Dendritic Cells originate in the Bone Marrow. In order to efficiently encounter,
process, and transport foreign antigens to lymph nodes for presentation to T cells.
Dendritic cells, like most cells of the immune system, comprise a number of groups
or subsets that are distinct either in origin, function, or both:
1) conventional dendritic cells (cDCs),
2) Langerhans cells,
3) plasmacytoid dendritic cells (pDCs),
4) monocyte-derived dendritic cells (moDCs),
5) and the myeloid DCs (mDCs).

Main functions of the Dendritic cells

the most important antigen presenting cells
play a major role in presenting antigen to T cells and activating them
They are the main link between the innate and the adaptive immune system
are widely distributed in lymphoid tissue, mucosal epithelium and in organs
 Eosinophils

An Eosinophil is a type of white blood cell. It is a

granulocyte, which means it releases granules of enzymes
to fight foreign substances and infections.

Two of their most important functions are related to the

immune system.
The first is killing invading germs such as parasites, bacteria
or viruses.
The second is promoting inflammation. This process helps
the body to isolate and control a disease or allergic
reaction.
 Basophils
Basophils are a type of white blood cell. Like most types of white blood cells,
basophils are responsible for fighting fungal or bacterial infections and viruses.
They are a granulocyte cell, which means that they release granules of enzymes to
fight against harmful bacteria and germs.

The enzymes that basophils release are called histamine and heparin. Histamine is a
vasodilator. This means it widens the blood vessels near an infection to open and
allow more blood flow to the site of the infection. Heparin is a naturally occurring
blood thinning substance which prevents clotting.

Basophils are responsible for the body’s immune response during allergic reactions.
When the body is exposed to an allergen, basophils release histamine which triggers
the physical symptoms of an allergic reaction. This causes the typical allergic reaction
of running nose, watering eyes etc.

They also help to produce a crucial antibody called Immunoglobulin E (IgE).

Immunoglobulin attaches to basophils and a similar type of cell called Mast Cells. The
cells then work together to release histamine and serotonin, which affects the
inflammatory response to the allergen.
Mast Cells

Mast cells derive from the bone marrow but unlike other white
blood cells, mast cells are released into the blood as mast cell
progenitors and do not fully mature until they are recruited into
the tissue where they undergo their terminal differentiation.

Mast cells are long-lived tissue-resident cells with an important

role in many inflammatory settings including host defence to
parasitic infection and in allergic reactions. Mast cells are
located at the boundaries between tissues and the external
environment, for example, at mucosal surfaces of the gut and
lungs, in the skin and around blood vessels.
Mast cells are key players in the inflammatory response as they can
be activated to release a wide variety of inflammatory mediators, by many
different antigens including allergens, pathogens and physiological
mediators.
 Lymphocyte

Lymphocyte, type of white blood cell (leukocyte) that is of

fundamental importance in the immune system because
lymphocytes are the cells that determine the specificity of the
immune response to infectious microorganisms and other
foreign substances.

In human adults lymphocytes make up roughly 20 to 40

percent of the total number of white blood cells. They are
found in the circulation and also are concentrated in central
lymphoid organs and tissues, such as the spleen, tonsils, and
lymph nodes, where the initial immune response is likely to
occur.
 Lymphocytes are the cells that specifically recognize and respond to foreign
antigens and are mediators of humoral and cellular immunity.
 Lymphocytes, the unique cells of adaptive immunity, are the only cells in the body
that express clonally distributed antigen receptors, each specific for a different
antigenic determinant.
 Each clone of T and B lymphocytes expresses antigen receptors with a single
specificity, which is different from the specificities of the receptors in all other
clones.
There are three main types of lymphocytes:
B cells,
T cells,
and Natural Killer cells.

Two of these types of lymphocytes are critical for specific immune

responses. They are B lymphocytes (B cells) and T lymphocytes (T cells).

T and B cells originate from stem cells in the bone marrow and are
initially similar in appearance. Some lymphocytes migrate to the thymus,
where they mature into T cells; others remain in the bone marrow,
where—in humans—they develop into B cells.
Most lymphocytes are short-lived, with an average life span of a week to
a few months, but a few live for years, providing a pool of long-lived T
and B cells.
These cells account for immunologic “memory,” a more rapid, vigorous
response to a second encounter with the same antigen.
T cells (thymus cells) and B cells (bone cells) are the main cells of the
adaptive immune response.
Natural killer cells (NK)

 Important part of the innate immune system

 Kill virus /bacteria infected cells (Intracellular pathogens)

 Kills cancer cells

 How does the killer kill ?

Kills both host cells and microbes

Release of granules with perforins and proteases

Major histocompatibility complex (MHC), group of genes that code for proteins found on the surfaces
of cells that help the immune system recognize foreign substances. MHC proteins are found in all
higher vertebrates. In human beings the complex is also called the human leukocyte antigen (HLA)
system.
Innate lymphoid cells (ILCs)
Innate lymphoid cells (ILCs) are immune cells that
belong to the lymphoid lineage but do not express
antigen-specific receptors. These cells have important
functions in innate immune responses to infectious
microorganisms and in the regulation of homeostasis
and inflammation.

ILCs react promptly to signals from infected or injured

tissues and produce an array of secreted proteins
termed cytokines that direct the developing immune
response into one that is adapted to the original insult.
 Platelets
Platelets have significant role in modulating
clot formation.
Recently more data shows that they are
also effector cells in the inflammatory
response and important elements of the
immunological response.
Platelets store and release many biologically active substances,
including growth factors, cytokines and chemokines, which actively
affect i.a. elements of the immune system, and thus become
regulators of immunity and mediators of inflammatory response.
Platelets gather at the damaged cite and adhere to white blood cells.
Therefore, platelets are necessary for targeting lymphocytes,
neutrophils and monocytes to inflammation site.
Those interactions enhance inflammation.
Moreover, platelets serve as an immune cell by engulfing microbes.
Various components of innate immunity work at
different stages of infection:

 Epithelial barriers impair microbial entry into the

host

 Resident and recruited phagocytes in subepithelial

and other tissues provide protection if the barriers
are breached

 Plasma proteins and circulating phagocytes provide

protection if microbes reach the blood stream
What does innate immunity recognise?
Molecular structures that are produced by microbial
pathogens – often shared by classes of microbes
– Pathogen associated molecular patterns (PAMPs).
– Essential for survival of microbes - ensures the target of the
immune response can’t just be discarded by the microbe to
evade recognition.

Endogenous molecules that are produced by or released from

damaged and dying cells
– Damage associated molecular patterns (DAMPs).
– Can be produced as a result of cell damage caused by
infection.
– Also produced in response to sterile injury to cells (chemical
toxins, burns, trauma or low blood supply).
Examples of microbial-associated PAMPs include:
- Lipopolysaccharide (LPS) from the outer membrane of the
Gram-negative cell wall,
- Bacterial lipoproteins and lipopeptides ,
- Peptidoglycan found abundantly in the Gram-positive cell
wall and to a lesser degree in the gram-negative cell wall,
- Flagellin found in bacterial flagella,
- Bacterial and Viral nucleic acid,
- Lipoteichoic acids, glycolipids from yeast cell walls…
Examples of Damage associated molecular patterns
(DAMPs):

-Nuclear proteins,
-Crystals,
-Stress-induced proteins…
How are PAMPs & DAMPs recognized?
 Pattern Recognition Receptors (PRR)

 Most cell types express PRR and are capable of

participating in innate immune responses.

 Phagocytes and Dendritic Cells express the different and

greatest amount of these receptors in keeping with their
fundamental roles.

 Expressed on cell surfaces, in phagocytic vesicles and in

the cytosol of cells - all of which are locations where
microbes may be present.
Pattern recognition receptors (PRRs)
Pattern recognition receptors (PRRs) are a class of receptors
that can directly recognize the specific molecular structures on
the surface of pathogens, apoptotic host cells, and damaged
senescent cells.
The activation of PRRs is crucial for the initiation of innate
immunity, which plays a key role in first-line defense until more
specific adaptive immunity is developed.

Currently identified PRR families are:

1) the Toll-like receptors (TLRs),
2) the C-type lectin receptors (CLRs),
3) the nucleotide-binding oligomerization domain-like
receptors (NLRs),
4) the retinoic acid-inducible gene-I-like receptors (RLRs).
Toll-like receptors (TLRs)

Transmembrane proteins

Present on macrophages / few other cells

Conserved across vertebrates

Important part of innate immune system

TLRs – in Action
- They look out for microbes (or their components)

- They bind to the microbes (or their components)

- They trigger a cascade of events to kill or protect

against pathogens

THEY ARE INNATE IMMUNE SENSORS

 Which microbial components are
recognized by TLRs ?
All TLRs are synthesized in the ER, traffic to the Golgi, and are
recruited to the cell surface or to intracellular compartments
such as endosomes.

TLRs are expressed in innate immune cells such as dendritic

cells (DCs) and macrophages as well as non-immune cells such
as fibroblast cells and epithelial cells.
Cell surface TLRs mainly recognize microbial membrane
components such as lipids, lipoproteins, and proteins.
Intracellular TLRs recognize nucleic acids derived from
bacteria and viruses, and also recognize self-nucleic acids in
disease conditions such as autoimmunity.
What happens when a TLR bind to a microbe ?

Secretion of
Cytokines /
Interferon

Phagocytosis
Inflammation TLR binding of infected
to microbe cell

Apoptosis of
infected cell
 C-type lectin receptors (CLRs)

C-type lectin receptors (CLRs) expressed by dendritic cells are

important pattern recognition receptors involved in
recognition and induction of adaptive immunity to
pathogens. Certain CLRs play an important role in viral
infections as they efficiently interact with viruses.
C-type lectin receptors (CLRs) are a large family of
transmembrane and soluble receptors that contain one or
more carbohydrate-recognition domain able to recognize a
wide variety of glycans on pathogens or on self-proteins.
Nucleotide-binding oligomerization domain-like
receptors (NLRs or NOD-like receptors)
Nucleotide-binding oligomerization domain-like receptors (NLRs)
are a family of intracellular proteins, which play a pivotal role in
host defense, recognizing conserved pathogen-associated
molecular patterns (PAMPs) from invading pathogens, but also
danger-associated molecular patterns (DAMPs). NLR genes plays
an important role in the development of innate immune
responses.
Unlike TLRs that mediate extracellular recognition of microbes,
several NLRs sense pathogens in the cytosol and upon activation
induce host defense signaling pathways. Although TLRs and NLRs
differ in their mode of pathogen recognition and function, they
share similar domains for microbial sensing and cooperate to
elicit immune responses against the pathogen.
Retinoic acid-inducible gene-I-like receptors (RLRs)

The RLRs recognize viral dsRNA in the cytoplasm of both immune

and nonimmune cells. Engagement of RLRs drives type 1 IFN
(IFNα/β) production and antiviral gene expression that elicits an
intracellular immune response to control virus infection.

Crosstalk between RLRs and TLRs along with other factors

underlies development of innate immunity and modulates the
adaptive immune response to viruses.
Summary: innate response – internal defenses – WBCs

Come into play when the external defenses are breached

- Neutrophils

- Monocytes /macrophages

- NK cells

- TLRs
 Cytokines

• Small proteins – secreted by

cells of the immune system

• Affect the behaviour of other

cells

• signalling molecules

• Key players in Innate and

Adaptive immunity
Which cells release cytokines ?

Cells of the immune system:

 Neutrophils – when they encounter a pathogen.

 Macrophages – when they encounter a pathogen.

 TLRs – bind to microbe / components of a microbe.

 NK cells – on encountering a microbe infected cell /tumour cell.

 Lymphocytes – when they are activated.

Cytokines

 Interferons (IFN)

 Interleukins (IL)

 Tumour necrosis factor (TNF)

Cytokines are regulators of host responses to infection,
immune responses, inflammation, and trauma.

Some cytokines act to make disease worse – pro-

inflammatory,
whereas others serve to reduce inflammation and
promote healing - anti-inflammatory.
 Important cytokines
Cytokine Principle Source Function
TNFa Macrophages Pro-inflammatory
IL-1 Macrophages Pro-inflammatory
IL-2 T cells T cell growth factor
IL-10 T cells Anti-inflammatory
IFNg T cells, NK cells Pro-inflammatory
TGFb Many Pro-inflammatory,
regulatory
Interferons (IFN)

• Signalling proteins produced by by virus infected monocytes

and lymphocytes

• Secreted proteins – Key anti-viral proteins

• “Interfere” with virus replication

• Warn the neighbouring cells that a virus is around...

Interferons (IFNs) are a group of signaling proteins made and released
by host cells in response to the presence of several pathogens, such as
viruses, bacteria, parasites, and tumor cells. In a typical scenario, a
virus-infected cell will release interferons causing nearby cells to
heighten their anti-viral defenses.
IFNs belong to the large class of proteins known as cytokines/molecules
used for communication between cells to trigger the protective
defenses of the immune system that help eradicate pathogens.
Interferon was named for its ability to interfere with viral proliferation.
Interferons can also combat bacterial and parasitic infections, inhibit cell
division, and promote or impede the differentiation of cells. They are
produced by all vertebrate animals and possibly by some invertebrates
as well.
IFNs also have various other functions: they activate immune cells, such
as natural killer cells and macrophages; they increase host defenses by
up-regulating antigen presentation by virtue of increasing the
expression of major histocompatibility complex (MHC) antigens.
 Interferons –released by viral-infected cells

Cause macrophages to phagocytose

Activate NK cells (apoptosis of injured cell)
Make enzymes that inhibit viral replication
Interleukins

• Not stored inside cells

• Quickly synthesized and secreted in response to

infection

• Key modulators of behaviour of immune cells

• Mostly secreted by T-lymphocytes and Macrophages

Interleukins (IL) are a type of cytokine first thought to
be expressed by leukocytes alone but have later been
found to be produced by many other body cells.

They have pro-inflammatory and anti-inflammatory

properties.
The primary function of interleukins is, therefore, to
modulate growth, differentiation, and activation during
inflammatory and immune responses.
Interleukins consist of a large group of proteins that can
elicit many reactions in cells and tissues by binding to
high-affinity receptors in cell surfaces.
 What to interleukins do ?

Proliferation of immune cells

Interleukins
Increase antibody production
Inflammation

Activation of immune cells

Tumour necrosis factor (TNF)
Tumour necrosis factor (TNF), also called cachectin, a naturally
occurring protein that is produced in the human body by macrophages.
TNF is produced by macrophages when they encounter the poisonous
substance in bacteria that is known as endotoxin. TNF seems to
perform both helpful and harmful functions within the body.

In a healthy person TNF helps the body to fight off infections. In people
with autoimmune diseases, however, high levels of TNF in the blood
can cause unnecessary inflammation, resulting in painful symptoms.

TNF is a protein that plays a role in the natural healing process. When a
person sustains an injury or experiences bacterial or viral infections,
their body creates inflammation to protect the area and allow it to
heal.
Tumour necrosis factor (TNF)

TNF

Killing of cancer Fever

Inflammation
Tumour necrosis factor (TNF)

To create inflammation, TNF proteins begin to circulate in the

blood. They arrive at the target area to trigger the inflammation
process.

In healthy people, the body deactivates any excess TNF in the

blood so it does not cause excess inflammation. When this
process does not work properly, people can develop an
autoimmune condition.

Excess inflammation, even when the body is not damaged,

characterize autoimmune conditions. Examples of these include
rheumatoid and psoriatic arthritis.
Complement (C`)

• a large number of distinct plasma proteins that react with one

another (C1 thro’ C9)

• Complement can bind to microbes and coat the microbes

• Complement recognizes PAMPs on microbes and binds to them

• Essential part of Innate Immune Response

• Enhances Adaptive Immune Resposne

Complement (C`)

The complement system represents the humoral arm of innate

immunity, and consists of a number of proteins (found in solution
in the blood) that can interact directly, or indirectly, with infective
bacteria (through different activation pathways). Inflammation, as
a result of infection, allows plasma, containing complement
proteins, to enter infected tissues. Once activated, the member
proteins assemble to form complexes on the surface of microbes
that punch holes in the membrane.
Complement can be activated via three different pathways:
1) Classical Pathway,
2) Alternative Pathway,
3) Mannose-binding Lectin Pathway.
Complement pathways
 Complement proteins: role in innate immune system

C`proteins

Facilitates phagocytosis Direct lysis of pathogens Inflammation

Role of Complement in Disease
The complement system plays a critical role in inflammation and defence
against some bacterial infections. Complement may also be activated
during reactions against incompatible blood transfusions, and during the
damaging immune responses that accompany autoimmune disease.
Deficiencies of individual complement components or inhibitors of the
system can lead to a variety of diseases, which gives some indication of
their role in protection against disease.

Diseases associated with complement deficiencies

 Complement Proteins
They have a number of functions to defend against pathogens

Opsonization Inflammation Cytolysis Elimination of

immune complexes
Complement Complement
Antigen

C Mast cell Basophil Neutrophil Macrophage MAC Antibody

protein Complement
C
Pathogen Erythrocyte
Pathogen
Inflammation
Macrophage
Complement (C) cross-links
immune (antigen-antibody)
Complement (C) binds to Complement activates and attracts various cells of Complement proteins create complexes to erythrocyte and
pathogen; acts as opsonin innate immunity. MAC to lyse cell. transports to liver and spleen.

Opsonin – coats pathogen to make appear different and thus recognizable by

macrophages.
Inflammation - Activates mast cells, basophils, neutrophils, and macrophages to
increase inflammatory response.
Cytolysis – causes cell lysis (Big Membrane Attack Complex (MAC) attack.
Eliminates Antigen-Antibody complexes on RBCs killed in spleen.
Coagulation proteins

• Coagulation: mechanism to stop bleeding after injury to blood

vessels

Complex pathway involves

• Platelets
• Coagulation factors
• Vitamin K
Blood clotting is also called coagulation.
Hemostasis is a word for the process where a blood clot forms.
Blood clots form to stop excess blood leaking from your body
after you break or cut the surface of your skin. If a blood vessel
(a capillary, vein or artery) is damaged (internally or by external
injury like a cut) bleeding occurs until a clot forms.
Once the site of injury has healed, the blood clot will naturally
dissolve.
If no blood clot forms it is called a hemorrhage.
A hemorrhage is uncontrolled bleeding and can be highly
dangerous.
For instance - Hemophiliacs are people with a blood disorder
where there blood does not clot. A small injury can lead to
uncontrolled bleeding.
How does blood clot ?
 Coagulation: Delicate balance
Antithrombin, protein C and
protein S are anticoagulants.

Coagulation proteins Anticoagulants

Blood clotting Prevent blood clotting

Inflammation Inhibit inflammation
Apoptosis (prog. Cell death) Inhibit apoptosis

Too much of clotting – Problem

Maintenance of a balance
Too little clotting - Problem
Coagulation and Innate Immunity

Pathogens and cytokines

Anticoagulants

Antithrombin, protein C
and protein S are
anticoagulants.
Coagulation proteins

Increased inflammation and increased apoptosis of infected cells

Summary: innate response – internal defenses

Cellular Extracellular

• Neutrophils • Cytokines

• Monocytes /macrophages
• Complement
• NK cells
• Coagulation
• TLRs
Inflammation

Antigens

Antibody
 Inflammation

 Complex biological process by which body responds

to pathogens and irritants

 Associated with swelling of tissue

 Key player in innate immune repsone

Inflammation is part of the body’s defense mechanism and
plays a role in the healing process.

When the body detects a foreign particle, it launches a

biological response to try to remove it.

Sometimes, the body mistakenly perceives its own cells or

tissues as harmful. This reaction can lead to autoimmune
diseases, such as type 1 diabetes.

Experts believe inflammation may contribute to a wide range

of chronic diseases. Examples of these are metabolic
syndrome, which includes type 2 diabetes, heart disease, and
obesity.
 All roads lead to inflammation

Neutrophils
Coagulation proteins

Monocytes /macrophages
Inflammation

C` proteins

NK cells

Cytokines /IFN
TLRs

Cellular Extracellular
 Signs of inflammation
– Redness - increased blood flow
– Heat - increased blood flow and increased metabolic activity
– Swelling - increase in fluid loss – capillaries to interstitial space,
capillaries become more permeable due to histamine and other
chemicals
– Pain - stimulation of pain receptors from compression from interstitial
fluid; chemical irritation by kinins, prostaglandins, microbe substances
– Loss of function - (may occur in severe cases)

Acute inflammatory response

• a local, nonspecific response -- typically lasts 8-10 days
• sometimes persists in process of chronic inflammation
• Products of Inflammation Necrosis Local tissue destruction in area of injury
Pus Mixture of debris and necrotic tissue Abscess Pus accumulated in an
enclosed space
• Swelling- fluid out of damaged blood vessels
 Innate Immunity: Inflammation
 Immediate, local, nonspecific response
 Major effector of innate immunity that helps eliminate
infectious agents.

 1st step: chemicals like histamine and chemotactic factors released.

 2nd step: response in blood vessels = vasodilation and increased
capillary permeability.
 3rd step: leukocytes (WBCs) cells undertake chemotaxis and migrate
toward of chemical agents (bacterial secretions).
 Neutrophils, eosinophils, macrophages clean up the area.

Pus in an inflamed and infected area is due to a aggregation of

neutrophils (WBCs).
Fluid comes out of blood vessel, swelling, fluid uptake by lymphatic
capillary to resolve swelling.
Benefits of Fever
-Inhibits reproduction of bacteria and viruses.
-Promotes interferon activity.
-Increases activity of adaptive immunity.
-Accelerates tissue repair.
-Recommended to leave a low fever untreated.

Risks of a high Fever significant above 100 degrees F.

-Changes in metabolic pathways and denaturation of proteins.
-Possible seizures, irreversible brain damage.
 Summary: role of Inflammation in Innate
Immunity

 Initiation of phagocytosis – killing of pathogen

 Limiting the spread of infection

 Stimulate adaptive immune response

 Initiate tissue repair

 Immunogen and Antigen
• When foreign substances (Ag) are introduced into the
body, they lead to anti-foreign substance
• ( Anti-body ) formation
• Immunogenic when they are able to produce specific
immune response; that they will stimulate immune
cells and then give rise to immunological reaction
(Humoral or cellular).
• Antigenic substances cannot directly yield immune
response, but need some help by some proteins) and
then
• They can react with antibodies.
• All immunogens are antigenic but not all antigens
are immunogenic
Antigen may be:

- Carbohydrate, lipid, protein, nucleic acid,

phospholipids,
- B cell recognize any biological Ag,
-T cell recognize peptide Ag presented on Major
histocompatibility complex (MHC). MHC are group of
genes that code for proteins found on the surfaces of
cells that help the immune system recognize foreign
substances.
Epitope
• Epitope: the portion of an antigen that is recognized and bound by
an antibody (Ab) or a T-cell receptor (TCR)
• Epitope = Antigenic Determinant
• One protein may have multiple antigenic determinant
Hapten
 These are partial antigens. These are not
immunogenic.
 Hapten needs carrier proteins like albumin, globulin
and synthetic polypeptide to become immunogenic.
 Antibiotics, analgesics, penicilin and etc.
 Therefore haptens are antigenic and not
immunogenic
ADJUVANTS

Adjuvants are immunopotentiating agents.

( Ag+Ab)---Injected---->Increased immune
response.

Adjuvants are nonspecific stimulators of the immune

response. When mixed with an antigen or immunogen,
adjuvants help to deposit or sequester the injected
material thereby helping to increase antibody
response. Adjuvants enhance the immune response to
compounds that are already immunogenic.
 Antibody

• Produced by Plasma cell (B-lymphocytes producing

Ab)

• Essential part of Adaptive Immunity

• Members of the class of proteins called

immunoglobulins
Antibodies are compounds of protein and sugar that
circulate in the bloodstream. They are created by the
immune system to fight germs and foreign substances.
Antibodies can quickly detect germs and other
potentially harmful substances, and then attach to
them. This neutralizes the "intruders" and attracts
other immune system cells to help.

An antibody only attaches to an antigen if it matches

exactly, like a key in the lock of the antibody. That is
how antibodies detect the matching germs to initiate a
fast response from the adaptive immune system.
Antibodies have three main functions:

1) They neutralize germs, e.g. by directly attaching to the cell

surfaces of viruses or bacteria, or by attaching to their
toxins. This prevents the germs from latching onto the
regular cells of the body and infecting them.
2) They activate other immune system cells by attaching to
their surfaces. Scavenger cells are better able to fight off
germs that are loaded with antibodies, too.
3) They activate proteins that help in the immune system
response.

The antibodies of the Adaptive Immune system also support

the Innate Immune system.
Antibodies can also be divided into two
regions based on their functions.
The tip of the “Y”, consisting of one
constant and one variable domain from
each heavy and light chain of the
antibody, contains the region that binds
the antigen. It is for this reason that we
call it the Fab (fragment, antigen
binding) region.
The base of the “Y”, composed of two
heavy chains, plays a a role in
modulating immune cell activity.
This region is called the Fc (Fragment
constant, crystallizable) region. The Fc
region can bind to cell receptors,
complement proteins, as well as to
other immune molecules, thereby
initiating different physiological effects
including opsonization, cell lysis, and
degranulation. Antibody: structure and function
Antibody: Fab

Fab region
• Variable region of the
antibody

• Tip of the antibody

• Binds the antigen

Antibody: Fc

Fc region
• Constant region

• Base of the antibody

• Can bind cell receptors

and complement
proteins
 Antibodies exist in two forms

• Antibodies occur in 2 forms

1) Soluble Ag: secreted in blood and tissue

2) Membrane-bound Ag: found on surface of B-cell,

also known as a B-cell receptor (BCR)