Become an expert in Immunology!

This course provides you with a perfect overview of the human immune system. Dr. Peter Delves is your
lecturer and will teach you more than just the basics:

 Learn how the immune response works

 Learn how the immune system is organized
 Learn about the cells of the immune system

The download material includes presentation slides and related articles, and will help you learn the
subject in even greater detail. Quiz questions allow you to test your knowledge.

Lysozyme cleaves?

o Citrulline
o Elastase
o Arginine
o Lactoferrin
o Peptidoglycan (true)

Which phagocytic cells circulate in the blood in order to reach sites of

infection?
 Macrophages and Monocytes
 Neutrophils and Macrophages
 Basophils and Neutrophils
 Neutrophils and Monocytes (true)
Fc Receptors (FcR) on the surface of neutrophils and macrophages
recognize...?

o ...complement molecules on a pathogen.

o ...Pathogen-Associated Molecular Patterns.
o ...pathogens.
o ...macrophages that have encountered an antigen.
o ...antibodies that have coated antigens.

A person has a rare disorder in which they cannot produce lysozyme. Which
step of the phagocytic cell function would be compromised?
 o Enzymatic degradation of pathogens within the phagolysosome
(true).
o Invagination of phagocyte necessary to engulf organism.
o Recognition of pathogens.
o Effective binding of a PRR to a PAMP.
o Fusion of the phagosome with a lysosome.

 Monocytes and Mast cells

Introduction: Pathogens and the immune system

Immune response
Strategies to eliminate Pathogens
What structural organization allows immune cells access to all parts of the body?
The dual blood and lymphatic circulation.
Cells of the immune system circulate around the body through blood circulation and
lymphatic circulation with several different strategy:
1- Phagocytosis:
Particulate extra cellular pathogens are engulfed by phagocytic cells and
subsequently are destroyed by released toxic molecules.
2- Released molecules kill pathogen
3- Cells kills infected cells
Organization of the immune system
In the secondary lymphoid cells are get together and communicate
Functional organization of cellular interactions
1-Cell-cell contact-dependent interactions
Molecule on surface of one bind to molecule on surface of another cell
2- Interaction via secreted molecules
One cell release one molecule to be detected by another cell.
Cessation of the response
Antigen stimulates the response, and if response is successful, stimulus is eliminated.
In addition, regulatory cells suppress any residual response
Cells of the innate immune response
Hematopoiesis:
In Bone marrow, self-renewing multipotent, hematopoietic stem cell can differentiate into
two pathways; myeloid and lymphoid pathways.
Myeloid pathway give rise erythrocytes (RBCs), Megakaryocytes (platelets), and cells of
innate immunity; phagocytic cells, dendritic cells, eosinophils, basophils, mast cells.
Lymphoid pathway gives rise to cells of adaptive immunity (B and T cells), natural killer
cells and other innate lymphoid cells.
Cells of the adaptive immune system

Introduction: Pathogens and the Immune System

There are many different pathogens come across
vertebrates and invertebrates like viruses,
bacteria, fungi, and parasites. The immune
system has to recognize all these different type
and different sizes of pathogens. So the immune
system has multiple strategy to deal with these
very small or very big ones, inside or outside
cells.
First line of defense:
Intact skin forms a physical barrier
Mucous and cilia prevents colonization
Commensal microorganisms occupy niche.
Acid pH resists pathogens
 Enzymes and immune proteins like lysozyme and
defensins
Immune Response


 Peter Delves, PhD
2 years ago
Factors such as skin, mucus and commensal microorganisms are very
important for protection against infection but are not classed as being
components of the immune system. Defence against infection is sometimes
divided into 3 layers of protection. 1. Physical components of the type just
mentioned. 2. The innate immune response. 3. The adaptive (acquired)
immune response. They are all very important in defending the host against
pathogens and collectively are usually very successful in protecting us from
infection.

 By definition, pattern recognition receptors (PRR) of all types (Toll-like receptors,

NOD-like receptors, RIG-like receptors, etc) respond to foreign pathogen-
associated molecular patterns (PAMPs) and host damage/danger- associated
molecular patterns (DAMPs). The stimulation of PRRs on blood vessel
endothelium by PAMPS and/or DAMPs can lead to the upregulation of adhesion
molecules and the release of cytokines by the endothelial cells. This would
include blood capillaries contributing to the initiation of an attack against Gram-
negative bacteria bearing LPS, e.g. by stimulation through TLR4 on the surface
of the endothelial cell.
 Pathogen-Associated Molecule Patterns are molecular structures that are
present on the surface of, or inside, pathogens (bacteria, viruses, fungi,
parasites), but these structures are not present in the host (e.g. human). They
are usually molecules that are present on/in several different pathogens rather
than just one pathogen (e.g. lipopolysaccharide is found on all Gram-negative
bacteria, not just one particular strain). They are detected by molecules in the
host called Pattern Recognition Receptors (PRRs), sometimes alternatively
called Pathogen Recognition Receptors.
 Innate and adaptive immune response:

Innate immune response adaptive immune response

In Vertebrates and Invertebrates - In Vertebrates only

-Recognition with broad specificity for PAMPS -with high specificity for antigens

- same intensity - stronger and faster upon reinfection

- - primary & secondary immune response

- no memory - immunological memory

- Rapid response - slow response

Minutes to hours - days

Cells already in body tissues Cells have to proliferate in secondary

or recruited from blood circulation lymphoid tissues

Recognizing the enemy:

How does the immune system detect the enemy?

Immune system attacks harmful pathogens but not commensal microbiota,

food antigens, etc. as well as self-components.

There are a number of different molecules on innate immune cells refer to as

receptors and called pattern or pathogen recognition receptors (PRR).

These receptors, on healthy immune cell, recognize pathogen –associated

molecular pattern (PAMP) on surfaces or inside the pathogen, and bind to it.

This binding results in signals send into the cells of immune system and
become activated and mount an immune response.

PRR also recognize damage–associated molecular pattern (DAMP) on

damaged self-tissue.

On contrast, Adaptive immune cells have receptors highly specific for

antigens.

Factors such as skin, mucus and commensal microorganisms are very important
for protection against infection but are not classed as being components of the
immune system. Defense against infection is sometimes divided into 3 layers of
protection. 1. Physical components of the type just mentioned. 2. The innate
 immune response. 3. The adaptive (acquired) immune response. They are all
very important in defending the host against pathogens and collectively are
usually very successful in protecting us from infection.

Two characteristics distinguish the innate and adaptive immune responses. The
innate responses have a very broad specificity, recognizing ‘pathogen-associated
molecular patterns’ (PAMPs) that are shared by many different pathogens, and
do not have immunological memory. Most cells of the immune system
(neutrophils, eosinophils, monocytes, macrophages, dendritic cells, follicular
dendritic cells, basophils, mast cells) are innate cells. In contrast, the adaptive
responses are highly antigen-specific and have immunological memory (have
stronger and faster responses upon re-encounter with the same specific antigen).
Immunological memory and a very high degree of antigen-specificity is a property
of lymphocytes (T-cells and B-cells) and therefore it is the lymphocytes that
mediate the adaptive response.


 Mucosa, also called mucus membrane, is an epithelial membrane containing
mucosal cells that secrete mucus. The mucosa lines the respiratory,
gastrointestinal and genitourinary tracts.

It is clear that during pregnancy there is a degree of immunosuppression seen in

the mother that is, presumably, related to the need to prevent immunological
rejection of the semi-allogeneic fetus. Research suggests that much of this
immunosuppression is located at the fetal-maternal interface in the placenta
rather than a more generalised immunosuppression. Several different
immunological mechanisms have been proposed to prevent rejection of the fetus,
but the relative importance of each in human pregnancy is still rather unclear.
Certainly alterations in adaptive immunity have been described and there is good
evidence for an increase in regulatory T cell activity in the placenta.

Immunity refers to the ability of the immune system to defend against infection.

Adaptive responses are antigen-specific, exhibit a faster and bigger response if

the same antigen is re-encountered (secondary immune response based upon
immunological memory) and is mediated by T and B lymphocytes. All other
responses are innate, are carried out by all the other cells of the immune
response (e.g. neutrophils, macrophages, mast cells, eosinophils, etc), are not
antigen-specific, and are of the same intensity if the antigen is re-encountered.
Immunology
Branch of medicine and science
Immune system overview and cells
Innate immune system
Adaptive immune system
Humoral and cell-mediated immunity
Immunodeficiency, Hypersensitivity, Autoimmunity, Transplantation and tumor immunology.
Vaccine immunology and immunodiagnostics

Description
Immunology is a branch of biology that covers the study of immune systems in all organisms.
Immunology charts, measures, and contextualizes the physiological functioning of the immune
system in states ... Wikipedia
Significant diseases: Autoimmune disease; Hypersensitivity; Immune disorder; Immunodeficiency
Significant tests: Agglutination; Immunoassay; Immunoprecipitation; Serology
System: Immune
Subdivisions: Cellular; Clinical; Genetic (Immunogenetics): Humoral; Molecular
Specialist: Immunologist
What is Immunology?
 
Immunology is the study of the immune system, which protects us from infection. There are
three main ways in which the immune system contributes to disease.
1. Activation: The immune system may be active when fighting infections and mounting an
immune response, and this results in fever, inflammation and eventual removal of the offending
pathogen. It also results in the immune system retaining a very good memory of that pathogen
which enables the immune system to mount a rapid and even more effective response to that
pathogen should it decide to infect again.

2. Immunodeficiency: The immune system may be functioning poorly (immunodeficiency)

which makes us less able to fight off infections. Immunodeficiency can occur because a
component of the immune system is missing or because other factors are stopping it from
working properly e.g. cancer, drugs and HIV infection.

3. Hypersensitivity: The immune system may be inappropriately active (hypersensitive)

against the normal body (autoimmunity) or against harmless substances (allergy). Autoimmunity
includes diseases such as rheumatoid arthritis, systemic lupus erythematosis and coeliac disease.
Allergy includes conditions such as asthma, hayfever and anaphylaxis. 
  

Useful links:
More about immunology: Bite sized immunology

Discover immunology on a whole new level!

Immunology is one of the most important subjects in USMLE Step 1. Understanding the basics of
our immune system and its protection against pathogens and exogenous substances, as well as
related disorders and dysfunctions, are essential aspects of the examination.
Prof. Dr. Peter Delves covers the entire subject of immunology, from the cells, molecules, organs
and tissues right through to applied clinical aspects including immunodeficiency, allergy,
autoimmune disease, transplantation, tumor immunology, vaccination and immunodiagnostics.
The most important learning outcomes of this course are:

 Analyzing the structural organization of the immune response

 Appreciating the medical consequences of defects in the immune system
 Understanding the diagnosis and treatment of immunological conditions

Professor Delves has nearly 40 years of experience teaching both medical and science students at
top universities and medical schools across the globe. He has authored and edited a number of
award winning textbooks, encyclopedias, and e-learning resources. Due to his extensive
involvement in student assessment, he has superb insight into the needs of students who are
studying for exams.
The download material, which includes articles and presentation slides, as well as questions on the
lectures, will provide you with the best exam preparation available.
Start learning immunology online now—with Prof. Dr. Peter Delves and Lecturio!

Immunity refers to the ability of the immune system to defend against infection.
Immunology is the study of the immune system and is a very important branch of the medical
and biological sciences. The immune system protects us from infection through various lines of
defence. If the immune system is not functioning as it should, it can result in disease, such as
autoimmunity, allergy and cancer.

What is an immunologist?
An immunologist is a scientist and/or clinician who specialises in immunology.
Many immunologists work in a laboratory focusing on research, either in
academia or private industry (e.g. in the pharmaceutical industry). Other
immunologists – “clinical immunologists” – are clinicians who focus on the
diagnosis and management of diseases of the immune system, such as
autoimmune diseases and allergies.
For more detailed information on immunology careers, please refer to
our careers section.

The immune system is an integrated defense system

composed of tissues, cells, and molecules. The
tissues are called lymphoid tissues.
There are two types of lymphoid tissues:
Primary and secondary lymphoid tissues.
1-Primary lymphoid tissues:
Bone marrow:
All the cells of the immune response originate from
multipotent hematopoietic stem cells in the bone
marrow, and B- cells mature there.
Thymus: T cells migrate from bone marrow and
reside here where they become mature and develops
its functionality.
2-Secondary Lymphoid Tissues:
Mucosal Associated Lymphoid Tissue Malt:
pathogen at mucosal surfaces are first
encountered and found in respiratory tract,
gastrointestinal tract, and genitourinary tract.
Lymph nodes: where pathogens in tissues are
encountered and trapped.
Spleen: where pathogens in blood are
encountered and trapped.
The immune system is a complex system of structures and processes that has
evolved to protect us from disease. Molecular and cellular components make up
the immune system.
There are two types of immune response:
The function of these components is divided up into nonspecific mechanisms,
those which are innate to an organism, and responsive responses, which
are adaptive to specific pathogens. Fundamental or classical immunology
involves studying the components that make up the innate and adaptive immune
system.

Innate immunity is the first line of defense and is non-specific. That is, the
responses are the same for all potential pathogens, no matter how different they
may be. Innate immunity includes physical barriers (e.g. skin, saliva etc.) and
cells (e.g. macrophages, neutrophils, basophils, mast cells etc). These
components ‘are ready to go’ and protect an organism for the first few days of
infection. In some cases, this is enough to clear the pathogen, but in other
instances the first defense becomes overwhelmed and a second line of defense
kicks in.
Adaptive immunity is the second line of defense which involves building up
memory of encountered infections so can mount an enhanced response specific
to the pathogen or foreign substance. Adaptive immunity involves antibodies,
which generally target foreign pathogens roaming free in the bloodstream. Also
involved are T cells, which are directed especially towards pathogens that have
colonized cells and can directly kill infected cells or help control the antibody
response.
The closest equivalent in the innate response to the cytotoxic T cell of the
adaptive response is the? Mast cell, eosinophil, NK cell, macrophage.
Cells of the adaptive immune response:
Helper T cells: activate macrophages, cytotoxic T- cells and B –cells.
Regulatory T-cells suppress other cells of the immune cells of the immune
response.
Cytotoxic T- cells kill infected cells
B-cells and fully differentiated progeny produce antibody molecules
Can immunity be recovered completely once depleted?
Potentially yes, using an HLA-compatible hematopoietic stem cell transplant.

Immune dysfunction and clinical immunology

The immune system is a highly regulated and balanced system and when the
balance is disturbed, disease can result. Research in this area involves studying
disease that is caused by immune system dysfunction. Much of this work has
significance in the development of new therapies and treatments that can
manage or cure the condition by altering the way the immune system is working
or, in the case of vaccines, priming the immune system and boosting the immune
reaction to specific pathogens.
Immunodeficiency disorders involve problems with the immune system that
impair its ability to mount an appropriate defence. As a result, these are almost
always associated with severe infections that persist, recur and/or lead to
complications, making these disorders severely debilitating and even fatal. There
are two types of immunodeficiency disorders: primary immunodeficiencies are
typically present from birth, are generally hereditary and are relatively rare. Such
an example is common variable immunodeficiency (CVID). Secondary
immunodeficiencies generally develop later in life and may result following an
infection, as is the case with AIDS following HIV infection.
For more information, please see our briefing on immunodeficiency.
Autoimmune diseases occur when the immune system attacks the body it is
meant to protect. People suffering from autoimmune diseases have a defect that
makes them unable to distinguish 'self' from ‘non-self’ or 'foreign' molecules. The
principles of immunology have provided a wide variety of laboratory tests for the
detection of autoimmune diseases. Autoimmune diseases may be described as
'primary' autoimmune diseases, like type-1 diabetes, which may be manifested
from birth or during early life; or as 'secondary' autoimmune diseases, which
manifest later in life due to various factors. Rheumatoid arthritis and multiple
sclerosis are thought to belong to this type of autoimmunity. Also, autoimmune
diseases can be localised, such as Crohn’s Disease affecting the GI tract, or
systemic, such as systemic lupus erythematosus (SLE).
For more information, please see our briefing on autoimmune diseases.
Allergies are hypersensitivity disorders that occur when the body's immune
system reacts against harmless foreign substances, resulting in damage to the
body's own tissues. Almost any substance can cause allergies (an allergen), but
most commonly, allergies arise after eating certain types of food, such as
peanuts, or from inhaling airborne substances, such as pollen, or dust. In allergic
reactions, the body believes allergens are dangerous and immediately produces
substances to attack them. This causes cells of the immune system to release
potent chemicals like histamine, which causes inflammation and many of the
symptoms associated with allergies. Immunology strives to understand what
happens to the body during an allergic response and the factors responsible for
causing them. This should lead to better methods of diagnosing, preventing and
controlling allergic diseases.
For more information, please see our breifing on allergies. 
 
Asthma is a debilitating and sometimes fatal disease of the airways. It generally
occurs when the immune system responds to inhaled particles from the air, and
can lead to thickening of the airways in patients over time. It is a major cause of
illness and is particularly prevalent in children. In some cases it has an allergic
component, however in a number of cases the origin is more complex and poorly
understood.
Cancer is a disease of abnormal and uncontrolled cell growth and proliferation
and is defined by a set of hallmarks, one of which is the capacity for cancer cells
to avoid immune destruction. With the knowledge that evasion of the immune
system can contribute to cancer, researchers have turned to manipulating the
immune system to defeat cancer (immunotherapy). Cancer immunotherapy
seeks to stimulate the immune system’s innate powers to fight cancerous tissue
and has shown extraordinary promise as a new weapon in our arsenal against
the disease. Other applications of immunological knowledge against cancer
include the use of monoclonal antibodies (proteins that seek and directly bind to
a specific target protein called an antigen. An example is Herceptin, which is a
monoclonal antibody used to treat breast and stomach cancer). Moreover, a
number of successful cancer vaccines have been developed, most notably the
HPV vaccine.
For more information, please see our briefing on cancer immunotherapy.
Transplants involve transferring cells, tissues or organs from a donor to a
recipient. The most formidable barrier to transplants is the immune system’s
recognition of the transplanted organs as foreign. Understanding the
mechanisms and clinical features of rejection is important in determining a
diagnosis, advising treatment and is critical for developing new strategies and
drugs to manage transplants and limit the risk of rejection.
For more information, please see our briefing on transplant immunology.
Vaccines are agents that teach the body to recognise and defend itself against
infections from harmful pathogens, such as bacteria, viruses and parasites.
Vaccines provide a sneak 'preview' of a specific pathogen, which stimulates the
body's immune system to prepare itself in the event that infection occurs.
Vaccines contain a harmless element of the infectious agent that stimulate the
immune system to mount a response, beginning with the production of
antibodies. Cells responsive to the vaccine proliferate both in order to
manufacture antibodies specific to the provoking agent and also to form 'memory
cells'. Upon encountering the infectious agent a second time, these memory cells
are quickly able to deal with the threat by producing sufficient quantities of
antibody. Pathogens inside the body are eventually destroyed, thereby thwarting
further infection. Several infectious diseases including smallpox, measles,
mumps, rubella, diphtheria, tetanus, whooping cough, tuberculosis and polio are
no longer a threat in Europe due to the successful application of vaccines.
For more information, please see our briefing on vaccines.

Veterinary immunology
Veterinary immunology is a branch of Immunology dedicated to improving animal
health. Like humans, animals also suffer from diseases caused either when
organisms try to invade their body, or when their immune system does not
function properly. Wild, domestic, and farm animals are commonly exposed to a
whole range of dangerous bacteria, viruses and parasites, which threaten their
welfare. Animal infections can have widespread effects on human working
sectors, like food and agriculture. Moreover, many animal infections can be
naturally transmitted across the species barrier to infect humans and vice-versa,
a process termed zoonosis. For example, well-studied infections including swine
and avian influenza, as well as, malaria and Lyme disease are due to
transmission from animals and insects to humans. It is therefore extremely
important that these types of diseases are effectively controlled. These measures
not only prevent any further transmission to other animals and humans, but also
reduce any potentially devastating social and economic consequences.
See the BSI briefing on Lyme disease.

BITESIZED IMMUNOLOGY

Introduction
Immunology has its origins in the study of how the body protects itself against
infectious diseases caused by microorganisms, such as bacteria, viruses,
protozoa, and fungi, and also parasitic organisms, such as helminth worms.
Important initial barriers to infection are physical (e.g. the skin), enhanced by
substances secreted by the body, such as saliva and tears, that contain
molecules that can neutralise bacteria. The internal mucosal tissues (e.g. lungs
& airways, and the gut) are coated with mucus that is able to trap potential
infectants. In the airways, mobile ciliate hairs work together to transport
contaminants away from vulnerable areas. Tissues such as the skin, mucosal
surfaces and airways also contain populations of immune cells that can respond
to infectants that breach these physical defences.
In its most complex forms, the immune system consists of two branches:
the innate immune system that utilises certain ‘hard-wired’ strategies to provide
a rapid, general, response when alerted by certain typical signals of infection
(essentially forming a first-line of defence); and the adaptive immune
system that is able to develop highly specific responses (and a persistent
‘immune memory’) to target infection with extraordinary accuracy. Both systems
work in close cooperation and, to an important extent, the adaptive immune
system relies upon the innate immune system to alert it to potential targets, and
shape its response to them.

Immune tissues
All immune cells originate in the bone marrow, deriving from haematopoietic
stem cells, but an important set of immune cells (T lymphocytes) undergo
maturation in an organ known as the thymus. The thymus and bone marrow are
known as primary lymphoid tissues. Secondary lymphoid tissues, namely
the lymph nodes, spleen and mucosa-associated lymphoid tissues (MALT)
are important sites for generating adaptive immune responses and contain
the lymphocytes (key adaptive cells). The lymphatic system is a system of
vessels draining fluid (derived from blood plasma) from body tissues. Lymph
nodes, that house lymphocytes, are positioned along draining lymph vessels, and
monitor the lymph for signs of infection. MALT tissues are important in mucosal
immune responses, and reflect the particular importance of the gut and airways
in immune defence. The spleen essentially serves as a ‘lymph node’ for the
blood.

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]). 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. Once activated, the member
proteins assemble to form complexes on the surface of microbes that punch
holes in the membrane. The complement activation pathways are termed:
the classical pathway, the alternative pathway, and the mannose-binding
lectin pathway.

Adaptive immunity
Key to the adaptive immune response is the lymphocyte. There are several
subtypes, however these fall under two broad designations: T
lymphocytes and B lymphocytes (commonly known as T cells and B cells).
Although both originate in the bone marrow, T cells mature in the thymus, whilst
B cells mature in the bone marrow. During an organism’s early development a
large number of B- and T cells are produced, each of which has the ability to
recognise a specific, and essentially unique, molecular target. An important
aspect of this maturation process is that, for both of these cell types, cells that
recognise targets within the body (‘self’ tissue) are identified and weeded-out. An
additional aspect of the maturation process for T cells is that further distinct
subsets are produced – helper T cells (also called CD4+ T cells) and cytotoxic
T cells (also called CD8+ T cells). The individual specificity of lymphocytes is
key to the generation of adaptive responses.
Adaptive immunity utilises many kinds of receptor to coordinate its activities. T
cells carry T-cell receptors (TCR), whilst B cells carry B-cell receptors (BCR),
and variations in the fine structure of these receptors account for the individual
specificity described above. In addition, another set of receptors, encoded by
the major histocompatibility complex (MHC), play an important role in
adaptive immunity. MHC class I receptors are displayed on a majority of body
cells, whilst MHC class II receptors are restricted to antigen-presenting
cells (APCs). Both of these receptor types interact with TCRs.
The adaptive immune response consists of two branches, a cellular adaptive
response (effected by cytotoxic T cells) and a humoral adaptive
response (effected by B cells). The former is directed especially towards
pathogens that have colonised body cells or body cells that have become
malignant (as in cancer). The latter generally targets pathogens or molecules
(antigens) that are free in the bloodstream or present at mucosal surfaces. As
suggested by its name, the helper T cell plays a central role in both of these
responses since, once activated, it can shape the subsequent immune response
through the particular molecules that it secretes – in particular, controlling the
activation of other cell types – as such it is an important ‘gatekeeper’. Two
subtypes of helper T cells (Th1 and Th2) have been identified as being
responsible for guiding adaptive responses towards either a cellular profile (Th1)
or a humoral profile (Th2). Th17 cells have recently been identified and are
thought to play a further specialised role. Effective regulation of immune
responses is also vital to ensure that they don’t themselves cause unnecessary
tissue damage, and regulatory T cells (Tregs) are a subset of T cell that play an
important role in this process.
Initiation of adaptive immunity
Antigen-presenting cells are functionally-defined cells that are able too initiate
adaptive immune responses by presenting antigen to T cells. Major APCs
are dendritic cells (DCs), which are found throughout the body – however
macrophages and B cells may also serve as APCs, with the former providing an
important link from innate immunity. Dendritic cells continuously monitor the
bodily environment by absorbing protein fragments that they acquire from their
surroundings, and presenting them on the their cell surface in association with
MHC receptors. DCs may be activated by local innate immune signals (induced
by infection) causing them to migrate through the lymph (or blood) to lymph
nodes where they present antigen to T cells. If a protein fragment is recognised
by a particular cytotoxic T cell this will suggest that it is of foreign origin (due to
elimination of cells recognising ‘’self’’) leading to a cellular adaptive response.
Similarly, B cells in the lymph node may encounter free antigen carried in the
lymph, leading to a humoral adaptive response. In both cases, concurrent
activation of helper T cells is usually necessary to ensure an effective overall
response.
The cellular adaptive response
Body cells are continuously processing protein derived from the internal cellular
environment and presenting it in association with MHC class I receptors. This will
typically be ‘self’ antigen (that is ignored by the immune system), but can also be
peptides derived from infecting viruses or bacteria, or aberrant cancer peptides.
Activated cytotoxic T cells of a given specificity proliferate in the lymph and then
migrate to sites of infection where they monitor body cells for signs of intracellular
infection or aberrant self proteins associated with cancer –  presented on MHC
class I molecules – using  their TCRs. If they encounter antigen that they
recognise, this indicates infection or malignancy, and they are then able to
induce apoptosis (autodestruction) of targeted body cells. This constitutes the
cellular adaptive response.
The humoral adaptive response
As already stated, B cells can recognise antigen through direct recognition of
antigen via their BCRs, without the need for prior processing or presentation via
a receptor – so they are key to identifying extracellular pathogens (e.g. bacteria
in the lymph). Once activated, B cells differentiate into plasma cells that are
capable of secreting antibody molecules into the circulation (small molecules
that match the individual specificity of the parent cell) that are then able to find
their targets elsewhere in the body. Once bound to a target, antibody molecules
can activate the classical pathway of the complement system, thereby
directing it to neutralise its targets with great specificity. Binding of antibody also
enhances phagocytosis.
Immune memory
It is important to note that an effective primary adaptive response (e.g. relating
to a pathogen that hasn’t previously been encountered) takes some time to
develop, since only small numbers of target-specific B- and T cells are present
initially and, once activated, they must first proliferate through a process known
as clonal selection, to form effector cells. A proportion of these effector cells
go on to form a stock of long-lived memory cells ensuring that if a particular
pathogen is encountered again, any subsequent secondary adaptive
response (or ‘memory response’) develops more quickly and is thus more
effective.

Cytokines and chemokines

Cytokines form an important family of proteins that function as immune
mediators and have important roles during immune responses – they can serve
to both stimulate or inhibit the differentiation, proliferation or activity of immune
cells. A subset of cytokines, chemokines, play an important role in guiding
immune cells to sites of infection by forming a chemical ‘trail’.

Immune dysfunction
Important pathologies may result from immune dysfunction. Inborn (‘congenital’)
immunodeficiencies, with a genetic basis, can disable all, or part, of the immune
response (both innate and adaptive) – resulting in vulnerabilities to infection or
cancers. Examples include severe combined immunodeficiency (SCID)
and common variable immunodeficiency (CVID). In
addition, autoimmunity occurs when the immune system mistakenly targets self
tissues, resulting in chronic inflammatory conditions and tissue destruction.
Examples include: type 1 diabetes, rheumatoid arthritis, and multiple
sclerosis.

Transplantation science
Identification of the important role of the MHC in allowing the body to discriminate
between self/non-self tissues has greatly enhanced the success of tissue and
organ transplantation, by allowing tissue matching. This has been aided by
the development of immunosuppressive drugs that are becoming increasingly
sophisticated as we identify more specific elements within the immune system to
target.

Vaccines
Vaccines can utilise harmless elements from particular pathogens to prime the
immune system, so that if the pathogen is actually encountered, it is met with a
stronger secondary (‘memory’) response and dealt with more quickly.
Alternatively, vaccines may also utilise live, but attenuated, variants of the
pathogen to induce a protective immune response. The role of vaccines remains
central to the importance of immunology as a healthcare science – with keystone
contributions in the disease areas
of smallpox, polio, tuberculosis, measles, mumps, rubella and papillomavir
us, amongst many others. However, success can depend on the target
pathogen, and effective vaccines for HIV, hepatitis C and malaria remain
elusive, in large part due to the mutability of these organisms as targets for the
immune system.
© The copyright for this work resides with the author
Pattern recognition receptors (PRRs): toll-like
receptors
Toll-like receptors (TLRs) are pattern recognition receptors (PRRs) which
play a crucial in the initiation of innate immune response by detecting potential
harmful pathogens. In mammals, the number of TLRs varies between species:
human have 10 TLRs whereas mouse have 12 TLRs. They are specialised in the
recognition of conserved molecular structures in bacteria, viruses, fungi and
parasites. Each TLR has a broad range of specificities (Figure 1).

 TLR1, 2, 4 and 6 recognise bacterial lipids
 TLR3, 7 and 8 recognise viral RNA
 TLR9 recognises bacterial DNA
 TLR5 and 10 recognise bacterial or parasite proteins
 TLRs are type I transmembrane receptors composed of an extracellular
domain involved in the recognition of the microbial product, and a TIR
domain in the cytoplasmic tail that recruits different signalling
molecules that will in turn activate the transcription of genes involved in
inflammation and in anti-microbial defences. Each TLR tailors the immune
response to the pathogen that they sense.

TLR signalling initiates with the recruitment of adaptors proteins to their

cytoplasmic tail.
There are two main adaptors: MYD88 and TRIF.

 TLR 1,2,4,5,6,7,8 and 9 use MYD88
 TLR 3 and 4 use TRIF

In addition, TLR1, 2, 4 and 6 need a second adaptor called TIRAP to recruit

MYD88 and TLR4 needs TRAM to recruit TRIF. These adaptors recruit several
proteins, such as kinases, which initiate different signalling cascades.
Three main pathways are activated by TLRs:

 MAP kinase pathway (ERK, p38 and JNK)

 NFkB pathway
 IRF pathway
In addition, TLR1, 2, 4 and 6 need a second adaptor called TIRAP to recruit
MYD88 and TLR4 needs TRAM to recruit TRIF. These adaptors recruit several
proteins, such as kinases, which initiate different signalling cascades.

Three main pathways are activated by TLRs:

 MAP kinase pathway (ERK, p38 and JNK)

 NFkB pathway
 IRF pathway

TLR-mediated signalling pathways lead to the translocation of transcription

factors, such as NFkB and IRFs in the nucleus, where they activate the
transcription of several genes involved in the immune response which eventually
result in the elimination of the pathogen.
The following are some of the elements induced upon TLR stimulation:

 Pro-inflammatory cytokines such as IL-6, TNF-alpha and IL-12

 Anti-inflammatory cytokines such as IL-10

These cytokines shape the T-cell response.

 Type I IFNs which are involved in anti-viral responses

TLR-mediated signalling pathways lead to the translocation of transcription
factors, such as NFkB and IRFs in the nucleus, where they activate the
transcription of several genes involved in the immune response which eventually
result in the elimination of the pathogen.
The following are some of the elements induced upon TLR stimulation:

 Pro-inflammatory cytokines such as IL-6, TNF-alpha and IL-12

 Anti-inflammatory cytokines such as IL-10

These cytokines shape the T-cell response.

 Type I IFNs which are involved in anti-viral responses

 Chemokines which attract other immune cells to the site of infection
 Chemokine receptors which, for example, allow TLR-activated cells to
migrate to lymph nodes
 Anti-microbial molecules
 Co-stimulatory molecules such as CD80/86 and CD40 which are
involved in T-cell activation by antigen presenting cells
 TLR signalling is also important for enhancing antigen
uptake and presentation.
 Despite the different TLRs having several signalling pathways in common
they are nonetheless able to tune the quality, the intensity and the duration
of each of these signalling cascades to generate an immune response
specific for the pathogen they are sensing.