Immunology_Introduction

1. 1.
Basic Immunology.
Introduction
COURSE OF CLINICAL IMMUNOLOGY
2015-2016

2. WHY DO WE NEED AN IMMUNE SYSTEM?
We encounter many thousands of microbes every day – many harmless, many
beneficial but some that cause disease. The immune system defends us against
infections caused by the huge variety of microorganisms we encounter,
including viruses, bacteria, fungi and parasites. Microbes divide rapidly, each
division allowing genetic variation and change.Thus microbes can change
within days or even hours. It takes years for humans to reproduce and generate
genomic variation. The immune system has developed elegant mechanisms
that facilitate somatic change without genomic variation in response
to infection and other stimuli.
THE MAJOR DEFENCE MECHANISMS AGAINST INFECTIONS
Microorganisms come in all shapes and sizes, with some penetrating into cells
and others entering the body but remaining outside the cells. Thus the immune
system has had to develop several different mechanisms to recognise and kill
microbes depending on their characteristics. From the immune systems point
of view, microbes can be divided according to type of infection caused.
Extracellular infection
◆ Bacteria enter tissues but usually remain outside the cells. However, as they
are smaller than cells of the immune system, specialised immune cells can

3. ingest, kill and digest the bacteria.
◆ Multi-cellular parasites also remain outside cells, however, as they are larger
than immune cells, they cannot be ingested and so additional immune
mechanisms are required to fight infection.
Intracellular infection
◆ Viruses enter the cytoplasm, hijack the host cells protein synthesis
machinery and assemble new virus particles, which bud from the cell surface
and infect new cells. Immune mechanisms which act in the extracellular space
are ineffective once virus enters the cells.
◆ Intra-vesicular organisms (e.g. Mycobacteria) are taken up into cells but
remain within vesicles, never entering the cytoplasm. Immune mechanisms
that kill virus-infected cells are ineffective as the organisms are in a different
cell compartment – therefore requiring an additional immune strategy.
Infecting organisms must first breach the body’s natural defences (skin,
mucous membranes etc.). The pathogen then faces the two major types of
immune response, the innate immune response, and the adaptive or specific
immune response. When thinking about how these systems work it is helpful
to consider (1) the recognition phase where the microorganism/pathogen is
recognised as foreign, and (2) the effector phase, which kills the organism.

4. The innate immune response is immediately available to fight pathogens
without the requirement for prior exposure to the pathogen. This is the first
line of defence against pathogens, recognising microbes by the presence of
molecular patterns not present on mammalian cells. Innate immunity is
moderately effective at controlling infection and does not improve with
repeated exposure to a particular organism.
The adaptive immune response is refined and expanded after infection, taking
several days to provide protection on first exposure to a particular pathogen.
The cells and molecules produced are highly specific for the pathogen. The
adaptive immune system remembers when a microbe has previously invaded
the body resulting in a rapid and efficient removal of the pathogen on the
second and third time that it invades the body (immunological memory).
Innate and adaptive immunity depend on white blood cells or leucocytes.
Innate immunity involves granulocytes and macrophages. Adaptive immune
responses depend on lymphocytes, which provide the lifelong immunity that
can follow exposure to disease or vaccination. However, the two systems do
not operate independently – there are many examples of co-operation. Killing
of microorganisms by the adaptive immune response frequently depends upon
linking antigen-specific recognition to activation of effector mechanisms

5. that are also used in the innate response.
Together, the innate and adaptive immune systems provide an amazing defence
system. Despite the fact that we are surrounded by a multitude of potentially
pathogenic microorganisms, we rarely succumb to infection. Many infections
are eliminated by the innate immune system and cause no disease. Infections
that cannot be resolved by innate immunity trigger adaptive immunity, which
usually eliminates the infection (often before we are aware of it) and generates
immunological memory.
WHAT HAPPENS WHEN THE IMMUNE SYSTEM GOES WRONG?
The immune system is only apparent when it goes wrong, and virtually any
clinical presentation may be the sign of an underlying immunological disorder.
The immune system must find a balance between producing a life-saving
response to infection and tissuedamaging reactions. It is also essential that the
immune system only mounts a vigorous response to pathogens that pose a
threat, and ignores our own tissues, as well as environmental substances
including foods and medicines.
Immunodeficiency diseases
Immunodeficiency means a failure of the immune system to protect us from
infection. It may be primary (due to an intrinsic defect in the immune system)

6. or secondary, (due to drugs, infection, malnutrition etc.).
Overactivity of part of the immune system
The immune response can cause incidental tissue damage as well as the
intended removal and/or destruction of microorganisms. Additionally the
immune system may fail to distinguish between pathogens and innocuous
stimuli such as pollen or self-tissue. In this case a vigorous immune response
causes disease.
Allergy
An over-response to environmental stimuli, which pose no threat, is called
allergy. Several different immune mechanisms may be involved. The most
common mechanism causes rapid responses varying in severity from hayfever
to potentially fatal anaphylactic shock.
Autoimmunity
Autoimmune diseases can affect any tissue in the body, and occur when the
immune system fails to distinguish between self (which should be ignored) and
non-self (which should be attacked). Many autoimmune diseases can be
diagnosed by testing for immune products (antibodies) against self-tissues in
patients’ blood.
Transplantation

7. Transplantation involves transfer of cells, tissues or solid organs from one
person to another. As the transplanted tissue is seen as non-self, the immune
system attempts to eliminate it. Powerful immunosuppression has been
required to make clinical transplantation a reality. Transplantation of bone
marrow, kidney, pancreas, liver, heart and lung are now routine treatments for
irreversible organ failure.
VACCINATION
Vaccination is one of the great success stories of immunology. By generating
an adaptive immune response that leads to immunological memory, people can
be protected from severe disease. Vaccination has led to the eradication of
smallpox, and the World Health Organization aims to eradicate poliomyelitis in
the near future. The incidence of many severe infectious diseases has been
hugely reduced by vaccination campaigns.
Clinical immunology is the specialty that focuses on diagnosis and treatment
of immune mediated disease. An understanding of the immune system and
how it works is essential for treating patients with these disorders. However,
immunological disorders impinge on all medical specialties to a greater or
lesser degree. Thus all healthcare professionals require some understanding of
basic and clinical immunology.