Immunity (derived from immunitas: Latin for exemption from civic duties and prosecution) means protection from disease and especially infectious disease. Cells and molecules involved in such protection constitute the immune system and the response to introduction of a foreign agent is known as the immune response. Not all immune responses protect from disease; some foreign agents, such as the allergens found in house dust mite, cat dander or rye grass pollen, cause disease as a consequence of inducing an immune response. Likewise some individuals mount immune responses to their own tissues as if they were foreign agents. Thus, the immune response can cause the autoimmune diseases common to man such as multiple sclerosis, diabetes, rheumatoid arthritis or myasthenia gravis. Most individuals do not suffer from autoimmune disease because they have developed tolerance towards their own (self) tissues.
Innate and Adaptive Immunity
The normal individual has two levels of defence against foreign agents. The first type is present in neonatal animals and in invertebrates namely natural or innate immunity. This type of immunity is sometimes referred to as non-specific but broadly specific would be a better description. The second type of immunity is adaptive or acquired immunity and is confined to vertebrates.
Innate (or natural) immunity
This is made up of several components.
- Physical barriers are the first line of defense against infection. The skin and mucous membranes provide a continous surface which must be breached and back this up with mechanical protection through cilia and mucous.
- Physiological factors such as pH, temperature and oxygen tension limit microbial growth. The acid environment of the stomach combined with microbial competion from the commensal flora inhibits gut infection.
- Protein secretions into external body fluids such as lysozyme also help resist invasion. Soluble factors within the body such as complement, interferons and collectins and other "broadly specific" molecules such as C-reactive protein are of considerable importance in protection against infection.
- Phagocytic cells are critical in the defense against bacterial and simple eukaryotic pathogens. Macrophages and Polymorphonuclear leucocytes (PMN) can recognise bacterial and yeast cell walls through broadly specific receptors (usually for carbohydrate structures) and this recognition is greatly enhanced by activated complement (opsonin) [as well as by specific antibody, see on].
Acute Inflammation
The acute inflammatory response which has been described in previous lectures is a key part of the innate immune system. Many infections, especially where small wounds are the route of entry, are eliminated by the combination of complement and recruitment of phagocytes, which flow from the acute inflammatory response.
A defining aspect of the innate immune system is that it carries no memory of an encounter with a foreign organism.
What is an antigen?
An antigen is defined as "anything that can be bound by an antibody". This can be an enormous range of substances from simple chemicals, sugars, small peptides to complex protein complexes such as viruses. The small antigens are not, however immunogenic in themselves and need to be coupled to a carrier to elicit an immune response. Such small antigens are referred to as haptens.
In fact antibodies interact specifically with relatively small parts of molecules. These are known as antigenic determinants or epitopes. Sometimes the epitope is composed of a string of amino acids as might be found in a short peptide, such epitopes are said to be linear. Other epitopes are formed by more complex 3-dimensional structures present only as part of a native protein, such epitopes are called conformational.
Adaptive immunity
The second level of defence increases in
strength and effectiveness with each encounter. The foreign agent is
recognised in a specific manner and the immune system acquires
memory towards it.
The
first encounter with an antigen is known as the primary response.
Re-encounter with the same antigen causes a secondary response that
is more rapid and powerful.
Acquired immunity is a useful evolutionary adaptation because it improves
the efficacy of the innate immune response by focusing the response to the
site of invasion/infection as well as providing additional effector
mechanisms that are unique to lymphocytes. The difference between
innate and acquired immunity lies in the antigen specificity of
lymphocytes. This property is conferred upon lymphocytes by the expression
of cell surface receptors that recognise discrete parts of the antigen
known as antigenic epitopes. The cell surface receptor of B
lymphocytes, derived from Bone marrow in mammals or the Bursa
of fabricius in chickens, is an immunoglobulin molecule which,
when secreted by the B cell, is known as an antibody. Evolution in
mammals has led to expansion of the antibody gene pool and a mechanism for
generating a vast number of antibodies with a wide range of different
specificities. This large repertoire of different antibody
specificities arms the immune system to respond to practically all of the
potential antigens nature can devise.
Antibodies work in three ways.
- Neutralisation. blocking the
biological activity of their target molecule e.g a toxin binding to
it's receptor
- Opsonisation. interact with
special receptors on various cells, including macrophages, neutrophils,
basophils and mast cells allowing them to "recognise" and
respond to the antigen
- Complement Activation. cause
direct lysis by complement complement recruitment also enhances
phagocytosis
Antibodies have two ends. One end interacts with the antigen (the variable
part) leaving the other (constant) end free to interact with
the immunoglobulin receptors on these cells. During an immune response, a
complex lattice of interlinked antigens and antibodies, known as an immune
complex, will present an array of constant regions which can activate
the various cells mentioned above through ligation of their immunoglobulin
receptors.
Information provided by: http://www-immuno.path.cam.ac.uk