Immunology By Assistant Professor Dr. Ahmed Ali Mohammed

Immunology: Immunity: is the science that studying our protection from foreign macromolecules or invading organisms and our responses to them. These invaders include viruses, bacteria, protozoa or even larger parasites. it is studying our developed immune responses against our own proteins (and other molecules) in autoimmunity and against our own aberrant cells in tumor immunity.  It is also studying the development, anatomy functions and malfunctions of the immune system, which all are of fundamental importance to the understanding of human disease. Immunity: is the protection against diseases, usually infectious diseases, mediated by a collection of molecules, cells and tissues, collectively called the immune system. In a broader sense, immunity refers to the ability to respond to foreign substances, including microbes or molecules. It is the ability of an organism to resist a particular infection or toxin by the action of specific antibodies or sensitized white blood cells.

Antigens -Immunogen: a substance that induces a specific immune response. -Antigen (Ag): a substance which induces an immune response, reacts with the products of a specific immune response. Its properties: Foreign (not a shared human molecule). Large (>10 KDa), complex molecule. Biodegradable (not inert). Examples: infectious microorganisms, allergens, any large complex biomolecule. -Hapten: a substance that is non-immunogenic but can react with the products of a specific immune response. Haptens are small molecules which could never induce an immune response when administered by themselves but it can be when coupled to a carrier molecule. Free haptens can react with the products of the immune response after such products have been elicited. Haptens have the property of antigenicity but not immunogenicity.

Factors influencing immunogenicity Contribution of the Immunogen 1. Foreignness The immune system normally discriminates between self and non-self such that only foreign molecules are immunogenic. 2. Size There is not absolute size above which a substance will be immunogenic. However, in general, the larger molecule is likely to be the more immunogenic. 3. Chemical Composition In general, the chemically more complex substance will be more immunogenic. 4. Physical form In general, antigens particulates are more immunogenic than soluble ones and denatured antigens more immunogenic than the native form. 5. Degradability Antigens that are easily phagocytosed are generally more immunogenic.

Contribution of the Biological System 1. Genetic Factors Some substances are immunogenic in one species but not in another. Similarly, some substances are immunogenic in one individual but not in others (i.e. responders and non- responders). 2. Age Usually the very young and the very old have a reduced ability to develop an immune response in response to an immunogen.

 Method of Administration 1. Dose The dose of administration of an immunogen can influence its immunogenicity. There is a dose of antigen above or below which the immune response will not be optimal. 2. Route Generally, the subcutaneous route is better than the intravenous or intragastric routes. The route of antigen administration can also alter the nature of the response 3. Adjuvants Substances that can enhance the immune response to an immunogen are called adjuvants. The use of adjuvants, however, is often hampered by undesirable side effects such as fever and inflammation.

Chemical nature of immunogens Proteins The vast majority of immunogens are proteins. These may be pure proteins or they may be glycoproteins or lipoproteins. In general, proteins are usually very good immunogens. Polysaccharides  Pure polysaccharides and lipopolysaccharides are good immunogens. Nucleic Acids Nucleic acids are usually poorly immunogenic. However, they may become immunogenic when single stranded or when complexed with proteins. Lipids In general, lipids are non-immunogenic, although they may be haptens.

Antibodies Antibody (Ab) also known as an immunoglobulin (Ig) is a specific protein which is produced in response to an immunogen and reacts with an antigen. It is large and Y-shaped produced mainly by plasma cells and is used by the immune system to neutralize pathogens such as pathogenic bacteria and viruses. Each tip of the "Y" of an antibody contains a paratope (analogous to a lock) that is specific for one particular epitope (similarly analogous to a key) on an antigen, allowing these two structures to bind together with precision (see figure below).

The antibody recognizes a unique molecule of the pathogen, called an antigen, via the Fab's variable region. Using this binding mechanism, an antibody can tag a microbe or an infected cell for attack by other parts of the immune system, or can neutralize its target directly (for example, by blocking a part of a microbe that is essential for its invasion and survival). The ability of an antibody to communicate with the other components of the immune system is mediated via its Fc region (located at the base of the "Y"). The production of antibodies is the main function of the humoral immune system. They are secreted by differentiated B cells called plasma cells.

Immunoglobulin classes Antibody and antigen interact by spatial complementarity (lock and key). The antibody's paratope interacts with the antigen's epitope. Often, once an antibody and antigen bind, they become an immune complex, which functions as a unitary object and can act as an antigen in its own, being countered by other antibodies. Immunoglobulin classes The immunoglobulins can be divided into five different classes, based on differences in the amino acid sequences in the constant region of the heavy chains. The five immunoglobulin classes are: • IgG - Gamma heavy chains. (Found as monomer) • IgM - Mu heavy chains. (Found as pentamer) • IgA - Alpha heavy chains. (Found as dimer) • IgD - Delta heavy chains. (Found as monomer) • IgE - Epsilon heavy chains. (Found as monomer) The classes of immunoglobulins can be divided into subclasses based on small differences in the amino acid sequences in the constant region of the heavy chains: IgG Subclasses: IgG1, IgG2, IgG3, IgG4. IgA Subclasses: IgA1 and IgA2

Types of Immunity We are constantly being exposed to infectious agents and yet, in most cases, we are able to resist these infections. It is our immune system that enables us to resist infections. The immune system is composed of two major subdivisions: the innate or non-specific immune system and the adaptive or specific immune system. The innate immune system is our first line of defense against invading organisms while the adaptive immune system acts as a second line of defense and also affords protection against re-exposure to the same pathogen. Each of the major subdivisions of the immune system has both cellular and humoral components by which they carry out their protective function. The innate immune system also has anatomical features that function as barriers to infection.

The elements of the innate (non-specific) immune system include mechanical anatomical barriers, secretory molecules and cellular components. Among the mechanical anatomical barriers are the skin and internal epithelial layers, the movement of the intestines and the oscillation of broncho-pulmonary cilia. Associated with these protective surfaces are chemical and biological agents. The anatomical barriers are very effective in preventing colonization of tissues by microorganisms. However, when there is damage to tissues the anatomical barriers are breached and infection may occur. Once infectious agents have penetrated tissues, another innate defense mechanism comes into play. The other mechanisms includes Humoral and Cellular barriers to infection

Anatomical barriers to infections Mechanical factors Chemical factors Biological factors

Acquired (or passive) immunity Immunity can be acquired, without the immune system being challenged with an antigen. This is done by: transfer of serum or gammaglobulins from an immune donor to a non-immune individual. Alternatively, immune cells from an immunized individual may be used to transfer immunity. Passive immunity may be acquired naturally or artificially. Tolerance Tolerance refers to the specific immunological non-reactivity to an antigen resulting from a previous exposure to the same antigen. While the most important form of tolerance is non-reactivity to self antigens, it is possible to induce tolerance to non-self antigens. When an antigen induces tolerance, it is termed tolerogen. When the immune system recognizes a self antigen and mounts a strong response against it, autoimmune disease develops.

Autoimmunity Immunodeficiency It is the breakdown of the mechanisms responsible for self tolerance and induction of an immune response against self components. The immune response may not always be harmful (e.g., anti-idiotype antibodies). However, in numerous autoimmune diseases it is well recognized that products of the immune system cause damage to the self. effector mechanisms in autoimmune diseases are both antibodies and effector T cells which can be involved in the damage in autoimmune diseases. Autoimmunity manifest by diverse clinical problems related to the tissues or organs involved. Autoimmune diseases are caused by a combination of inherited genes and environmental factors that result in a failure of the mechanisms of self-tolerance and immune regulation. Immunodeficiency They are manifested by an increased risk of infections and tumors and are caused by gene mutations, malnutrition, certain viruses such as HIV, or by treatments for cancer. Immunodeficiency is the failure of the immune system to protect against disease or malignancy. Primary Immunodeficiency is caused by genetic or developmental defects in the immune system. These defects are present at birth but may show up later on in life. Secondary or acquired immunodeficiency is the loss of immune function as a result of exposure to disease agents, environmental factors, immunosuppression, or aging. Individuals with immunodeficiency are susceptible to a variety of infections and the type of infection depends on the nature of immunodeficiency.

The immune system The bodily system that protects the body from foreign substances, cells, and tissues by producing the immune response and that includes especially the thymus gland, spleen, lymph nodes, special deposits of lymphoid tissue (as in the gastrointestinal tract and bone marrow), macrophages, lymphocytes including the B cells and T cells, and antibodies. It is made up of many types of molecules and cells that are distributed in every tissue of the body, as well as specialized lymphoid organs, which act in a coordinated manner to prevent or eliminate microbial infections, to suppress the growth of tumors, and to initiate repair of damaged tissues.