IMMUNITY, IMMUNE RESPONSE, HYPERSENSITIVITY

           IMMUNITY

          The term ‘immunity’ has traditionally referred to the resistance exhibited by the host towards injury caused by micro-organisms and their products. However, protection against infectious diseases is only one of the many consequences of immune response, which in its entirety is concerned with the reaction of the body against any foreign antigen.

            Immunity against infectious diseases is of different types –

            1. INNATE (Native) IMMUNITY:- Innate or native immunity is the resistance to infections that an individual possesses by virtue of its genetic and constitutional make-up. It is not affected by prior contact with micro-organisms or immunization.

            Based on the degree of resistance to infection, innate immunity may be – specific, racial and individual immunity.

            Species immunity refers to the total or relative refractoriness to a pathogen, shown by all members of a species. For example – All human beings are totally insusceptible to plant pathogens and many animal pathogens such as rinderpest or distemper. Within a species, different races may show differences in susceptibility to infection. This is known as a racial immunity. Example – High resistance of Algerian sheep to anthrax. The differences in innate immunity exhibited by different individuals in a race, is known as individual immunity.

            2. ACQUIRED IMMUNITY:- The resistance that an individual acquires during life is known as acquired immunity. Acquired immunity is of two types – Active and Passive immunity.

            Active immunity is the resistance developed by an individual as a result of an antigenic stimulus. It is also known as adaptive immunity as it represents the adaptive response of the host to a specific pathogen or other antigen. Active immunity is of two types – natural and artificial active immunity. Natural active immunity results from either a clinical or an in-apparent infection by a microbe. Example – A person who has recovered from the attack of measles develops natural active immunity. Artificial active immunity is the resistance induced by vaccines. Vaccines are preparations of live or killed micro-organisms or their products used for immunization. Examples – Tetanus toxoid, Polio, Hepatitis B vaccine, etc.

            Passive immunity is the resistance that is transmitted passively to a recipient in a readymade form. Passive immunity may be natural or artificial. Natural passive immunity is the resistance passively transferred from mother to baby. In human infants, maternal antibodies are transmitted predominantly through the placenta, while in animals such as pigs, transfer of antibodies occurs orally through the colostrum. Artificial passive immunity is the resistance passively transferred to a recipient by the administration of the antibodies. The agents used for this purpose are hyperimmune sera of human and animal origin, convalescent sera and pooled human gammaglobulin.

            3. HERD IMMUNITY:- This refers to the overall level of immunity in a community and is relevant in the control of epidemic diseases. When a large proportion of individuals in a community (herd) are immune to a pathogen, the herd immunity to a pathogen is satisfactory. When herd immunity is low, epidemics are likely to occur on the introduction of a suitable pathogen, due to the presence of large numbers of susceptible individuals in the community.

IMMUNE RESPONSE

             The specific reactivity induced in a host by an antigenic stimulus is known as the immune response. In infectious disease it is generally equated with protection against invading micro-organisms. But the immune response has a much wider scope and includes reactions against any antigen, living or non-living. It may lead to consequences that are beneficial, indifferent or injurious to the host. It also includes the state of specific non-reactivity (tolerance) induced by certain type of antigenic stimuli.

            TYPES OF IMMUNE RESPONSE

            The immune response can be of two types – humoral (antibody mediated) and cellular (cell mediated). The two are usually developed together, though at times one or the other may be predominant or exclusive. They usually act in conjunction but may sometimes act in opposition.

            1. Humoral Immune Response:- Humoral or antibody mediated  immunity is the aspect of immunity that is mediated by macromolecules found in extracellular fluids such as secreted antibodies, complement proteins, and certain antimicrobial peptides. Humoral immunity is so named because it involves substances found in the humors, or body fluids.

            Humoral immunity provides primary defense against most extracellular bacterial pathogens, helps in defense against virus that infect through the respiratory or intestinal tracts, prevents recurrence of virus infections and participates in the pathogenesis of immediate (types 1, 2 and 3) hypersensitivity and certain autoimmune diseases.

             2. Cellular Immune Response:- Cellular or cell mediated does not involve antibodies, but rather involves the activation of phagocytes, antigen-specific cytotoxic T-lymphocytes, and the release of various cytokines in response to an antigen.

            Cellular immunity protects against fungi, viruses and facultative intracellular bacterial pathogens, participates in the rejection of homografts and graft-versus-host reaction, provides immunological surveillance and immunity against cancer, and mediates the pathogenesis of delayed (type 4) hypersensitivity and certain autoimmune diseases.

            PRIMARY AND SECONDARY IMMUNE RESPONSE

            1. Primary Immune Response:- To protect from bacteria, viruses and any other foreign substances (known as antigens), which have never been introduced before, the immune system needs to recognize these substances and develop a weak immune response known as primary immune response.

            The primary immune response can be divided into lag, log, steady and declining phases.

            Lag (latent) phase – This is the time from initial antigen exposure to the time when antibodies are detected in the blood and takes about a week. In this time specialized B and T cells are activated by contact with the antigen.

            Log (exponential) phase – This is the phase in which there is a sharp rise in the levels of antibodies which are secreted by large numbers of plasma cells (differentiated B cells).

            Steady (plateau) phase – In this phase, the antibody levels stay relatively constant due to the continuous secretion of antibodies to replenish any that have degraded.

            Decline phase – Here, antibody gradually decrease due to the existing plasma cells dying off, with no new plasma cells generated to replace them. The immunogen has probably been eliminated from the body, so no further antibody production is needed.

            2. Secondary Immune Response:- When an immune system encounters the same antigen for the second time, it produces a secondary immune response. The response developed will be more powerful, rapid and require less antigens to trigger the reaction.

            In secondary immune response, the lag phase is shorter and high and steady levels of antibodies are generated within a few days. This is due to antigen specific memory T and B cells initially developed during primary immune response.

            Due to the rapidness of the secondary immune response the antigen can be eliminated from the body fairly soon after it has entered and before it causes disease. The antibodies produced remain in circulation longer to ensure the infection has disappeared.

DIFFERENCES BETWEEN PRIMARY AND SECONDARY IMMUNE RESPONSES

PRIMARY IMMUNE RESPONSE	SECONDARY IMMUNE RESPONSE
1. After initial exposure to a foreign antigen, there is a lag phase where B cells are differentiating into plasma cells, but not yet producing antibodies. Antibody generation can take anytime from 2 days to several months.	1. If a previously encountered antigen enters the body again, a few days up to several years later, a secondary immune response develops. This time, the lag phase is greatly reduced, to about 3-4 days.
2. Low quantities of antibodies are normally secreted.	2. High levels of antibodies are produced.
3. After a while, the amount of antibody decreases to minimal levels.	3. Antibody levels remain elevated for longer.
4. Antibodies are mostly IgM, but some IgG antibodies are produced.	4. IgGs are the main antibody secreted, with some small amounts of IgM sometimes.

HYPERSENSITIVITY

            Hypersensitivity is an immune response that damages the body's own tissues. They are divided into four classes (Type I – IV) based on the mechanisms involved and the time course of the hypersensitive reaction.

            Type I hypersensitivity is an immediate or anaphylactic reaction, often associated with allergy. Symptoms can range from mild discomfort to death. Type I hypersensitivity is mediated by IgE, which triggers degranulation of mass cells and basophils when cross-linked by antigen.

         Type II hypersensitivity occurs when antibodies bind to antigens on the patient's own cells, marking them for destruction. This is also called antibody-dependent (or cytotoxic) hypersensitivity, and is mediated by IgG and IgM antibodies.

            Type III hypersensitivity is triggered by Immune complexes (aggregations of antigens, complement proteins, and IgG and IgM antibodies) deposited in various tissues reactions.

            Type IV hypersensitivity (also known as cell-mediated or delayed type hypersensitivity) usually takes between two and three days to develop. Type IV reactions are involved in many autoimmune and infectious diseases, but may also involve contact dermatitis (poison ivy). These reactions are mediated by T cells, monocytes, and macrophages.

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