Immunity: the word

To the ancient Romans, immunity meant exemption from military service. The Latin word immunis means not serving. The meaning has been extended to include exemption from lots of other things. During charities week, shops on Byres Road used to be able to buy an immunity that protected them from invasion by can-rattling students.

Immunity: the phenomenon

Immunity is the state of resistance, or insusceptibility to toxic molecules, microorganisms, and foreign cells. The study of immunology, a broad field encompassing basic research and clinical application, deals with antigens, anti bodies and cell mediated functions.

Classification

Innate (native) immunity

Species

a. Non specific Racial

Individual

Species

a. Specific Racial

Individual

Acquired (adaptive) immunity

Natural

a. Active

Artificial

Natural

b. Passive

Artificial

Innate immunity

Innate or native immunity is the resistance to infections that an individual possesses by virtue of his genetic and constitutional make-up. It is not affected by prior contact with microorganism or immunization. It may be nonspecific, when it indicates a degree of resistance to infections in general, or specific where resistance to a particular pathogen is concerned.

Innate immunity may be considered at the level of the species, race or individual. Species immunity refers to the total or relative refractoriness to a pathogen, shown by all members of a species. For e.g., all human beings are totally unsusceptible to plant pathogens and to many animal pathogens such as rinderpest or distemper.

Within the species, different races may show difference in susceptibility to infections. This is known as racial immunity. E.g. High resistance of Algerian sheep to Anthrax, Negroid origins in the USA are more susceptible than Caucasians to tuberculosis.

The difference in innate immunity exhibited by the individuals in a race is known as individual immunity. The genetic basis of the individual immunity is evident from studies on the incidence of infectious diseases in twins. It is well documented of infectious disease in twins. It is well documented that homozygous twins exhibit similar degree of resistance to lepromatous leprosy and tuberculosis. Such correlation is not seen in heterozygous twins.

Several factors influences the level of innate immunity in an individual:

Age: the two extremes of life carry higher susceptibility to infectious diseases as compared with adults.

Hormonal influences: Endocrine disorders such as diabetes mellitus, hypothyroidism and adrenal dysfunction are associated with an enhanced susceptibility to infections.

Nutrition: the interaction between mal-nutrition and immunity is complex but in general, both humoral and cell mediated immunity will reduce when there is malnutrition.

Mechanism of innate immunity

1.Epithelial surfaces: the intact skin and mucous membrane covering the body protect it considerably against invasion of microorganisms. They provide much more than a mechanical barrier. Healthy skin possess bactericidal activity to which the presence of high concentration of salt in the drying sweat, the sebaceous secretions and the long chin fatty acids and soaps contribute

2.Antibacterial substances in blood and tissue: The complement system is a biochemical substance, which helps to clear pathogens from an organism. It is one part of the larger immune system. The complement system consists of a number of small proteins found in the blood, which work together to kill target cells by disrupting the target cell's plasma membrane. Eg. Interferon

3.Microbial antagonism: the skin and mucous have resident bacterial flora, which prevent colonization by the pathogens. The importance of normal bacterial flora is exemplified by the extreme susceptibility of germ free animals to all types of infections.

4.Cellular factors in innate immunity: natural defense against the invasion of blood and tissues by microorganisms and other foreign particles is mediated to a large extent by phagocytic cells, which ingest and destroy them. Phagocytic cells are two type; 1. Microphages or poly-morpho nuclear cells 2. Macrophages. Macrophages consist of histiocytes, which are the wandering amoeboid cells seen in tissues, the fixed reticuloendothelial cells and the monocytes in the blood.

5.Inflammation: Inflammation is one of the first responses of the immune system to infection or irritation. Inflammation is stimulated by chemical factors released by injured cells and serves to establish a physical barrier against the spread of infection, and to promote healing of any damaged tissue following the clearance of pathogens.Chemical factors produced during inflammation (histamine, bradykinin, serotonin, leukotrienes) sensitize pain receptors, cause vasodilation of the blood vessels at the scene, and attract phagocytes, especially neutrophils.

6.Fever: a rise of temperature following infection is a natural defense mechanism. It not merely helps to accelerate the physiological processes but may, in some cases, actually destroy the infecting pathogens. E.g. Therapeutic induction of fever employed in the destruction of treponema pallidum.

Acquired immunity

The resistance that individual acquires during life is known as acquired immunity as distinct from inborn innate immunity. Acquired immunity is of two types, active and passive. 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 an adaptive response of the host to specific pathogen or other antigen. This involves the active functioning of the host’s immune apparatus leading to the synthesis of the antibodies and the production of immunologiclly active cells. Active immunity sets in only after a latent period, which is required for the immunological machinery to be set in motion. If the individual who has been actively immunized against an antigen experiences same antigen subsequently, the immune response occurs more quickly and abundantly than during the first encounter. This is known as secondary response.

The resistance that is transmitted passively to a recipient in a readymade form is known as passive immunity. Here the recipient’s immune system plays no active role. There is no antigenic stimulus; instead performed antibodies are administered. There is no latent period in passive immunity, protection being effective immediately after passive immunization. No secondary type response occurs in passive immunity. In fact, passive immunity diminishes in effect with repetition. The main advantage of passive immunity is that it acts immediately and, there fore can be employed when instant immunity desired.

Active immunity may be artificial or natural. Naturally acquired active immunity occurs when a person is exposed to a live pathogen, and develops a primary immune response, which leads to immunological memory. Artificial active immunity is the resistance induced by the vaccines. Vaccines are preparations of live or killed microorganisms or their products used for immunization.

Examples of vaccines as follows

1.Bacterial vaccines

• Live BCG vaccine

• Killed cholera vaccine

• Sub-unit typhoid anti bacillus

• Bacterial products tetanus toxoid

2.Viral vaccines

• Live oral polio vaccine

• Killed injectable polio vaccine

• Subunit hepatitis vaccine

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 mainly orally through the colostrum. The human colostrum is also rich in IgA antibodies resistant to intestinal digestion, gives protection to the neonate.

Artificial passive immunity is the resistance passively transferred to a recipient by the administration of anti bodies. E.g. ATS

Mechanism of acquired immunity

Acquired immunity is given lymphocytes. Lymphocytes come in two major types: B cells and T cells. The peripheral blood contains 20–50% of circulating lymphocytes; the rest move in the lymph system. Roughly 80% of them are T cells, 15% B cells and remainder are null or undifferentiated cells. B cells are produced in the stem cells of the bone marrow; they produce antibody and oversee humoral immunity. T cells are non-antibody-producing lymphocytes which are also produced in the bone marrow but sensitized in the thymus and constitute the basis of cell-mediated immunity. The production of these cells is diagrammed below. Parts of the immune system are changeable and can adapt to better attack the invading antigen. There are two fundamental adaptive mechanisms: cell-mediated immunity and humoral immunity.

Cell-mediated immunity

Macrophages engulf antigens, process them internally, then display parts of them on their surface together with some of their own proteins. This sensitizes the T cells to recognize these antigens. All cells are coated with various substances. CD stands for cluster of differentiation and there are more than one hundred and sixty clusters, each of which is a different chemical molecule that coats the surface. B cells are coated with CD21, CD35, CD40, and CD45 in addition to other non-CD molecules. T cells have CD2, CD3, CD4, CD28, CD45R, and other non-CD molecules on their surfaces.

Cytotoxic or killer T cells (CD8+) do their work by releasing lymphotoxins, which cause cell lysis. Helper T cells (CD4+) serve as managers, directing the immune response. They secrete chemicals called lymphokines that stimulate cytotoxic T cells and B cells to grow and divide, attract neutrophils, and enhance the ability of macrophages to engulf and destroy microbes. Suppressor T cells inhibit the production of cytotoxic T cells once they are unneeded, lest they cause more damage than necessary. Memory T cells are programmed to recognize and respond to a pathogen once it has invaded and been repelled.

Diagram showing mechanism of humoral and cellar immunity

Humoral immunity

An immuno-competent but as yet immature B-lymphocyte is stimulated to maturity when an antigen binds to its surface receptors and there is a T helper cell nearby (to release a cytokine). This sensitizes or primes the B cell and it undergoes clonal selection, which means it reproduces asexually by mitosis. Most of the family of clones becomes plasma cells. These cells, after an initial lag, produce highly specific antibodies at a rate of as many as 2000 molecules per second for four to five days. The other B cells become long-lived memory cells.

Antibodies, also called immunoglobulins or Igs, constitute the gamma globulin part of the blood proteins. They are soluble proteins secreted by the plasma offspring (clones) of primed B cells. The antibodies inactivate antigens by, (a) complement fixation (proteins attach to antigen surface and cause holes to form, i.e., cell lysis), (b) neutralization (binding to specific sites to prevent attachment—this is the same as taking their parking space), (c) agglutination (clumping), (d) precipitation (forcing insolubility and settling out of solution), and other more arcane methods.

Constituents of gamma globulin are: IgG-76%, IgA-15%, IgM-8%, IgD-1%, and IgE-0.002% (responsible for autoimmune responses, such as allergies and diseases like arthritis, multiple sclerosis, and systemic lupus erythematosus). IgG is the only antibody that can cross the placental barrier to the fetus and it is responsible for the 3 to 6 month immune protection of newborns that is conferred by the mother. IgM is the dominant antibody produced in primary immune responses, while IgG dominates in secondary immune responses. IgM is physically much larger than the other immunoglobulins.

Notice the many degrees of flexibility of the antibody molecule. This freedom of movement allows it to more easily conform to the nooks and crannies on an antigen. The upper part or Fab (antigen binding) portion of the antibody molecule (physically and not necessarily chemically) attaches to specific proteins [called epitopes] on the antigen. Thus antibody recognizes the epitope and not the entire antigen. Lest you think that these are the only forms of antibody produced, you should realize that the B cells could produce as many as 10¹⁴ conformationally different forms.

Summary

Immunity can be either natural or artificial, innate or acquired=adaptive, and either active or passive.

• Active natural (contact with infection): develops slowly, is long term, and antigen specific.

• Active artificial (immunization): develops slowly, lasts for several years, and is specific to the antigen for which the immunization was given.

• Passive natural (Transplacental = mother to child): develops immediately, is temporary, and affects all antigens to which the mother has immunity.

• Passive artificial (injection of gamma globulin): develops immediately, is temporary, and affects all antigens to which the donor has immunity.

Reference:

1. Anathanarayan R, Jayaram CK. Text book of microbiology. 7^th ed. Chenni: Orient Longman;2005

2. Brooks FG, Brtel SJ, et al. Medical microbiology. 18^th ed. East Norwalk: Prentice-Hall; 1989

3. Greenwood D, Slack RCB. Medical microbiology. 17^th ed. Edinburgh: Churchill Livingston; 2003

4. Roitt, I Blackwell. Essential Immunology. Scientific Publications 3rt edition, subsequent revisions. Available from: http://en.wikipedia.org/wiki/Artificial_induction_of_immunity

5. Hartford education [homepage on the internet]. USA [updated march 2001] Available from: http://uhaweb.hartford.edu/BUGL/immune.htm

6. microbiology and immunology online [homepageon the internet] Available from:http://pathmicro.med.sc.edu/ghaffar/immunization.htm

Category: Pathology Notes