Lecture 3: Immunity (PDF)

**LECTURE 3** **IMMUNITY** **Definition** Immunity can be defined as the way in which the body can protect itself from invasion by pathogenic microorganism and provide a defense against their harmful effect. The reaction to foreign substances is etymologically described as inflammation while the...

**LECTURE 3** **IMMUNITY** **Definition** Immunity can be defined as the way in which the body can protect itself from invasion by pathogenic microorganism and provide a defense against their harmful effect. The reaction to foreign substances is etymologically described as inflammation while the non-reaction to self substances is described as immunity. The two components of the immune system create a dynamic biological environment where \"health\" can be seen as a physical state where the self is immunologically spared, and what is foreign is inflammatorily and immunologically eliminated. \"Disease\" can arise when what is foreign cannot be eliminated or what is self is not spared. https://upload.wikimedia.org/wikipedia/commons/thumb/5/55/Immunity.svg/600px-Immunity.svg.png **Fig 1** **The cells of both parts of the immune system are made in different organs of the body, including:** - **Adenoids.** Two glands located at the back of the nasal passage. - **Bone marrow. **The soft, spongy tissue found in bone cavities. - **Lymph nodes. **Small organs shaped like beans, which are located all over the body and connect via the lymphatic vessels. - **Lymphatic vessels. **A network of channels all over the body that carries lymphocytes to the lymphoid organs and bloodstream. - **Peyer patches. **Lymphoid tissue in the small intestine. - **Spleen. **A fist-sized organ located in the belly (abdominal) cavity. - **Thymus.** Two lobes that join in front of the windpipe (trachea) behind the breastbone. - **Tonsils.** Two oval masses in the back of the throat. **Immunity is classified in to two major groups:** \- Non specific immunity \- Specific immunity **A. NON SPECIFIC (NATURAL OR INNATE) IMMUNITY.** A fetus naturally acquires passive immunity from its mother during pregnancy. Maternal passive immunity is antibody-mediated immunity. The mother\'s antibodies (MatAb) are passed through the placenta to the fetus by an FcRn receptor on placental cells. This occurs around the third month of gestation. IgG is the only antibody isotype that can pass through the placenta. Passive immunity is also provided through the transfer of IgA antibodies found in breast milk that are transferred to the gut of a nursing infant, protecting against bacterial infections, until the newborn can synthesize its antibodies. Colostrum present in mother's milk is an example of passive immunity. Non-specific immunity, also called natural or innate immunity, is the first line of defense against any infectious agent. Non specific host responses provide an effective barrier that prevents the microorganisms from penetrating, inhibit or destroy the invader if it gains access to the tissues, and eliminate or neutralize any toxic substance elaborated by infectious agent. Several mechanisms are available in the immunocompetent host. These include: - physical or mechanical barrier, - biochemical factors, - cellular mechanism, - role of normal flora - Inflammatory reactions. **Physical or mechanical barrier** The unbroken skin and mucus membrane are effective mechanical barriers to infectious agents. The surface of the skin is also inhibitory to the growth of most microorganisms because of low moisture, low pH, and the presence of secreted inhibitory substance. However, it is possible for some microorganisms to enter the skin through hair follicles, sebaceous glands or sweet glands. Similarly, mucus membranes consist of an epithelial layer and an underlying connective tissue layer. They line the entire digestive, respiratory, urinary, and reproductive tracts. For example, the epithelial surface that lines the nasal cavity and throat are protected by a combination of mucous production and cilliary movement. Because mucous is so viscous, microorganisms adhere to it. Epithelial cells with cilia constantly move the mucus layer toward the mouth, where it along with the trapped microorganism is swallowed and eliminated. Besides, the action of coughing removes mucus that contains microorganisms. In the urethra rapid flow of urine washes away most microorganisms. Tear that wash the conjunctiva perform a similar defensive function. **Biochemical factors** These are chemical secretions produced by the body that inhibit microbial growth. The following are included as an example, keratin is a skin protein produced by the outer most cells of the skin, since it has very little water, the skin becomes very dry and therefore to most species of microorganism. The growth of microorganisms is inhibited in the gastrointestinal tract by hydrochloric acid and bile salt, which are secreted by the stomach and liver, respectively. Lysozyme is an enzyme found in many body fluids and secretions such as tears. It can break down the cell wall of Gram-positive bacteria and a few gram-negative bacteria by hydrolyzing the peptidoglycan layer. Complement is a family of more than twenty different proteins in serum that function as a non-specific defense against infection. Interferons are small proteins produced by eukaryotic cells in response to viral infection. The virally infected cell produces interferon for a few hours, even for a day, and it will excrete and used by other cells. When these cells become infected with the same or unrelated virus, the interferons cause the cells to produce molecules that prevent replication of the infecting virus. **Cellular mechanism** Alveolar macrophages like neutrophils and natural killers remove particles and organisms that enter the alveoli. Neutrophils are the first phagocytes in the infected area that can non- specifically phagocytize some microbes. Natural killer cells are large lymphocytes whose function is to kill undesirable cells such as tumor cells and virus infected cells. **Role of normal flora** The human body is inhabited by a large number of microorganisms, mainly bacteria, which together, are called the body's normal flora or commensals. The term normal flora implies that such microbial inhabitants are harmless. For the most part, normal flora microorganisms do not cause disease. The commensals can stop the growth of potentially pathogenic organisms through different mechanism such as occupying attachment sites and by producing substance against pathogenic organism. They also compete for essential nutrients for their growth. **Inflammatory reactions** The inflammatory response is the vascular and cellular reaction to the presence of invading microorganisms or injury. It is one of the most effective defense mechanism in human and other animals. The process of inflammation may be divided in to the following stages: - Initiation (Damage to tissue) - Tissue response - Leukocyte response - Tissue repair (resolution) - Cure The damaged cells at the site of injury initiate the tissue response by releasing chemical factors such histamine, which in turn trigger vasodilatation and increased permeability of capillaries, permitting influx of fluids and blood cells in to the site. Then, the phagocytic cells accomplish the leukocyte response, by engulfing the microbes and damaged tissue. In addition to destroying and removing an injurious agent such as a microbe or its products, the inflammatory response also limits the effects of the agent or its products by confining it or walling it of from the surrounding tissues. This is possible because blood clots around the site prevent the microbe or its products from spreading to the other part of the body **TYPES OF INNATE IMMUNITY** ---------------------------- It includes individual, racial, and species immunity.  - **Individual immunity**: Some individuals of the same race and same species can have varied experiences with certain infections. For example, children are more susceptible to viral fever than adults. Innate immunity in an individual is also influenced by other factors, such as: - **Age:** Very old people and young ones are more susceptible to infections when compared to adults.  - **Hormonal level:** Any individual under corticosteroid hormone treatment is more susceptible to infection. Likewise, hormonal disorders like hypothyroidism, diabetes mellitus, etc., can make the individual more prone to infections.  - **Nutritional status:** Nutritional status of the host, like deficiency of vitamins and proteins, makes an individual more susceptible to infections. - **Racial immunity**: Individuals of different races within the same species have varied susceptibility or resistance toward infection caused by the same etiological agent. For example, races with sickle cell anaemia prevalent in Africans on the Mediterranean coast are resistant to malaria caused by Plasmodium falciparum. This is because sickle cell anaemia causes an alteration of the shape of the erythrocyte, which prevents its parasitisation. - **Species immunity**: Individuals from different species have different susceptibilities toward any infection. For example, humans are not affected by chicken cholera, infectious horse anaemia, etc., while animals are resistant to many human diseases like syphilis, gonorrhoea, measles, etc.  **Significance of innate immunity** ----------------------------------- 1. Physical and chemical barriers prevent the entry of foreign materials. 2. If the infection is established, a cascade of complement reactions and phagocytosis helps clearance of the infecting agents. 3. It activates the adaptive immune system by the release of cytokines and antigen presentation.  [ ]**Innate immunity examples** ------------------------------------------- 1. Gastric acidity, whose high pH prevents the entry of pathogens inside the body by microbicidal effect. 2. Skin that acts as a barrier against invasion of foreign bodies inside the body. 3. Phagocytosis of *Mycobacterium tuberculosis* by antigen-presenting cells.