Immunity.pptx Human anatomy and physiology

Human Immunity

1. IMMUNITY: basics & types Sarita Sharma Associate professor Department of pharmacology MMCP, MMDU

2. IMMUNITY An individual is under constant attack from an enormous range of potentially harmful invaders, from the months spent in the womb to the end of his life. These invaders include such diverse entities as bacteria, viruses, cancer cells, parasites and foreign (non-self) cells. The body therefore has developed a wide selection of protective measures against these pathogens. Immunity or resistance is the ability to ward off damage or disease through our defenses . OR The term immunity refers to the resistance exhibited by the host towards infection caused by micro organisms and their products(toxins). Vulnerability or lack of resistance is termed susceptibility. The two general types of immunity are

3. 1. Innate immunity or Non-specific defence mechanisms It refers to defenses that are present at birth. Innate immunity does not involve specific recognition of a microbe and acts against all microbes in the same way. Among the components of innate immunity are the first line of defense (the physical and chemical barriers of the skin and mucous membranes) and the second line of defense (antimicrobial substances, natural killer cells, phagocytes, inflammation, and fever). Innate immune responses represent immunity’s early warning system and are designed to prevent microbes from gaining access into the body and to help eliminate those that do gain access.

4. NON-SPECIFIC DEFENCE MECHANISMS Four main non-specific defence mechanisms: 1) Defence at body surfaces (first line) 2) Phagocytosis 3) Natural antimicrobial substances (second line) 4) The inflammatory response The first lines of general defence They prevent entry and minimise further passage of microbes and other foreign material into the body.

5. 1) DEFENCE AT BODY SURFACES SKIN AND MUCOUS MEMBRANES The first line of defense against pathogens. Both physical and chemical barriers That discourage pathogens and foreign substances from penetrating the body and causing disease. The outer epithelial layer of the skin—the epidermis— Provides a formidable physical barrier to the entrance of microbes. In addition, periodic shedding of epidermal cells Helps remove microbes at the skin surface.

6. MUCOUS MEMBRANES Line body cavities, Secretes a fluid called mucus That lubricates and moistens the cavity surface. Mucus is slightly viscous, it traps many microbes and foreign substances. The mucous membrane of the nose Has mucus-coated hairs That trap and filter microbes, dust, and pollutants from inhaled air. The mucous membrane of the upper respiratory tract contains Cilia, microscopic hairlike projections on the surface of the epithelial cells. The waving action of cilia propels inhaled dust and microbes that have become trapped in mucus toward the throat. Coughing and sneezing Accelerate movement of mucus and its entrapped pathogens out of the body. Swallowing mucus Sends pathogens to the stomach where gastric juice destroys them.

7. OTHER NON SPECIFIC DEFENSE Other fluids produced by various organs Also help protect epithelial surfaces of the skin and mucous membranes. The lacrimal apparatus of the eyes Manufactures and drains away tears in response to irritants. Blinking Spreads tears over the surface of the eyeball, and The continual washing action of tears Helps to dilute microbes and keep them from settling on the surface of the eye. Tears also contain Lysozyme, an enzyme capable of breaking down the cell walls of certain bacteria. Besides tears, lysozyme is present in Saliva, sweat, nasal secretions, and tissue fluids.

8. OTHER NON SPECIFIC DEFENSE Saliva, produced by the salivary glands, Washes microbes from the surfaces of the teeth and from the mucous membrane of the mouth. The flow of saliva reduces colonization of the mouth by microbes. The cleansing of the urethra By the flow of urine Retards microbial colonization of the urinary system. Defecation and vomiting also expel microbes. For example, In response to some microbial toxins, The smooth muscle of the lower gastrointestinal tract contracts vigorously; The resulting diarrhea rapidly expels many of the microbes.

9. OTHER NON SPECIFIC DEFENSE Certain chemicals also Contribute to the high degree of resistance of the skin and mucous membranes To microbial invasion. Sebaceous (oil) glands of the skin Secrete an oily substance called sebum That forms a protective film over the surface of the skin. The unsaturated fatty acids in sebum inhibit the growth of certain pathogenic bacteria and fungi. The acidity of the skin (pH 3–5) is caused in part by the secretion of fatty acids and lactic acid. Perspiration helps Flush microbes from the surface of the skin. Gastric juice, Produced by the glands of the stomach, Is a mixture of hydrochloric acid, enzymes, and mucus. The strong acidity of gastric juice (pH 1.2–3.0) destroys many bacteria and most bacterial toxins. Vaginal secretions also are Slightly acidic, which discourages bacterial growth.

10. SECOND LINE OF DEFENSE Internal Defenses:- When pathogens penetrate the physical and chemical barriers of the skin and mucous membranes, They encounter a second line of defense: 1) Internal antimicrobial substances, 2) Natural Killer cells 3)Phagocytes Inflammation Fever

11. 1) ANTIMICROBIAL SUBSTANCES Four main types of antimicrobial substances That discourage microbial growth: Interferons , complement, iron-binding proteins, and antimicrobial proteins. a) INTERFERONS :- Lymphocytes, macrophages, and fibroblasts infected with viruses Produce proteins called interferons or IFNs. IFNs induce Synthesis of antiviral proteins That interfere with viral replication. An important defense against Infection by many different viruses. The three types of interferon are Alpha-, beta-, and gamma-IFN.

12. b) COMPLEMENT SYSTEM A group of normally inactive proteins in blood plasma and on plasma membranes Makes up the complement system. When activated, These proteins “complement” or enhance certain immune reactions. The complement system Causes cytolysis (bursting) of microbes, Promotes phagocytosis, and Contributes to inflammation.

13. c) IRON-BINDING PROTEINS:- Inhibit the growth of certain bacteria By reducing the amount of available iron. Examples include Transferrin (found in blood and tissue fluids), Lactoferrin (found in milk, saliva, and mucus), Ferretin (found in the liver, spleen, and red bone marrow), and Hemoglobin (found in red blood cells). d) ANTIMICROBIAL PROTEINS (AMPS):- Short peptides that Have a broad spectrum of antimicrobial activity. Examples of AMPs are Dermicidin (produced by sweat glands), Defensins and cathelicidins (produced by neutrophils, macrophages, and epithelia), and Thrombocidin (produced by platelets). Besides killing a wide range of microbes, AMPs can attract mast cells, which participate in immune responses.

14. 2) NATURAL KILLER CELLS When microbes penetrate the skin and mucous membranes or bypass the antimicrobial substances in blood, The next nonspecific defense consists of natural killer cells and phagocytes. About 5–10% of lymphocytes in the blood are Natural killer (NK) cells. They are also present in the spleen, lymph nodes, and red bone marrow. NK cells But they have the ability to kill a wide variety of infected body cells and certain tumor cells.

15. The binding of NK cells to a target cell, Such as an infected human cell, Causes the release of granules containing toxic substances from NK cells. Some granules contain A protein called perforin That inserts into the plasma membrane of the target cell and Creates channels (perforations) in the membrane. As a result, extracellular fluid flows into the target cell and the cell bursts, a process called cytolysis . Other granules of NK cells Release granzymes , Which are protein-digesting enzymes That induce the target cell to undergo apoptosis, or self-destruction. This type of attack kills Infected cells, But not the microbes inside the cells. The released microbes, which may or may not be intact, can be destroyed by phagocytes.

16. 3) PHAGOCYTES Specialized cells that Perform phagocytosis , the ingestion of microbes or other particles such as cellular debris. The two major types of phagocytes are Neutrophils and macrophages. When an infection occurs, Neutrophils and monocytes migrate to the infected area. During this migration, The monocytes enlarge and develop into actively phagocytic macrophages called wandering macrophages. Other macrophages, called fixed macrophages, Stand guard in specific tissues. Among the fixed macrophages are Histiocytes (connective tissue macrophages), Stellate reticuloendothelial cells ( kupffer cells) in the liver, Alveolar macrophages in the lungs, Microglia in the nervous system, and Tissue macrophages in the spleen, lymph nodes, and red bone marrow. In addition to being an innate defense mechanism, phagocytosis plays a vital role in adaptive immunity.

17. Occurs in five phases: chemotaxis , adherence, ingestion, digestion, and killing 1 Chemotaxis :- Phagocytosis begins with chemotaxis , A chemically stimulated movement of phagocytes to a site of damage. Chemicals that attract phagocytes might come from invading microbes, white blood cells, damaged tissue cells, or activated complement proteins. 2 Adherence:- Attachment of the phagocyte to the microbe or other foreign material is termed adherence. The binding of complement proteins to the invading pathogen enhances adherence. 3 Ingestion:- The plasma membrane of the phagocyte extends projections, called pseudopods, that engulf the microbe in a process called ingestion. When the pseudopods meet, they fuse, surrounding the microorganism with a sac called a phagosome .

18. 4 Digestion:- The phagosome enters the cytoplasm and merges with lysosomes to form a single, larger structure called a phagolysosome . The lysosome contributes lysozyme, which breaks down microbial cell walls, and other digestive enzymes that degrade carbohydrates, proteins, lipids, and nucleic acids. The phagocyte also forms lethal oxidants, such as superoxide anion (O2), hypochlorite anion ( OCl ), and hydrogen peroxide (H2O2), in a process called an oxidative burst. 5 Killing:- The chemical onslaught provided by lysozyme, digestive enzymes, and oxidants within a phagolysosome quickly kills many types of microbes.

19. 4) INFLAMMATION A defensive response of the body to tissue damage. Causes:- Pathogens, abrasions, chemical irritations, distortion or disturbances of cells, and extreme temperatures. Signs and symptoms of inflammation:- Redness, pain, heat, and swelling. Role of inflamation :- Dispose of microbes, toxins, or foreign material at the site of injury To prevent their spread to other tissues To prepare the site for tissue repair.

20. INFLAMMATION PROCESS The inflammatory response has three basic stages: (1) Vasodilation and increased permeability of blood vessels, (2) Emigration (movement) of phagocytes from the blood into interstitial fluid (3) Tissue repair.

21. 5) Fever An abnormally high body temperature Occurs because the hypothalamic thermostat is reset. It commonly occurs During infection and inflammation. Many bacterial toxins Elevate body temperature, Sometimes by triggering release of fever-causing cytokines such as interleukin-1 from macrophages. Elevated body temperature Inhibits the growth of some microbes, and Speeds up body reactions that aid repair.

22. ADAPTIVE /Acquired /Specific IMMUNITY

23. The ability of the body to defend itself against specific invading agents Such as bacteria, toxins, viruses, and foreign tissues Called adaptive (specific) immunity. Antigens ( Ags ):- Substances that are recognized as foreign and provoke immune responses . Properties distinguish adaptive immunity from innate immunity: (1) Specificity for particular foreign molecules (antigens) (2) Memory for most previously encountered antigens. Immunology:- The branch of science that deals with the responses of the body when challenged by antigens is called .

24. Types of adaptive/specific immunity Two types : Cell-mediated immunity Antibody-mediated immunity Both are triggered by antigens. In cell-mediated immunity, Cytotoxic T cells Directly attack invading antigens. In antibody mediated immunity, B cells transform into plasma cells, which synthesize antibodies (Abs) or immunoglobulins .

25. (A) CELL-MEDIATED IMMUNITY Particularly effective against:- Intracellular pathogens , Include any viruses, bacteria, or fungi that are inside cells (2) Some cancer cells (3) Foreign tissue transplants.

26. ANTIBODY-MEDIATED IMMUNITY Works mainly against Extracellular pathogens Include any viruses, bacteria, or fungi that are in body fluids outside cells . Involves antibodies That bind to antigens in body humors or fluids (such as blood and lymph). It is also referred to as Humoral immunity.

27. The cell type involved in immunity is the lymphocyte. This WBC is manufactured in the bone marrow, and has a characteristically large, single nucleus. Once released into the bloodstream from the bone marrow, lymphocytes are further processed to make two functionally distinct types: A) the T-lymphocyte and B) the B-lymphocyte.

28. T-lymphocytes: These are processed by the thymus gland , which lies between the heart and the sternum. The hormone thymosin , produced by the thymus, is responsible for promoting the processing, which leads to the formation of fully specialised (differentiated), mature, functional T-lymphocytes. It is important to recognise that a mature T-lymphocyte has been programmed to recognise only one type of antigen, and during its subsequent travels through the body will react to no other antigen. Thus, eg . a T-lymphocyte manufactured to recognise the chickenpox virus will not react to any other virus, a cancer cell, or a tuberculosis bacterium. T-lymphocytes provide cell-mediated immunity .

29. 2. B-lymphocytes: These are processed in the bone marrow. Their role is in production of antibodies ( immunoglobulins ), which are proteins designed to bind to, and cause the destruction of, an antigen. As with T lymphocytes, each B-lymphocyte targets one specific antigen; the antibody released reacts with one type of antigen and no other. B-lymphocytes provide antibody mediated immunity . From this description of T- and B-lymphocytes, it is clear that for every one of the millions of possible antigens that might be encountered in life there is one corresponding T- and B-lymphocyte. There is therefore a vast number of different T- and B-lymphocytes in the body, each capable of responding to only one antigen.

30. Cell-mediated immunity T-lymphocytes that have been activated in the thymus gland are released into the circulation. When they encounter their antigen for the first time, they become sensitised to it. If the antigen has come from outside the body, it needs to be 'presented ' to the T-lymphocyte on the surface of an antigen-presenting cell. There are different types of antigen-presenting cell, including macrophages. Macrophages are part of the non-specific defences , because they engulf and digest antigens, but they also participate in immune responses. To do this, after digesting the antigen they transport the most antigenic fragment to their own cell membrane and display it on their surface.

31. On their movement around the body, still displaying the antigen fragment, they eventually come into contact with the T-lymphocyte that has been processed to target that particular antigen. Three main types of specialised T-lymphocyte are produced, each of which is still directed against the original antigen, but which will tackle it in different ways and they are; Memory T-cells, Cytotoxic T-cells, Helper T-cells.

32. 1. Memory T-cells: These provide cell-mediated immunity by responding rapidly to another encounter with the same antigen. 2. Cytotoxic T-cells: ( T cells that display CD8 ) These directly inactivate any cells carrying antigens. They attach themselves to the target cell and release powerful toxins, which are very effective. The main role of cytotoxic T-lymphocytes is in d estruction of abnormal body cells, e.g. infected cells and cancer cells. 3 . Helper T-cells: ( T cells that display CD4 ) These are essential for correct functioning of not only cell-mediated immunity, but also antibody-mediated immunity. Their central role in immunity is emphasised in situations where they are destroyed, as by the human immunodeficiency virus (HIV). When helper T-lymphocyte numbers fall significantly, the whole immune system is compromised. T-helpers are the commonest of the T-lymphocytes; their main functions include: production of special chemicals called cytokines, e.g. interleukins and interferons , which support and promote cytotoxic T-lymphocytes and macrophages cooperating with B-lymphocytes to produce antibodies

33. Antibody-mediated ( humoral ) immunity B-lymphocytes, which are free to circulate around the body, are fixed in lymphoid tissue (e.g. the spleen and lymph nodes). B-lymphocytes, recognise and bind antigen particles without having to be presented with them by an antigen presenting cell. Once its antigen has been detected and bound, and with the help of a helper T-lymphocyte, the B-lymphocyte enlarges and begins to divide. It produces two functionally distinct types of cell, plasma cells and memory B-cells.

34. 1. Plasma cells These secrete antibodies into the blood. Antibodies are carried throughout the tissues, while the B-lymphocytes themselves remain fixed in lymphoid tissue. Plasma cells live no longer than a day, and produce only one type of antibody, which targets the specific antigen that originally bound to the B-lymphocyte. Antibodies: bind to antigens, labelling them as targets for other defence cells such as cytotoxic T-lymphocytes and macrophages bind to bacterial toxins & neutralising them 2. Memory B-cells These cells remain in the body long after the initial episode has been dealt with, and rapidly respond to another encounter with the same antigen by stimulating the production of antibody-secreting plasma cells.

35. Acquired immunity Adaptive immunity is based on a specific response to a specific microbe; that is, it adapts or adjusts to handle a specific microbe. When antigens, e.g. microbes, are encountered for the first time there is a primary response in which a low level of antibodies can be detected in the blood after about 2 weeks. Although the response may be sufficient to combat the antigen, the antibody levels then fall unless there is another encounter with the same antigen within a short period of time (2 to 4 weeks). The second encounter produces a secondary response in which there is a rapid response by memory B-cells resulting in a marked increase in antibody production.

36. Immunity may be acquired naturally or artificially and both forms may be active or passive Active immunity : Active immunity means that the individual has responded to an antigen and produced his own antibodies. Lymphocytes are activated and the memory cells formed provide long lasting resistance. Passive immunity: In passive immunity the individual is given antibodies produced by someone else. The antibodies are then destroyed and unless lymphocytes are stimulated, passive immunity is short lasting.

37. 1. Active immunity: a). Active naturally acquired immunity: The body may be stimulated to produce its own antibodies by: (i). Having the disease: During the course of the illness, B lymphocytes develop into plasma cells that produce antibodies in sufficient quantities to overcome the infection. After recovery, the memory B-cells retain the ability to produce more plasma cells that produce the specific antibodies, conferring immunity to future infection by the same microbe or strain of microbe. (ii). Having a subclinical ( subminiminal ) infection: In this case the microbial infection is not sufficiently severe to cause clinical disease but stimulates sufficient memory B-cells to establish immunity.

38. b). Active artificially a cquired immunity: This type of immunity develops in response to the administration of dead or live artificially microbes (vaccines) or deactivated toxins (toxoids). The vaccines and toxoids retain the antigenic properties that stimulate the development of immunity but they cannot cause the disease. Active immunisation against some infectious disorders confers lifelong immunity, e.g. diphtheria, whooping cough or mumps. In other infections the immunity may last for a number of years or for only a few weeks before r evaccination is necessary. Many microbial diseases can be prevented by artificial immunisation . Diseases preventable by vaccination eg are; anthrax, cholera, Diphtheria, Hopatitls B, Pollomyelitis , Rubella, Smallpox, Tetianus , Tuberculosis, Typhoid, Whooping Cough

39. 2. Passive immunity: a). Passive naturally acquired immunity: This type of immunity is acquired before birth by the passage of maternal antibodies across the placenta to the fetus and to the baby in breast milk. The variety of different antibodies provided depends on the mother's active immunity. The baby's lymphocytes are not stimulated and the immunity is short lived. b). Passive artificially acquired immunity: In this type, ready-made antibodies, in human or animal serum, are injected into the recipient. The source of the antibodies may be an individual who has recovered from the infection, or animals, commonly horses, that have been artificially actively immunised .