Immunity * The term immunity refers to the body’s specific protective response to an invading foreign agent or organism. * The human body has the ability to resist almost all types of organisms or toxins that tend to damage the tissues and organs. The capability is called immunity.Types of immunity ey (aanINNATE IMMUNITY ADAPTIVE IMMUNITY Resistance to infection which individual possesses by virtue of his genetic and constitutional make up Early defense response against microbes Immune response Non specific Innate response do not alter on repeated exposure Memory effect absent Not affected by immunization or prior contact The resistance that an individual acquires during life Later defense response Immune response is_ highly specific Adaptive response improves with each successive encounter with same pathogen Memory effect present Is improved by immunizationNatural (Innate immunity) * The basis of natural defense mechanisms is the ability to distinguish between self and non-self. Such natural mechanisms include a Physical and chemical barriers Skin and mucous membrane Antimicrobial substance in body secretions The action of WBCs Inflammatory response.Classifications of Innate immunity SpeciesSpecies immunity * Refers to the total or relative refractoriness to a pathogen, shown by all members of species. * Person obtains by virtue of being a part of the human species. * Determines whether or not a pathogen can multiply in them. Example * All human beings are totally unsusceptible to plant pathogens and to many animal pathogens, such as render pest or distemper. * Pasteur’s experiments on anthrax in frogs, which are naturally resistant to the disease but become susceptible when their body temperature is raised from 25° to 35°C.Racial immunity * Racial differences are known to be genetic in origin Example * People of Negroid origin in USA are more susceptible than the Caucasians to tuberculosis. * Genetic resistance to Plasmodium falciparum Malaria seen in some parts of Africa and Mediterranean coast. * A hereditary abnormality of red cells (sickling) prevalent in the area, confer immunity to infections by malarial parasite.Individual immunity * The difference in innate immunity exhibited by different individuals in a race * The genetic basis of individual immunity is seen in twins. Example * Homozygous twins exhibit similar degrees of resistance or susceptibility to Lepromatous leprosy and Tuberculosis.Determinants of innate immunity 1. Species and strains 2. Age 3. Hormonal Influences 4, NutritionPR uaF WN MECHANISMS OF INNATE IMMUNITY . Epithelial surfaces * Skin * Mucosa of the respiratory tract - Human eye. » Flushing action of urine . Antibacterial substances in Blood and tissues . Inflammation . Fever . Cellular factorsACQUIRED IMMUNITY » A person is said to be immune when he possesses specific protective antibodies or cellular immunity as a result of previous infection or immunization or is so conditioned by such previous experience as to respond adequately to prevent infection. > This form of immunity develops as a response to infection and is adaptive to the infection, it is called adaptive immunity. > The characteristics of adaptive immunity are - Specificity for distinct molecules. An ability to remember and respond more vigorously to repeated exposure to the same microbe. Hence it is also called as specific immunity.* Natural Active immunity ~ This results from either a clinical or inapparent infection. — Immunity following chicken pox and measles infection is usually life long * Artificial Active Immunity — This is the resistance induced by vaccines. — Vaccines are preparations of live or killed microorganisms or their products used for immunization.Naturally acquired passive immunity » This is the resistance passively transferred from the mother to the baby. In human infants, maternal antibodies are transmitted predominantly through the placenta. » Human colostrums, which is also rich in IgA antibodies and resistant to intestinal digestion. » Synthesis of antibodies (IgM) occurs at 20th week of IUL but its immunogenic capacity is still inadequate at birth, It is only by about the age of three month that the infants acquire a_ satisfactory level of immunological independence.Naturally acquired active immunity + 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Artificially acquired passive immunity Artificially acquired passive immunity is a short-term immunization induced by the transfer of antibodies, which can be administered in several forms; as human or animal blood plasma, as pooled human immunoglobulin for intravenous (IVIG) or intramuscular (1G) use, and in the form of monoclonal antibodies (MAb). This is the resistance passively transferred to a recipient by administration of antibodies. Passive immunization is indicated for immediate and temporary protection in a non-immune host Employed for the suppression of active immunity, when the latter may be injurious. Used as treatment of some infections. Hyper immune sera of animal or human origin, convalescent sera and pooled human gamma globulins are used for prophylaxis and therapy. > Rh immune globulin is used during delivery to prevent immune response to the Rhesus factor in Rh-negative women with Rh-positive babies.Artificially acquired active immunity + Artificially acquired active immunity can be induced by a vaccine, a substance that contains antigen. A vaccine stimulates a primary response against the antigen without causing symptoms of the disease.ACTIVE IMMUNITY PASSIVE IMMUNITY 1. Produced actively by host's immune system Received passively by the host 2. Induced by infection or by contact with immunogens (vaccines, allergens etc). No participation by the host’s immune system 3. Affords desirable and effective protection Conferred by introduction of readymade antibodies 4, Immunity effective only after a lag period (time required for generation of antibodies). Protection transient and less effective Immunity effective immediately 5. Immunological memory present; subsequent challenge more effective (booster effect) No immunological memory subsequent administration of antibodies _ less effective due to immune elimination 6, Negative phase may occur No negative phase 7. Not applicable in immunodeficient hosts Applicable in immunodeficient hostsInactivated vaccines are composed of micro-organisms that have been killed with chemicals and/or heat and are no longer infectious. Examples are vaccines against flu, cholera, plague, and hepatitis A. Live, attenuated vaccines are composed of micro- organisms that have been cultivated under conditions which disable their ability to induce disease. — Examples include yellow fever, measles, rubella, and mumps. Toxoids are inactivated toxic compounds from micro- organisms in cases where these (rather than the micro- organism itself) cause illness, used prior to an encounter with the toxin of the micro-organism. — Examples of toxoid-based vaccines include tetanus and diphtheria, Subunit vaccines are composed of small fragments of disease causing organisms. A characteristic example is the subunit vaccine against Hepatitis B virusTypes of Vaccine: Immunizing agents that are used for immunoprophylaxis ~ Bacterial vaccines: ~ Live (BCG vaccine for T.B.). - Killed (Cholera vaccine), Subunit (Typhoid Vi antigen). - Bacterial products (Tetanus Toxoid). ~~ Viral Vaccine: Live (Oral polio vaccine = Sabin). Killed (Injectable polio vaccine = Salk). — Subunit (Hepatitis B-vaccine). = Combinations If more than one kind of immunizing agent is included in the vaccine, it is called a mixed or combined vaccine. + DPT (Diphtheria — pertussis - tetanus) MMR (Measles, mumps and rubella). * DPTP (DPT plus inactivated polio),Physical and chemical barriers Skin and mucous membrane When skin and mucous membrane are intact and healthy they provide a physical barrier to invading microbes. Sebum and sweat secreted on to the skin surface contains antibacterial and antifungal substances. Hairs in the nose acts as a filter. One way flow of urine from the bladder during micturitionno fs WN Antimicrobial substance in body secretions . Hydrochloric acid in gastric juice . Lysosomes Saliva . Immunoglobulin in nasal secretions and saliva . Interferons. White blood cell action WBGs participate in both the natural and the acquired immune responses. Granulocytes include neutrophils, eosinophils and basophils. Nongranular leucocytes include monocytes or macrophages and lymphocytes. Lymphocytes consisting of B cells and T cells, play major role in humoral and cell mediated immune responses.Inflammatory response * Major function of the natural (non specific or innate) immune system. * Chemical mediators assist this response by minimizing blood loss, walling off the invading organism, activating phagocytes and promoting formation of fibrous scar tissue and regeneration of injured tissueDysfunction of the natural immune system * Immunodeficiency * Persistent inflammatory response * Autoimmune bodiesResponse to invasion * When the body is invaded or attacked by bacteria, viruses, or other pathogens, it has three means of defending itself: 1. The phagocytic immune response 2. The humoral or antibody immune response 3. The cellular immune responsePhagocyte immune response * The first line of defense * Involves the WBCs (granulocytes and macrophages), which have the ability to ingest foreign particles. + Phagocytes also remove t the _body’s own dying or dead cells. f C —— phagosome ~~ phagochegsis S75 @) \ lysosome een \ at ew, = eacuu ~ exocytosisHUMORAL IMMUNITY Antibody Lymphocyte Antibody Antigen > oo LymphocyteHumoral immune response » A second response, the humoral immune response (sometimes called the antibody response), begins with the B lymphocytes, which can transform themselves into plasma cells that manufacture antibodies. >The third mechanism of defense, the cellular immune response, also involves the T lymphocytes, which can turn into special cytotoxic (or Killer) T cells that can attack the pathogens themselves.1. Humoral immune response Before exposure to a specific antigen, the clones of B lymphocytes remain dormant in the lymphoid tissue. On entry of a foreign antigen, macrophages in the lymphoid tissue phagocytize the antigen and then present it to adjacent B lymphocytes. Those B lymphocytes specific for the antigen immediately enlarge and take on the appearance of lymphoblasts.Humoral immune response cont... . Some of the lymphoblasts further differentiate to form plasmablasts, which are precursor of plasma cells. . The mature plasma cells then produces gamma globulin antibodies. . Other B lymphocytes differentiate into B- lymphocyte clones with a memory for the antigen.Primary response and secondary response Primary response 1. Response for forming antibodies that occur on first exposure to a specific antigen. 2. Appears 1 week after, with weak potency and short life a 2, Secondary response Response that occurs after second exposure to the same antigen. Begins rapidly after exposure to the antigen (often within hours) is far more potent (energy), and forms antibodies for many months rather than for only a few weeks.Role of antibodies Antigen binding sites | Variable region \ ‘ F: Variable region light chai Disulfide - on light chain bridges \ Constant region \ on light chain Constant region on heavy chain Heavy chainAntibodies The antibodies can inactivate the invading agent in one of the several ways, as follows: 1. Agglutination: in which the multiple large particles with antigens on their surface. 2. Precipitation: in which the molecular complex of soluble antigen and antibody becomes so large that it is rendered insoluble and precipitates. 3. Neutralization: in which the antibodies cover the toxic sites of the antigenic agent. 4. Lysis: in which some potent antibodies are occasionally capable of directly attacking membranes of cellular agents and thereby cause rupture of the agent.Types of immunoglobulin IgG IgE IgD YY IgM IgA MS leIgG IgG (75% of total immunoglobulin) > Appears in serum and tissues (interstitial fluid) >» Assumes a major role in bloodborne and tissue infections. > Activates the complement system. > Enhances phagocytosis > Crosses the placentaIgA IgA (15% of total immunoglobulins) > Appears in body fluids (blood, saliva, tears, breast milk, and pulmonary, gastrointestinal, prostatic and vaginal secretions). > Protection against respiratory, gastrointestinal and genitourinary infections. > Prevents absorption of antigens from food. > Passes to neonate in breast milk for protection.IgM IgM (10% of total immunoglobulins) * Appears mostly in intravascular serum * Appears as the first immunoglobulin produced in response to bacterial and viral infections. * Activates the complement system.IgD IgD (0.2% of immunoglobulins) > Appears in small amounts in serum > Possibly influences B-lymphocytes differentiation , but role is unclear, IgE IgE (0.004% of immunoglobulins) > Appears in serum > Takes part in allergic and hypersensitivity. of reactions > Combats parasitic infections.Cellular immune response These develop gradually over a period of 24 to 48 hours after the second encounter with an antigen. T lymphocytes are primarily responsible for cellular immunity. Stem cells continuously migrate from the bone marrow to the thymus gland, where they develop into T cells. By spending time in the thymus, these cells are programmed to become T cells rather than antibody producing B lymphocytes.Cellular immune response cont... * T cells attack foreign invaders directly. Cellular reactions are initiated by the binding of an antigen with an antigen receptor. The T cells then carry the antigenic message, or blue print, to the lymph nodes, where the production of other T cells is stimulated. * Some T cells remain in the lymph nodes and retain a memory for the antigen. Other T cells migrate from the lymph nodes into the general circulatory system and ultimately to the tissues.Types of T cells 1. Helper T cells: When activated, helper T cells secrete cytokines that attract and activate B cells, cytotoxic T cells, natural killer cells, macrophages and other cells of the immune system. Helper T cells produce different types of cytokines and determine whether the immune response will be the production of antibodies or cell mediated immune response.virus white blood cell vital antigen ° e e E e e os * @ °e 2° <= ‘ a e e Fae °. Reel Thelperce! Thelpercell = T me eal me Teel : ane B stimulate sod gyictoxiar kills infected antibodies cells Soe 5 fe2. Cytotoxic T cells * Cytotoxic T cells is a direct attack cell that is capable of killing micro-organisms and, at times, even some of the body’s own cells. * For this reason these are called killer cells. * Cytotoxic attack the antigen directly by altering the cell membrane and causing cell lysis and releasing cytolytic enzymes and cytokines.Cytotoxic T-cell ‘2 Release cytokines tg os ‘[Link] of og = — wea } infected call [Link] death v4 [Link] with i Fedease pero panayes, ac graruyen3. Supressor T cells * They are capable of suppressing the functions of both cytotoxic and helper T cells. * It is believed that these suppressor functions serve the purpose of preventing the cytotoxic cells from causing excessive immune reactions that might be damaging to the body’s own tissues.Complement system * Circulatory plasma proteins which are made in the liver and activated when an antibody couples with its antigen, are known as complement. * Complement has three major physiological functions: a. ‘defending the body against bacterial infection b. bridging natural and acquired immunity c. Disposing (placing) of immune complexes and the byproducts associated with inflammation.Complement system Complement mediated immune response are summarized as: 1. Cytolysis: Lysis and destruction of cell membranes of body cells or pathogens. 2. Isonization: Targeting of the antigen so that it can be easily engulfed and digested by the macrophages and other phagocytic cells. 3. Chemotaxis: chemical attraction of neutrophils and phagocytic cells to the antigen. 4, Anaphylaxis: activation of mast cells and basophils with release of inflammatory mediators that produce smooth muscle contraction and increased vascular permeability.Abnormal immune reactions 1. Antibody mediated 2. Cell-mediated 3. Mixed antibodyAntibody mediated reactions * These occur within minutes of exposure to an allergen (antigen). * The most common manifestations of this type of allergic reaction include: food allergies, childhood eczema, hay fever, extrinsic asthma. * In these conditions the released chemicals act locally, causing different effects that depend on the site.Acute systemic anaphylaxis (anaphylactic shock) . . It is caused by the entry of an allergen into the blood e.g. snake venom, injectable penicillin. There are profound effects throughout the body, including generalized vasodilatation, leading to severe hypotension and contraction of smooth muscle in the respiratory tract, causing acute breathing difficulties,Other antibody mediated reactions: * Reaction of antibodies with cells that have antigens on their cytoplasmic membranes may cause the cells to rupture. * Abnormal reactions to antibody/antibody complexes sometimes result in them adhering to the endothelium of blood vessels causing inflammation and local damage.Cell mediated reactions The antigen include: 1. Intracellular microbes, e.g. those causing tuberculosis, measles, mumps. . Some vaccines, e.g. against smallpox. . Some metals and compounds that combine with protein in the skin and cause allergic contact dermatitis.Mixed reactions Autoimmune diseases: * Tissue damage and signs of disease as the body fails to recognize its own tissues. Destruction of the body's own cells may be either humoral or cell-mediated. — Thyroid- Hashimoto's thyroiditis — Stomach- Addisonian pernicious anemia — Cortex of the adrenal gland- addison’s disease. — Pancreas-type I diabetes mellitus Organ transplantation and rejection * GVHDHealth education About the signs and symptoms that indicate infection. Whenever they experience a symptom that is not typical for them, they should contact their health care provider. About any prophylactic medication regimen, including dosage, indications, times, actions, and side effects. Avoid others with infections and crowds.Health education cont... > The patient and family also need to learn about other ways to prevent infection. > Instructed to monitor for subtle changes in physical status and must be informed of the importance of seeking immediate health care if changes occur. > About the importance of continuing the treatment regimen and assisted in incorporating it into their lives.References 1. Wilson KJW, Waugh A. Ross and Wilson Anatomy and physiology in Health and illness. Eigth edition. NewYork; Churchill Livingstone:1998. 2. Smeltzer SC, Bare B. Textbook of Medical surgical Nursing. 10" edition. Philadelphia; Lippincott Williams and wilkins: 2004. 3, Guyton AC, Hall JE. Textbook of Medical Physiology. Eleventh edition. Philadelphia; Saunder (Elsevier) : 2006.