Lecture 4 Host-Parasite Relationship and Immunity By Dr. Doaa Mahdy El-Wakil Lecturer of Medical Microbiology and Immunology Scanned with CamScannerDefinitions . Saprophytic bacteria: Bacteria that live freely in nature on decaying organic matter + Parasitic bacteria Bacteria which live in/on a living host 1) Pathogenic: causes disease 2) Commensals: the normal body flora which is beneficial to the host 3) Opportunistic: commensals may cause disease under certain conditions Scanned with CamScannerSources of infection 1- Man is a source of pathogenic organisms as a clinical case or a carrier. A carrier: an apparently healthy individual who carries a pathogenic organism without showing clinical manifestations, and can transmit this organism to other susceptible individuals. 2- Environment: floors, walls, soil, utensils, food and water. Invasive equipment such as intravenous or urinary catheter allows entry of organisms into the host. 3- Animals and birds: These may be the source of some infections, e.g. brucellosis, bovine tuberculosis. Scanned with CamScannerPathogenic Properties of Microbes: Pathogenicity: is the ability of the microorganism to produce disease. Virulence: is the degree of pathogenicity. Virulence factors: are the structures or products of the invading microorganism that allow it to produce the disease. These include: 1) Structures needed for adherence (e.g. pili). 2) Structures needed for invasion (e.g. capsule). 3) Survival within phagocytes (resistance to lysosomal enzymes). 4) Enzyme production (e.g. coagulase, fibrinolysin, hyaluronidase). 5) Toxin production (endotoxins or exotoxins, e.g. tetanospasmin, diphtheria toxin). Scanned with CamScannerGeneralized infections * Bacteraemia Circulation of bacteria in the blood, may be: 1) Transient by commensals of oral and intestinal tracts, usually removed by phagocytes 2) For long duration by pathogenic organism Scanned with CamScannerGeneralized infections = Septicaemia: circulation and multiplication of bacteria in blood, forming toxic products and causing high fever. * Pyaemia: a condition in which pyogenic bacteria produce septicaemia with multiple abscesses in internal organs e.g. liver, kidneys. * Toxaemia: circulation of bacterial toxins in the blood (e.g. C. diphtheriae toxaemia). Scanned with CamScannerGENERAL PROPERTIES OF VIRUSES Viruses are minute infectious agents measured innm viruses vary in size between 19 Scanned with CamScannerViruses differ from bacteria as follows: 1) Due to their small size, viruses are only seen by electron microscope and can pass through bacterial filters. 2) Virus contains either DNA or RNA, but never both. 3) Viruses are metabolically inert. 4) Obligate intracellular parasites that can not grow on artificial culture media. 5) Are not affected by antibiotics. Scanned with CamScannerViruses and Malignancy * Viruses appear to play a role in the development of some human cancers. 1. Human papilloma virus and cancer cervix. 2. Epstein-Barr virus and Burkitt's lymphoma. 3. Hepatitis B and C viruses and hepatocellular carcinoma (HCC). 4. human herpes virus 8 and Kaposi's sarcoma. Scanned with CamScannerPROPERTIES OF FUNGI Fungi are eukaryotic (having true nucleus), spore forming organisms. Only few of them are pathogenic. EUKARYOTE PROKARYOTE Scanned with CamScannerMorphology 1) Filaments (moulds): grow as hyphae and reproduce by production of spores. 2) Yeasts: grow as single cells and reproduce by budding (e.g. Candida albicans). Deore og 3) Dimorphic: grow as yeasts at body ae are temperature (37°C) and as filaments at 22°C. coma andl Or Scanned with CamScanner* Fungi cause infections that range from superficial mycoses affecting the horny layer of skin to subcutaneous mycoses to deep systemic mycoses which may be severe and fatal. * There is only a small group of antifungal drugs that are not toxic. * Fungi are not affected by antibiotics. Prolonged course of broad-spectrum antibiotics may cause some fungal infections, a condition known as superinfection (e.g., Candida albicans causing oral thrush). “| Scanned with CamScanner[— Antibody Antigen The main function of the immune system is to prevent or limit infections by microorganisms Immunity IMMUNITY ACQUIRED | IMMUNITY | INNATE IMMUNITY Scanned with CamScannerInnate immunity The natural inborn barriers against invasion by microorganisms. It is non-specific acting against all microbes through: 1) Mechanical barriers: . Intact skin and mucous membrane. - Coughing, sneezing and blinking expel foreign particles and microbes. 2) Chemical barriers: - Sweat, tears, lysozyme. - Hydrolytic enzymes as those in saliva and HCI of stomach. - Acid pH in the adult vagina. Scanned with CamScannerInnate immunity 3) Normal bacterial flora: * Prevents infection by competing with pathogenic bacteria for essential nutrients, or by the production of inhibitory substances (e.g. lactobacilli in the adult vagina metabolise glycogen forming lactic acid. The pH of the healthy adult vagina is approximately 4.5, inhibiting the growth of other organisms). * Suppression of normal flora by a broad-spectrum antibiotic leads to superinfection by a resistant organism. 4) Non-specific inflammatory response and phagocytosis: An organism entering a host will stimulate a series of reactions, such as vasodilatation and aggregation of many WBCs called inflammatory reaction. Some of these cells are called phagocytic cells, that engulf and destroy invading microorganisms. Scanned with CamScannerFactors that affect innate immunity - Species factors. - Racial and genetic factors. - Age. - Nutritional status. - Hormones. Scanned with CamScannerAcquired (Specific) Immunity * The immunity acquired by previous exposure to a microbe or one of its products or antigens and is directed specifically against this particular microbe. * There are two mechanisms for the acquired immune response: 1) The humoral immune response 2) The cell-mediated immune response Scanned with CamScanner1) The humoral immune response * The immunoglobulins (antibodies) are produced by B lymphocytes. * There are 5 classes of immunoglobulins ((IgG, IgM, IgA, IgD and IgE). * Functions of antibodies: 1) Antibodies can bind specifically to the microbe that induced their production. 2) They may also neutralize the antigen (as with viruses) or toxin. 3) The antibody binds to the antigen and the resulting complex is much more easily phagocytosed. This is known as opsonization (enhanced phagocytosis). 4) The antibody also binds to antigens on the cell surface which allows cytotoxic cells to destroy the infected cells. This is known as antibody-dependent cellular cytotoxicity (ADCC). Scanned with CamScanner2) The cell mediated immune response * There is a generation of certain sensitized T-lymphocytes. * These cells can recognize specifically the microbe or the cells infected with it and destroy them Scanned with CamScannerImmune responses 1) Primary immune response: After the first exposure to antigen, there is a lag of several days (7-10 days) before antibody appears. The immunoglobulin produced in the primary immune response is |gM. 2) Secondary immune response: Occurs on subsequent exposure to the same antigen After 2-3 days, a marked increase occurs in the level of the antibodies, continues for several days, and finally results in antibody level which is higher than that of the primary immune response, especially of IgG. Scanned with CamScannerInduction (lag) Long (7-10 days) period Antibody level Duration Ig class Memory cells Immune responses Primary response Secondary response low Short (antibodies decline rapidly) Predominantly [gM Absent Short (few hours to few days) High (10 times greater) Long (months) Predominantly IgG Present Scanned with CamScannerPrimary and secondary antibody response > 3 3 a € 5 6 ie Primary Secondary z response response 3 I E < 1 2 3 4 5 weeks 6 months ‘ t Time First Second exposure exposure Scanned with CamScannerTypes of acquired immunity ACQUIRED IMMUNITY ACTIVE aha ARTIFICIAL Scanned with CamScannerTypes of acquired immunity 1) Active acquired immunity: on exposure to foreign antigen or microbes. The individual actively produces his own antibodies or sensitized lymphocytes. Immunity develops slowly but lasts for a long time. It can be naturally or artificially induced: a) Natural active immunity follows clinical or subclinical infections. b) Artificial active immunity after vaccination. Scanned with CamScannerTypes of acquired immunity 2) Passive acquired immunity: in which ready-made antibodies are transferred. This gives rapid protection but immunity is short lasting. It can also be natural or artificial: a) Natural passive immunity: when antibodies are transferred from mother to foetus through the placenta (IgG) and colostrum (IgA). b) Artificial passive immunity (following administration of antiserum or immunoglobulins) as in prophylaxis and treatment of some diseases such as diphtheria, tetanus or Hepatitis B virus. Scanned with CamScannerComplement System * Complement is a complex of proteins present in all body fluids (except urine and CSF) * It has the property of combining with the antigen-antibody complex. Scanned with CamScannerTolerance and autoimmunity * Tolerance is the ability of the immune system to recognize self from non-self antigens. Failure of such recognition leads to autoimmune diseases. EB f ' 7 * Organ-specific: Hashimoto's thyroiditis or pernicious anaemia. * Non-organ-specific: rheumatoid arthritis, systemic lupus erythematosis (SLE). Scanned with CamScannerHYPERSENSITIVITY REACTIONS * Inappropriate or excessive activation of the immune system that can be harmful to the host. * There are 4 types of hypersensitivity reactions: Type | (Immediate hypersensitivity): IgE mediated (e.g. atopy or anaphylaxis). Type II (cytotoxic or cytolytic reactions): IgM or IgG mediated (e.g. ABO incompatibility, erythroblastosis fetalis). Type Ill (Immune complex formation): IgM or IgG mediated (e.g: arthus reaction, serum sickness). Type IV (cell-mediated hypersensitivity): e.g. tuberculin skin test. Scanned with CamScannerType | (Immediate) hypersensitivity 1. Systemic anaphylaxis: * This is the most severe form of type | hypersensitivity, in which severe bronchospasm and hypotension (shock) can be life-threatening. * Anaphylaxis may occur due to antitoxic serum prepared in animals for the treatment of tetanus and diphtheria. It also occurs with penicillin and many other drugs. 2. Localized anaphylaxis (Atopy): * The symptoms are localized in one organ or system. The allergens to which the individual is sensitized are widely distributed in nature. They are classified as inhalants, e.g. pollens, house dust, molds, contactants like wool, animal fur, nylon, and ingestants including many food stuffs. + The symptoms vary widely from one individual to another depending on the site of the reaction. Thus, it may take the form of bronchial asthma, urticaria, conjunctivitis, gastrointestinal symptoms, or allergic rhinitis. Scanned with CamScannerDiagnosis of type | hypersensitivity 1. Detection of the allergen by skin test in which extracts of various allergens are introduced into the skin of the patient. Positive cases show a wheal and flare reaction that appears within 15-25 minutes at the site of the allergen to which the individual is allergic. 2. Measurement of IgE levels in serum. Scanned with CamScannerTherapeutic Measures: I. Management of anaphylactic shock: * Anaphylactic shock is an emergency that must be dealt immediately by administration of adrenaline, corticosteroids together with oxygen inhalation. Il. Management of atopy: Avoidance of the responsible allergen. Desensitization involves injecting the patient, over time, with gradually increasing doses of the responsible allergen. Scanned with CamScannerIMMUNODEFICIENCY DISEASES Defects in the immune system may increase the chances of acquiring infection. Such defects may be primary (congenital) or secondary (acquired). Scanned with CamScanner|_Primary (congenital) = immunodeficiency 1. Defects of the innate immune system: a. Phagocytic cell defects. b. Complement deficiencies. c. Deficiency of NK cells. 2. Deficiency of the acquired (specific) immunity due to: a. Bcell defects. b. T cell defects. c. Band T cell defects Scanned with CamScannerIl. Secondary (acquired) immunodeficiency * Malnutrition. * Some viral infections: e.g. HIV causes acquired immune deficiency syndrome (AIDS). * Severe bacterial infections, e.g. Tuberculosis. * Parasitic infestations, e.g. Schistosomiasis. * Malignancies, especially those affecting the immune system such as Hodgkin’s disease and leukaemias. * Chronic debilitating diseases, e.g. diabetes and renal failure. * Others, e.g. treatment with x-ray, cytotoxic drugs, steroids, immunosuppressive drugs and burns. Scanned with CamScanner+ Immunodeficiency should be suspected in the following cases: - Increased frequency of infections. - Failure to clear infections rapidly despite adequate therapy. - Dissemination of local infections to distant sites. - Occurrence of opportunistic infections. - Failure to thrive in infants and children. - Development of certain kinds of tumours. Scanned with CamScannerMCQs 1) Which statement is NOT true about viruses? a) Obligate intracellular pathogens b) Contains both DNA and RNA c) Not inhibited by antibiotics d) Failure of cultivation on ordinary media Scanned with CamScannerMCQs 2) Regarding the primary immune response: a) The antibody level is very high b) There is a very short induction period c) Memory cells are the main effector cells d) Immunoglobulin produced are mainly IgM Scanned with CamScannerMCQs 3) Vaccination is an example of: a) Natural active immunity b) Artificial active immunity c) Natural passive immunity d) Artificial passive immunity Scanned with CamScannerScanned with CamScanner