NAJRAN UNIVERSITY College of Medicine NAJRAN UNIVERSITY College of Medicine Microbiology &Immunology Course Lecture No. 10 Microbiology &Immunology Course Lecture No. 10 By Dr. Ahmed Morad Asaad Associate Professor of Microbiology Dr. Ahmed Morad Asaad Associate Professor of Microbiology

HOST RESISTANCE TO MICROBIAL INFECTION : The outcome of any microbial infection is the result of a dynamic interaction between microbial factors and host resistance factors, which oppose the microbial infection. The same virulent organism given in the same dose to two different hosts may result in a severe fulminating disease in one of them and in a mild disease or even subclinical infection in the other.

Host resistance to microbial infection is dependent upon many complex factors, which can be conveniently divided into two categories : 1.Non ‑ specific factors: are inborn with every one and operate against many or all microbes. 2.Specific responses against certain microbes: These factors are based upon specific immunologic responses due to previous contact with certain organisms or their products.

Non ‑ specific Host Defence Mechanisms: The host is normally equipped with many barriers against infection The following are important examples of those factors: 1. Skin: Intact skin is unpenetrable by most bacteria., only very few microbes can penetrate the healthy skin. In addition, the sweat and sebaceous secretions contain antimicrobial substances, e.g. fatty acids and an enzyme “lysozyme” which destroys the cell wall of many bacteria.

2. The respiratory tract : a) The hairs of the nares act as filter to foreign particles inhaled with air. b) The cough and sneezing reflexes help to expel foreign particles. c) The cilia of respiratory mucosa drive inhaled particles towards the outside. d) The sticky mucous layer fixes inhaled microbes., in addition it contains antimicrobial substances. e) The pulmonary macrophages are very active in clearing out microbes, which reach the lungs.

3. The gastrointestinal tract: a) The buccal cavity contains normal bacterial flora, which oppose establishment of pathogenic species. b) The hydrochloric acid of the stomach is bactericidal. c) The digestive enzymes throughout the gastrointestinal system have antimicrobial action. d) The normal bacterial flora of the large intestine is often inhibitory to introduction of pathogenic species.

4.The genital system: The stratified epithelium of the adult vagina is resistant to penetration by bacteria. The lactobacilli normally inhabiting the vagina account for an acid pH which inhibits growth of pathogens. 5- The conjunctiva: The blinking reflex helps to expel foreign particles entering the conjunctival sac. The circulation of tears acts as a continuous clearing mechanism. In addition tears are rich in lysozyme, the enzyme with antibacterial action.

a) Cells involved non-specific immunity : 1.Natural killer (NK) cells: These are non ‑ T, non ‑ B lymphocytes which have natural ability to kill foreign cells (e.g. tumour cells, virally ‑ infected cells and grafts). NK cells are activated by interferons and interleukin 2 (IL ‑ 2). 2. Phagocytic cells: (a)- Granulocytes (polymorphnuclear leucocytes or neutrophils), forming about 60% of leucocytes in blood. (b)- Macrophages (circulating phagocytic monocytes). They are derived from monocyte stem cells in bone marrow and have a longer life span than circulating neutrophils. These macrophages may be :

These macrophages may be : a) Blood monocytes. b) Tissue macrophages; either wandering in body spaces or fixed macrophages such as kupffer cells in the liver, histiocytes of tissues and lining of spleen sinusoids. Other macrophages are mesangial cells in the kidney glomeruli, brain microglia and osteoclasts in bone.

Phagocytosis : It is the process by which phagocytic cells engulf organisms and other foreign particles. The process of phagocytosis involves the following steps: 1. Chemotaxis: The phagocytic cells are attracted to the site of infection due to release of chemotactic factors from the organism, tissues or the inflammatory cells.

2. Attachment: The organism is attached to the phagocytic cell non ‑ specifically. Sometimes the process of attachment occurs specifically due to the presence of specific antibodies (opsonins) against the organism. These opsonins coat the organism by their (Fab) fragments and are attached to the phagocytic cells by their (Fc) fragments. This process of specific attachment is called opsonization. Opsonization may also occur by complement fixation (the organism is coated by a specific antibody, the complement components are fixed to this complex and the complement is attached to macrophages which have specific receptors to the complement component C 3 ). Opsonization enhances the process of phagocytosis.

3. Engulfment (endocytosis): The phagocytic cell engulfs the organism, which becomes surrounded by the phagocytic cell membrane forming a ­vacuole called phagosome. 4. Intracellular digestion and killing : This is achieved by 2 mechanisms : a) Oxidative mechanism: Involving peroxidase and myeloperoxidase, which converts O 2 to superoxide and H 2 O 2 which are toxic to the ­ organisms. b) Oxygen ‑ independent (non ‑ oxidative) mechanism: which is less powerful than the oxidative mechanism. The organism is killed and digested by hydrolytic enzymes, low pH, lysozyme, lactoferrin and leukine.

5. Antigen representation : After digestion of microbes, microbial antigens are integrated with specific receptors in the cytoplasm. Outcome of Phagocytosis : All phagocytic cells may kill ingested microorganisms, however some bacteria e.g. M. tuberculosis and brucella may remain viable and multiply within these cells.

b) Chemical barriers (bactericidal factors) in blood, body fluids and tissues : 1. Complement: Protein components present in serum and other body fluids.. 2. Properdin: A serum protein, which can activate complement, thus providing a non ‑ specific defence mechanism. 3. Beta lysin: It is another bactericidal protein present in the blood and secreted by the blood platelets.

4. Interferons: A group of proteins produced by virally ‑ infected cells (alpha and beta interferons) or by stimulated lymphocytes (gamma ‑ interferon). They have 2 main functions: ‑ Interfere with viral replication (inhibit viral infection). ‑ Activate T ‑ lymphocytes, macrophages and natural killer cells. 5. Lysozyme: It is an enzyme that destroys the peptidoglycan layer of bacterial cell wall. It is secreted in tears, saliva and other body fluids.

REACTION TO INFECTION : When microbes overcome all the above ‑ mentioned natural barriers and establish themselves in a tissue, the body reacts to this form of injury by two mechanisms: 1. Non ‑ specific reaction : intended to limit the extent of injury. This is usually in the form of a local inflammatory response, which may be accompanied by a general reaction, i.e. fever. 2. Specific reaction : through stimulation of the immunological system. The result of this would be formation of specific immune response (antibodies and/or cell ‑ mediated immunity).

Non ‑ specific Reactions to Bacterial Infection : 1. inflammation : The presence of multiplying bacteria in a tissue stimulates vasodilatation and increased permeability of local arterioles and capillaries. Plasma escapes into the extravascular space leading to oedema and swelling of the inflammed area. 2. Fever: The most frequent systemic manifestation of microbial infection is rise of the body temperature. The mechanism of fever production is through the action of chemical stimuli on the thermoregulatory center of the brain. In microbial infections, these chemical stimuli arise from two sources. a) Bacterial endotoxin b) Disintegrated leukocytes and tissue debris: These are termed “endogenous pyrogens”.