Host parasite relationship notes 2023.pdf

Host-Parasite interactions Introduction In the host-parasite relationships there are two separate but interrelated aspects. 1. The specific properties of the organism causing the infection 2. The host response to infectious agents The primary protective factor of the host is resistan...

Host-Parasite interactions Introduction In the host-parasite relationships there are two separate but interrelated aspects. 1. The specific properties of the organism causing the infection 2. The host response to infectious agents The primary protective factor of the host is resistance. There are 4 types of resistance. ▪ Genetic (natural) resistance. Because of natural resistance, the disease agent may not multiply in the host. If it does multiply it will not cause disease. For example all non mammals are resistant to rabies; all species of animals except pigs are resistant to hog cholera (ASF) and horses and mules are naturally resistant to anthrax. ▪ Age resistance. A particular agent may cause disease in younger animals and be harmless or less harmful in older animals and the revere may also occur. Many agents are involved strictly with neonatal disease, while others are involved with disease in adults, e.g. parvovirus infection in puppies ▪ Immune resistance. The host may have developed immunity either through previous natural infection or through vaccination ▪ Nutritional resistance. An animal in good nutrition is more resistant to disease than one in poor nutritional condition. 1. Factors in the causative agent that are responsible for the production of disease (a) Virulence Virulence is the ability of a disease agent to invade and cause lesions. Some virulent agents cause massive tissue damage (e.g. tuberculosis), while others cause rapid death (e.g. botulism). Highly virulent strains of an agent produce severe disease. Less virulent agents produce sub clinical disease. The destructive agent may cause death of cells by its own presence or secretions (e.g. aflatoxins produced by fungi, endotoxins produced by bacteria). (b) Tropism Tropism is the affinity of an agent to a certain tissue. It is the property of an agent to strike a vital site to cause lesions in particular tissues. This is possibly because a particular local environment in a tissue supports the growth and survival of an agent. The predilection may be due to biochemical preference or the availability of a particular substrate. For example, rabies virus causes lesions in nervous tissue, whereas brucella organisms cause lesions in the uterus of females and testes of males. Some causes of viral tropism include: o Presence or absence of receptors that allow the virus to attach thus infecting specific cells only o The ability of the virus to replicate inside some cells but not others e.g. Rabies virus 1 2. Environment Many factors that are of importance in initiating and influencing the disease process are environmental. They have become increasingly important with intensive animal husbandry practices. For example: ▪ Ammonia gas and dust in poultry houses increase the incidence of chronic respiratory disease. ▪ Over crowding, low temperatures and humidity increases the incidence of pneumonia in calves. ▪ Stress like shipping affects the production of lesions in shipping fever ▪ Changes in the feed affects ruminal and intestinal flora causing subsequent disease e.g. grain overload in ruminants causes metabolic acidosis 3. Reaction of the body to disease causing agents The body will react in different ways depending on the disease causing agent it has been exposed to. (a) Nutritional deficiencies Generally nutritional deficiencies are of a multiple nature. Deficiency of a single nutrient is not common. Examples of nutritional deficiencies: ▪ Iodine deficiency causes hyperplasia of the thyroid gland. ▪ In iron deficiency there is anaemia and hyperplasia of the bone marrow. ▪ In mineral deficiencies e.g. Ca and P, there is hyperplasia of cartilage in growing bones (b) Mechanical and thermal injuries In mechanical injuries and burns, the body reaction is through the inflammatory process, regeneration and repair. (c) Poisons and toxins (i) The reaction of the body to poisons mostly depends on the mode of entry into the body. ▪ In some ingested poisons, the body reacts by vomiting and diarrhoea to try to reduce the effect of the poison ▪ When poison enters through the skin, there is inflammatory exudation in the area to dilute the poison and its effects (ii) Toxic agents cause disease either by direct contact or by absorption ▪ In direct contact, potent toxins cause degeneration and/or necrosis of the tissue ▪ Toxins that are absorbed into the circulatory system reach the liver which tries to detoxify the toxin to convert it to non harmful products that could be excreted through the kidneys. (d) Living organisms Parasites, fungi, bacteria and viruses elicit different body reactions. 2 (i) Parasites ▪ Metazoan parasites mostly cause mechanical injury to the host tissue. The host reacts to this usually by fibrosis and granulomas formation. If they are in the digestive tract they also cause nutritional deficiency. Blood sucking parasites cause anaemia and release anticoagulants. Some can cause mechanical obstruction of the lumen of the organ or duct or vessel where they parasitize. Some parasites liberate some toxic substances. In parasitic cysts like cysticercosis, the body reaction is by hyalinization and calcification around the dead cyst. Local reactions to migrating parasites are usually the formation of granulomas. Humoral antibodies are usually not formed in response to metazoan parasites. Complement fixing antibodies develop against certain parasites but are not protective and are mainly used for diagnosis. ▪ Pathogenic protozoa cause serious injury to the host. The body defence generally is by regeneration of destroyed cells (red and white blood cells) and tissues (intestinal epithelium). There is a gradual development of immunity against the parasite. ▪ Ectoparasites like fleas and ticks cause an inflammatory reaction on the skin and may also elicit an allergic reaction. Mites generally elicit a type of hyperplastic inflammatory skin reaction. (ii) Fungi. Fungal agents cause disease by three ways ▪ Toxicosis. This occurs by eating foods that contain fungal toxins. Generally fungal toxins are strong hepatotoxins. Many species of fungi are known to produce such toxins. Aspergillus spp, Fusarium spp and Mucor spp are known to produce toxins in groundnuts, corn cake and other foods. Eating such contaminated feed results in toxicity. ▪ Allergy. This results from contact with and development of hypersensitivity to fungal antigens. Some fungi present in hay cause allergy in man and animals. ▪ Invasion. The majority of fungi produce lesions by direct invasion into tissues. Such fungi mostly cause disease in the skin, lungs and mucous surfaces. They produce slow necrotic lesions which later on result into granulomatous lesions. (iii) Bacteria ▪ Simple bacteria cause acute disease. Some bacteria produce toxic substances like haemolysin and leukocidins. Many bacteria of this group have a special affinity for certain tissues where they localise and cause disease with acute exudation. For example, salmonellae produce lesions in the intestines, Corynebactera produce lesions in the kidneys, lymph nodes and respiratory tract. ▪ Higher bacteria produce chronic slowly progressive chronic disease similar to invasive fungi. There is necrosis near the colonies of bacteria which causes a strong cellular reaction and fibrous tissue proliferation. In most of these 3  infections, the humoral and cellular reaction of the body is not enough to destroy them although there is a strong cellular reaction composed of lymphocytes, monocytes and plasma cells along with fibrosis which results in granulomas formation. This reaction of the body separates the infection from the rest of the body. Examples of such bacteria are Mycobacterium tuberculosis, Actinobacillus lignieresii, Pseudomonas mallei and Actinomyces bovis. (iv) Viruses. Three types of disease are produced by viruses: ▪ Cytotoxic (destructive) viruses produce necrotic lesions with acute exudation. They produce necrotic lesions which are similar to diseases produced by simple bacteria. ▪ Proliferative viruses cause hyperplasia in tissues and have been associated with neoplastic conditions, e.g. marecks disease ▪ Slow virus infection. These are slow growing viruses with an incubation period of months to years causing chronic disease. Such persistent infections lead to immune complex diseases, e.g. ovine progressive pneumonia in sheep (maedi visna) caused by a retrovirus, pulmonary adenomatosis in sheep (jaagsiekte) caused by a retrovirus and scrapie in sheep caused by a prion. The body reacts by marked proliferation of lymphoid cells. 4. Host barriers to infection and how they break down System Host barrier Causes of break down of the barrier Skin ▪ Dense keratinized outer skin layer to ▪ Warm moist skin, heat and prevent penetration humidity enhance penetration ▪ Low pH of skin and fatty acids to inhibit by larvae. microbial growth ▪ Superficial pricks, ▪ Bites by fleas, mites, lice and animals Urogenital ▪ Frequent flushing daily by urination ▪ Obstruction of the urinary flow tract keeps the urinary tract sterile ▪ Reflux of urine from the ▪ Acid pH of the vagina prevents bacterial bladder into the ureters proliferation ▪ Adherence of pathogens to urinary epithlium Respiratory ▪ Cilia and mucous in the nasal cavity and ▪ Smoking tract upper respiratory tract trap pathogens ▪ Intubation ▪ Alveolar macrophages and neutrophils ▪ Some viruses reduce the phagocytose pathogens viscosity of mucous preventing it from trapping ▪ Some pathogens release factors that inhibit the motion of the cilia Intestinal ▪ Mucous covering of the epithelial layer ▪ Decrease of gastric acid tract in the gastrointestinal tract ▪ Treatment with antibiotics ▪ Acid in the gastric secretions which also kill the normal flora 4  ▪ Pancreatic enzymes ▪ Resistance to stomach acids, ▪ Bile salts pancreatic enzymes and bile ▪ Competition for nutrients between acids pathogenic and non-pathogenic ▪ Attachment of bacteria via organisms (normal flora) specific adhesions ▪ Passage through stool ▪ Invasion causing ulceration Table 1: Some host barriers to infection and how the break down Spread of microbes through the body occurs in various ways: ▪ Rapid spread along the wet epithelial surfaces of the intestines, lungs and urogenital tract, and slowly on the dry surface of the skin ▪ Penetration via secretion of hyaluronidase (hydrolyses connective tissue – hydroxyapetite) ▪ Routes of microbial spread follow tissue planes of least resistance and the regional and vascular anatomy. 5. How infectious agents cause disease There are three general mechanisms. (i) Infectious agents can contact or enter host cells and directly cause cell death (ii) Pathogens can release endotoxins or exotoxins that: ▪ Kill cells at a distance ▪ Release enzymes that degrade tissue components ▪ Damage blood vessels and cause ischaemic injury (iii) Pathogens can induce host cell responses that may cause additional tissue damage, usually by immune mediated mechanisms. (a) Mechanisms of virus induced-injury Viruses enter host cells and replicate at the hosts expense. Specific viral proteins (ligands) bind to particular host proteins (receptors), e.g. HIV binds to CD4 cells. Attachment to the cell membrane and penetration into cell cytoplasm is by: (i) translocation of the entire virus across the plasma membrane (ii) fusion of the viral envelop with the cell membrane, or (iii) receptor-mediated endocytosis and fusion with endosomal membranes. Within the cell, the virus uncoats, separates its genome and loses its infectivity. It then replicates. The newly synthesised viral genomes and capsid proteins are assembled into progeny virions in the nucleus (e.g. pox virus, herpes virus) or cytoplasm (e.g. rabies, HIV) and are either released directly (unencapsulated viruses) or bud through the plasma membrane (encapsulated viruses). Viruses kill host cells and cause tissue damage in a number of ways: viruses may inhibit host cell DNA, RNA or protein synthesis viral proteins may insert into the host cells’ plasma membrane and directly damage its integrity or promote fusion (HIV, measles and herpes virus) 5  viruses replicate efficiently and lyse host cells, e.g. respiratory epithelial cells are killed by explosive rhinovirus or influenza virus multiplication, liver cells by infectious canine hepatitis virus, and neurons by poliovirus or rabies virus. Virus proteins on the surface of the host cells may be recognized by their immune system, and the host lymphocytes attack the virus infected cells, e.g. hepatocytes infected with hepatitis B Virus. Viruses may also damage cells involved in host antimicrobial defence, leading to secondary infections, e.g.; viral damage to respiratory epithelium predisposes to the subsequent development of pneumonia, while HIV depletes CD4 helper lymphocytes and opens flood gates for many opportunistic infections. Viral killing of cells of one type may cause damage to other cells that are dependent on their integrity, e.g. denervation by the attack of poliovirus on motor neurons causes atrophy, and sometimes death of distal skeletal muscle cells. Slow virus infections culminate in severe progressive disease after a long latency period, e.g. Scrapie Certain viruses cause cell proliferation and transformation, resulting in the formation of cancer e.g. Transmissible venereal tumour (TVT), marecks. (b) Mechanisms of bacteria-induced injury – bacterial adhesins and toxins Bacterial damage to host tissues depends on their ability to adhere and to enter host cells or to deliver toxins. Bacterial adhesins are molecules that bind bacteria to host cells. They are limited in type, but have a broad range of host cell specificity. Bacterial endotoxin is a lipopolysaccharide that is a structural component of the outer cell wall of gram-negative bacteria. Endotoxins induce fever, septic shock, DIC, acute respiratory distress syndrome, and a variety of effects on cells of the immune system. Bacterial exotoxins are harmful products secreted by bacteria, e.g. leukocidins, haemolysins, hyaluronidases, coagulases, fibrinolysins and other enzymes extracted from bacterial cultures. Certain bacterial exotoxins directly cause cellular injury and determine disease manifestations. Diphtheria toxin causes neural and myocardial dysfunction The heat-labile enterotoxins of Vibrio cholerae and of E. coli generate excess cAMP which causes intestinal epithelial cells to secrete iso-osmotic fluid, resulting in voluminous diarrhoea and loss of water and electrolytes. The gram positive anaerobic Clostridium perfringens digests host tissues and its α-toxin is a lecithinase that disrupts plasma membranes, including those of red and white blood cells. Clostridium tetani secretes an exotoxin called tetanoplasmin that interferes with release of inhibitory transmitter substances such as γ-aminobutyric acid from presynaptic terminals of the spinal interneurons, resulting in violent muscle contractions that characterise the tetanic spasm. 6  Clostridium botulinum toxins block the release of cholinergic neurotransmitters at neuromuscular junctions resulting in progressive paralysis of the limbs, respiratory muscles and cranial motor neurons. (c) Immune evasion by microbes Micro-organisms escape the host immune system by: (i) remaining inaccessible: Microbes that propagate in the lumen of the intestine or gallbladder are inaccessible to the host immune defences, including secretory IgA. Viruses shed from the luminal surface of epithelial cells or those that infect the keratinized epithelium (e.g. pox virus in crocodiles) are also inaccessible to the host immune system. Some organisms establish infections by rapidly invading host cells before the host humoral response becomes effective (malaria sporozoites, Trypanosoma cruzi). Some larger parasites e.g. the larvae of tapeworms, form cysts in host tissues that are covered by a dense fibrous capsule that walls them off from the host immune reponses. (ii) cleaving antibody, resisting complement-mediated lysis, or surviving in phagocytic cells: The carbohydrate capsule on the surface of all major pathogens that cause pneumonia or meningitis make them more virulent by covering bacterial antigens and preventing phagocytosis of the organisms by neutrophils. Pseudomonas bacteria secrete a leukotoxin that kills neutrophils Some E. coli have K antigens that prevent activation of complement by the alternative pathway and lysis of the cells. Some gram negative bacteria have very long polysaccharide O antigens which bind host antibody and activate complement at such distance from the bacterial cells that the organisms fail to lyse Staphylococci are covered by protein A molecules that bind the Fc portion of the antibody and so inhibit phagocytosis. Certain bacteria secrete proteases that degrade antibodies (iii) varying or shedding antigens (antigenic variation) Certain viruses and bacteria with many antigenic variants cannot be recognized by specific antibodies thus preventing immune clearance, e.g. HIV, influenza viruses (iv) and causing specific or non-specific immunosuppression Viruses that infect lymphocytes (HIV and Epstein Barr Virus) directly damage the host immune system and cause opportunistic infections e.g. AIDS 7 6. Special techniques for diagnosis of infectious agents Some infectious agents or their products can be directly observed in H&E stained sections e.g. inclusion bodies formed by rabies virus; bacterial clumps which usually stain blue; fungi e.g. Candida and Mucor; most protozoans and Helminths. However, many infectious agents are best visualized after staining with special stains that identify organisms based on particular characteristics of their cell walls or coat (Gram, acid-fast, silver, mucicarmine, and Giemsa stains) or after labelling with specific antibody probes. Regardless of the staining technique, organisms are usually best visualized at the advancing edge of the lesion, rather than at its centre, particularly if there is necrosis. Because these morphologic techniques cannot determine species, drug sensitivity, or identify virulence characteristics, cultures of lesional tissue must be performed. PCR-based methods can be used to identify to species and strain level. DNA sequence analysis can be used to classify the infectious agent. Technique Agents detected Gram stain Most bacteria Acid-fast stain Mycobacteria, Nocardiia (modified) Silver stains Fungi, legionella, Pneumocystis Periodic acid-Schiff Fungi, amoeba Mucicarmine Cryptococci Giemsa Camplylobacter, Theileria Antibody probes Viruses, rickettsiae Culture All classes DNA probes, PCR All classes Regardless of the method of microbial identification, the final step in diagnosis of infectious pathogens is correlation of the suspect organisms with the lesion caused and the signs and symptoms produced. 7. Inflammatory response to infectious agents In contrast to the vast molecular diversity of parasites, the pattern of inflammatory response to these agents is limited, as are the mediator mechanisms that direct these responses. Microscopically, therefore, many pathogens evoke similar identical reaction patterns, and few of the features are unique to or pathognomonic of each agent. The patterns of tissue reaction are useful for analyzing the infective processes, but they frequently overlap. Similar patterns of inflammation can also be seen in tissue responses to physical or chemical agents and in inflammatory diseases of unknown causes e.g. sarcoidosis. Many factors that relate to the invader and host modify the development and nature of the microbe-induced disease and its outcome. Considering the multiplicity of potential invaders, most infectious diseases are caused by a relatively small number of 8 agents that differ in geographical location and are determined largely by environmental, socioeconomic, and public health factors. 9