This book provides immunopathology of animals, their etiology, clinical signs, diagnosis and treatment with the suitable references.
Immune system has evolved to protect the living body from the infections, which are themselves are evolving. The disorders of the immune system cause immunopathological diseases. Immunopathology is mainly characterized by the three responses in the body. These are increased response to an antigen, also known as hypersensitivity; decrease response to an antigen, also known as immunodeficiency; and response to self-antigen i.e., autoimmunity. Hemolytic anemia of newborn horse and piglets occurs because of immune-mediated destruction of the red blood cells of neonates by antibodies acquired from the dam in colostrum. Diagnosis of type II hypersensitivity is done by Coomb test and type IV hypersensitivity is mainly done by skin testing. Equine agammaglobulinemia is a primary immunodeficiency occurs due to B cell defect. Equine recurrent uvitis is one of the very common causes of vision loss in horses throughout the world. Autoantibodies are produced against the interphotoreceptor retinoid-binding protein and S-protein. The antibody produced against Leptospira interrogans cross reacts with the retinoid binding protein. Equine polyneuritis is the uncommon disease of the horses characterised by sacral and coccygeal nerve paralysis. Affected horses have circulating antibodies against peripheral myelin protein i.e., P2. Purpura hemorrhagica is an acute, non-contagious, aseptic necrotizing vasculitis, characterized by edema and petechial or ecchymotic hemorrhage of the mucosa and subcutaneous tissue. The M antigen of Streptococcus equi helps in the formation of immune complexes. Recurrent airway obstruction or heaves is a asthma like condition in mature horses following stabling and exposure to dusty hay and straw. Fungus like Aspergillus fumigatus, Faenia rectivirgula and Thermoactinomyces vulgaris are present in the hay or straw act as allergen.
The immune system deals with the collection of cells and proteins in the body, that functions to protect the skin, respiratory passages, intestinal tract, and other areas from foreign antigens such as bacteria, viruses, fungi, parasites, cancer cells, and toxins. Innate immunity is entitled as the first line of defense towards any intruding pathogen and it is the rapid immune response. The innate immune response is an antigen-independent (non-specific) defense mechanism and has no immunologic memory. Certain immunopathological diseases take place when there is defect in either system. Immunopathology is the study of diseases caused by immune reaction; therefore, the word immunopathology connotes that protective immune response may cause the tissue damage and diseases. Immunopathological diseases are characterized into immunodeficiency, hypersensitivity, and autoimmunity. Immunodeficiency disorders have been described as diseases caused by one or more defects of the immune system, leading to increased susceptibility to infections. Hypersensitivity reactions are immune responses that are exaggerated or inappropriate against an antigen or allergen and classified into type I (anaphylaxis), type II (cytotoxic), type III (immune-mediated), and type IV (T-cell mediated). Type I, Type II, and Type III are also known as antibody-mediated hypersensitivity; whereas, Type IV is also known as cell-mediated hypersensitivity. Autoimmune diseases occur when the immune system attack the self–antigens as a result of breakdown of immunologic tolerance to autoreactive immune cells.
Immunity is the resistance of body against extraneous etiological factors of diseases, which is afforded by the interaction of chemical, humoral and cellular reactions in the body. Immunity can be classified as natural or paraspecific and acquired or specific immunity. Acquired immunity develops in the body as a result of prior stimulation with antigens. It can be classified as humoral and cell-mediated immunity. The antibody mediated immunity is called as humoral immunity and is present in body fluids mainly in the blood. Antigen is a foreign substance, which is able to stimulate the production of antibodies. Antibodies are protein in nature and are produced as a result of antigenic stimulation. Cell-mediated immunity is a form of immune response mediated by T-lymphocytes and macrophages. Cytokines are hormone like glycoproteins in nature with a molecular weight of 8–25 kDa and composed of a single chain.
The lungs are continuously exposed to diverse array of microbes, organic and inorganic particulate materials. Pulmonary immunity determines the outcome of infections and failure of immune defenses may lead to development of pneumonia. Predisposing factors weaken the lung defenses and lead to infection with any pathogens including viruses, bacteria, parasites, and fungi. Pneumonia is an inflammation of the lungs that can cause mild to severe illness in animals of all ages. Pneumonia is one of the leading causes of death due to infection in animals in younger ages worldwide. Very young, older animals and animals with underlying health problems or immunosuppression were at high risk for pneumonia. Pathogens could interfere with different respiratory defenses, allowing two or more bacteria to colonize the lungs. Inhalants like microbes and environmental particles need to be eliminated quickly by the immune system, as failure to do so can lead to inflammatory responses that result in swelling that closes the airways results in increased incidence of infections. Most viruses and bacteria cause ciliary dysfunction and alteration of the mucosal surfaces that predisposes the bacterial and/or viral pneumonia. Further, virus and bacterial infections cause alteration of alveolar macrophage function, suppression of lymphocyte proliferation, induces apoptosis, and modified cytokine and other inflammatory mediator release resulted in modification of innate and adaptive immune responses. Viscosity of the mucus interferes with clearance, leading to airway obstruction, colonization with bacteria, and impaired migration and bactericidal activity of neutrophils. Elevated ammonia levels are associated with overcrowding and reduced ventilation results in ciliary dysfunction, degeneration and inflammation of the nasal epithelium, and increased susceptibility to pneumonia.
Skin is the body’s largest organ. The primary function is to act as a shield that protects internal organs from physical and chemical attacks, pathogen invasion and excessive loss of water. The body is rich in immune cells, forming a complex network called as the “skin immune system”, as the main immunological barrier to the external environment. Any immune system disruption or defects can lead to immunological skin diseases. Excessive and undesirable immune responses can cause hypersensitivity or autoimmune diseases, while hypoimmunity can lead to infectious diseases and skin tumor. In body, the immune system is located in both major structural compartments: epidermis and dermis, and consists of several essential types of immunocompetent cells. Primary skin-resident immune cells, Langerhans cells (LCs) and melanocytes that produce melanin inhabit epidermis, while other types of immune-specialized cells, such as various subpopulations of dendritic cells (DCs), macrophages, and several types of T cells reside in the deeper layer — dermis. The efficacy of the skin immune system strongly depends on the close interplay and interaction between immune cells and the skin environment, such as adjacent keratinocytes and fibroblasts. The fundamental premise for protective immunity is the ability to distinguish between self and non-self. This ability is acquired during the growth of the fetus. In the normal system, when the above process fails, immune-mediated disease occurs. Some of the most interesting and challenging issues in immune-mediated dermatological diseases are discussed in this book chapter.
Immune system protects the body from various infectious agents, toxic and allergic substances. It contains two interrelated responses i.e., innate immune response and acquired immune response. Immunopathological disorders arise when there is defect in the immune system, which are characterized by hypersensitivity, immunodeficiency, and autoimmunity. Hypersensitivity reaction is an exaggerated or elevated immune responses against any antigen and are categorized into four types namely, Type I (immediate or IgE mediated); type II (cytotoxic); type III (immune-complex mediated); and type IV (delayed-type) hypersensitivities. The first three hypersensitivity reactions are the antibody-mediated, while Type IV is T-cell mediated hypersensitivity. Immunodeficiency occurs due to failure or absence of essentials of the immune system such as complement system, lymphocytes, and phagocytes. Autoimmunity is defined as an immune response of the body against self-antigens or own tissues of body. Reactivity against self-antigen can arise either by triggering the receptors directly by autoantigen or through cross-reaction between foreign and self-antigens. In sheep, goat, wild and laboratory animals there are several immunopathological disorders that may prove fatal to animals including acute systemic anaphylaxis, allergic rhinitis, blood transfusion reactions, hemolytic diseases, immune complex mediated glomerulonephritis, transient hypogammaglobulinemia, bluetongue disease, mouse mammary tumor virus infection, simian immunodeficiency virus infection, murine leukemia virus infection, pemphigus foliaceus, autoimmune hemolytic anemia, autoimmune encephalitis etc. Cytokines plays major role in the modulation of immune responses results in development of several immunopathological disorders.
This study evaluated the haematological effects of the oral administration of silver nanoparticle in Wistar rats. A total of 35 rats, six weeks of aged, both male and female, were randomly divided into two groups. Group 1 was kept as control and comprised of 20 rats. Group II comprised of 15 rats and the rats were orally administered silver nanoparticle mixed in distilled water at no-observed-adverse-effect level (NOAEL) dose rate of 30 mg/kg body weight/day daily for 90 days of experiment. Blood was collected from 5 rats from each group at 0, 30th, 60th and 90th days post-treatment. A traditional Manual method was used to measure Hematological parameters and data analyzed by one-way ANOVA (post hoc Dunnett's test). The hematological parameters studied were significantly altered in treatment group as compared to control animals. Morphology of erythrocytes indicates normocytic hypochromic anaemia. Our results indicated that the silver nanoparticles have adverse effects on general clinical condition and hematological parameters of rats at NOAEL dose.
Immunotoxicology examines the adverse effects of xenobiotics- including pesticides, heavy metals from emissions, drugs and other substances- on the body’s defense system of humans and animals. The term pesticide encompasses a diverse array of substances, including insecticides, fungicides, herbicides, rodenticides, etc. Pesticides are widely used around the globe; however, there has been an increase in reports highlighting their harmful effects. The broad-spectrum activity of methyl parathion allows elimination a vast range of pests, making it a popular choice for pest control in agriculture. However, its use is increasingly regulated due to its high toxicity to humans, non-target organisms and the environment. Methyl parathion, a widely used organophosphate pesticide, is reported to pose significant health risks through its neurotoxic, immunotoxic and oxidative stress-inducing effects. Methyl parathion primarily exerts toxicity by inhibiting acetylcholinesterase, leading to neural overstimulation. This study investigates the in vitro immunotoxic effects of methyl parathion induced due to increased oxidant stress (OS) in mitogen-stimulated avian lymphocytes. Utilizing lymphocyte proliferation and nitric oxide (NO) estimation assays, the findings showed a marked reduction in B and T-cell proliferation following exposure to a thousand-fold dilution of the No Observable Effect Level (NOEL/103) dose of methyl parathion. Additionally, oxidative stress, as indicated by NO levels, was significantly elevated in methyl parathion treated cells as compared to control cells. Thus, our results indicate that in vitro exposure to methyl parathion caused considerable immunotoxic effects in the exposed lymphocytes that could be linked with enhanced OS.
The field of molecular diagnostics in veterinary sciences is rapidly growing. The advances in the field of biotechnology have significantly contributed to the development of novel, rapid, and precise molecular diagnostic assays for several animal diseases that can ultimately be used in point-of-decision making during an outbreak. A range of molecular biological techniques of different specificity and sensitivity are available to facilitate the rapid and precise diagnosis of animal diseases. The choice for the molecular technique dependents up on the aim, availability of reagents, disease, knowledge about the test, and its limitations. The quick detection of pathogens and their characteristics would allow for accurate decision-making and implementation of control measures such as appropriate therapy, vaccination, and biosecurity procedures to control the disease outbreaks. In practice, rapid diagnosis using the molecular techniques makes a strong collaboration between the veterinarians in the laboratory and the field practitioners. In the recent times, numerous molecular biological techniques have been identified for the detection and characterization of pathogens in the field of veterinary science. Nowadays, PCR and real-time PCR have been the most commonly used technology for the detection of pathogens that are slow or difficult to isolate in the clinical microbiology laboratory, molecular detection of antimicrobial resistance genes, and microbial load determination. Although, some of the new technologies such as liquid-phase hybridization, DNA/protein microarray, isothermal nucleic acid amplification methods etc. have high sensitivity and specificity but, these tests are not frequently used for clinical veterinary diagnosis. This book chapter describes the basic principles and applications of recently developed molecular biological techniques used for the veterinary clinical diagnosis.
Mastitis is derived from Greek words ‘Mastos’ means breast and ‘itis’ means inflammation. It is an inflammatory condition of the mammary gland caused by bacterial, viral and fungal infections. Mastitis occurs most oftenly in lactating mammals. Mastitis is characterized by physical, chemical, and bacteriological changes in the milk. It is a common disease of high milking cows like exotic and cross breeds. Mastitis incidence is higher in cows from third lactation onwards, when optimum milk production occurs. It is the most costly disease for dairy farmers and industry, as a consequence of decreased milk production and quality, treatment costs, animal replacement costs, and difficulties in marketing of poor quality dairy products. Mastitis arises as a result of complex interplay between infectious agents, managemental practices and environmental factors. It is a response to injury or infection, which serve to neutralize and destroy the infectious agents and promote healing and then return to normal function. The most important changes in milk include discolouration of milk and presence of flakes. Innumerable genera and species of bacteria cause mastitis. Predominant organisms are Staphylococcus aureus followed by Streptococcus agalactia. The other organisms include E. coli, Streptococcus uberis, Streptococcus dysagalactia, Streptococcus pyogenes, Corynebacterium pyogens, Corynebacterium bovis, Mycobacterium bovis, Nocardia asteroids, Leptospira interrogans serovar Pomona, Leptospira interrogans hardjo, etc. Fungal agents such as Trichophyton spp., Aspergillus fumigatus, and yeast such as Candida spp., Cryptococcus neoformans, etc can cause mastitis. Viruses causing mastitis are infectious bovine rhinotracheitis, bovine viral diarrhea, foot-and-mouth disease, pseudo cowpox, etc, and predispose cows to bacterial mastitis.
The immune system in the body has also evolved with the development of the microorganisms to shield us from their harmful effects. The immune system protects not only from infectious organisms, but also from poisonous and allergic substances. There is a complex network of different organs, cells, proteins, humoral and cellular factors functioning in cascade to maintain the normal homeostasis in the body. The immune system has three main pillars, including anatomical and physical barriers, innate and acquired immunity. In conjunction with each other, these three elements of the immune system provide protection against any harmful agents. Immunopathological disorder happens when one of these mechanisms fails. This means that the defensive immune responses can also cause tissue damage. Accordingly, the study of diseases caused by the immune system is known as immunopathology and the diseases are known as immunopathological disorders. Such conditions are mainly described by excessive immune responses i.e., hypersensitivity, response to self-antigen i.e., autoimmunity, and inadequate immune response i.e., immunodeficiency. In joints, these immunopathological changes lead to the alteration in normal cartilaginous structure, joint capsule, and synovial membrane. However, the etiology of most of these conditions remains unknown, but it is suspected that both genetic and environmental factors play a pivotal role in the development of synovial inflammation as in diseases like rheumatoid arthritis, spondyloarthritis and osteoarthritis. Rheumatoid arthritis (RA) is an etiologically unknown, chronic inflammatory autoimmune disease. It is characterized by rheumatoid factor and peptide antibodies that are anticitrullinated. Various bacterial, viral, protozoal and fungal agents are involved in the infectious arthritis of domestic animals.
Enteritis is defined as an inflammation of the intestine and affects wide age groups and is characterized by dull and depressed appearance, abdominal pain, weight loss and characteristically diarrhea. Diarrhea is defined as increase in frequency of faeces output (more than 3 to 4 times a day) and a decrease in the consistency. Globally, billions of peoples are found to be affected with diarrhea, and most badly driven is people of the developing countries. Crucial management of diarrhea is necessary as excess loss of water and electrolyte may lead to death. Diarrhea is mainly seen as a manifestation of gastrointestinal infection, which may be bacterial, viral, and parasitic in origin. It spreads mainly through ingestion of the contaminated food and water, and poor hygienic condition. Worst struck are the young and immuno-compromised animals. Disease and infections affecting large intestine causes diarrhea due to disturbances in water conservation; whereas, in the small intestine, it is osmotic or secretary activity. Balance between secretion and absorption of electrolytes is a dynamic process and its imbalance results into diarrhea. There are multiple causes for diarrhea and the following classification provides a useful framework for approaching diarrhea; 1) Diarrhea secondary to altered mucosal transport or secretory dysfunction, 2) Osmotic diarrhea, 3) Diarrhea secondary to malabsorption, 4) Exudative diarrhea, and 5) Diarrhea secondary to altered bowel motility. Besides above, there are various mediators involved in diarrhea and are broadly mentioned in this book chapter.
The uterus’ endometrial lining is pivotal for reproductive cycles, implantation, and fetal health until parturition. Serving as gatekeepers, mucosa lining and epithelial cells prevent pathogen entry from the vagina into the uterus, with infections reaching through the vaginal route or cervix. Vaginal innate immunity involves physical, chemical, and cellular components, creating a microenvironment regulating immune responses influenced by sex hormones and the microbiome. Physiological processes like menstruation, conception, and pregnancy impact the vaginal mucosal immune system. The vagina’s stratified squamous epithelium acts as a barrier, sensing pathogens and activating immune cells to drive inflammation and responses. During healthy pregnancy, the uterus maintains a sterile environment, as bacterial presence poses a risk of fetal impact and systemic inflammation. Bacteria typically invade the uterine cavity from the lower urogenital tract, ascending through the cervix, breaching the placental barrier to reach the amniotic fluid and placenta. Uterine infections, common in animals, can cause infertility, abortion, and clinical disease. Some infections ascend via the cervix, while others reach the uterus through circulation. This book chapter delves into the intricacies of immunity and inflammation in the uterus.
The coronavirus disease 2019 (COVID-19) pandemic has recently created huge global health concerns and because of significant morbidity, socio-economic impact, and death in immune-compromised and elderly patients, WHO announced COVID-19 as a global public health emergency. The COVID-19 is caused by a newly-emerged novel coronavirus known as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) The virus belongs to the subfamily Orthocoronavirinae, family Coronaviridae, and genus Betacoronavirus. The CoVs are enveloped, positive-sense and single-stranded RNA viruses. The CoVs are reported to cause respiratory, nervous, and enteric diseases. The virus has reportedly originated from Wuhan, China in December, 2019 and rapidly spread to more than 215 countries with above 600.45 million confirmed cases and nearly 6.5 million deaths as on August, 2022. Various possible efforts were made to mitigate the COVID-19 pandemic by early diagnosis and prompt clinical care of affected individuals, along with adequate prevention and control measures. Many treatment options, including antivirals, protease inhibitors, and immunotherapeutics (neutralizing/monoclonal antibodies and convalescent plasma), and other therapeutics (antimalarial and antiparasitic drugs) were attempted with largely partial success. Hence, only prevention strategies to avoid virus infection and further transmission and spread may be considered. This reflects an urgent need for combined cooperation and collaborative efforts of common people, health workers, and research wings in a coordinated manner on regional, national, and international platforms.
Biomarkers are the biological molecules or characteristics, which can be distinctively and consistently assessed as an indication of normal physiological, pathobiological, or pharmacodynamic processes. Specific cells of the innate immune system, receptors for microbial ligands, antimicrobial molecules, and inflammatory mediators are the potential biomarkers of immunopathology, which are frequently employed for biological research, disease diagnosis, and monitoring as well as therapeutic prognostication in veterinary medicine. Immune cells and some parenchymal cells of the body are expressing a group of receptor molecules targeting specific epitopes on various pathogenic organisms are called as pattern recognition receptors (PRRs) and the corresponding target epitopes are termed as pathogen associated molecular patterns (PAMPs). PRRs act as a first line of defence against invasion of pathogens and they trigger both innate and adaptive immune responses. TLRs play an important role in recognizing microbes and in triggering inflammation. Cytokines are small secreted proteins released by cells, which have a specific effect on the interactions and communications between cells. Interleukins are a type of cytokines that was once considered to be produced only by leukocytes, but has now been discovered to be produced by a variety of different body cells. Chemokines are a broad class of small secreted proteins that signal through G protein-coupled heptahelical chemokine receptors on cell surfaces. Antimicrobial peptides (AMPs) are essential components of the innate immune system in humans, animals, and plants, and they serve as the first line of defence against foreign invaders. This book chapter extensively discusses about the different biomarkers and their role in the evaluation of health status, risk, diagnosis, prognosis, progression of disease, and to predict and monitor the response to therapy.