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Infectious diseases 
Guvera Vasireddy 
Department of Pathology 
Osmania Medical College
Historical perspective 
• Infectious agents have probably always caused disease in humans. 
• Smallpox has been described ...
Robert Koch 
• Bacteria were discovered in 1675 by Antony van Leeuwenhoek, but it wasn’t until 1876 that a German physicia...
Koch’s Postulates 
• Koch developed four criteria to demonstrate that a specific disease is caused by 
a particular agent....
Definitions and Terms 
• Disease – a pathological condition of body parts or tissues characterized by an identifiable 
gro...
Infectious diseases – present status 
• Despite the availability and use of effective vaccines and antibiotics, infectious...
Transmission of Infectious Diseases 
Agents that cause infectious diseases can be transmitted in many ways. 
• Through the...
How Infectious Agents Cause Disease 
• Production of poisons, such as toxins and enzymes, that destroy cells and 
tissues....
Phases of infectious diseases 
• Incubation period – time between infection and the appearance of signs and 
symptoms. 
• ...
Classification of infectious diseases 
By duration 
• Acute – develops and runs its course quickly. 
• Chronic – develops ...
Taxonomy Size Site of Propagation Examples Disease 
Prions 30–50 kD Intracellular Prion protein Creutzfeld-Jacob 
disease ...
Prions 
• Prions are composed of abnormal forms of a host protein, termed prion protein (PrP). 
• These agents cause trans...
Viruses 
• Viruses are obligate intracellular parasites that depend on the host cell's metabolic 
machinery for their repl...
Human 
Immunodeficiency 
Virus. 
HIV-1 virions can be 
seen on surface of 
lymphocytes.
The variety of viral structures, 
as seen by electron 
microscopy. 
A, Adenovirus, an icosahedral 
nonenveloped DNA virus ...
Influenza
Bacteria 
• Prokaryotes. 
• Most bacteria are bound by a cell wall consisting of peptidoglycan, a polymer of long sugar 
c...
Molecules on 
the surface of 
gram-negative 
and gram-positive 
bacteria 
involved in 
pathogenesis.
The variety of bacterial morphology. The bacteria are 
indicated by arrows in each panel. A, Gram stain of 
sputum from a ...
Fungi 
• Fungi are eukaryotes that possess thick chitin-containing cell walls and ergosterol-containing 
cell membranes. 
...
Fungal infections 
• Fungi may cause superficial or deep infections. 
• Superficial infections involve the skin, hair, and...
Protozoa 
• Parasitic protozoa are single-celled eukaryotes. 
• Protozoa can replicate intracellularly within a variety of...
Helminths 
• Parasitic worms are highly differentiated multicellular organisms. 
• Their life cycles are complex; most alt...
Ectoparasites 
• Ectoparasites are insects (lice, bedbugs, fleas) or arachnids (mites, ticks, spiders) 
that attach to and...
DIAGNOSING INFECTIOUS AGENTS 
• Some infectious agents or their products can be directly observed in 
hematoxylin and eosi...
Techniques Infectious Agents 
Gram stain Most bacteria 
Acid-fast stain Mycobacteria, nocardiae (modified) 
Silver stains ...
Serological and nucleic acid detection tests 
• Acute infections can be diagnosed serologically by detecting pathogen-spec...
Health ecosystem and emergence of new infectious 
diseases 
• Human demographics and behaviour are among the many variable...
Emerging and newly discovered infectious 
diseases 
• Surprising number of new infectious agents continue to be discovered...
Date 
Recognized Infectious Agent Manifestations 
1977 Ebola virus Epidemic Ebola hemorrhagic fever 
Hantaan virus Hemorrh...
AGENTS OF BIOTERRORISM 
Category A Diseases/Agents 
Anthrax (Bacillus anthracis) 
Botulism (Clostridium 
botulinum toxin) ...
Category B Diseases/Agents 
Brucellosis (Brucella sp.) 
Epsilon toxin of Clostridium perfringens 
Food safety threats (e.g...
TRANSMISSION AND DISSEMINATION OF 
MICROBES 
• Microbes can enter the host by inhalation, ingestion, sexual transmission, ...
HOW MICROORGANISMS CAUSE DISEASE 
• They can contact or enter host cells and directly cause cell death. 
• They may releas...
Mechanisms of Viral Injury 
• Viruses can directly damage host cells by entering them and replicating at 
the host's expen...
Mechanisms of Bacterial Injury 
• Bacterial Virulence. 
• Bacterial Adherence to Host Cells. 
• Virulence of Intracellular...
IMMUNE EVASION BY MICROBES 
• Microorganisms have developed many means to resist and evade the 
immune system. 
(1)growth ...
Mechanisms of Antigenic Variation 
Type Example Disease 
High mutation rate HIV AIDS 
Influenza virus Influenza 
Genetic r...
SPECTRUM OF INFLAMMATORY RESPONSES TO 
INFECTION 
• Suppurative or purulent inflammation. 
• Mononuclear and granulomatous...
Suppurative inflammation 
• This pattern is the reaction to acute tissue damage is characterized by increased vascular 
pe...
Mononuclear and Granulomatous Inflammation 
• Diffuse, predominantly mononuclear, interstitial infiltrates are a common fe...
Cytopathic-Cytoproliferative Reaction 
• The lesions are characterized by cell necrosis or 
cellular proliferation, usuall...
Tissue Necrosis 
• Clostridium perfringens and other organisms that secrete powerful toxins can 
cause such rapid and seve...
Chronic Inflammation and Scarring 
• Chronic HBV infection may cause cirrhosis of 
the liver, in which dense fibrous septa...
Thank you
Infectious diseases: an introduction
Infectious diseases: an introduction
Infectious diseases: an introduction
Infectious diseases: an introduction
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Infectious diseases: an introduction

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Infectious diseases: an introduction

  1. 1. Infectious diseases Guvera Vasireddy Department of Pathology Osmania Medical College
  2. 2. Historical perspective • Infectious agents have probably always caused disease in humans. • Smallpox has been described in ancient Egyptian and Chinese writings and may have been responsible for more deaths than all other infectious diseases combined. • There is evidence that malaria and poliomyelitis have existed since ancient times. • In the 14th Century, the bubonic plague, or Black Death, killed about 20 million people in Europe alone. • In the 20th Century, the 1918 influenza may have killed up to 50 million people worldwide • Close to 20 million people have died of AIDS to date.
  3. 3. Robert Koch • Bacteria were discovered in 1675 by Antony van Leeuwenhoek, but it wasn’t until 1876 that a German physician named Robert Koch first demonstrated that specific diseases are associated with particular microorganisms. • Koch developed a set of criteria to show that anthrax, a disease of cattle, was caused by a specific bacterium, named Bacillus anthracis, and that tuberculosis was caused by a separate distinct bacterium. • Koch presented his discovery of Mycobacterium tuberculosis in a lecture in March of 1882. • He brought his entire laboratory setup to the lecture hall and demonstrated his procedures for his audience, inviting them to check his findings themselves. • His methods were so innovative that his criteria still are useful today in identifying disease-causing agents. • Difficulties in applying these criteria can arise, however, for agents that are difficult to grow in culture or where a suitable, susceptible experimental host cannot be found. This is an especially difficult situation, and raises ethical concerns, where humans are the only known host. • Robert Koch was awarded the Nobel Prize in Physiology and Medicine in 1905 for his work in tuberculosis.
  4. 4. Koch’s Postulates • Koch developed four criteria to demonstrate that a specific disease is caused by a particular agent. • The specific agent must be associated with every case of the disease. • The agent must be isolated from a diseased host and grown in culture. • When the culture-grown agent is introduced into a healthy susceptible host, the agent must cause the same disease. • The same agent must again be isolated from the infected experimental host.
  5. 5. Definitions and Terms • Disease – a pathological condition of body parts or tissues characterized by an identifiable group of signs and symptoms. • Infectious disease – disease caused by an infectious agent such as a bacterium, virus, protozoan, or fungus that can be passed on to others. • Infection – occurs when an infectious agent enters the body and begins to reproduce; may or may not lead to disease. • Pathogen – an infectious agent that causes disease. • Host – an organism infected by another organism. • Virulence – the relative ability of an agent to cause rapid and severe disease in a host.
  6. 6. Infectious diseases – present status • Despite the availability and use of effective vaccines and antibiotics, infectious diseases remain an important health problem worldwide. • Infectious diseases are particularly important causes of death among the elderly, people with acquired immunodeficiency syndrome (AIDS), those with chronic diseases, and those receiving immunosuppressive drugs. • In developing countries, unsanitary living conditions and malnutrition contribute to a massive burden of infectious diseases that kills more than 10 million people each year. • Most of these deaths are among children, especially from respiratory and diarrheal infections.
  7. 7. Transmission of Infectious Diseases Agents that cause infectious diseases can be transmitted in many ways. • Through the air • Through contaminated food or water • Through body fluids • By direct contact with contaminated objects • By animal vectors such as insects, birds, bats, etc.
  8. 8. How Infectious Agents Cause Disease • Production of poisons, such as toxins and enzymes, that destroy cells and tissues. • Direct invasion and destruction of host cells. • Triggering responses from the host’s immune system leading to disease signs and symptoms. • Derangement of normal physiological functions of organs or organelles.
  9. 9. Phases of infectious diseases • Incubation period – time between infection and the appearance of signs and symptoms. • Prodromal phase – mild, nonspecific symptoms that signal onset of some diseases. • Clinical phase – a person experiences typical signs and symptoms of disease. • Decline phase - subsidence of symptoms. • Recovery phase – symptoms have disappeared, tissues heal, and the body regains strength.
  10. 10. Classification of infectious diseases By duration • Acute – develops and runs its course quickly. • Chronic – develops more slowly and is usually less severe, but may persist for a long, indefinite period of time. • Latent – characterized by periods of no symptoms between outbreaks of illness. By location • Local – confined to a specific area of the body. • Systemic – a generalized illness that infects most of the body with pathogens distributed widely in tissues. By timing • Primary – initial infection in a previously healthy person. • Secondary – infection that occurs in a person weakened by a primary infection.
  11. 11. Taxonomy Size Site of Propagation Examples Disease Prions 30–50 kD Intracellular Prion protein Creutzfeld-Jacob disease Viruses 20–300 nm Obligate intracellular Poliovirus Poliomyelitis Bacteria 0.2–15 μm Obligate intracellular Chlamydia trachomatis Trachoma, urethritis Extracellular Streptococcus pneumoniae Pneumonia Facultative intracellular Mycobacterium tuberculosis Tuberculosis Fungi 2–200 μm Extracellular Candida albicans Thrush Facultative intracellular Histoplasma capsulatum Histoplasmosis Protozoa 1–50 μm Extracellular Trypanosoma gambiense Sleeping sickness Facultative intracellular Trypanosoma cruzi Chagas disease Obligate intracellular Leishmania donovani Kala-azar Helminths 3 mm–10 m Extracellular Wuchereria bancrofti Filariasis Intracellular Trichinella spiralis Trichinosis
  12. 12. Prions • Prions are composed of abnormal forms of a host protein, termed prion protein (PrP). • These agents cause transmissible spongiform encephalopathies, including kuru (associated with human cannibalism), Creutzfeldt-Jakob disease (CJD), bovine spongiform encephalopathy (BSE; better known as mad cow disease), and variant Creutzfeldt-Jakob disease (vCJD; probably transmitted to humans from BSE-infected cattle). • PrP is normally found in neurons. • Diseases occur when the PrP undergoes a conformational change that confers resistance to proteases. • The protease-resistant PrP promotes conversion of the normal protease-sensitive PrP to the abnormal form, explaining the infectious nature of these diseases. • Accumulation of abnormal PrP leads to neuronal damage and distinctive spongiform pathologic changes in the brain. • Spontaneous or inherited mutations in PrP, which make PrP resistant to proteases, have been observed in the sporadic and familial forms of CJD, respectively. CJD can be transmitted from person to person iatrogenically, by surgery, organ transplant, or blood transfusion.
  13. 13. Viruses • Viruses are obligate intracellular parasites that depend on the host cell's metabolic machinery for their replication. • They consist of a nucleic acid genome surrounded by a protein coat (called a capsid) that is sometimes encased in a lipid membrane. • Viruses are classified by their nucleic acid genome (DNA or RNA but not both), the shape of the capsid (icosahedral or helical), the presence or absence of a lipid envelope, their mode of replication, the preferred cell type for replication (called tropism), or the type of pathology. • Because viruses are only 20 to 300 nm in size, they are best visualized with the electron microscope. • Some viral particles aggregate within the cells they infect and form characteristic inclusion bodies, which may be seen with the light microscope and are useful for diagnosis. • Cytomegalovirus (CMV)-infected cells are enlarged and show a large eosinophilic nuclear inclusion and smaller basophilic cytoplasmic inclusions; herpes viruses form a large nuclear inclusion surrounded by a clear halo; and both smallpox and rabies viruses form characteristic cytoplasmic inclusions. Many viruses do not produce inclusions (e.g., Epstein- Barr virus [EBV]).
  14. 14. Human Immunodeficiency Virus. HIV-1 virions can be seen on surface of lymphocytes.
  15. 15. The variety of viral structures, as seen by electron microscopy. A, Adenovirus, an icosahedral nonenveloped DNA virus with fibers. B, Epstein-Barr virus, an icosahedral enveloped DNA virus. C, Rotavirus, a nonenveloped, wheel-like, RNA virus. D, Paramyxovirus, a spherical enveloped RNA virus. RNA is seen spilling out of the disrupted virus.
  16. 16. Influenza
  17. 17. Bacteria • Prokaryotes. • Most bacteria are bound by a cell wall consisting of peptidoglycan, a polymer of long sugar chains linked by peptide bridges. • There are two forms of cell wall structures: a thick wall surrounding the cell membrane that retains crystal-violet stain (gram-positive bacteria) or a thin cell wall sandwiched between two phospholipid bilayer membranes (gram-negative bacteria). • Bacteria are classified by Gram staining (positive or negative), shape (spherical ones are cocci; rod-shaped ones are bacilli), and need for oxygen (aerobic or anaerobic). • Many bacteria have flagella, long helical filaments extending from the cell surface that enable bacteria to move. • Some bacteria possess pili, another kind of surface projection that can attach bacteria to host cells or extracellular matrix. • Most bacteria synthesize their own DNA, RNA, and proteins, but they depend on the host for favorable growth conditions.
  18. 18. Molecules on the surface of gram-negative and gram-positive bacteria involved in pathogenesis.
  19. 19. The variety of bacterial morphology. The bacteria are indicated by arrows in each panel. A, Gram stain of sputum from a patient with pneumonia. There are gram-positive cocci in clusters (Staphylococcus aureus) with degenerating neutrophils. B, Gram stain of sputum from a patient with pneumonia. Gram-positive, elongated cocci in pairs and short chains (Streptococcus pneumoniae) and a neutrophil are seen. C, Gram stain of Clostridium sordellii grown in culture. A mixture of gram-positive and gram-negative rods, many of which have subterminal spores (clear areas), are present. Clostridia species often stain as both gram-positive and gram-negative, although they are true gram-positive bacteria. D, Gram stain of a bronchoalveolar lavage specimen showing gram-negative intracellular rods typical of Enterobacteriaceae such as Klebsiella pneumoniae or Escherichia coli. E, Gram stain of urethral discharge from a patient with gonorrhea. Many gram-negative diplococci (Neisseria gonorrhoeae) are present within a neutrophil. F, Silver stain of brain tissue from a patient with Lyme disease meningoencephalitis. Two helical spirochetes (Borrelia burgdorferi) are indicated by arrows. The panels are at different magnifications.
  20. 20. Fungi • Fungi are eukaryotes that possess thick chitin-containing cell walls and ergosterol-containing cell membranes. • Fungi can grow either as rounded yeast cells or as slender filamentous hyphae. Hyphae may be septate (with cell walls separating individual cells) or aseptate, which is an important distinguishing characteristic in clinical material. • Some of the most important pathogenic fungi exhibit thermal dimorphism; that is, they grow as hyphal forms at room temperature but as yeast forms at body temperature. • Fungi may produce sexual spores or, more commonly, asexual spores referred to as conidia. The latter are produced on specialized structures or fruiting bodies arising along the hyphal filament.
  21. 21. Fungal infections • Fungi may cause superficial or deep infections. • Superficial infections involve the skin, hair, and nails. Fungal species that are confined to superficial layers of the human skin are known as dermatophytes. These infections are commonly referred to by the term “tinea” followed by the area of the body affected (e.g., tinea pedis, “athlete's foot”; tinea capitis, “ringworm of the scalp”). Certain fungal species invade the subcutaneous tissue, causing abscesses or granulomas (e.g., sporotrichosis and tropical mycoses). • Deep fungal infections can spread systemically and invade tissues, destroying vital organs in immunocompromised hosts, but usually heal or remain latent in otherwise normal hosts. • Some deep fungal species are limited to a particular geographic region (e.g., Coccidioides in the south-western United States and Histoplasma in the Ohio River Valley). • Opportunistic fungi (e.g., Candida, Aspergillus, Mucor, and Cryptococcus), by contrast, are ubiquitous organisms that either colonize individuals or are encountered from environmental sources. • In immunodeficient individuals, opportunistic fungi give rise to life-threatening infections characterized by tissue necrosis, hemorrhage, and vascular occlusion, with little or no inflammatory response. AIDS patients are often infected by the opportunistic fungus Pneumocystis jiroveci (previously called Pneumocystis carinii).
  22. 22. Protozoa • Parasitic protozoa are single-celled eukaryotes. • Protozoa can replicate intracellularly within a variety of cells (e.g., Plasmodium in red blood cells, Leishmania in macrophages) or extracellularly in the urogenital system, intestine, or blood. • Trichomonas vaginalis are flagellated protozoal parasites that are sexually transmitted and can colonize the vagina and male urethra. • The most prevalent intestinal protozoans, Entamoeba histolytica and Giardia lamblia, have two forms: (1) motile trophozoites that attach to the intestinal epithelial wall and may invade, and (2) immobile cysts that are resistant to stomach acids and are infectious when ingested. • Blood-borne protozoa (e.g., Plasmodium, Trypanosoma, and Leishmania) are transmitted by insect vectors, in which they replicate before being passed to new human hosts. • Intestinal protozoa are acquired by ingestion of cysts from contaminated food or water. • Toxoplasma gondii is acquired either by contact with oocyst-shedding kittens or by eating cyst-ridden, undercooked meat.
  23. 23. Helminths • Parasitic worms are highly differentiated multicellular organisms. • Their life cycles are complex; most alternate between sexual reproduction in the definitive host and asexual multiplication in an intermediary host or vector. • Thus, depending on parasite species, humans could harbour adult worms (e.g., Ascaris lumbricoides) or immature stages (e.g., Toxocara canis) or asexual larval forms (e.g., Echinococcus species). • Once adult worms take up residence in humans, they do not multiply but they produce eggs or larvae that are usually passed out in stool. • Often, the severity of disease is in proportion to the number of organisms that have infected the individual. • In some helminthic infections, disease is caused by inflammatory responses to the eggs or larvae rather than to the adults (e.g., schistosomiasis).
  24. 24. Ectoparasites • Ectoparasites are insects (lice, bedbugs, fleas) or arachnids (mites, ticks, spiders) that attach to and live on or in the skin. • Arthropods may produce disease directly by damaging the human host or indirectly by serving as the vectors for transmission of an infectious agent into a human host. • Some arthropods cause itching and excoriations (e.g., pediculosis caused by lice attached to hair shafts, or scabies caused by mites burrowing into the stratum corneum). • At the site of the bite, mouth parts may be found associated with a mixed infiltrate of lymphocytes, macrophages, and eosinophils. • Arthropods can be vectors for other pathogens. For example, deer ticks transmit the Lyme disease spirochete Borrelia burgdorferi
  25. 25. DIAGNOSING INFECTIOUS AGENTS • Some infectious agents or their products can be directly observed in hematoxylin and eosin–stained sections . • Many infectious agents are best visualized by special stains that identify organisms on the basis of particular characteristics of their cell wall or coat— Gram, acid-fast, silver, mucicarmine, and Giemsa stains—or after labeling with specific antibody probes. • Regardless of the staining technique, organisms are usually best visualized at the advancing edge of a lesion rather than at its center, particularly if there is necrosis.
  26. 26. Techniques Infectious Agents Gram stain Most bacteria Acid-fast stain Mycobacteria, nocardiae (modified) Silver stains Fungi, legionellae, pneumocystis Periodic acid–Schiff Fungi, amebae Mucicarmine Cryptococci Giemsa Campylobacteria, leishmaniae, malaria parasites Antibody probes All classes Culture All classes DNA probes All classes
  27. 27. Serological and nucleic acid detection tests • Acute infections can be diagnosed serologically by detecting pathogen-specific antibodies in the serum. • Nucleic acid–based tests. • Nucleic acid amplification tests, such as polymerase chain reaction (PCR) and transcription-mediated amplification, have become routine for diagnosis of gonorrhea, chlamydial infection, tuberculosis, and herpes encephalitis.
  28. 28. Health ecosystem and emergence of new infectious diseases • Human demographics and behaviour are among the many variables that contribute to the emergence of infectious diseases. • Reforestation of the eastern United States has led to massive increases in the populations of deer and mice, which carry the ticks that transmit Lyme disease, Babesiosis, and ehrlichiosis. • Failure of DDT to control the mosquitoes that transmit malaria and the development of drug-resistant parasites have dramatically increased the morbidity and mortality of Plasmodium falciparum in Asia, Africa, and Latin America. • Microbial adaptation to widespread antibiotic use contributed to the emergence of drug resistance in many species of bacteria, including Mycobacterium tuberculosis, Neisseria gonorrhoeae, Staphylococcus aureus, and Enterococcus faecium. • Infections with antibiotic-resistant bacteria are becoming a serious problem, such as methicillin-resistant staphylococcus.
  29. 29. Emerging and newly discovered infectious diseases • Surprising number of new infectious agents continue to be discovered. • The infectious causes of some diseases with significant morbidity and mortality were previously unrecognized, because some of the infectious agents are difficult to culture; examples include Helicobacter pylori gastritis, HBV and HCV, and Legionnaires pneumonia. • Some infectious agents are genuinely new to humans, e.g., HIV, which causes AIDS, and B. burgdorferi, which causes Lyme disease. • Other infections have become much more common because of immunosuppression caused by AIDS or therapy for transplant rejection and some cancers. • Infectious diseases that are common in one area may be introduced into a new area. For example, West Nile virus has been common in Europe, Asia, and Africa for years but was first described in the United States in 1999.
  30. 30. Date Recognized Infectious Agent Manifestations 1977 Ebola virus Epidemic Ebola hemorrhagic fever Hantaan virus Hemorrhagic fever with renal syndrome Legionella pneumophila Legionnaires disease Campylobacter jejuni Enteritis 1980 HTLV-I T-cell lymphoma or leukemia, HTLV-associated myelopathy 1981 Staphylococcus aureus Toxic shock syndrome 1982 Escherichia coli O157:H7 Hemorrhagic colitis, hemolytic-uremic syndrome Borrelia burgdorferi Lyme disease 1983 HIV AIDS Helicobacter pylori Gastric ulcers 1988 Hepatitis E Enterically transmitted hepatitis 1989 Hepatitis C Hepatitis C 1992 Vibrio cholerae O139 New epidemic cholera strain Bartonella henselae Cat-scratch disease 1995 KSHV (HHV-8) Kaposi sarcoma in AIDS 1999 West Nile virus West Nile fever, neuroinvasive disease 2003 SARS coronavirus Severe acute respiratory syndrome
  31. 31. AGENTS OF BIOTERRORISM Category A Diseases/Agents Anthrax (Bacillus anthracis) Botulism (Clostridium botulinum toxin) Plague (Yersinia pestis) Smallpox (Variola major virus) Tularemia (Francisella tularensis) Viral hemorrhagic fevers (filoviruses [e.g., Ebola, Marburg] and arenaviruses [e.g., Lassa, Machupo]) Category C Diseases/Agents Emerging infectious disease threats such as Nipah virus and Hantavirus
  32. 32. Category B Diseases/Agents Brucellosis (Brucella sp.) Epsilon toxin of Clostridium perfringens Food safety threats (e.g., Salmonella sp., Escherichia coli O157:H7, Shigella) Glanders (Burkholderia mallei) Melioidosis (Burkholderia pseudomallei) Psittacosis (Chlamydia psittaci) Q fever (Coxiella burnetti) Ricin toxin from Ricinus communis (castor beans) Staphylococcal enterotoxin B Typhus fever (Rickettsia prowazekii) Viral encephalitis (alphaviruses [e.g., Venezuelan equine encephalitis, eastern equine encephalitis, western equine encephalitis]) Water safety threats (e.g., Vibrio cholerae, Cryptosporidium parvum)
  33. 33. TRANSMISSION AND DISSEMINATION OF MICROBES • Microbes can enter the host by inhalation, ingestion, sexual transmission, insect or animal bites, or injection. • The first defenses against infection are intact skin and mucosal surfaces, which provide physical barriers and produce antimicrobial substances. • In general, respiratory, gastrointestinal, or genitourinary tract infections that occur in healthy persons are caused by relatively virulent microorganisms that are capable of damaging or penetrating intact epithelial barriers. • In contrast, most skin infections in healthy persons are caused by less virulent organisms entering the skin through damaged sites (cuts and burns).
  34. 34. HOW MICROORGANISMS CAUSE DISEASE • They can contact or enter host cells and directly cause cell death. • They may release toxins that kill cells at a distance, release enzymes that degrade tissue components, or damage blood vessels and cause ischemic necrosis. • They can induce host immune responses that, though directed against the invader, cause additional tissue damage. • They are necessary to overcome the infection but at the same time may directly contribute to tissue damage.
  35. 35. Mechanisms of Viral Injury • Viruses can directly damage host cells by entering them and replicating at the host's expense. • The predilection for viruses to infect certain cells and not others is called tropism and is determined by several factors, including (1)expression of host cell receptors for the virus, (2)presence of cellular transcription factors that recognize viral enhancer and promoter sequences, (3)anatomic barriers, (4)local temperature, pH, and host defences.
  36. 36. Mechanisms of Bacterial Injury • Bacterial Virulence. • Bacterial Adherence to Host Cells. • Virulence of Intracellular Bacteria. • Bacterial Toxins. • Injurious Effects of Host Immunity
  37. 37. IMMUNE EVASION BY MICROBES • Microorganisms have developed many means to resist and evade the immune system. (1)growth in niches that are inaccessible to the host immune system, (2)antigenic variation, (3)resistance to innate immune defenses, and (4)impairment of effective T-cell antimicrobial responses by specific or nonspecific immunosuppression.
  38. 38. Mechanisms of Antigenic Variation Type Example Disease High mutation rate HIV AIDS Influenza virus Influenza Genetic reassortment Influenza virus Influenza Rotavirus Diarrhea Genetic rearrangement (e.g., gene recombination, gene conversion, site-specific inversion) Borrelia burgdorferi Lyme disease Neisseria gonorrhoeae Gonorrhea Trypanosoma sp. African sleeping sickness Plasmodium sp. Malaria Large diversity of serotypes Rhinoviruses Colds Streptococcus pneumoniae Pneumonia Meningitis
  39. 39. SPECTRUM OF INFLAMMATORY RESPONSES TO INFECTION • Suppurative or purulent inflammation. • Mononuclear and granulomatous inflammation • Cytopathic or cytoproliferative reaction. • Tissue necrosis • Chronic inflammation and scarring.
  40. 40. Suppurative inflammation • This pattern is the reaction to acute tissue damage is characterized by increased vascular permeability and leukocytic infiltration, predominantly of neutrophils. • The neutrophils are attracted to the site of infection by release of chemoattractants from the “pyogenic” (pus-forming) bacteria that evoke this response, mostly extracellular gram-positive cocci and gram-negative rods. • Massing of neutrophils and liquefactive necrosis of the tissue form pus. • The sizes of exudative lesions range from tiny microabscesses formed in multiple organs during bacterial sepsis secondary to a colonized heart valve to diffuse involvement of entire lobes of the lung in pneumonia. • How destructive the lesions are depends on their location and the organism involved. • Pneumococci usually spare alveolar walls and cause lobar pneumonia that resolves completely, whereas staphylococci and Klebsiella species destroy alveolar walls and form abscesses that heal with scar formation. • Bacterial pharyngitis resolves without sequelae, whereas untreated acute bacterial inflammation of a joint can destroy it in a few days.
  41. 41. Mononuclear and Granulomatous Inflammation • Diffuse, predominantly mononuclear, interstitial infiltrates are a common feature of all chronic inflammatory processes. • They often are a response to viruses, intracellular bacteria, or intracellular parasites. In addition, spirochetes and helminths provoke chronic inflammatory responses. • Which mononuclear cell predominates within the inflammatory lesion depends on the host immune response to the organism. • Granulomatous inflammation is a distinctive form of mononuclear inflammation usually evoked by infectious agents that resist eradication and are capable of stimulating strong T cell–mediated immunity • Granulomatous inflammation is characterized by accumulation of activated macrophages called “epithelioid” cells, which may fuse to form giant cells. In some cases there is a central area of caseous necrosis.
  42. 42. Cytopathic-Cytoproliferative Reaction • The lesions are characterized by cell necrosis or cellular proliferation, usually with sparse inflammatory cells. • Some viruses replicate within cells and make viral aggregates that are visible as inclusion bodies (e.g., herpesviruses or adenovirus) or induce cells to fuse and form multinucleated cells called polykaryons (e.g., measles virus or herpesviruses). • Focal cell damage in the skin may cause epithelial cells to become detached, forming blisters • Some viruses can cause epithelial cells to proliferate (e.g., venereal warts caused by HPV or the umbilicated papules of molluscum contagiosum caused by poxviruses). • Finally, viruses can contribute to the development of malignant neoplasms.
  43. 43. Tissue Necrosis • Clostridium perfringens and other organisms that secrete powerful toxins can cause such rapid and severe necrosis (gangrenous necrosis) that tissue damage is the dominant feature. • Because few inflammatory cells are present, these lesions resemble infarcts with disruption or loss of basophilic nuclear staining and preservation of cellular outlines. • Clostridia are often opportunistic pathogens that are introduced into muscle tissue by penetrating trauma or infection of the bowel in a neutropenic host. • Similarly, the parasite E. histolytica causes colonic ulcers and liver abscesses characterized by extensive tissue destruction with liquefactive necrosis and without a prominent inflammatory infiltrate. • By entirely different mechanisms, viruses can cause widespread and severe necrosis of host cells associated with inflammation, as exemplified by total destruction of the temporal lobes of the brain by herpesvirus or the liver by HBV.
  44. 44. Chronic Inflammation and Scarring • Chronic HBV infection may cause cirrhosis of the liver, in which dense fibrous septae surround nodules of regenerating hepatocytes. • Sometimes the exuberant scarring response is the major cause of dysfunction. • “pipe-stem” fibrosis of the liver or fibrosis of the bladder wall caused by schistosomal eggs or the constrictive fibrous pericarditis in tuberculosis
  45. 45. Thank you

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