Infectious Diseases Infectious Diseases P. B. Casuela, Jr. MD, FSP P. B. Casuela, Jr. MD, FSP
Inflammation – tissue reaction to injury of whatever etiology Inflammation – tissue reaction to injury of whatever etiology Infection – tissue reaction to injury due to microbiologic agents Infection – tissue reaction to injury due to microbiologic agents Importance of Infectious Diseases
Importance of Infectious Diseases 1.
1. They are major causes of morbidity and mortalityThey are major causes of morbidity and mortality 2.
2. Greater transmission (vertical or horizontal) than anyGreater transmission (vertical or horizontal) than any other disease.
other disease. 3.
3. Versatile diseases evolving and adapting throughVersatile diseases evolving and adapting through time.
time. 4.
4. Some are self-limiting and requires no specificSome are self-limiting and requires no specific treatments.
treatments. 5.
5. Many are preventable.Many are preventable. 6.
6. Association with congenital diseases:Association with congenital diseases: Varicella
Varicella (German (German measles) measles) - - multiplemultiple congenital anomalies congenital anomalies Syphilis Syphilis HIV HIV 7.
7. Association with neoplastic conditionsAssociation with neoplastic conditions Enterobacter pylori – gastric CA Enterobacter pylori – gastric CA
Herpes (Type 2) genitalis virus and HPV – Herpes (Type 2) genitalis virus and HPV – squamous cell carcinoma of the cervix squamous cell carcinoma of the cervix Ebstein-Barr
Ebstein-Barr virus virus – – Nasopharyngeal Nasopharyngeal CACA Burkitt’s lymphoma Burkitt’s lymphoma S. japonicum ,Aspergillus flavus
S. japonicum ,Aspergillus flavus: Hepatocellular CA: Hepatocellular CA S. hematobium
S. hematobium: urinary bladder transitional cell CA: urinary bladder transitional cell CA Clonorchis sinensis & Opistorchis felineus Clonorchis sinensis & Opistorchis felineus -cholangiocarcinoma
cholangiocarcinoma Epidemiology
Epidemiology – Branch of medicine dealing with the incidence – Branch of medicine dealing with the incidence and prevalence of diseases in large populations and with and prevalence of diseases in large populations and with detection of the source of epidemics of infectious disease. detection of the source of epidemics of infectious disease. Incidence Rate
Incidence Rate – occurrence in 100,000 population per given – occurrence in 100,000 population per given time
time
Prevalence –
Prevalence – widespread; of wide extent or occurrencewidespread; of wide extent or occurrence Endemic
Endemic – belonging exclusively or confined to a particular place. – belonging exclusively or confined to a particular place. Epidemic
Epidemic – affecting many persons at the same time and – affecting many persons at the same time and spreading from person to person in a locality where the diseas spreading from person to person in a locality where the diseas is not permanently prevalent.
is not permanently prevalent. Pandemic
Pandemic – prevalent throughout an entire country , continent, – prevalent throughout an entire country , continent, or the whole world.
or the whole world.
General Principles of Microbial Pathogenesis General Principles of Microbial Pathogenesis
Pathology deals with host response to different infectious Pathology deals with host response to different infectious agents, the different classes of agents, their mode of agents, the different classes of agents, their mode of
transmission, how they cause disease, and possible outcome transmission, how they cause disease, and possible outcome (biologic behavior).
(biologic behavior). The Triad
The Triad
Patient: Patient: Age Age
Physiology Physiology Genetics Genetics Immune state Immune state Malnutrition Malnutrition Environment:
Environment: Infectious Agent:Infectious Agent: Extraneous
Extraneous factors factors “Koch’s “Koch’s Postulate”Postulate” Sanitation Pathogenicity/Virulence Sanitation Pathogenicity/Virulence Climate
Climate and and temperature temperature TropismTropism
Categories of Infectious Agents Categories of Infectious Agents
PrionsPrions – composed only of a modified host protein that – composed only of a modified host protein that
can cause transmissible spongiform encephalopathy can cause transmissible spongiform encephalopathy
VirusesViruses – obligate intracellular parasites that are – obligate intracellular parasites that are
dependent on host cell metabolism for their replication dependent on host cell metabolism for their replication
-- Classified by the nucleic acid content of the coreClassified by the nucleic acid content of the core (DNA or RNA) and by the shape of their protein (DNA or RNA) and by the shape of their protein coat or capsid
coat or capsid
Bacteriophages, Plasmids, TransporonsBacteriophages, Plasmids, Transporons – mobile genetic – mobile genetic
elements that encode bacterial virulence factors elements that encode bacterial virulence factors
-- Can infect bacteria and incorporate themselvesCan infect bacteria and incorporate themselves in their genome --> converting to virulent one or in their genome --> converting to virulent one or an antibiotic-resistant one
an antibiotic-resistant one
-- Exchange of these elements between strains &Exchange of these elements between strains & species endow survival advantage
species endow survival advantage
BacteriaBacteria – prokaryotes that lack nuclei and ER – prokaryotes that lack nuclei and ER
-- Relatively rigid cell wall, classifiable as gram (-)Relatively rigid cell wall, classifiable as gram (-) or Gram (+)
or Gram (+)
-- Bacteria synthesize their own DNA, RNA andBacteria synthesize their own DNA, RNA and proteins, but depend on the host for favorable proteins, but depend on the host for favorable conditions
conditions
-- Second to viruses as most frequent & diverseSecond to viruses as most frequent & diverse class of human pathogen
class of human pathogen
Chlamydiae, Rickettsia and MycoplasmasChlamydiae, Rickettsia and Mycoplasmas – similar to – similar to
bacteria in that they divide by binary fission and are bacteria in that they divide by binary fission and are susceptible to antibiotics but lack:
susceptible to antibiotics but lack: -- Cell wall – MycoplasmaCell wall – Mycoplasma -- ATP synthesis – ChlamydiaATP synthesis – Chlamydia
Transmitted by insect vectors - RickettsiaTransmitted by insect vectors - Rickettsia
FungiFungi – possess thick, ergosterol-containing cell walls and – possess thick, ergosterol-containing cell walls and
grow as perfect, sexually producing forms in vitro and as grow as perfect, sexually producing forms in vitro and as imperfect forms in vivo, which include budding yeasts and imperfect forms in vivo, which include budding yeasts and hyphae
hyphae
-- Classified Classified as: Deas: Dermatophytes rmatophytes SystemicSystemic Subcutaneous Opportunistic Subcutaneous Opportunistic
ProtozoaProtozoa – parasitic, single-celled organisms endowed – parasitic, single-celled organisms endowed
with motility, pliable plasma membranes and complex with motility, pliable plasma membranes and complex cytoplasmic organelles
cytoplasmic organelles
-- Classified Classified as: as: Flagellates Flagellates Blood-borneBlood-borne Intestinal
Intestinal
HelminthsHelminths – parasitic worms that are highly differentiated – parasitic worms that are highly differentiated
multicellular organisms multicellular organisms
-- With complex life cycles; most alternateWith complex life cycles; most alternate
between sexual reproduction in definitive hosts between sexual reproduction in definitive hosts and asexual reproduction in intermediate hosts and asexual reproduction in intermediate hosts
EctoparasitesEctoparasites – arthropods (lice, ticks, bedbugs, fleas) that – arthropods (lice, ticks, bedbugs, fleas) that
attach and live on the skin attach and live on the skin
-- Can be vectors for other pathogensCan be vectors for other pathogens Transmission and Dissemination of Microbes Transmission and Dissemination of Microbes
Hosts Barriers to InfectionHosts Barriers to Infection
-- 11stst – intact host skin, mucosal surfaces & their – intact host skin, mucosal surfaces & their secretory-excretory products
secretory-excretory products
-- Respiratory tract – mucociliary blanket of upper airRespiratory tract – mucociliary blanket of upper air passages, cough reflex, alveolar macrophage passages, cough reflex, alveolar macrophage
-- GITGIT – acid gastric juice, viscous mucous layer covering – acid gastric juice, viscous mucous layer covering the gut, lytic pancreatic enzymes & bile detergents, the gut, lytic pancreatic enzymes & bile detergents, secreted IgA antibodies
secreted IgA antibodies
-- GUTGUT – regular flushing of the urinary tract with urine – regular flushing of the urinary tract with urine serves as a defense against invading microorganisms, serves as a defense against invading microorganisms, vagina with low pH is protective
vagina with low pH is protective
-- SkinSkin – dryness and constant shedding of impermeable – dryness and constant shedding of impermeable keratinized epithelium and competition from
keratinized epithelium and competition from commensal bacteria
Spread and Dissemination of MicrobesSpread and Dissemination of Microbes
-- Some microorganisms proliferate locally at siteSome microorganisms proliferate locally at site of infection
of infection
-- Others penetrate the epithelial barrier & spreadOthers penetrate the epithelial barrier & spread to other sites via the lymphatics, the blood, or to other sites via the lymphatics, the blood, or nerves
nerves
-- Major manifestations of infectious disease mayMajor manifestations of infectious disease may arise at sites distant from those of microbe entry arise at sites distant from those of microbe entry -- Placental-fetal route is an important mode ofPlacental-fetal route is an important mode of
transmission transmission
Release of Microbes from the BodyRelease of Microbes from the Body
-- In transmission of disease, exit of the organismIn transmission of disease, exit of the organism in the host’s body is as important as its entry in the host’s body is as important as its entry -- Depends on the location of the infection: skinDepends on the location of the infection: skin
shedding, coughing, sneezing, voiding in shedding, coughing, sneezing, voiding in urine/stool, through insect vectors urine/stool, through insect vectors Mode of transmission:
Mode of transmission:
Respiratory, fecal-oral, sexual routes, direct contact, Respiratory, fecal-oral, sexual routes, direct contact, through blood & blood products, through vertebrate & through blood & blood products, through vertebrate & invertebrate vector, zoonotic transmission
invertebrate vector, zoonotic transmission How microorganisms cause disease
How microorganisms cause disease
Infectious agent can contact or enter host cells andInfectious agent can contact or enter host cells and
directly cause cell death directly cause cell death
May release toxins, enzymesMay release toxins, enzymes
Can induce host cellular responses (though directedCan induce host cellular responses (though directed
against the invader) cause additional tissue damage, against the invader) cause additional tissue damage, usually immune-mediated
usually immune-mediated Mechanisms of Viral Injury Mechanisms of Viral Injury
Viruses can directly damage host cells by entering them and Viruses can directly damage host cells by entering them and replicating at the host’s expense
replicating at the host’s expense Tissue tropism
Tissue tropism
-- Predilection of viruses for certain cells and not othersPredilection of viruses for certain cells and not others Factors that determine tissue tropism:
Factors that determine tissue tropism: 1.
1. Host cell receptors for the virus (major)Host cell receptors for the virus (major) 2.
2. Cellular transcription factors that recognize viralCellular transcription factors that recognize viral enhancer & promoter sequences
enhancer & promoter sequences 3.
3. Anatomic barriersAnatomic barriers 4.
4. Local temperature, pH, host defensesLocal temperature, pH, host defenses
Viruses once inside the host cells can Viruses once inside the host cells can kill &/or cause tissue damage thru: kill &/or cause tissue damage thru:
1.
1. Inhibit host cell DNA, RNA or protein synthesisInhibit host cell DNA, RNA or protein synthesis 2.
2. Viral proteins may insert into the host cell’s plasmaViral proteins may insert into the host cell’s plasma membrane & directly damage its integrity/ promote membrane & directly damage its integrity/ promote cell fusion
cell fusion 3.
3. May lyse host cellsMay lyse host cells 4.
4. May manipulate programmed cell death (apoptosis)May manipulate programmed cell death (apoptosis) 5.
5. Viral proteins on the surface of the host cellsViral proteins on the surface of the host cells recognized by the immune system will cause recognized by the immune system will cause lymphocytic attack
lymphocytic attack 6.
6. May damage cells involved in host antimicrobialMay damage cells involved in host antimicrobial defense, leading to secondary infections
defense, leading to secondary infections 7.
7. Viral killing of one cell type may cause the death ofViral killing of one cell type may cause the death of other cells that depend on them
other cells that depend on them 8.
8. Some can cause proliferation & transformatSome can cause proliferation & transformationion of cells resulting in cancer
Mechanisms of Bacterial Injury Mechanisms of Bacterial Injury
1.
1. Bacterial VirulenceBacterial Virulence – depends on the ability of the – depends on the ability of the bacteria to adhere to host cells, invade cells and bacteria to adhere to host cells, invade cells and tissues, or deliver toxins
tissues, or deliver toxins o
o Pathogenic bacteria have virulence genesPathogenic bacteria have virulence genes that encode proteins that confer these that encode proteins that confer these properties – grouped together in clusters properties – grouped together in clusters called “
called “ pathogenicity isla pathogenicity islands”nds” o
o Increase in concentration in tissues ofIncrease in concentration in tissues of bacteria will increase virulence factors bacteria will increase virulence factors 2.
2. Bacterial Adherence to Host CellsBacterial Adherence to Host Cells o
o Adhesins – Adhesins –bacterial surface molecules thatbacterial surface molecules that bind
bind o
o Fibrillae –Fibrillae –covering the surface of Gram(+)covering the surface of Gram(+) organism, S. pyogenes
organism, S. pyogenes composed of composed of lipoteichoic acids and M protein, protein F lipoteichoic acids and M protein, protein F o
o FimbriaeFimbriaeoror pili pili – filamentous proteins on – filamentous proteins on the surface of Gram (-) bacteria, tip the surface of Gram (-) bacteria, tip determine
determine 3.
3. Virulence of Intracellular BacteriaVirulence of Intracellular Bacteria
Facultative intracellular bacteria infect either Facultative intracellular bacteria infect either
epithelial cells, macrophages or both epithelial cells, macrophages or both -- Bacteria may reproduce within theBacteria may reproduce within the
phagolysomes or cytosol phagolysomes or cytosol 4.
4. Bacterial endotoxin is a lipopolysaccharide thatBacterial endotoxin is a lipopolysaccharide that induces fever via host lymphokines, including tumor induces fever via host lymphokines, including tumor necrosis factor and interleukin-1.
necrosis factor and interleukin-1. 5.
5. Bacterial exotoxins are composed of a binding partBacterial exotoxins are composed of a binding part and a catalytic part, which ADP-ribosylates and and a catalytic part, which ADP-ribosylates and inactivates host proteins or degrades host proteins inactivates host proteins or degrades host proteins Immune Evasion by Microbes
Immune Evasion by Microbes
Microbes avoid the host immune response by: Microbes avoid the host immune response by:
Remaining inaccessible within the lumen of thRemaining inaccessible within the lumen of th e smalle small
intestine or rapidly entering host cells intestine or rapidly entering host cells
Producing a capsule that covers antigens andProducing a capsule that covers antigens and
prevents phagocytosis prevents phagocytosis
Changing their surface antigensChanging their surface antigens
Infecting lymphocytes and damaging the hostInfecting lymphocytes and damaging the host
immune system immune system
Special Techniques for Diagnosing Infectious Agents Special Techniques for Diagnosing Infectious Agents
Some can be directly observed in hematoxylin andSome can be directly observed in hematoxylin and
eosin-stained sections eosin-stained sections
Best visualized after special stains that identifyBest visualized after special stains that identify
organisms based upon particular characteristics of organisms based upon particular characteristics of their cell walls or coat.
their cell walls or coat.
Cultures of lesional tissues are performed to separateCultures of lesional tissues are performed to separate
organisms and determine drug sensitivity organisms and determine drug sensitivity Gram stain
Gram stain Most bacteria (Gram (-); (+)Most bacteria (Gram (-); (+) Acid fast stain
Acid fast stain Mycobacteria, NocardiaMycobacteria, Nocardia (modified)
(modified) Silver stains
Silver stains Fungi, Legionella, PneumocystisFungi, Legionella, Pneumocystis Periodic acid-Schiff
Periodic acid-Schiff Fungi, amoebaeFungi, amoebae Mucicarmine/india ink
Mucicarmine/india ink CryptococciCryptococci Giemsa
Giemsa Campylobacteria, Leishmania,Campylobacteria, Leishmania, malaria, Herpes
malaria, Herpes Antibody probes
Antibody probes Viruses, ricketssiaeViruses, ricketssiae Culture
Culture All classesAll classes DNA probes
DNA probes Viruses, bacteria, protozoaViruses, bacteria, protozoa
Spectrum of Inflammatory Responses To Infection Spectrum of Inflammatory Responses To Infection
1.
1. Suppurative Inflammation (Neutrophils)Suppurative Inflammation (Neutrophils) -- Caused by “pyogenic” bacteria, mostlyCaused by “pyogenic” bacteria, mostly
extracellular gram positive cocci and extracellular gram positive cocci and gram-negative rods
gram-negative rods
-- Secondary to/increased by vascular permeabilitySecondary to/increased by vascular permeability and leukotaxis of neutrophils attracted by and leukotaxis of neutrophils attracted by bacterial peptides, which contains N-formyl bacterial peptides, which contains N-formyl methionine residues
methionine residues
-- Follows the path of acute inflammationFollows the path of acute inflammation Vascular eventsVascular events
Cellular eventsCellular events
-- Recruitment of leukocytes into the site ofRecruitment of leukocytes into the site of infection
infection
Chemotaxis – emigration ofChemotaxis – emigration of neutrophils towards the site of neutrophils towards the site of inflammation
inflammation
Chemoattractant - most commonChemoattractant - most common exogenous agent are bacterial exogenous agent are bacterial products
products •
• Peptides that containsPeptides that contains N-formylmethionine terminal N-formylmethionine terminal amino acid and some
amino acid and some chemoattractant. chemoattractant. •
• Binds to specificBinds to specific transmembrane G transmembrane G
protein-coupled receptor on protein-coupled receptor on the surface of leukocytes. the surface of leukocytes.
o
o Initiates reactionInitiates reaction within leukocytes within leukocytes with the end result with the end result of the leukocytes of the leukocytes migrating towards migrating towards the stimulus the stimulus -- Leukocytes infiltration varies with the age ofLeukocytes infiltration varies with the age of
inflammatory response and the type of stimulus. inflammatory response and the type of stimulus.
Leukocytes 6 – 24 hours. ApoptosisLeukocytes 6 – 24 hours. Apoptosis and disappear after 24 to 48 hours and disappear after 24 to 48 hours Neutrophils first appear because theyNeutrophils first appear because they
are numerous in the circulation are numerous in the circulation Respond more rapidly to chemokinesRespond more rapidly to chemokines Attached more firmly to the adhesionAttached more firmly to the adhesion
molecule molecule -- Disappear after 48 hoursDisappear after 48 hours
-- Exceptions – like pseudomonas – continuousExceptions – like pseudomonas – continuous recruitment of neutrophils for several days recruitment of neutrophils for several days Recognition of microbes
Recognition of microbes
Activation of leukocytes at the site of inflammation by:Activation of leukocytes at the site of inflammation by: o
o Recognition of the offending agents, whichRecognition of the offending agents, which delivers the signal
delivers the signal o
o Activate the leukocytes to ingest andActivate the leukocytes to ingest and destroys the offending agents destroys the offending agents o
o Amplify the inflammatory reactionAmplify the inflammatory reaction
Receptors for microbial products –Receptors for microbial products –
(TLRs) Toll-like receptors (TLRs) Toll-like receptors
Response to:Response to: o
o Bacterial lipopolysaccharideBacterial lipopolysaccharide o
o Bacterial proteoglycans and lipidsBacterial proteoglycans and lipids o
o Unmethylated CpG nucleotideUnmethylated CpG nucleotide
G protein-coupled receptorsG protein-coupled receptors o
o Found in neutrophils, macrophages andFound in neutrophils, macrophages and other leukocytes
other leukocytes o
o
o Also recognizes chemokines, C5aAlso recognizes chemokines, C5a o
o Bindings of these ligands to G proteinBindings of these ligands to G protein couple receptor induces migration of couple receptor induces migration of leukocytes from blood also activation of leukocytes from blood also activation of respiratory burst
respiratory burst
Receptors for opsonins- coating of microbes to targetReceptors for opsonins- coating of microbes to target
it for phagocytosis it for phagocytosis
o
o C3 – also potent opsoninC3 – also potent opsonin
Binds to microbes and phagocytesBinds to microbes and phagocytes Expresses a receptor called Type 1Expresses a receptor called Type 1
complement receptor (CR1) complement receptor (CR1) o
o Receptors for cytokines – leukocytesReceptors for cytokines – leukocytes expresses receptors for cytokines that are expresses receptors for cytokines that are produced in response to microbes. produced in response to microbes. o
o Interferon-Interferon-γγ – secreted by natural killer cells – secreted by natural killer cells
reacting to microbes and by antigen reacting to microbes and by antigen activated T-lymphocytes during adaptive activated T-lymphocytes during adaptive immune response
immune response
Major macrophage-activatingMajor macrophage-activating cytokines.
cytokines.
Furuncle or boils – recurrent, most frequent in moistFuruncle or boils – recurrent, most frequent in moist
hairy areas hairy areas 2.
2. Mononuclear and granulomatous InflammationMononuclear and granulomatous Inflammation -- Induced by viruses, intracellular bacteria,Induced by viruses, intracellular bacteria,
spirochetes, intracellular parasites, or helminths spirochetes, intracellular parasites, or helminths -- Includes mostly lymphocytes or macrophages,Includes mostly lymphocytes or macrophages,
depending upon the characteristics of the depending upon the characteristics of the organism and the host plasma cells – syphilis organism and the host plasma cells – syphilis
Syphillis with plasma cell infiltrates Syphillis with plasma cell infiltrates 3.
3. Cytopathic-Cytoproliferative InflammationCytopathic-Cytoproliferative Inflammation -- characterized by virus-mediated damage tocharacterized by virus-mediated damage to
individual host cells in the absence of host individual host cells in the absence of host inflammatory response
inflammatory response
-- may show inclusion bodies (CMV), polykaryons,may show inclusion bodies (CMV), polykaryons, blisters and warty changes
blisters and warty changes
-- Polykaryon – cell to cell fusion. Mechanism isPolykaryon – cell to cell fusion. Mechanism is poorly understood
poorly understood
Characteristic nuclear changes Characteristic nuclear changes
-- MultinucleationMultinucleation -- Molding of nucleiMolding of nuclei
-- Margination of chromatinMargination of chromatin Formation of Inclusion Bodies
Formation of Inclusion Bodies
Alteration of cytoskeleton organization by virusAlteration of cytoskeleton organization by virus
infection infection
o
o Normal cells have networks ofNormal cells have networks of
microtubules, and intermediate filaments microtubules, and intermediate filaments throughout the cytoplasm. Infection with throughout the cytoplasm. Infection with reovirus causes a perinuclear aggregation of reovirus causes a perinuclear aggregation of microtubules, and infection with
microtubules, and infection with
cytomegalovirus causes a modification of cytomegalovirus causes a modification of intermediate filaments proteins, including intermediate filaments proteins, including their relocation into the nuclear and their relocation into the nuclear and cytoplasmic inclusion bodies. cytoplasmic inclusion bodies.
Stages of TransformationStages of Transformation: Transformation involves at: Transformation involves at
least two processes: first, the cell gains the capacity least two processes: first, the cell gains the capacity for unlimited cell division (immortalization), and for unlimited cell division (immortalization), and second, the immortalized cells acquire additional second, the immortalized cells acquire additional heritable genetic changes by which the cell is able to heritable genetic changes by which the cell is able to produce a tumor in an appropriate host.
produce a tumor in an appropriate host.
Mechanisms of Oncogenic TransformationMechanisms of Oncogenic Transformation : There are: There are
two general patterns by which cell transformation two general patterns by which cell transformation may be accomplished: 1) the tumor virus may may be accomplished: 1) the tumor virus may introduce and express a so-called transforming gene introduce and express a so-called transforming gene in the cells or 2) the tumor virus may alter the in the cells or 2) the tumor virus may alter the expression and (or) coding capacity of preexisting expression and (or) coding capacity of preexisting cellular genes. After development of a malignant cellular genes. After development of a malignant phenotype the relevant segment(s) of the viral phenotype the relevant segment(s) of the viral genome may or may not be retained in the genome may or may not be retained in the
transformed cells, depending on the mechanism of transformed cells, depending on the mechanism of transformation. These mechanisms are not mutually transformation. These mechanisms are not mutually exclusive, and both may occur in the same cell. exclusive, and both may occur in the same cell.
Development and progression of viral cytopathology Development and progression of viral cytopathology Human embryo skin muscle cells were infected with human Human embryo skin muscle cells were infected with human cytomegalovirus and stained at selected times to demonstrate cytomegalovirus and stained at selected times to demonstrate (A) uninfected cells, (B) late virus cytopathic effects (nuclear (A) uninfected cells, (B) late virus cytopathic effects (nuclear inclusions, cell enlargement), (C) cell degeneration, and (D) a inclusions, cell enlargement), (C) cell degeneration, and (D) a focus of infected cells in a cell monolayer (i.e., a plaque), focus of infected cells in a cell monolayer (i.e., a plaque), hematoxylin and eosin stain.
hematoxylin and eosin stain. 4.
4. Necrotizing InflammationNecrotizing Inflammation
-- Caused by uncontrolled viral infection (egCaused by uncontrolled viral infection (eg fulminant hepatitis B infection), secreted fulminant hepatitis B infection), secreted bacterial toxins (Clostridium perfringes), or bacterial toxins (Clostridium perfringes), or contact- mediated cytolosis of host cells by contact- mediated cytolosis of host cells by protozoa (E. histolytica)
protozoa (E. histolytica)
-- Results in severe tissue necrosis in the absenceResults in severe tissue necrosis in the absence of inflammatory infiltrates
of inflammatory infiltrates
Tissue necrosis Tissue necrosis
Caused by toxins:Caused by toxins:
E.g ,E.g ,αα-toxin of C. Perfringens –-toxin of C. Perfringens – o
o Has phospholipase C that degrades lecithinHas phospholipase C that degrades lecithin Cause myonecrosisCause myonecrosis
o
o Has spingomyelinase – nerve sheathHas spingomyelinase – nerve sheath damage
damage
HBV – massive apoptosisHBV – massive apoptosis o
o Cause fulminant hepatitisCause fulminant hepatitis
E. Histolytica – cytotoxic to epithelial cells,E. Histolytica – cytotoxic to epithelial cells,
neutrophils and macrophages neutrophils and macrophages
o
o Adherence to target cellsAdherence to target cells o
o Complement mediatedComplement mediated
5.
5. Chronic Inflammation and ScarringChronic Inflammation and Scarring
-- Caused by certain acute infections (GonococcalCaused by certain acute infections (Gonococcal salpingitis) or chronic infections
salpingitis) or chronic infections (Schistosomiasis)
(Schistosomiasis)
-- May be severe despite a paucity or organismsMay be severe despite a paucity or organisms present (M. tuberculosis)
present (M. tuberculosis)
Common Infectious Diseases Involving Different Organs Common Infectious Diseases Involving Different Organs Skin: Skin: FuruncleFuruncle CarbuncleCarbuncle
Exanthematous diseasesExanthematous diseases
HerpesHerpes
TineaTinea
Leprosy (Hansen’s disease)Leprosy (Hansen’s disease)
NS: NS:
Viral and bacterial meningitis/encephalitis/Viral and bacterial meningitis/encephalitis/
meningoencephalitis meningoencephalitis RabiesRabies TetanusTetanus AbcessAbcess PoliomyelitisPoliomyelitis
Head & Neck: Head & Neck:
ConjunctivitisConjunctivitis MumpsMumps Respiratory: Respiratory: PneumoniaPneumonia TuberculosisTuberculosis URTIURTI DiphtheriaDiphtheria BronchitisBronchitis CVS: CVS:
Viral myocarditisViral myocarditis
GIT: GIT:
Acute gastro-enteritisAcute gastro-enteritis
Diarrheal diseasesDiarrheal diseases o o CholeraCholera o o ViralViral o o E. coliE. coli o
o Bacillary dysenteryBacillary dysentery
Infectious ulcerative diseasesInfectious ulcerative diseases o
o Typhoid feverTyphoid fever o o TB enteritisTB enteritis o o AmebiasisAmebiasis Hepato-Biliary: Hepato-Biliary: HepatitisHepatitis AbscessAbscess SchistosomiasisSchistosomiasis GUT: GUT: UTI,UTI,
STD (Gonorrhea, Chlamydia, Trichomosiasis, Syphilis,STD (Gonorrhea, Chlamydia, Trichomosiasis, Syphilis,
Tuberculosis, HIV, HPV) Tuberculosis, HIV, HPV) Hematopoietic:
Hematopoietic:
Dengue H. feverDengue H. fever
