INFECTIOUS DISEASES  Typhus fever (Rickettsia prowazekii)  Helminths  Synthesize their own DNA, RNA, &

 Still an important cause of death  Viral encephalitis (alphaviruses [e.g.,  Ectoparasites proteins but depend on hosts for
among elderly & immunocompromised Venezuelan equine encephalitis, eastern favorable growth conditions
patients equine encephalitis, western equine
encephalitis]) Obligate Intracellular Bacteria
PRION
BIOTERRORISM AGENTS  Water safety threats (e.g., Vibrio
 With prion protein (PrP) Chlamydia Rickettsia
cholerae, Cryptosporidium parvum)
Category A  Normally found in neurons Cannot synthesize Depend on host cell
Category C Diseases/Agents
 Highest risk  (+) disease in conformational changes ATP for ATP
 Emerging infectious disease threats such
 Readily disseminated  protease resistance Replicate inside Replicate inside
as Nipah virus and Hantavirus
 Highly mortality membrane-bound membrane-bound
 Spongiform encephalitis
 Eg: anthrax, botulism, smallpox. vacuoles in vacuoles in
o Kuru (human cannibalism)
plaque epithelial cells endothelial cells 
TABLE 8-1 -- Classes of Human o Creutzfeld Jacob Disease hemorrhagic
Pathogens and Their Lifestyles (corneal transplant) vasculitis
Category B o Bovine Spongiform
Taxonomic Site of Disease/ C.trachomatis – Transmitted by
 Moderately easy to disseminate Encephalopathy (mad cow
Propagation causative most common cause arthropod vectors
 Moderately morbidity disease)
agents of female sterility &
 Low mortality Variant CJD
Prions Intracellular Creutzfeld- o blindness
 Foodborne or waterborne Jacob disease Causes:
 Eg: brucelliosis, epsilon toxin, Viruses Obligate Poliomyelitis VIRUSES -Q fever
glandera, etc. intracellular -RMSF
 Obligate intracellular parasite
Bacteria Obligate Chlamydia  20-300 nm Mycoplasma
Category C intracellular  Extracellular bacteria; lacks cell wall
 Nucleic acid genome surrounded by
 Can be engineered for mass Extracellular Streptococcus  Tiniest free living org.like ureaplasma
CAPSID
dissemination pneumonia  Person to person
 Classified according to:
 Potential high morbidity & high Facultative Mycobacterium  Atypical pneumonia
o Nucleic acid genome
mortality intracellular tuberculosis UREAPLASMA
o Shape & capsid
 Emerging infectious disease threats Fungi Extracellular Candida  Sexually transmitted
o (+)/(-) of lipid envelope
 Eg: nipah virus, hantavirus albicans  Nongonococcal urethritis
o Mode of replication
Facultative Histoplasma
o Tropism
TABLE 8-4 -- Potential Agents of intracellular capsulatum FUNGUS
Bioterrorism
o Type of pathology
Protozoa Extracellular Trypanosoma  Eukaryote
Category A Diseases/Agents  (+) inclusion bodies
gambiense  Chitin (+) cell wall
 Anthrax (Bacillus anthracis) Facultative Trypanosoma
o CMV
o Herpesvirus  Ergosterol – cell membrane
 Botulism (Clostridium botulinum toxin) intracellular cruzi
o Smallpox & Rabies  Yeast cells or hyphae
 Plague (Yersinia pestis) Obligate Leishmania
 Transient, latent infection, tumor  Some dimorphic
 Smallpox (Variola major virus) intracellular donovani
 Tularemia (Francisella tularensis) production o Hyphae @ room temp
Helminths Extracellular Wuchereria
 Viral hemorrhagic fevers (filoviruses [e.g., o Yeast @ body temp
bancrofti
Ebola, Marburg] and arenaviruses [e.g., BACTERIA  (+) sexual spores or asexual spores
Intracellular Trichinella
Lassa, Machupo]) (conidia)
spiralis  Prokaryotes – have cell membrane but
Category B Diseases/Agents  Superficial (nails, hairs, skin,
lack membrane-bound nuclei &
 Brucellosis (Brucella sp.) dermatophytes, tinea)
organelles
 Epsilon toxin of Clostridium perfringens  Subcutaneous (tropical mycosis)
CATEGORIES OF INFECTIOUS AGENTS  Cell wall with peptidoglycan
 Food safety threats (e.g., Salmonella sp.,  Deep (coccidiodes)
Escherichia coli O157:H7, Shigella)  Prion o Thick (gram positive)
 Opportunistic fungi (Candida,
 Glanders (Burkholderia mallei)  Viruses o Thin (gram negative)
Aspergillus, Mucor, Cryptococcus
 Melioidosis (Burkholderia pseudomallei)  Bacteria  Classified according to
 Pneumocystis jiroveci in AIDS patients
 Psittacosis (Chlamydia psittaci) o Chlamydiae o Gram staining
 Q fever (Coxiella burnetti) o Ricketssiae o Shape
PROTOZOA
 Ricin toxin from Ricinus communis (castor o Mycoplasma o Need for oxygen
 Some with flagella or pilli  Single cell eukaryotes
beans)  Fungus
 Staphylococcal enterotoxin B  Colonize body parts of normal people  Can replicate intracellularly or
 Protozoa
extracellularly

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 o Trichomonas vaginalis
o Entamoeba histolytica
o Giardia lambia
o Plasmodium
o Trypanosoma
o Leishmania
o Toxoplasma gondii
HELMINTHS
 Highly differentiated
 Multicellular
 Complex life cycle
o Sexual – definitive host
o Asexual – intermediate
host/vector
 Disease is due to reaction to eggs or
larvae
 Disease is proportionate to number of
organism
ECTOPARASITE
 Insects or arachnids
 Direct effect or as vector
 Itching & excoriation
 Transmitted disease
SPECIAL TECHNIQUES FOR
DIAGNOSING INFECTIOUS AGENTS
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TABLE 8-3 -- Some Recently
Recognized Infectious Agents and
Manifestations
TRANSMISSION &
DISSEMINATION OF MICROBES
 Need to infect before transmission
 Factors: infecting organism & host,
virulaent factor
 Host barriers:
o Prevent microbe’s entry
o Innate or adaptive
 INNATE – physical barriers, phagocytic
cells, NK cells, plasma proteins
 ADAPTIVE – mediated by T & B o Blood & blood products (drug
lymphos abusers, needle sticks)
 o Animals to humans
TRANSMISSION & DISSEMINATION OF MICROBES
1. Routes of entry of microbes
4. Sexually transmitted
2. Spread & dissemination of microbes
3. Release of microbes from the body infections
4. Sexually transmitted infections  Infection w/ one STI increases the risk
5. Healthcare-associated infections with another STD
6. Host Defenses against infections  Can be spread from pregnant mother
to the fetus  severe damage to
fetus/child
1. Routes of entry of microbes  INITIAL SITE: urethra, vagina, cervix,
rectum, oral, pharynx
 Inhalation
 Ingestion TABLE 8-5 -- Classification of Important Sexually
 Sexual transmission Transmitted Diseases
 Insect or animal bites
 Injection
2. Spread & dissemination of
microbes
 Initially, spreads LOCALLY (Cholera,
dermatophytes) or INVADE & SPREAD
thru blood (malaria), LYMPHATICS
(staphylococcus), or NERVES (rabies)
 Placental fetal route (rubella &
syhphilis), birth canal (gonococcal),
milk (CMV, HBV)
 Major manifestations at distant sites
(airway)
o Chickenpox & Measles
3. Release of microbes from the
body
 Skin shedding
 Coughing
 Sneezing
 Urine or feces
 Insect vectors
TRANSMISSION OF MICROBES FROM
PERSON TO PERSON
 Respiratory – virus & bacteria
(*important)
 Fecal-Oral – water borne viruses
 Sexual – STDs, HBV, HIV, HSV, HPV
 Others
o Skin penetration (hook worm)
 HOST DEFENSES AGAINST INFECTION:
5. Healthcare-associated RESPIRATORY TRACT
 Mucociliary defense
infections  Alveolar macrophages
 “nosocomial” infections  hospital  Damage to mucocilliary defense by:
acquired (usually after 5 days of o Smoking
admission) o Cystic fibrosis
 Transmitted through blood o Aspiration
transfusions, organ transplant, invasive o Intubation
procedures
 Most common, hands of healthcare *There are some bacteria that
providers (wash hands after every avoid phagocytosis
patient) (eg.pneumococcus TB)
 Hygiene & hand washing greatly reduce
transmission of MRSA & VRE HOST DEFENSES AGAINST INFECTION:
GENITOURINARY TRACT
6. Host Defenses against  Urination
infections  Low vaginal pH (glycogen lactobacilli)
 Anatomy
HOST DEFENSES AGAINST INFECTION:
 Obstruction
SKIN
 Antibiotics (vaginal infection) – w/c
 Keratin layer - *good factor
destroyed by lactic bacilli
 Low pH (5.5)
o *Female – more prone to
 Fatty acids
infection
 Microbes penetrate INTACT skin or thru
breaks
o Schistosoma – can enter intact
the skin HOW MICROORGANISMS
HOST DEFENSES AGAINST INFECTION:
CAUSE DISEASE
Mechanisms of Injury
GIT
1. Enter host cells & directly cause
 Acidic gastric
disease
 Secretions
 Mucus layer 2. Release of toxins/ enzymes (during cell
 Pancreatic enzymes lysis)
 Bile 3. Host cellular response
 Defensins
 Normal flora MECHANISMS OF VIRAL INJURY
 IgA  Directly damage host cells by entering
 Host defenses weakened by: & replicating inside host cells
o Low gastric acidity  Direct cytopathic effects, antiviral
o Antibiotics immune responses, & transformation of
o Disturbance in peristalsis infected cells
o Obstruction  Has factors for tissue tropism, d/t:
 Enterotoxins, exotoxins invasion & o Host cell receptor – for the
mucosal damage, systemic infection virus
o Cellular transcription Fs
o Anatomic barriers (ex.polio)
o Local temp.,pH & host
defenses
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BACTERIAL VIRULENCE
 Virulence genes in pathogenicity
islands
o *encode proteins for their
ability to adhere, invade, or
deliver toxins
 PLASMIDS or BACTERIOPHAGES –
virulence factors
 PLASMIDS or TRANSPOSONS –
antibiotic resistance
 QUORUM SENSING – expression of
virulence Fs related to concentration
(more bacteria = increase virulence)
 Secretion of autoinducer peptides –
toxin production
 BIOFILMS – viscous layer of
extracellular polysaccharides that
adhere to host tissue or devices 
adherence, immune evasion,
inc.antibiotic resistane
o Ex: Pseudomonas aeruginosa
BACTERIAL ADHERENCE
 ADHESINS – adhere to host cells or
ECM fibrillae (eg. S. pyogenes)
o S. pyogenes adheres to host
MECHANISMS OF BACTERIAL INJURY
 Bacterial virulence
tissues by protein F and
teichoic acid projecting from
 Bacterial adherence to host cells
the bacterial cell wall
 Virulence of intracellular bacteria
 PILI/ FIMBRIAE are filamentous
 Bacterial toxins
proteins on the surface of bacteria
 Injurious effect of host immunity
o Eg. E. coli, N. gonorrhoeae
VIRULENCE OF INTRACELLULAR
BACTERIA
 Infect epithelial cell, macrophage, or
both
 Escape immune response or facilitate
spread
 Gain entry thru immune response
o Eg.coating with Abs or C3b
(opsonization)  phagocytosis
 When inside the cell – inhibit host
protein synthesis, replicate rapidly, &
lyse host cell
o *phagolysosome – kills most
bacteria
o MTB – prevent fusion of
phagosome &lysosome
BACTERIAL TOXINS
 EDOTOXINS – component of bacterial
cell
o Eg.LPS (in gm (-) bacteria
o Induce cytokines & chemokines
o Plays a role in Septic shock,
DIC, ARDS – d/t excessive
cytokines
 EXOTOXINS – secreted by bacterium
o Enzyme (proteases,
hyaluronidases, coagulases,
fibrinolysins)
o Toxins that alter INTRAcellular
signals or regular pathways (A-
B toxins)
o Neurotoxins
(C.botilinum/tetani) - paralysis
o Superantigens – stimulate very
large amounts of T
lymphocytes  cytokines 
capillary leak & shock
 Superantigens made
by S. aureus and S.
pyogenes cause toxic
shock syndrome (TSS)
INJURIOUS EFFECTS OF HOST IMMUNITY
 Tuberculosis – type IV hypersensitivity
 HBV & HBC – immune reponse
 Rheumatic Fever – cross reaction
 Post.Strep GN – type III
hypersensitivity
o Can develop infection –
S.pyogenes
*Chronic inflammation – provides fertile
ground for the development of cancer
IMMUNE EVASION BY
MICROBES
Microorganisms have developed many means
to resist and evade the immune system.
Mechanisms:
 (1) Growth in niches that remains
inaccessible/ hidden to host immune
response. Eg.intestinal lumen,
gallbladder
 (2) Variation or shedding antigens
Prepared by: EGBII w/ AFB; 09-17-11
 (3) Resistance to innate immune
defenses – capsule, host proteins,
VIRAL INFECTIONS
protease  can destroy host body Transient infections Transforming
 (4) Impairment of effective T-cell .Measles infections
antimicrobial responses by specific or .Mumps .EBV
nonspecific immunosuppression .Poliovirus .HPV
.West Nile Virus
*after viral infection = decrease immune .Viral H’gic virus
response Chronic LATENT Chronic
infections PRODUCTIVE
.HSV infections
INFECTIONS IN .VZV .Hepa B
IMMUNOSUPPRESSED HOSTS .CMV
 Inherited or acquired defects in
immunity  partial  susceptible to
specific types of infection
 X-linked agammaglobulinemia – severe
bacterial infections
o S.pneumoniae
o H.influenzae
o S.aureus
 T-cell defects – intracellular pathogens
 Complement protein deficiency –
susceptible to
o S.pneumonia
o H.influenzae
o N.meningitides
 AIDS (destroys CD4 T-helper cells),
leukemia – opportunistic infections
o Pneumocystis jirovecii –
common opportunistic
5 PATTERNS of INFLAMMATORY RESPONSE
 Suppurative inflammation –
pyogenic bacteria
o d/t digestion of normal
structures
 Mononuclear & Granulomatous
inflammation – caused by:
o Virus, intracellular bacteria, or
intracellular parasites
o *EXCEPT acute viral infection –
by macrophage
 Cytopathic-Cytoproliferative
inflammation
o Usually, by a virus
 Tissue necrosis – without or few
inflammatory cells but NO inflammation
o C.perfringes, E.histolytica
 Chronic inflammation & Scarring –
by HBV (cirrhosis)
 TRANSIENT INFECTIONS
1. Measles (Rubeola)
 Single standed RNA
 Paramyxovirus family
 Only 1 strain
 Cell surface receptors:
o CD46 – all nucleated cells
o Signaling lymphocytic
activation molecule (SLAM) –
cells of immune systems
 a molecule involved in
T-cell activation
 MOT: respiratory droplets
Characteristics/ Morphology:
 WARTHIN-FINKELDEY CELLS
o Multinucleated giant cells
w/eosinophilic nuclear &
cytoplasmic inclusion bodies
o Seen in lymphoid organs with
follicular hyperplasia
 REDDISH BROWN RASH
o Dilated vessels, edema,
mononuclear perivascular
infiltrates
 KOPLIK SPOT (pathognomonic)
o Mucosal ulcerated lesions
o Marked by: Necrosis,
neutrophils, neovascularization
o Appear during 4th day of fever;
usually in 2nd molar
Complications of measles
 Croup, pneumonia
 Diarrhea
 Keratitis (blindness), encephalitis
(Subacute sclerosing
panencephalitis)
 Hemorrhagic measles (“black
measles”)
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2. Mumps
 Paramyxovirus
 2 types of surface glycoproteins
o Hemagglutinin (w/c enter the
cell) & neuramidase (w/c exit
the cell) activities
o Cell fusion & cytolytic activities
 Inhalation of respiratory droplets 
regional LN  replicate in lymphocytes
 blood  tropisms: salivary glands &
other tissues  desquamation of
involved cells, edema, & inflammation
 swelling (both side of parotid) & pain
 Other sites: CNS, testis, ovary,
pancreas
Morphology
 Salivary gland pain & swelling
o 70% bilateral
o Mononuclear cells compress
acini
o PMN & debris – lumen
(parotitis)
 Aseptic meningitis 0 most common
extrasalivary complication (10%)
 Mumps orchitis – scar & atrophy –
causing sterility
 Pancreatic parenchyman & fat necrosis,
pmn-rich
 Mumps encephalitis – monos
3. Polivirus
 Spherical, unencapsulated RNA
 Enterovirus
 w/ 3 major stains, all included in
vaccine
 it uses human CD155 to gain entry into
cells
 Fecal-oral route
 Infects oropharynx  secreted into
saliva  swallowed  multiplies in
intestinal mucosa & LN  transient
viremia & fever  1/100 invades CNS
 replicates in SPINAL motor neurons
or BRAIN STEM (bulbar)  POLIO
4. West Nile Virus
 Arthropod-borne virus
 Flavivirus (includes Dengue & Yellow
fever)
 Mosquitoes to bird to mammals
 Humans – accidental host
 Transmitted by blood transfusion,
transplanted organs, breast milk, &
transplacental route
 Usually asymptomatic, 20% mild febrile
illness
 DANGEROUS complicationsL
o Meningitis
o Encephalitis
o Meningoencephalitis
5. Viral Hemorrhagic Fever
 Enveloped RNAs of arena virus:
Filoviruses
o
Bunyaviruses
o
o Flaviviruses
 Depend on animal or insect host for
survival and transmission
 Transmitted on contact with infected
hosts or insect vectors, humans NOT
the natural reservoir
 Some can spread from person to
person: Lassa, Ebola, Marburg
 Mild to acute disease to life-threatening
disease with sudden hemodynamic
deterioration & shock
 NO cure or vaccines
 Potential biologic weapons
 Pathogenesis NOT well-understood
 Manifestations:
o d/t thrombocytopenia or
severe platelet (as low as 500)
or endothelial dysfunction 
increased vascular
permeability
 Activates innate immune response
 *there are 4 serotypes of dengue
CHRONIC LATENT INFECTIONS
1. Herpes Simplex virus
 Includes: HSV 1 & HSV 2
 Differ serologically
 Genetically similar
 Acute & laten
 Replicate – skin & mucus membrane
 Vesicular lesions
 Spread thru sensory neurons
 Latency associated transcripts
 Repeated reactivations
 HSV-1 – associated with CORNEAL
blindness, FATAL sporadic
encephalopathy
 Neonates & immunocompromissed,
disseminated HSV infection
 Large, pink to purple intranuclear
inclusions (Cowdry tupe A)
o Also with halo
Manifestations
 Fever, blisters, cold sores (bilateral)
 Gingivostomatitis (HSV-1)
 Genital herpes (HSV 2>1)
 2 types of corneal lesions:
o Epithelial keratitis - virus-
induced cytolysis of the
superficial epithelium
o stromal keratitis - is
characterized by infiltrates of
mononuclear cells
 KAPOSI varicelliform eruption
 eczema herpeticum is characterized
by confluent, pustular, or hemorrhagic
blisters
 esophagitis - superinfection with
bacteria or fungi
 bronchopneumonia – d/t intubation
o NOT a typical manifestation
 Herpes hepatitis
2. Varicella Zoster Virus
 Chicken pox & shingles
 Mild in children
 Infects mucous membrane, skin, &
neurons
 LATENT infections – sensory ganglia
 Transmitted thru AEROSOLA
 Spread hematogenously
 Spread vesicular lesions
o Centrifugal = trunk to
extremities
Chickenpox Shingles
.2wks after .Chickenpox
respiratory infection Latent 
.Rash (macule in REACTIVATION
torso to head &
extremities) *Dorsal root ganglia
.Vesicles rupture,
crusts, heal
SHINGLES
 Vesicular lesions, intense itching,
burning or sharp pain (radiculoneuritis)
 Facial paralysis (geniculate nucleus)
o RAMSAY HUNT SYND
 Other VZV associated diseases:
o Intestinal Pneumonia
Encephalitis
o  Viral ingestion  in normal person, it
o Tranverse Myelitis
o Necrotizing Visceral lesions
3. Cytomegalovirus
 Beta group herpesvirus
 Major envelop CHON binds with
epidermal growth factor receptor
 Latent with WBCs
 Asymptomatic or mononucleosis like
infection in healthy people
 Gigantism of cell & nucleus
 Inclusion body surrounded by HAL
(OWL’s eye)
Mode of transmission
 Transplacental (congenital)
 Thru vaginal/ cervical secretions
(neonatal) or milk (perinatal)
 Thru saliva – preschool
 Venereal – after 15 years – ONLY in
U.S.
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 Iatrogenic/ blood transfusion – any age
 Respiratory secretions & fecal-oral
o Intranuclear & cytoplasmic
basophilic inclusions
o Seropositive for life – already
with antibody
High Risks
 Solid organ transplant patients
allogenic BM transplant patients AIDS
patient (most common opportunistic
organism)
Manifestations of CMV: disseminated
 Pneumonitis, Colitis, Retinitis
Diagnosis:
 Morphology
 Culture
 Antibody
 Antigens
 PCR (DNA)
CHRONIC PRODUCTIVE
INFECTION
1. Hepatitis B Virus
 Serum hepatitis
 Hepadnavirus
 DNA virus
 Spread: percutaneously, perinatally,
sexually
 Cell injury secondary to reponse to
infected liver cells
 Envade immune defenses by inhibiting
INF-B & down regulating viral gene
expression
o Infected hepatocytes
destroyed by CTL
o Replicating virus is eliminated
o Infection is cleared
 If the rate of infection of hepatocytes
outpaces the ability of CTLs to
eliminate infected cells, a chronic
infection is established. This may
happen in about 5% of adults and up
to 90% of children infected
perinatally. In this setting the liver
develops a chronic hepatitis, with
lymphocytic inflammation, apoptotic
hepatocytes resulting from CTL-
mediated killing, and progressive
destruction of the liver parenchyma.
 Long-term viral replication and
recurrent immune-mediated liver injury
can lead to cirrhosis of the liver and
an increased risk for hepatocellular
carcinoma.
 CTL response is dormant, resulting in
the establishment of a “carrier” state,
without progressive liver dam
TRANSFORMING INFECTIONS
1. Epstein-Barr Virus
 Causes infectious mononucleosis (IM)
 Associated with lymphomas (Burkitt) &
nasopharyngeal carcinomas
 IM occurs in late adolescents & young
adults
 Close contact (*saliva) “kissing virus”
EBV spread
 The major alterations involve the
blood, lymph nodes, spleen, liver, CNS,
and, occasionally, other organs
resolves in 4-6 weeks
 In immunosuppressed  EBV targeted
nasopharynx & oropharynx  causing
B-cell neoplasms
IM diagnosis depends on:
 90% lymphocytosis with atypical
lymphocytes in PBS
 Positive heteophile antibody reaction
 Specific EBV antigens (viral capsid
antigen, early antigen, EB nuclear
antigen)
2. Human Papilloma virus
 Non-enveloped DNA virus
 Papovavirus family
 >100 types
 Warts, benign tumors, squamous cell
CA (cervix)
 Initially infect basal cells of epithelium
 Koilocytosis (perinuclear vacuolization)
GRAM POSITIVE BACTERIAL DISEASES
1. Staphycoccal infections
2. Streptococcal & Enterococcal
infections
3. Diptheria
4. Listeriosis
5. Anthrax
6. Nocardia
1. Staphylococcus
 Gram (+) cocci
 Grapelike clusters
 Skin lesions, TSS, respiratory
infections, heart lesions, osteomyelitis,
food poisoning
 S. epidermis, S. saprophyticus, S.
aureus
 Toxins
o Hemolytic toxins
o Exfoliative toxins (bullous
impetigo)
o Superantigens (TSS & food
poisoning)
 Pyogenic inflammation
Morphology
 Furuncle or boil
 Carbuncle
 Hidradenitis suppurativa - infection of
apocrine glands, most often in the
axilla
 Paronychia (nailbeds)
 Felons (fingertips)
 Staphylococcal scalded skin syndrome
or ritter disease - infections of the
nasopharynx or skin in children
2. Streptococcus
 Facultative or obligate anaerobe
 Gram (+) cocci in pairs or chains
 S.pyogenes: pharyngitis, scarlet fever,
erysipelas, impetigo, RF, TSS, GN
 S. agalactiae: neonatal sepsis,
meningitis, chorioamnionitis
 S. Pneumoniae: community acquired
pneumoniae
 S. mutans: dental caries
3. Diphtheria o Activates macrophages  Disseminated infection in those lacking o Hyperemia
 Corynebacterium diptheriae complement proteins (MAC)  septic o Copious mucopurulent exudate
 Gm (+) rod 6. Nocardia arthritis + hemorrhagic papules &  Peripheral lymphocytosis (90%)
 MOT: person to person, aerosol or skin  Aerobic pustules o Hypercellularity & enlargement
shedding  Gram (+)  Neonatal gonorrhea  blindness of mucosal lymph follicales &
 Tough pharyngeal membrane  (+) terminal spores (conjunctivitis), rarely, sepsis peribronchial LN
 Toxin mediated damage to tissues  “beaded” o Tx: silver nitrate or antibiotics
 Phage encoded A-B toxin blocks CHON  Branching 3. Pseudomonas infection
synthesis  N. asteroids – respiratory infection Pathogenesis  P.aeruginosa
 Immunization – protection against  N. brasiliensis – skin infection  Use antigenic variation to escape o Common cause of hospital
lethal effect of toxin  Patients with defective T-cell mediated immune response: acquired
immunity o Pili proteins are altered by  Opportunistic, aerobic, gm (-) bacillus
genetic recombination
4. Anthrax  Suppurative lesion with liquefaction,
o Has three or four genes for
o a frequent, deadly pathogen of
 Bacillus antharcis granulation & fibrosis people with cystic fibrosis,
OPA proteins severe burns, or neutropenia
 Spore former  OPA-ability to change
 Gm (+) rod  d/t sepsis
their antigen; They  Resistant to antibiotics
 Box-car shaped Gram Negative Bacterial infections
increase binding of  Hospital acquired infection, corneal
 Spore – potent biological weapon 1. Neisserial infections
Neisseria organisms to keratitis (contact lenses), endocarditis
 Major anthrax syndromes: 2. Whooping cough
epithelial cells and & osteomyelitis (IV abuses), otitis
o Cutaneous 3. Pseudomonas infection
promote entry of media (swimmers/diabetics)
o Inhalational 4. Plaque
bacteria into cells
o Gastrointestinal 5. Chancroid (Soft chancre)
 Has multiple serotypes  disease with
6. Granuloma Inguinale Virulence factors
new strain
CUTANEOUS Anthrax  PILI & adherence proteins  binds to
 Adhere to pili+CD46) & invade (OPA
 95% 1. Neisserial infections proteins) non ciliated epithelial cells at
epithelial cells & lung mucin
 Painless pruritic papule  vesicle  Gm (-) diplococcic  ENDOTOXIN – symptoms & signs of gm
site of entry (nasopharynx, urethra, or
(2days)  rupture  black eschar  Coffee bean shaped (-) sepsis
cervix)
 Bacteremia, rare  Grow best in enriched media (lysed in  ALGINATE – slimy biofilm, protects
sheeps’s blood agar, “chocolate” agar) bacteria from antibody, complement,
2. Whooping cough phagocytes, antibiotics
INHALATIONAL Anthrax  N.meningitides & N.gonorrhea –
 Inhaled  growth in LN  spore  Bordatella pertussis  EXOTOXIN – inhibits protein synthesis
clinically significant
germinates  toxin release   Gm (-) coccobacillus  PHOSPHOLIPASE C – lyze rbc &
hemorrhagic  Acute, highly communicable degrades pulmonary surfactant
N.meningitides
 Paroxysms of violent coughing followed  ELASTASE – degrades IgG & ECM
 13 serotypes
GASTROINTESTINAL Anthrax by “whoop”  Iron containing compounds – toxic to
 Bacterial meningitis in 5-19 years old
 Uncommon  Vaccine available but high rate due to E.C.  causing vasculitis
 Colonize oropharynx  invade
 Eating undercooked meat antigenic divergence & waning
respiratory epithelium  circulation 
 Nausea, abdominal pain, vomiting immunity Manifestations
capsule reduces opsonization &
 Severe bloody diarrhea  Dx: PCR, culture (less sensitive)  Necrotizing pneumonia – terminal
destruction by complement
 Mortality – 50%  Pathogenesis: airways in a fleur-de-lis pattern
 Spread by respiratory route
o Colonizes brush border of  Gram (-) vasculitis + thrombosis +
 Tx: antibiotics
bronchial epithelium & invades
5. Listeria  10% death
macrophages
hemorrhage – highly suggestive
 Bronchial obstruction in CF +
 Gm (+) bacillus  Bortedella virulence gene (bvg) –
N.gonorrhea P.aeruginosa  bronchiectasis &
 Intracellular regulates transcription of adhesins &
 Motile, facultative  Causes of STD: pulmonary fibrosis
toxins  Skin burns  Ecthyma gangrenosum
 Food borne o 1st – C.trachomatis
 Hemaglutinin adhesins binds with  Bacteremia  DIC
 Exudative pattern of inflammation o 2nd – N.gonorrhea
CHON on surface of cells
 INTERNALIS – leucine rich proteins on  Urethritis in men
 EXOTOXINS – paralyze cilia
surface bind E-cadherins  Asymptomatic in women  PID 
 Cause: LARYNGOTRACHEOBRONCHITIS
 Protection mediated by IFN-y sterility or ectopic pregnancy
o Bronchial mucosal erosions

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4. Plague
 Yersinia pestis, gm (-) facultative
intracellular bacterium
 Transmitted from rodents to humans
by fleabites or human to humans by
aerosols
 Causes invasive, frequently fatal
infection (black death)
 Y.enterocolitica &
Y.pseudotuberculosis:
o Cause fecal-oral transmitted
ileiteis & mesenteric
lymphadenitis
 Proliferative within lymphoid cells
 Yop virulon genes  proteins
assemble into type 3 secretion system
 binds & injects bacterial toxins
(Yops) to host cells  kill host
phagocytes & block phagocytosis &
production of cytokines
Histologic features
 Massive proliferation of organism
 Appearance of protein rich &
polysaccharide rich effusion
 Necrosis of tissues & blood vessels with
hemorrhage & thrombosis
 Neutrophilic infiltrates
Manifestations
 BUBONIC PLAQUE – fleabite on legs
with pustule or ulceration  draining
LN enlarges become soft, pulpy &
plum-colored (buboes)  may infarct
or rupture thru skin
 PNEUMONIC PLAQUE – severe,
confluent, hemorrhagic & necrotizing
bronchopneumonia with fibrinous
pleuritis
 SEPTICEMIC PLAQUE – LN & REC all
throughout the body develop foci of
necrosis + neutrophilia
 FULMINANT BACTEREMIAS – DIC with
hemorrhages & thrombosis
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5. Chancroid (Soft Chancre)
 Versus Syphilis (Hard chancre)
 Hemophilus ducreyi, coccobacilli
 Acute, sexually transmitted, ulcerative
infection
 4-7 days after inoculation  tender,
erythematous papule
 Males – lesion in penis; females –
vagina and periurethral area
 Erodes  irregular ulcer 
enlargement of regional lymph nodes
(buboes)  erodes overlying skin 
chronic, draining ulcers
 Must be cultured in special conditions;
PCR
Chancroid
 Irregular ulcer:
o neutrophil debris and fibrin
granulation tissue with
o 
necrosis & thrombosed vessels
o dense lymphoplasmatic
infiltrates
 Gram or silver stain – coccobacilli
6. Granuloma Inguinale
(Donovanosis)
 Klebsiella granulomatosis (formerly
Calymmatobacterium donovani)
 minute, encapsulated, coccobacillus
 Sexually transmitted
 Untreated  entensive scarring asst’d
with lymphatic obst’n & lymphadema
(elephantiasis) of external genetalia
 Dx: microscopy of smears or ulcer
biopsy
 Raised papule  ulceration 
granulation tissue  disfiguring scars
 pseudoepitheliomatous hyperplasia
 neutrophils and monos in ulcer base
 Donovan bodies (bacteria in
macrophage on Giemsa stain/silver
stain smears of exudates)
MYCOBACTERIA
1. Tuberculosis
2. Mycobacterium avium-
intracellulare complex
3. Leprosy
 Slender, aerobic rods that grow in
straight or branching chain
 Waxy cell wall composed of mycolic
acid
 Acid fast
 Weakly gram (+)
Tuberculosis
 M. tuberculosis, M. bovis
 Infection thru airborne droplets
 Organism may be dormant for years
within macrophages
 Reactivation occurs with depressed
immune status
Delayed hypersensitivity to antigen
 Tuberculin (mantoux) test
 NOT specific!
 (+) means there is exposure or
immunization received
 induration that peaks in 48 to 72
hours
 Macrophages - 1° cells infected
 Replicate w/ phagosomes
 Bacteremia
 NRAMP1 gene – gen. of anti-microbial
oxygen radicals
 TH1 response in 3 wks makes
macrophages bactericidal
 Other roles of TH1:
 INF-y – for competence of
macrophages
 iNOS – for oxidative destruction
formation of granulomas and
caseous necrosis
Non-specific signs:
 early dse: malaise, anorexia, wt. loss
low grade fever, night sweats
 hemoptysis, pleuritic pain
 AFB. culture, PCR
1. 1° TB – ghon (parenchyma)
 occurs in prev. unexposed (usually in
children), unsensitized person
 usually w/ latent dse
 some progressive
 pneumonia like,hillar adenopathy,
pleural effusion
 Ghon complex:
o parenchymal lung lesion
o nodal involvement
 Ranke complex:
o radiologically detectable
o calcification
2. 2° TB @ apex
 seen in prev. sensitized host
 shortly after primary or reactivation or
exogenous reinfection
 @ apex of upper lobes
 cavitation is common
 initial lesion may heal
 progressive pulmonary TB in elderly &
immunocompromised
 Miliary pulmonary dse
o organism drain through
lymphatics into ducts or thru
the pulmonary artery
 microscopic/visible (2mm)
 Systemic military TB
o liver,BM,spleen,adrenals,menig
es,kidneys,FT,epididymis
 isolated-organ TB (mostly systemic,
EXCEPT this!)
o TB meningitis, renal
TB,adrenals,osteomylelitis,salpi
ngitis,scrofula,GIT TB
* FIGURE 8-28 The natural history and spectrum of
tuberculosis. (at the back)
MYCOBACTERIUM AVIUM –
INTRACELLULARE COMPLEX
 MAC
 Uncommon except in AIDS & low
levels of CD4 lymphocytes (<60
cell/mm3)
 widely dessiminated
 lungs
 mononuclear system
 granuloma, lymphocyte, & tissue
destruction rare
LEPROSY
 Hansen dse
 M. leprae
 Aerosols
 Grow in cool tissues of skin (32-34C)
 acid fast, obligate intracellular
organisms
o tuberculoid
o lepromatous
o intermediate
Tuberculoid Type
 dry, scaly skin w/o sensation
 TH1 (IL-2,IFN-y)
 hyperpigmented margins w/
depressed centers – seen in
patients with intact immune sys.
 granulomatous, no bacilli or very
few anesthesia
Lepromatous Type
 more severe from, anergic type –
severe form of leprosy*
 symmetric skin thickening &
nodules
 defective TH1 response or dominant
TH2 response
 lepra cells w/ numerous acid fast
bacilli - *a macrophage
 leonine facies
 hypoesthetic or anesthetic
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SPIROCHETES OBLIGATE INTRACELLULAR
1. Syphilis BACTERIA
2. Relapsing fever  Chlamydia
3. Lyme Disease
o gram (-)
o STD
Syphilis (3 stages)
o urethritis, lymphogranuloma
 1° stage
venereum
o 3 wks after contact
 Ricketssia
single,firm,nontender,raise
o gram (-)
d,red lesion (chancre)
o typhus fever, rocky mountain
o numerous spirochetes
spotted fever, scrub typhus
o heals in 3 – 6 wks
 2° stage
o 2-10 wks after primary
SUMMARY OF BACTERIAL INFECTIONS
skin & tissues
maculopapular,scaly, or
pustular
o condylomata lata
o lymphadenipahty, mild
fever, malaise, weight loss
 Tertiary stage
o rare
o after a latent period of 5 ANAEROBIC BACTERIA
yrs 1. Abscesses caused by anaerobes
o CVS, neurosyphilis,benign 2. Clostridial infections
tertiary Sy
o gummas – white gray Abscess
rubbery lesions  mixed anaerobic and facultative
bacteria
Congenital Syphilis  foul smelling, pus filled
 crosses the placenta during 1° and
2° early (infantile), late (tardive) Clostridium Infections
homework: “take note of the  Gram (+), anaerobes, spore former
differences”  C.perfringes – gas gangrene
 C.tetani – tetanus
Serologic Tests for Syphilis  C.deficilli – pseudomembranous
 Serology - mainstay colitis
 PCR  C.botolinium 0 botulism
 Nontreponemal tests - measure
antibody to cardiolipin, a phospholipid present in
both host tissues and T. pallidum
 RPR,VDRL measure Ab to cardiolipin
 Treponemal tests
 FTA-Abs, MHATP
 FUNGAL INFECTIONS PARASITIC INFECTIONS Plasmodium falciparum, which causes severe
2 general categories: malaria, and the three other malaria parasites
1. Candidiasis
1. Protozoa that infect humans (P. vivax, P. ovale, and P.
2. Cryptococcosis malariae) are transmitted by female
3. Aspergillosis  Malaria, Babesiosis, Leishmaniasis, Anopheles mosquitoes that are widely
4. Zygomycosis (Mucormycosis) African typanosomiasis, Chagas distributed throughout Africa, Asia, and Latin
dse. America. Nearly all of the approximately 1500
2. Metazoa new cases of malaria each year in the United
1. Candidiasis States occur in travelers or immigrants,
 Strongyloidiasis, Tapeworms,
 superficial infections although rare cases transmitted by Anopheles
 esophagitis Trichinosis, Schistosomiasis, mosquitoes or blood transfusion do occur.
Filariasis, Onchoceriasis Worldwide public health efforts to control
 vaginitis
malaria in the 1950s through 1980s failed,
 cutaneous leaving mosquitoes resistant to DDT and
*read about MALARIA!
 chronic mucocutaneous malathion and Plasmodium resistant to
 invasive chloroquine and pyrimethamine.

2. Cryptococcosis Life Cycle and Pathogenesis.

 Encapsulated yeast
 Meningoencephalitis
 Opportunistic infection in AIDS,
leukemic lymphoma patients
 In soil, bird droppings
3. Aspergillosis
 Mold
 brewer’s lung in healthy people
 sinusitis, pneumonia,fungermia in
immunocompromised individuals
 neutropenia,corticosteroids
 aspergilloma, invasive aspergillosis
4. Zygomycosis
 mucomycosis
 bread mold fungi
 no harm to immunocompetent
 infect immunosuppressed
individuals
 neutropenia, corticosteroid,
diabetes, breakdown of cutaneous
barriers
 nonseptate, irreg. wide hyphae
 rhinocerebral mucormycosis, lung
involvement
Malaria, caused by the intracellular parasite
Plasmodium, is a worldwide infection that
affects 500 million and kills more than 1
million people each year. According to the
World Health Organization, 90% of deaths
from malaria occur in sub-Saharan Africa,
where malaria is the leading cause of death in
children younger than 5 years old.
Plasmodium vivax, P. ovale, and P. malariae
cause low levels of parasitemia, mild anemia,
and, in rare instances, splenic rupture and
nephrotic syndrome. P. falciparum causes high
levels of parasitemia, severe anemia, cerebral
symptoms, renal failure, pulmonary edema,
and death. The life cycles of the Plasmodium
species are similar, although P. falciparum
differs in ways that contribute to its greater
virulence.
The infectious stage of malaria, the
sporozoite, is found in the salivary glands of
female mosquitoes. When the mosquito takes
a blood meal, sporozoites are released into
the human's blood and within minutes attach
to and invade liver cells by binding to the
hepatocyte receptor for the serum proteins
thrombospondin and properdin[112] ( Fig. 8-49
). Within liver cells, malaria parasites multiply
rapidly, releasing as many as 30,000
merozoites (asexual, haploid forms) when
each infected hepatocyte ruptures. P. vivax
and P. ovale form latent hypnozoites in
hepatocytes, which cause relapses of malaria
long after initial infection.
Once released from the liver, Plasmodium
merozoites bind by a parasite lectin-like
molecule to sialic acid residues on glycophorin
molecules on the surface of red cells. Within
the red cells the parasites grow in a
membrane-bound digestive vacuole,

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hydrolyzing hemoglobin through secreted
enzymes. The trophozoite is the first stage of
the parasite in the red cell and is defined by
the presence of a single chromatin mass. The
next stage, the schizont, has multiple
chromatin masses, each of which develops
into a merozoite. On lysis of the red cell, the
new merozoites infect additional red cells.
Although most malaria parasites within the
red cells develop into merozoites, some
parasites develop into sexual forms called
gametocytes that infect the mosquito when it
takes its blood meal.
Plasmodium falciparum causes more severe
disease than the other Plasmodium species
do. Several features of P. falciparum account
for its greater pathogenicity:
• P. falciparum is able to infect red
blood cells of any age, leading to high
parasite burdens and profound
anemia. The other species infect only
young or old red cells, which are a
smaller fraction of the red cell pool.
• P. falciparum causes infected red cells
to clump together (rosette) and to
stick to endothelial cells lining small
blood vessels (sequestration), which
blocks blood flow. Several proteins,
including P. falciparum erythrocyte
membrane protein 1 (PfEMP1), form
knobs on the surface of red cells ( Fig.
8-49 ).[113] PfEMP1 binds to ligands on
endothelial cells, including CD36,
thrombospondin, VCAM-1, ICAM-1,
and E-selectin. Ischemia due to poor
perfusion causes the manifestations of
cerebral malaria, which is the main
cause of death due to malaria in
children.
• P. falciparum stimulates production of
high levels of cytokines, including
TNF, IFN-γ, and IL-1. GPI-linked
proteins, including merozoite surface
antigens, are released from infected
red cells and induce cytokine
production by host cells by a
mechanism that is not yet understood.
These cytokines suppress production
of red blood cells, increase fever,
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stimulate nitric oxide production
(leading to tissue damage), and
induce expression of endothelial
receptors for PfEMP1 (increasing
sequestration).
Host Resistance to Plasmodium.
There are two general mechanisms of host
resistance to Plasmodium. First, inherited
alterations in red cells make people resistant
to Plasmodium. Second, repeated or
prolonged exposure to Plasmodium species
stimulates an immune response that reduces
the severity of the illness caused by malaria.
Several common mutations in hemoglobin
genes confer resistance to malaria. People
who are heterozygous for the sickle cell trait
(HbS) become infected with P. falciparum, but
they are less likely to die from infection. The
HbS trait causes the parasites to grow poorly
or die because of the low oxygen
concentrations. The geographic distribution of
the HbS trait is similar to that of P.
falciparum, suggesting evolutionary selection
of the HbS trait in people by the parasite.
HbC, another common hemoglobin mutation,
also protects against severe malaria by
reducing parasite proliferation. People can
also be resistant to malaria due to the
absence of proteins to which the parasites
bind. P. vivax enters red cells by binding to
the Duffy blood group antigen. Many Africans,
including most Gambians, are not susceptible
to infection by P. vivax because they do not
have the Duffy antigen.
Individuals living where Plasmodium is
endemic often gain partial immune-mediated
resistance to malaria, evidenced by reduced
illness despite infection. Antibodies and T
lymphocytes specific for Plasmodium reduce
disease manifestations, although the parasite
has developed strategies to evade the host
immune response. P. falciparum uses
antigenic variation to escape from antibody
responses to PfEMP1. Each haploid P.
falciparum genome has about 50 var genes,
each encoding a variant of PfEMP1. The
mechanism of var regulation is not known, but
at least 2% of the parasites switch PfEMP1
genes each generation. CTLs may also be
important in resistance to P. falciparum. shock with DIC may cause death, sometimes
Despite enormous efforts, there has been little in the absence of other characteristic lesions.
progress in developing a vaccine for malaria.
Morphology. Plasmodium falciparum
infection initially causes congestion and
enlargement of the spleen, which may
eventually exceed 1000 gm in weight.
Parasites are present within red cells, which is
the basis of the diagnostic test, and there is
increased phagocytic activity of the
macrophages in the spleen. In chronic malaria
infection, the spleen becomes increasingly
fibrotic and brittle, with a thick capsule and
fibrous trabeculae. The parenchyma is gray or
black because of phagocytic cells containing
granular, brown-black, faintly birefringent
hemozoin pigment. In addition, macrophages
with engulfed parasites, red blood cells, and
debris are numerous.
With progression of malaria, the liver becomes
progressively enlarged and pigmented.
Kupffer cells are heavily laden with malarial
pigment, parasites, and cellular debris, while
some pigment is also present in the
parenchymal cells. Pigmented phagocytic cells
may be found dispersed throughout the bone
marrow, lymph nodes, subcutaneous tissues,
and lungs. The kidneys are often enlarged and
congested with a dusting of pigment in the
glomeruli and hemoglobin casts in the tubules.
In malignant cerebral malaria caused by P.
falciparum, brain vessels are plugged with
parasitized red cells ( Fig. 8-50 ). Around the
vessels there are ring hemorrhages that are
probably related to local hypoxia incident to
the vascular stasis and small focal
inflammatory reactions (called malarial or
Dürck granulomas). With more severe
hypoxia, there is degeneration of neurons,
focal ischemic softening, and occasionally
scant inflammatory infiltrates in the meninges.
Nonspecific focal hypoxic lesions in the heart
may be induced by the progressive anemia
and circulatory stasis in chronically infected
people. In some, the myocardium shows focal
interstitial infiltrates. Finally, in the
nonimmune patient, pulmonary edema or
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