Infectious disease of pathology

Infectious Disease of Pathology

1. INFECTIOUS DISEASE OF
PATHOLOGY
(Part-1)
Dr.Naila Awal
(Postgraduate student)

2. Categories of infectious agents
•Prion
•Viruses
•Bacteria
•Fungi
•Protozoa
•Helminths
•Ectoparasites

3. PRION
•DefinitionDefinition- Infectious particle composed of protein
(prp)
•Diseases-Diseases-
Human
1) kuru
2)Creutzfeldt- Jackob Disease (CJD)
3)Variant CJD
Animal-
Bovine spongiform encephalopathy
Transmission-Transmission-
Iartogenically Organ transplantation
Surgery Blood transfusion

4. PathogenesisPathogenesis-- Prp normally found in neuron. Disease
occur when prp conformational change protease
resistant prp
I
Normal Protease I Abnormal
Sensitive prp ------ prp ---Neuronal damage
Inactivation-Inactivation- By protein and lipid disrupting agent such
as -
Phenol NaOH
Ether Hypochlorite

5. New and Emerging infectious
diseases
•Definition-Definition-
Newly identified & previously unknown
agent that appeared in human population
& causes public health problem is known
as emerging infectious disease.

6. These includes-
1) Disease caused by newly developed strains/
microorganism-
Ex- MDR-TB MRSA
XDR-TB Chloroquine resistant malaria
2) Disease caused by pathogens, endemic in other
species (birds) that recently entered into human population-
Ex-HIV, SARS
3) Disease caused by pathogens that have been present in
human population but show recent incidence
Ex-Dengue fever

7. Factors contributing to emergence—
1)Enviornment–
Climate & changing ecosystem
Urbanization & deforestation
2)International travel
3)Breakdown of public health measures
(war, overcrowding)

8. Bioterrorism
•Definition- Intentional release of viable
bacteria, virus & toxin in order to harm
people, animal/plant.

9. •Category A
-->Highest risk
-->Easily disseminated/
transmitted from person
to person
-->High mortality
•Anthrax- Bacillus
anthracis
•Botulism- Clostridium
botulinum
•Plague- Yersinia pestis
•Small pox- Variola
major virus
•Viral hemorrhagic
fever- Filovirus

10. •Category B
Moderately easy to
disseminated
Moderate morbidity but low
mortality
•Brucellosis- Brucella
•Melioidosis- Burkholderia
pseudomallei
•Glanders- Mallei
•Staphylococcal
enterotoxin B
•Epsilon toxin of Clost.
perfringes
•Food safety threats
Salmonella, Shigella, E.coli
•Water safety threats-
V.cholerae, Cryptosporidium
pavum

11. •Category C •Emerging pathogens-
Nipah virus
Hanta virus

12. Transmission & dissemination of
microbes
•ROUTE OF ENTRYROUTE OF ENTRY
•SKIN-
Natural barrier-
1)Dense keratinized layer of skin
2)Low pH
3)Fatty acid- the growth of micro organism

13. •Unbroken skin-
•Penetrate through broken
skin
•I/V catheter
•Schistosoma larva
Release collagenase, elastase
dissolve ECM penetrate
swimmers skin
•Superficial prick-Fungus
•Wound-Staph
•Burn-Pseudomonas
•Bacteremia

14. •Needle stick
•Insect bite
•Animal bite
•HBV,HCV,HIV
•Tick transmit-
Rickettsiae-RMSF
Brucella-Lyme disease
•Flea--Y.pestis- plague
•Mosquito-Malaria, Filaria
•Sand fly- L.donavani-
leishmaniasis
•Dog-Rabies

15. •GIT
•Natural defense-
1)Mucosal covering of intestinal epithelium
2) Mucosal antimicrobial agent-defensin
3)Lytic pancreatic enzyme & bile detergent
4)Normal flora
5)Secretory IgA

16. 1)Enteropathogenic bacteria-1)Enteropathogenic bacteria-
1)Staphgrow in contaminated food release
enterotoxin food poisoning without multiplication in the
gut.
2)V. cholerae, ETEC multiply inside the mucus layer
covering gut epithelium exotoxin release watery
diarrhea.
3)Salmoella,Shigella,Champylobacterinvade &
damage intestinal mucosa & lamina propria ulceration,
inflammation & hemorrhage dysentery.
4)S.typhisystemic infection.

17. •Fungus-Fungus-
Candidal infection- mainly in immunocompromised
person.
•Intestinal protozoa-Intestinal protozoa-
Giardia lamblia
Entamoeba histolytica
Cryptosporidia

18. •Intestinal helminths-Intestinal helminths-
Ascaris lumbricoides gut obstruction/invade &
damage the bile duct
Hookworm IDA
Diphyllobothrium latum vit B12 depletion-
megaloblastic anemia
T.Solium larva- encyst in muscle
E. Granulosus larva-encyst in lung, liver

19. •Respiratory tract-
•Natural defense-
1)Mucocilliary apparatus large particles are trapped.
2)Alveolar macrophage & neutrophil particle<5micro
meter alveoli phagocytosed by alveolar macrophage
& neutrophil.

20. Mechanism-
1)Micro organism attached to lower respiratory
tract & laryngeal epithelium
Example-
Influenza virus-has 2 cell surface proteins-
– Hemagglutinin (function at the beginning of the
infection)
-Neuraminidase-(function at the end of the infection.
They degrade the protective layer of mucus in
respiratory tract)

21. Influenza virus
Hemagglutinin Neuraminidase
Bind with epithelial surface receptor 1)Cleave the sialic acid allow
the virus to release from host cell
Host cell engulf the virus 2) the viscosity of mucus
facilitate viral transit within
respiratory tract
Replicate within the cell

22. 2) Impaired ciliary activity-
Example-
•H. Influenzae & B. pertussis- release toxin ciliary
paralysis.
•Mycoplasma pneumoniae- produce ciliostatic
substances
•Smoker/people with cystic fibrosis-chronic
damage to mucociliary apparatus

23. 3)Some respiratory pathogen avoid
phagocytosis/destruction after phagocytosis
Example-
•M tuberculosis- escape killing within phagolysosome
of macrophage
4)Opportunistic fungus- infect when CMI /when
leukocyte are in number.
Example-
Pneumocystis jirovechi in AIDS
Aspergillus followed by chemotherapy.

24. •Urinary tract
•Natural defense
Regular flushing of urinary tract by urine

25. Spread & dissemination of
microbes
Some micro-organism proliferate locally at the site
of infection & others spread to distant site via-
lymphatic's, blood & nerve.
•Local-
a)Confined to lumen of hollow viscera-
V. cholerae.
b) Adhere /proliferate in/on epithelial cell-
HPV/dermatophytes.

26. Invasive-
•Lymphatics-
Ex- Staphylococcus-localized abscess/furuncle through
lymphatic  drain into regional lymph node
sometimes bacteremia & colonize to distant organ.
•Blood-Most of bacteria & fungus,
Virus- HBV, Polio
Protozoa- African trypanosoma
All helminths.
WBC- MTB,LD, Toxoplasma, HIV, Herpes
RBC- Plasmodium, Babesia
•Nerve- Polio virus

27. Placental-fetal route-
•Bacteria-
Mycoplasma placentitis premature delivery/still birth.
T.Pallidum2
nd
trimester osteochondritis, periostitis
leads to multiple bony lesion.
•Virus-
Rubella1
st
trimester-Congenital heart disease,
Cataract,
Deafness.
3
rd
trimester-Little damage

28. •Infection during passage of birth canal-
Rickettsia/Chlamydia-Conjuctivitis
•Milk-- CMV,HBV,HTLV-1

29. Release of microbes from the
body
It depends on the location of infection.
Transmission from person-person-
•Respiratory route- Virus & bacteria.
•Saliva- EBV, CMV, Mumps
•Feco-oral route- HAV, HEV , Rota virus,
Hookworm, Schistosomes
•Blood & blood product- HBV, HCV,HIV
•Sexual transmission

30. •Transmission from animal-human-
1)Direct contact / Consumption of animal
fat
Ex- Bacillus anthracis.
2) Indirectly via invertebrate host.
Ex- Malaria – by mosquito.

31. Sexually Transmitted Infection
•Definition- Infection that are transmitted
through sexual route.
•High risk group-
1)Adolescent
2)Homosexual men
3)Illegal drug abuser
•Site- Initial site-
Vagina Urethra
Rectum Oropharynx

32. General features-
Infection with 1 STI associate organism the risk
for additional STI
Ex-
N. Gonorrhea/ Chlamydia trachomatis epithelial
injury local tissue damage chance of co-infection
with the other & also the risk of HIV infection. .
STI can spread by vertical transmission & causes
severe damage to fetus/ child
Ex- Chlamydia trachomatis Conjunctivitis
Syphilis Miscarriage

33. Examples of STI
•Bacteria
•Neisseria gonorrhoeae
•Treponema pallidum
•Haemophilus ducreyi
•Klebsiella granulomatis
•Chlamydia trachomatis
•Ureaplasma urealyticum
•Gonorrhea
•Syphilis
•Chancroid
•Granuloma inguinale
•Lymphogranuloma
venereum
•Urethritis

34. •Virus
•HSV
•HBV
•HPV
•HIV
•Protozoa
•Trichomonas vaginalis
•Herpes
•Hepatitis
•Condyloma acuminatum
•AIDS
•Urethritis
•Vaginitis

35. Nosocomial Infection
•Definition
These are hospital acquired infection which
develops 48hrs after hospitalization /within 48
hrs after release from hospital.
Source
1)Hands of health worker 4)Blood transfusion
2)Contaminated surface 5)Organ transplantation
3)Used equipment & instrument

36. Organism causing Nosocomial Infection
•Bacteria-
•Gram positive
•Gram negative
•Staph aureus
•MRSA,VRSA
•Staph epidermidis
•Strep pneumoniae
•Clostridium tetani
•E. coli
•Pseudomonas
•Proteus

37. •Virus
•Fungi
•Parasite
•HBV,HCV,HDV
•HIV, HSV,CMV
•Candida
•Pneumocystis jiroveci
•Toxoplasma

38. Risk factor-
•Long time hospital stay
•Mechanical ventilation
•I/V catheter
•Use of indwelling catheter
•Overdose of antibiotic
•Failure of health care worker to wash hand.

39. •Prevention
1) Frequent hand washing can transmission of MRSA &
VRE.
2) Proper sterilization & disinfection of inanimate object of
the hospital.
3) Proper disposal of hospital waste.
4) Rational use of antibiotics.
5)Personal hygiene of patient, attendants, doctor & medical
stuff.
6) Detection of proper carrier & proper diagnosis.

40. Host defense against infection
•1) Innate immunity-
a) Intact skin-Intact skin-
Sebaceous gland--> contain fatty acid antibacterial
& antifungal
Low pH- antimicrobial.
b) Mucous membrane-Mucous membrane-
Mucociliary apparatus- prevent the entry of microbes
through URT
Lysozyme in tear & mucus- degrade peptidoglycan
layer of bacterial cell wall protect from infection.

41. c) Cellular component-Cellular component-
Macrophage, neutrophil phagocytose the microbes.
N-K cellproduce toxic substances perforin destroy
microbes.
d) d) Soluble component-Soluble component-
Complement-formation of MAC destroy cellular
Ag.
IFNa, IFNb –released by virus infected cell this
IFN replication of viruses. (that’s why viral infection are
self limiting)

42. •2) Acquired immunity- are stimulated by
exposure to microbes.
They are B & T lymphocyte.

43. How micro-organism causes
diseaes
•By 3 mechanisms-
1)They can directly enter into host cell causes cell
death.
2)They may-release toxins kill the cell
3)They may-release enzymes degrade tissue
components/damage blood vessel ischemic necrosis.
4)They induce host cell responses causes
additional damage.

44. Mechanism of viral injury
Virus can directly damage the host cell by entering
& replicating within it.
•Virus has a affinity for specific body tissue which is
determined by –
1)Presence of receptor on host cell-1)Presence of receptor on host cell-
Ex-
gp120 of HIV binds with CD4 on Tcell
CXC R4(T cell)
CCR5(macrophage)
gp350 of EBV binds with CR2/CD21 on B cell

45. 2) Cellular transcription factor that recognize Cellular transcription factor that recognize
viral enhancer & promoter sequenceviral enhancer & promoter sequence
Ex- JC virus causes leuko encephalopathy, replicate
specially in oligodendroglia in CNS. (B/c enhancer &
promoter sequence regulating viral genes are active in
glial cell).
3) Physical barrier-Physical barrier-
Ex- Entero virus replicate in intestine b/c they can resist
inactivation by acid, bile & digestive enzyme.
4)Temparature-)Temparature-
Ex- Rhinovirus infect only within URT b/c they replicate at
lower temperature of URT.

46. Virus can damage the host cell by a number
of mechanism-
•1) Direct cytopathic effect-Direct cytopathic effect- Virus can kill the cell
directly by-
a) Prevent the synthesis of host macromolecules
(DNA,RNA/protein)
Ex-Polio virus- inactivate cap binding protein which is
essential for translation of host cell mRNA.
b) Producing degradative enzyme & toxic proteins
Ex- HSV-Produce protein that synthesis of cellular DNA &
mRNA & other proteins that degrade host DNA.
c) Inducing apoptosis by producing pro-apoptic protein
Ex- HIV vrp protein.

47. 2)Anti viral immune response-
•Viral protein on the surface of host cell may be
recognized by immune system & lymphocyte may
attack the virus infected cell.
Ex- In HBV infection, acute liver failure is caused by cytotoxic T cell
mediated destruction of infected hepatocytes.
3)Transformation of infected cells--> benign/
malignant neoplasm
•Oncogenic virus stimulate cell growth & survival by
following M/A-
Expression of virus encoded oncogene
Anti-apoptic strategies
Insertional mutagenesis

48. Mechanism of bacterial injury
•1) Adherence to the host cell surface-
a) Adhesin - is present in bacterial cell surface. Through
this they bind to host cell/ECM.
Ex- Strep. pyogens adhere to host tissue by protein F &
teichoic acid.
b) Pili -
Ex- E.Coli through P pili bind with gal-gal moiety of
uroepithelium.
c) Glycocalyx -
Ex-Stap. epidermidis/ Strep. viridians bind with heart
valve.

49. •2)Virulence of intracellular bacteria-
•Facultative intracellular bacteria infect
-->Epithelial cell (Shigella, ETEC)
-->Macrophage (MTB,ML)
-->Both (S. typhi)
•Growth of bacteria in cell may allow the bacteria
to escape the immune system /facilitate the
spread.
Ex- MTB macrophage lung to other site.

50. Bacteria have a number of mechanism
to enter into the cell-
a) Bacteria is coated with Ab/ complement 
phagocytosed by macrophage.
•Ex-MTB activate alternative pathway of complement
opsonization with C3b C3b coated MTB bind with CR3
on macrophage endocytosis into macrophage.
b) Gm- bacteria use complex secretion system to
enter into epithelial cell.
•This system consists of needle like structure form pore
inside host cell membrane inject protein
rearrangement of cell cytoskeleton bacteria entry.
•Ex- L. monocytogenes.

51. c) Effect of bacteria inside the host cell-c) Effect of bacteria inside the host cell-
a)Shigella, E. coli- host protein synthesis within 6
hours host cell lysis.
b)Within macrophage most bacteria killed when
phagosome fuse with lysosome & form
phagolysosome. But certain bacteria evade this
defense.
Ex- MTBMTB- block the fusion of phagosome with lysosome unchecked
proliferation within macrophage.
L. Monocytogenes-L. Monocytogenes- produce pore forming protein-listeriolysin O & 2
phospholipase degrade phagosome membrane bacteria
escape into cytoplasm.

52. 3) Toxin production-
•A) Endotoxin- is a LPS, component of Gm- bacterial cell wall.
It is both beneficial & harmful.
Beneficial-
Activate protective immunity.
 Induction of cytokine & chemokine
expression of co-stimulatory molecules enhance T cell
activation.
Harmful-
High level of LPS induction of excessive level of
cytokines TNF, IL-1,IL-12Septic shock, DIC, ARDS.

53. •B) Exotoxin- secreted from bacteria & causes celluar
injury.
1)Enzymes- bacteria secret protease, coagulase,
hyaluronidase, fibrinolysin
Ex-
•Stap. aureus produce protease degrade protein that
hold keratin together detachment of epidermis from
deeper skin.

54. 2)Toxin that alter intercellular signaling &
regulating pathway—
•Most of the toxins have
A sub unit- enzymatic activity
B sub unit- binds with the receptor on cell surface &
delivers the A subunit into cell cytoplasm.
Ex- Bacillus anthracis, V. cholerae.

55. 3) Neurotoxin-
•Clostridium botulinum, Clostridium tetani
• release of neurotransmitters paralysis respiratory
failure death.
•4) Super Ag-
•Stimulate T lymphocyte massive Tcell proliferation &
release of cytokines high level of cytokines Capillary
leakage & shock.

56. Injurious effects of host
immunity
1) Immune response to microbes
sometimes causes tissue injury.
•a) MTB- causes granulomatous inflammation--delayed
hypersensitivity prevents the spread of bacilli but also
causes tissue damage & fibrosis.
•b) HBV,HCV- causes liver damage due to immune
response to infected hepatocyte, not to cytopathic effect.

57. .
2)Humoral immune response to microbes has
also pathological consequence
•S. pyogenes- Ab produce against streptococcal M
protein cross react with cardiac protein damage
heart valve RHD.
•S. pyogenes- anti streptococcal Ab cross react with
glomerular basement membrane  form Ag-Ab
complexes deposit in renal glomeruli Post
streptococcal GN.

58. •3)Infection may be associated with chronic
inflammatory disorder as well as cancer.
Ex-
•HBV/HCV Hepatitis HCC
•H.Pylori Gastritis gastric adenocarcinoma
•Schistosomia Chronic cystitis bladder carcinoma.

59. Immune evasion by microbes
Micro organism develops many M/A to evade host immune
system.
1)Growth in niches that are inaccessible to host
immune response
a)Microbes are multiply in the lumen of the intestine (C.
difficili) / gall bladder (S. typhi)
b) Some organism are rapidly invade host cell before
humoral immune response become effective.
Ex-
•Malarial parasite--sporozoite enters into hepatocyte.
•Trichinella/T. cruzei-enters into skeletal/cardiac muscle.

60. c) Some Parasite form cyst in host cell.
Ex- Tapeworm
d) During viral latency, viral genes are not expressed.
Ex- Herpes virus

61. 2)Antigenic variation-
Virus can escape immune attack by changing their Ag.
Mechanism
•High mutation rate
•Genetic ressortment
•Genetic rearrangement
•HIV
•Influenza virus
•Influenza virus
•Rota virus
•N. gonorrhoeae
•Borrelia
•Trypanosoma
•Plasmodium

62. 3) Resistance to innate immune response
•Resistance to antimicrobial peptide
(defensin, cathelicidins& thrombocidin)-
prevents killing of microbes by neutrophil
& macrophage.
•Carbohydrate capsule -present on the
surface of the micro organism prevent
phagocytosis by neutrophil.
•Ex- Pneumococci, meningococci, H.influenza

63. •Bacteria by covering with host protein -evade
immune defense.
Ex- Staphylococcus aureus covered by protein A that bind
with Fc portion of Ab phagocytosis.
•Some bacteria secret protease degrade Ab.
Ex- Niesseria, Haemophilus, Streptococcus
•Some organisms replicate within phagocytic cell.
Ex- MTB, Liesteria, Leishmania, Trypanosoma,
Toxoplasma, Cryptococcus neoformans.

64. •Virus can produce molecules that innate
immunity.
Ex- Herpes virus, Pox virus produce protein block
complement activation.
•Some virus produce homologous of
IFNa IFNb /IFN R which the action of IFN.
4) Recognition of infected cell by CD4 TH cell/
CD8 cytotoxic T cell.
Ex- HSV,CMV,EBV bind/ alter the localization of MHC-1
impair the peptide presentation to CD8 T cell.

65. Infection in immunosuppressed
hosts
•Inherited-Inherited-
•1)Patient with Ab deficiency-
Ex- X-linked agglobulinaemia-
•Severe bacterial infection-
•Strep . pneumoniae
•Haemophilus influenzae
•Stap. Aureus
•2)T cell defect- susceptible to infection with
intracellular pathogens, virus, some parasite.

66. •3) Complement deficiency-
•Strep . pneumoniae
•Haemophilus influenzae
•Neisseria menigitidis
•4) Defect in neutrophilic function-
•Stap. Aureus
•Gm- bacteria
•Fungi

67. Acquired-
•1) AIDS
•2) Impaired production of leukocyte leukemia fills the bone
marrow with cancerous cell & vulnerable to infection.
•3)Iartogenic cause of immunosuppression-
•Ex-Immunosuppressive drug.
•Disease of organ systems other than immune
system-
•Cystic fibrosis---- RTI with P. aeruginosa
• S. aureus
•Sickle cell disease----Strep. pneumoniae
•Burn---- P. aeruginosa.

68. Spectum of inflammatory responses
to infection
•5 major histological patterns of tissue
reaction in infections are-
1) Suppurative inflammation-
2)Mononuclear & granulomatous
inflammation
3)Cytopathic- cytoproliferative reaction-
4)Tissue necrosis-
5) Chronic inflammation & scarring-

69. 1) Suppurative inflammation-
Characterized by production of large amount
pus/purulent exudates consisting of neutrophil,
liquefactive necrosis & edema fluid.
•Sometimes the lesion are destructive.
Ex- Pneumococci spare alveolar wall lobar
pneumonia.
Staphylococci & Klebsiella destroy alveolar wall
form abscess fibrosis.

70. Suppurative inflammation

71. 2)Mononuclear & granulomatous inflammation
Granulomatous inflammation- is a distinctive
pattern of chronic inflammation characterized by
accumulation of activated macrophages-
epithelioid cells which may fuse to form giant
cells. In some cases there is a central area of
caseous necrosis.
•Ex- TB

72. Mononuclear cell predominate-Mononuclear cell predominate-
•Plasma cell abundant Primary & secondary
syphilis.
•Lymphocyte predominate HBV infection/viral
infection of brain.

74. 3) Cytopathic- cytoproliferative reaction-
It is characterized by cell necrosis/cellular
proliferation, usually with scattered
inflammatory cell.
a) Some virus replicate within cytoplasm/nucleus
& visible as inclusion body.
•Ex-Herpes virus, Adeno virus.

75. b) Some virus induce cell to fuse & form
multinucleated giant cell.
•Ex- Warthin- Finkeldy cells in measles.
Herpes virus.
c) Some virus causes epithelial cell to detach &
form blister
•Ex- Herpes virus.
d) Some virus causes epithelial cell to proliferate &
form wart.
•Ex- HPV, Pox virus.
e) Finally they contribute to develop malignant
neoplasm.

76. 4)Tissue necrosis-
Ex-
•Clostridium perfringes- secret toxin gangrenous
necrosis.
•E. histolytica- liquefactive necrosis.
•Herpes virus (brain)/ HBV (Temporal lobe)-severe
necrosis.
•5) Chronic inflammation & scarring-
Ex-
•Chronic HBV cirrhosis
•Schistosoma egg Pipe-stem fibrosis of liver
•TB Constrictive fibrous pericarditis.