3. PRION
• Definition- Infectious particle composed of protein
Definition
(prp)
• DiseasesHuman
1) kuru
2)Creutzfeldt- Jackob Disease (CJD)
3)Variant CJD
AnimalBovine spongiform encephalopathy
TransmissionIartogenically
Surgery
Organ transplantation
Blood transfusion
4. Pathogenesis- 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- By protein and lipid disrupting agent such
as Phenol
Ether
NaOH
Hypochlorite
5. New and Emerging infectious
diseases
• DefinitionNewly identified & previously unknown
agent that appeared in human population
& causes public health problem is known
as emerging infectious disease.
6. These includes1) Disease caused by newly developed strains/
microorganismEx- MDR-TB
XDR-TB
MRSA
Chloroquine resistant malaria
2) Disease caused by pathogens, endemic in other
species (birds) that recently entered into human populationEx-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)
18. • Intestinal helminthsAscaris lumbricoides gut obstruction/invade &
damage the bile duct
Hookworm IDA
Diphyllobothrium latum vit B12 depletionmegaloblastic anemia
T.Solium larva- encyst in muscle
E. Granulosus larva-encyst in lung, liver
19. • Respiratory tract• Natural defense1)Mucocilliary apparatus large particles are trapped.
2)Alveolar macrophage & neutrophil particle<5micro
meter alveoli phagocytosed by alveolar macrophage
& neutrophil.
20. Mechanism1)Micro organism attached to lower respiratory
tract & laryngeal epithelium
ExampleInfluenza 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
Replicate within the cell
2) the viscosity of mucus
facilitate viral transit within
respiratory tract
22. 2) Impaired ciliary activityExample• 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.
ExamplePneumocystis 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 vialymphatic's, blood & nerve.
•
Local-
a) Confined to lumen of hollow visceraV. cholerae.
b) Adhere /proliferate in/on epithelial cell-
HPV/dermatophytes.
26. Invasive• LymphaticsEx- 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
28. • Infection during passage of birth canalRickettsia/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-human1) 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 group1)Adolescent
2)Homosexual men
3)Illegal drug abuser
• Site- Initial siteVagina
Rectum
Urethra
Oropharynx
32. General featuresInfection 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
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
2)Contaminated surface
3)Used equipment & instrument
4)Blood transfusion
5)Organ transplantation
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 immunitya) Intact skinSebaceous gland--> contain fatty acid antibacterial
& antifungal
Low pH- antimicrobial.
b) Mucous membraneMucociliary 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 componentMacrophage, neutrophil phagocytose the microbes.
N-K cellproduce toxic substances perforin destroy
microbes.
d) Soluble componentComplement activation-->formation of MAC
destroy cellular Ag.
IFNα, IFNβ –released by virus infected cell this
IFN replication of viruses. (that’s why viral infection are
self limiting)
42. • 2) Acquired immunity- develops after exposure to
microbes.
They are B & T lymphocyte.
Ex- Measles virus enters into the body
Ab production
Ab binds with measles virus
Virus eliminated
Provides specific immunity
43. How micro-organism causes
diseaes
• By 3 mechanisms1)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 cellExgp120 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
viral 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 barrierEx- Entero virus replicate in intestine b/c they can resist
inactivation by acid, bile & digestive enzyme.
4)TemparatureEx- 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- Virus can kill the cell
directly bya) 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/AExpression of virus encoded oncogene
Anti-apoptic strategies
Insertional mutagenesis
48. Mechanism of bacterial injury
• 1) Adherence to the host cell surfacea) 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 cella) 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 cella)
b)
Shigella, E. coli- host protein synthesis within 6
hours host cell lysis.
Within macrophage most bacteria killed when
phagosome fuse with lysosome & form
phagolysosome. But certain bacteria evade this
defense.
Ex- MTB- block the fusion of phagosome with lysosome unchecked
MTB
proliferation within macrophage.
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.
BeneficialActivate 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-12Septic 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 variationVirus 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
IFNα ΙFΝβ /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• 1)Patient with Ab deficiencyEx- X-linked aγglobulinaemia•
•
•
•
Severe bacterial infectionStrep . pneumoniae
Haemophilus influenzae
Stap. Aureus
• 2)T cell defect- susceptible to infection with
intracellular pathogens, virus, some parasite.
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 are1) Suppurative inflammation2)Mononuclear & granulomatous
inflammation
3)Cytopathic- cytoproliferative reaction4)Tissue necrosis5) Chronic inflammation & scarring-
69. 1) Suppurative inflammationCharacterized 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.
71. 2)Mononuclear & granulomatous inflammation
Granulomatous inflammation- is a distinctive
pattern of chronic inflammation characterized by
accumulation of activated macrophagesepithelioid cells which may fuse to form giant
cells. In some cases there is a central area of
caseous necrosis.
• Ex- TB
74. 3) Cytopathic- cytoproliferative reactionIt 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.