• Definition- Infectious particle composed of protein
2)Creutzfeldt- Jackob Disease (CJD)
AnimalBovine spongiform encephalopathy
Pathogenesis- Prp normally found in neuron. Disease
occur when prp conformational change protease
Normal Protease I Abnormal
Sensitive prp ------ prp
Inactivation- By protein and lipid disrupting agent such
New and Emerging infectious
• DefinitionNewly identified & previously unknown
agent that appeared in human population
& causes public health problem is known
as emerging infectious disease.
These includes1) Disease caused by newly developed strains/
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
Factors contributing to emergence—
Climate & changing ecosystem
Urbanization & deforestation
3)Breakdown of public health measures
• Definition- Intentional release of viable
bacteria, virus & toxin in order to harm
• Category A
transmitted from person
• Anthrax- Bacillus
• Botulism- Clostridium
• Plague- Yersinia pestis
• Small pox- Variola
• Viral hemorrhagic
• Category B
Moderately easy to
Moderate morbidity but low
• Brucellosis- Brucella
• Melioidosis- Burkholderia
• Glanders- Mallei
• Epsilon toxin of Clost.
• Food safety threats
Salmonella, Shigella, E.coli
• Water safety threatsV.cholerae, Cryptosporidium
• Category C
• Emerging pathogensNipah virus
Transmission & dissemination of
• ROUTE OF ENTRY
• SKINNatural barrier1)Dense keratinized layer of skin
3)Fatty acid- the growth of micro organism
• Intestinal helminthsAscaris lumbricoides gut obstruction/invade &
damage the bile duct
Diphyllobothrium latum vit B12 depletionmegaloblastic anemia
T.Solium larva- encyst in muscle
E. Granulosus larva-encyst in lung, liver
• Respiratory tract• Natural defense1)Mucocilliary apparatus large particles are trapped.
2)Alveolar macrophage & neutrophil particle<5micro
meter alveoli phagocytosed by alveolar macrophage
Mechanism1)Micro organism attached to lower respiratory
tract & laryngeal epithelium
ExampleInfluenza virus-has 2 cell surface proteins-
– Hemagglutinin (function at the beginning of the
-Neuraminidase-(function at the end of the infection.
They degrade the protective layer of mucus in
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
2) Impaired ciliary activityExample• H. Influenzae & B. pertussis- release toxin ciliary
• Mycoplasma pneumoniae- produce ciliostatic
• Smoker/people with cystic fibrosis-chronic
damage to mucociliary apparatus
3)Some respiratory pathogen avoid
phagocytosis/destruction after phagocytosis
Example• M tuberculosis- escape killing within phagolysosome
4)Opportunistic fungus- infect when CMI /when
leukocyte are in number.
ExamplePneumocystis jirovechi in AIDS
Aspergillus followed by chemotherapy.
• Urinary tract
• Natural defense
Regular flushing of urinary tract by urine
Spread & dissemination of
Some micro-organism proliferate locally at the site
of infection & others spread to distant site vialymphatic's, blood & nerve.
a) Confined to lumen of hollow visceraV. cholerae.
b) Adhere /proliferate in/on epithelial cell-
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
WBC- MTB,LD, Toxoplasma, HIV, Herpes
RBC- Plasmodium, Babesia
• Nerve- Polio virus
• Infection during passage of birth canalRickettsia/Chlamydia-Conjuctivitis
• Milk- CMV,HBV,HTLV-1
Release of microbes from the
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,
• Blood & blood product- HBV, HCV,HIV
• Sexual transmission
Transmission from animal-human1) Direct contact / Consumption of animal
Ex- Bacillus anthracis.
2) Indirectly via invertebrate host.
Ex- Malaria – by mosquito.
Sexually Transmitted Infection
• Definition- Infection that are transmitted
through sexual route.
• High risk group1)Adolescent
3)Illegal drug abuser
• Site- Initial siteVagina
General featuresInfection with 1 STI associate organism the risk
for additional STI
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
These are hospital acquired infection which
develops 48hrs after hospitalization /within 48
hrs after release from hospital.
1)Hands of health worker
3)Used equipment & instrument
Long time hospital stay
Use of indwelling catheter
Overdose of antibiotic
Failure of health care worker to wash hand.
1) Frequent hand washing can transmission of MRSA &
2) Proper sterilization & disinfection of inanimate object of
3) Proper disposal of hospital waste.
4) Rational use of antibiotics.
5)Personal hygiene of patient, attendants, doctor & medical
6) Detection of proper carrier & proper diagnosis.
Host defense against infection
• 1) Innate immunitya) Intact skinSebaceous gland--> contain fatty acid antibacterial
Low pH- antimicrobial.
b) Mucous membraneMucociliary apparatus- prevent the entry of microbes
Lysozyme in tear & mucus- degrade peptidoglycan
layer of bacterial cell wall protect from infection.
c) Cellular componentMacrophage, neutrophil phagocytose the microbes.
N-K cellproduce toxic substances perforin destroy
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
• 2) Acquired immunity- develops after exposure to
They are B & T lymphocyte.
Ex- Measles virus enters into the body
Ab binds with measles virus
Provides specific immunity
How micro-organism causes
• By 3 mechanisms1)They can directly enter into host cell causes cell
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
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)
gp350 of EBV binds with CR2/CD21 on B cell
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
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.
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
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.
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/
• Oncogenic virus stimulate cell growth & survival by
following M/AExpression of virus encoded oncogene
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 &
b) Pili Ex- E.Coli through P pili bind with gal-gal moiety of
c) Glycocalyx Ex-Stap. epidermidis/ Strep. viridians bind with heart
• 2)Virulence of intracellular bacteria• Facultative intracellular bacteria infect
-->Epithelial cell (Shigella, ETEC)
-->Both (S. typhi)
• Growth of bacteria in cell may allow the bacteria
to escape the immune system /facilitate the
Ex- MTB macrophage lung to other site.
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.
c) Effect of bacteria inside the host cella)
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
Ex- MTB- block the fusion of phagosome with lysosome unchecked
proliferation within macrophage.
L. Monocytogenes- produce pore forming protein-listeriolysin O & 2
phospholipase degrade phagosome membrane bacteria
escape into cytoplasm.
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
High level of LPS induction of excessive level of
cytokines TNF, IL-1,IL-12Septic shock, DIC, ARDS.
• B) Exotoxin- secreted from bacteria & causes celluar
1)Enzymes- bacteria secret protease, coagulase,
Ex• Stap. aureus produce protease degrade protein that
hold keratin together detachment of epidermis from
2)Toxin that alter intercellular signaling &
• 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.
3) Neurotoxin• Clostridium botulinum, Clostridium tetani
release of neurotransmitters paralysis respiratory
• 4) Super Ag• Stimulate T lymphocyte massive Tcell proliferation &
release of cytokines high level of cytokines Capillary
leakage & shock.
Injurious effects of host
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 .
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
• 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.
Immune evasion by microbes
Micro organism develops many M/A to evade host immune
1) Growth in niches that are inaccessible to host
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.
Malarial parasite--sporozoite enters into hepatocyte.
Trichinella/T. cruzei-enters into skeletal/cardiac muscle.
c) Some Parasite form cyst in host cell.
d) During viral latency, viral genes are not expressed.
Ex- Herpes virus
2)Antigenic variationVirus can escape immune attack by changing their Ag.
• High mutation rate
• Genetic ressortment
• Genetic rearrangement
3) Resistance to innate immune response
• Resistance to antimicrobial peptide
(defensin, cathelicidins& thrombocidin)prevents killing of microbes by neutrophil
• Carbohydrate capsule -present on the
surface of the micro organism prevent
phagocytosis by neutrophil.
• Ex- Pneumococci, meningococci, H.influenza
• Bacteria by covering with host protein -evade
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.
• Virus can produce molecules that innate
Ex- Herpes virus, Pox virus produce protein block
• 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.
Infection in immunosuppressed
• Inherited• 1)Patient with Ab deficiencyEx- X-linked aγglobulinaemia•
Severe bacterial infectionStrep . pneumoniae
• 2)T cell defect- susceptible to infection with
intracellular pathogens, virus, some parasite.
Acquired• 1) AIDS
• 2) Impaired production of leukocyte leukemia fills the bone
marrow with cancerous cell & vulnerable to infection.
• 3)Iartogenic cause of immunosuppression•
• Disease of organ systems other than immune
system• Cystic fibrosis---- RTI with P. aeruginosa
• Sickle cell disease----Strep. pneumoniae
• Burn---- P. aeruginosa.
Spectum of inflammatory responses
• 5 major histological patterns of tissue
reaction in infections are1) Suppurative inflammation2)Mononuclear & granulomatous
3)Cytopathic- cytoproliferative reaction4)Tissue necrosis5) Chronic inflammation & scarring-
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
Staphylococci & Klebsiella destroy alveolar wall
form abscess fibrosis.
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
• Ex- TB
3) Cytopathic- cytoproliferative reactionIt is characterized by cell necrosis/cellular
proliferation, usually with scattered
a) Some virus replicate within cytoplasm/nucleus
& visible as inclusion body.
• Ex-Herpes virus, Adeno virus.
b) Some virus induce cell to fuse & form
multinucleated giant cell.
• Ex- Warthin- Finkeldy cells in measles.
c) Some virus causes epithelial cell to detach &
• Ex- Herpes virus.
d) Some virus causes epithelial cell to proliferate &
• Ex- HPV, Pox virus.
e) Finally they contribute to develop malignant