The document discusses bacterial infection routes and the immune response to bacteria. It provides details on: 1) Bacteria can enter through the respiratory, gastrointestinal, or genitourinary tracts, or through breaks in skin or mucous membranes. The immune response depends on number and virulence of bacteria. 2) The humoral immune response produces antibodies that remove extracellular bacteria and toxins via phagocytosis, complement activation, and recruitment of immune cells. 3) The cell-mediated response activates NK cells and macrophages against intracellular bacteria via cytokines from CD4+ T cells.

1. Routes of Bacterial InfectionRoutes of Bacterial Infection
• Respiratory tractRespiratory tract
• Gastrointestinal TractGastrointestinal Tract
• Genitourinary tractGenitourinary tract
• Unnatural routes openedUnnatural routes opened
up by breaks in mucousup by breaks in mucous
membranes or skinmembranes or skin
• Different levels of hostDifferent levels of host
defense mechanisms aredefense mechanisms are
enlisted depending on theenlisted depending on the
number of organismsnumber of organisms
entering and theirentering and their
virulence.virulence.

2. Immune Response to BacteriaImmune Response to Bacteria
• Extracellular BacteriaExtracellular Bacteria
– Humoral immune responseHumoral immune response
– Humoral antibodies produced by plasma cellsHumoral antibodies produced by plasma cells
in regional lymph nodes and submucosa ofin regional lymph nodes and submucosa of
respiratory and gastrointestinal tractsrespiratory and gastrointestinal tracts
– The antibodies remove the bacteria andThe antibodies remove the bacteria and
inactivate bacterial toxins to protect the hostinactivate bacterial toxins to protect the host
cell from invading organisms.cell from invading organisms.

3. • Antibody neutralizesAntibody neutralizes
bacterial toxinsbacterial toxins
• Complement activationComplement activation
• Antibody andAntibody and
complement split productcomplement split product
C3b bind to bacteria,C3b bind to bacteria,
serving as opsonins toserving as opsonins to
increase phagocytosis.increase phagocytosis.
• C3a and C5a induce localC3a and C5a induce local
mast cell degranulationmast cell degranulation
• Other complement splitOther complement split
products are chemotacticproducts are chemotactic
for neutrophils andfor neutrophils and
macrophages.macrophages.

4. Immune Response to BacteriaImmune Response to Bacteria
• Intracellular BacteriaIntracellular Bacteria
– Cell-mediated immune response (Delayed-Cell-mediated immune response (Delayed-
type hypersensitivity)type hypersensitivity)
– Activate Natural Killer (NK) cells provide earlyActivate Natural Killer (NK) cells provide early
defense against bacteria.defense against bacteria.

5. • In delayed typeIn delayed type
hypersensitivity,hypersensitivity,
cytokines secreted bycytokines secreted by
CD4+ T cells, such asCD4+ T cells, such as
IFN gamma, activateIFN gamma, activate
macrophages to killmacrophages to kill
ingested pathogensingested pathogens
more effectively.more effectively.

6. Bacterial Evasion of Host DefenseBacterial Evasion of Host Defense
MechanismMechanism
• Four Steps in Bacterial InfectionFour Steps in Bacterial Infection
– Attachment to host cellsAttachment to host cells
– ProliferationProliferation
– Invasion of host tissueInvasion of host tissue
– Toxin-induced damage to host cellToxin-induced damage to host cell
Many bacteria have developed ways toMany bacteria have developed ways to
overcome some of these host defenseovercome some of these host defense
mechanismsmechanisms

8. Contribution of the ImmuneContribution of the Immune
Response to BacterialResponse to Bacterial
PathogenesisPathogenesis
• Disease can also be caused by theDisease can also be caused by the
immune response to the pathogen.immune response to the pathogen.
• Pathogen-stimulated overproduction ofPathogen-stimulated overproduction of
cytokines can lead to symptoms ofcytokines can lead to symptoms of
bacterial septic shock, food poisoning, andbacterial septic shock, food poisoning, and
toxic shock syndrome.toxic shock syndrome.

9. Contribution of the ImmuneContribution of the Immune
Response to BacterialResponse to Bacterial
PathogenesisPathogenesis
• Bacteria that can survive intracellularly withinBacteria that can survive intracellularly within
infected cells can result in chronic antigenicinfected cells can result in chronic antigenic
activation of CD4+ T-cells, leading to tissueactivation of CD4+ T-cells, leading to tissue
destruction by a cell-mediated response withdestruction by a cell-mediated response with
characteristics of a delayed type hypersensitivitycharacteristics of a delayed type hypersensitivity
reactionreaction
• Cytokines secreted by CD4+ cells canCytokines secreted by CD4+ cells can
accumulate, leading to the formation ofaccumulate, leading to the formation of
granulomas. The concentrations of lysosomalgranulomas. The concentrations of lysosomal
enzymes in the granulomas can cause tissueenzymes in the granulomas can cause tissue
necrosis.necrosis.

10. Diphtheria (Diphtheria (CorynebacteriumCorynebacterium
diphtheriaediphtheriae))
• Gram positive, rod-likeGram positive, rod-like
organismorganism
• Bacterial disease caused by aBacterial disease caused by a
secreted exotoxin.secreted exotoxin.
• Spread via airborne respiratorySpread via airborne respiratory
dropletsdroplets
• Exotoxin destroys underlyingExotoxin destroys underlying
tissue, forming a tough, fibroustissue, forming a tough, fibrous
membrane compose of fibrin,membrane compose of fibrin,
white blood cells and deadwhite blood cells and dead
respiratory cellsrespiratory cells
• Also responsible for systemicAlso responsible for systemic
manifestations.manifestations.

11. Symptoms of DiphtheriaSymptoms of Diphtheria
• Damage to different organsDamage to different organs
such as the heart, liver,such as the heart, liver,
kidneys and nervous system.kidneys and nervous system.
• Choking layer of bacteria andChoking layer of bacteria and
dead cells in the respiratorydead cells in the respiratory
system, accompanied by ansystem, accompanied by an
unworldly stenchunworldly stench
• Difficulty swallowing andDifficulty swallowing and
breathingbreathing
• Pus and blood dischargePus and blood discharge
through nostrils following deaththrough nostrils following death
from asphyxiationfrom asphyxiation

12. More info on diphtheria……More info on diphtheria……
• The exotoxin is encoded by the tox gene carried byThe exotoxin is encoded by the tox gene carried by
phage B (beta)phage B (beta)
• Some strains can exist in the state of lysogeny.Some strains can exist in the state of lysogeny.
• Exotoxin has two disulfide linked chains, a binding chainExotoxin has two disulfide linked chains, a binding chain
and a toxin chain. The binding chain interacts withand a toxin chain. The binding chain interacts with
ganglioside receptors on susceptible cells, facilitatingganglioside receptors on susceptible cells, facilitating
internalization of the exotoxin.internalization of the exotoxin.
• Inhibitory effect of toxin chain on protein synthesis leadsInhibitory effect of toxin chain on protein synthesis leads
to toxicity.to toxicity.
• Removal of the binding chain prevents exotoxin fromRemoval of the binding chain prevents exotoxin from
entering the cell.entering the cell.

13. How We Treat This Bad Boy….How We Treat This Bad Boy….
• Toxoid prepared by treating diphtheria toxin withToxoid prepared by treating diphtheria toxin with
formaldehyde.formaldehyde.
• Reaction with formaldehyde cross-links the toxin,Reaction with formaldehyde cross-links the toxin,
resulting in loss of toxicity and enhancement in itsresulting in loss of toxicity and enhancement in its
antigenicity.antigenicity.
• Usually administered with tetanus toxoid and inactivatedUsually administered with tetanus toxoid and inactivated
Bordetelal pertussisBordetelal pertussis in a combined vaccine that is givenin a combined vaccine that is given
to children 6-8 weeks of age.to children 6-8 weeks of age.
• Immunization with toxoid induces production ofImmunization with toxoid induces production of
antibodies which bind to the toxin and neutralize itsantibodies which bind to the toxin and neutralize its
activity.activity.

14. The reaction
that results
from the
vaccine

15. Photo Ops of DiphtheriaPhoto Ops of Diphtheria
(Smile!)(Smile!)

16. Tuberculosis (Tuberculosis (MycobacteriumMycobacterium
tuberculosistuberculosis))
• Bacilli shaped organismBacilli shaped organism
• Pulmonary infection by inhalation ofPulmonary infection by inhalation of
small droplets of respiratory secretionssmall droplets of respiratory secretions
containing a few bacillicontaining a few bacilli
• Inhaled bacilli are ingested by alveolarInhaled bacilli are ingested by alveolar
macrophages and multiplymacrophages and multiply
intracellulary by inhibiting formation ofintracellulary by inhibiting formation of
phagolysomes.phagolysomes.
• Macrophages lyse and large numbersMacrophages lyse and large numbers
of bacilli are released.of bacilli are released.
• Cell mediated response by CD4+ TCell mediated response by CD4+ T
cells may be responsible for much ofcells may be responsible for much of
the tissue damage of the disease.the tissue damage of the disease.
• Most common infection of tuberculosisMost common infection of tuberculosis
is pulmonary tuberculosis.is pulmonary tuberculosis.

17. Symptoms of TuberculosisSymptoms of Tuberculosis
• Symptoms of TB depend on whereSymptoms of TB depend on where
in the body the TB bacteria arein the body the TB bacteria are
growing. TB bacteria usually growgrowing. TB bacteria usually grow
in the lungs. TB in the lungs mayin the lungs. TB in the lungs may
causecause
– a bad cough that lasts longera bad cough that lasts longer
than 2 weeksthan 2 weeks
– pain in the chestpain in the chest
– coughing up blood or sputumcoughing up blood or sputum
(phlegm from deep inside the(phlegm from deep inside the
lungs)lungs)
• Other symptoms of TB diseaseOther symptoms of TB disease
areare
– weakness or fatigueweakness or fatigue
– weight lossweight loss
– no appetiteno appetite
– chillschills
– feverfever
– sweating at nightsweating at night

18. Immune Response to TuberculosisImmune Response to Tuberculosis
• Cytokines produced by CD4+ T cells activateCytokines produced by CD4+ T cells activate
macrophages, which kill the bacilli or inhibits theirmacrophages, which kill the bacilli or inhibits their
growth.growth.
• High levels of interleukin-2 (IL-2), produced byHigh levels of interleukin-2 (IL-2), produced by
macrophages, stimulates Th 1-mediated responses.macrophages, stimulates Th 1-mediated responses.
• IL-2 may also contribute to resistance by inducingIL-2 may also contribute to resistance by inducing
production of chemokines that attract macrophages toproduction of chemokines that attract macrophages to
the site of infection.the site of infection.
• CD4+ T cell mediated response mounted by thoseCD4+ T cell mediated response mounted by those
exposed toexposed to M. tuberculosisM. tuberculosis controls the infection andcontrols the infection and
protects against later infection.protects against later infection.

19. Treatment and VaccinesTreatment and Vaccines
• Tuberculosis is treated withTuberculosis is treated with
several drugs includingseveral drugs including
isoniazid, rifampin,isoniazid, rifampin,
streptomycin, pyrazinamide,streptomycin, pyrazinamide,
and ethambutol.and ethambutol.
• Drug therapy must continue forDrug therapy must continue for
at least 9 months to get rid ofat least 9 months to get rid of
the bacteria since thethe bacteria since the
intracellular growth of M.intracellular growth of M.
tuberculosis makes it difficulttuberculosis makes it difficult
for the drugs to reach thefor the drugs to reach the
bacilli.bacilli.
• Vaccine : attenuated strain ofVaccine : attenuated strain of
M. bovis called BCG (BacillusM. bovis called BCG (Bacillus
Calmette-Guerin) MostCalmette-Guerin) Most
effective againsteffective against
extrapulmonary tuberculosis.extrapulmonary tuberculosis.
Not used in the U.S. though.Not used in the U.S. though.
Sorry!Sorry!

20. Tuberculosis Links! Yay!Tuberculosis Links! Yay!
• http://www.phppo.cdc.gov/PHTN/tbmodules/mhttp://www.phppo.cdc.gov/PHTN/tbmodules/m
• http://www.phppo.cdc.gov/PHTN/tbmodules/mhttp://www.phppo.cdc.gov/PHTN/tbmodules/m
• http://www.phppo.cdc.gov/PHTN/tbmodules/mhttp://www.phppo.cdc.gov/PHTN/tbmodules/m
• http://www.cdc.gov/ncidod/diseases/submenuhttp://www.cdc.gov/ncidod/diseases/submenus

21. Lyme Disease (Lyme Disease (Borrelia burgdoferiBorrelia burgdoferi))
• Helical shaped bacteriaHelical shaped bacteria
• Disease spread by biteDisease spread by bite
from an infected deer tickfrom an infected deer tick
• Enters the bloodstreamEnters the bloodstream
and spreads to differentand spreads to different
organs in the bodyorgans in the body
• Arthritic symptoms andArthritic symptoms and
neurologic symptoms canneurologic symptoms can
develop. Most peopledevelop. Most people
complain of headachescomplain of headaches
and some people developand some people develop
meningitis or encephalitis.meningitis or encephalitis.

22. Immune ResponseImmune Response
• Antibodies to a protein associatedAntibodies to a protein associated
with the flagella ofwith the flagella of B. burgdorferiB. burgdorferi isis
usually detected after infection andusually detected after infection and
may contribute to pathogenesis.may contribute to pathogenesis.
• Antigen-antibody complexes canAntigen-antibody complexes can
activate complement system,activate complement system,
resulting in direct lytic damage toresulting in direct lytic damage to
the joints or vasculature.the joints or vasculature.
• Interleukin 1 (IL-1) said to beInterleukin 1 (IL-1) said to be
involved in pathogenesis of Lymeinvolved in pathogenesis of Lyme
disease, sincedisease, since BorreliaBorrelia has a cellhas a cell
wall containing lipopolysaccharidewall containing lipopolysaccharide
(LPS) and LPS is a well known(LPS) and LPS is a well known
inducer of IL-1inducer of IL-1
• Most humans develop antibodies toMost humans develop antibodies to
a flagellar antigen, while micea flagellar antigen, while mice
develop antibodies to two proteinsdevelop antibodies to two proteins
on the outer surface of the bacterialon the outer surface of the bacterial
envelope.envelope.

23. How do we treat it?How do we treat it?
• Lyme disease can beLyme disease can be
successfully treated withsuccessfully treated with
broad-spectrumbroad-spectrum
antibiotics such asantibiotics such as
penicillin and tetracycline.penicillin and tetracycline.
• A vaccine based onA vaccine based on
outer-surface protein Aouter-surface protein A
suggests that it offerssuggests that it offers
significant protection.significant protection.
The vaccine wasThe vaccine was
approved for use inapproved for use in
January 1999.January 1999.

24. Online Information on LymeOnline Information on Lyme
DiseaseDisease
• http://www.cdc.gov/ncidod/dvbid/lyme/index.hthttp://www.cdc.gov/ncidod/dvbid/lyme/index.ht
– This is just some general info on LymeThis is just some general info on Lyme
DiseaseDisease
• http://phil.cdc.gov/Phil/detail.asp?id=2417http://phil.cdc.gov/Phil/detail.asp?id=2417
– This is a up close and personal picture ofThis is a up close and personal picture of
Borrelia burgdorferiBorrelia burgdorferi