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SITE OF REPLICATION
EXTRACELLULAR
Interstitial spaces
Blood, lymph
Bronchial,
Gastrointestinal lumen
Viruses
Bacteria
Protozoa
Fungi
Worms
INTRACELLULAR
Epithelial surfaces
Neisseria gonorrhoeae
Worms
Mycoplasma
Streptococcus
pneumoniae
Vibrio cholerae
Escherichia coli
Candida albicans
Helicobacter pylori
Cytoplasmic
Viruses
Chlamydia ssp.
Richettsia ssp.
Listeria monocytogenes
Protozoa
Vesicular
Mycobacteria
Salmonella typhimurium
Seishmania spp.
Listeria ssp.
Trypanosoma spp.
Legionella pneumophila
Cryptococcus neoformans
Histoplasma
Yersinia pestis
PROTECTIVE IMMUNITY
Antibodies
Complement
Phagocytosis
Neutralization
IgA type Antibodies
Anti-microbial peptides
Cytotoxic T cells
NK cells
T cell and NK celldependent
macrophage activation
THE SITE OF PATHOGEN DEGRADATION DETERMINES THE TYPE
OF IMMUNE RESPONSES
PATHOGEN TYPE
PROCESSING
RESPONSE
Extracellular
ANTIBODY PRODUCTION
Acidic vesicles
MHCII
Neutralization
Complement activation
Phagocytosis
MHC II binding
CD4+ T cells
B-se jt
Intravesicular
KILLING BACTERIA OF
PARASITE IN VESICLES
Acidic vesicles
MHCII
MHC II binding
Intracellular killing
CD4+ T cells
Th1
Cytosolic
MHCI
Cytoplasm
MHC I binding
MHC II binding
CD8+ T cells
CD4+ T cells
MHCII
NK
KILLING OF INFECTED CELL
Extracellular killing
ANTIBODY PRODUCTION
THE IMMUNE RESPONSE TO EXTRACELLULAR BACTERIA
Polysaccharide capsule
Exotoxins – secreted by bacteria
- Cytotoxicity of various mechanisms
- Inhibition of various cellular functions
- Induction of cytokines
pathology, septic shock
Endotoxins – released by phagocytic cells
- Cell wall – Gram (-) rods LPS
Gram (+) cocci glycan
EVASION OF THE IMMUNE RESPONSE TO STREPTOCOCCI
B Lymphocyte
Bacterium
12 hrs
6x1010 Bacteria
Toxin
S. pneumoniae in the lung
ESCAPE
High carbohydrate
variability
Competition of
strains
~90 serotypes
Serotype-specific
Ab response
Opsonization
Fibrin mesh in fluid with PMN's at the area
of acute inflammation. It is this fluid
collection that produces the "tumor" or
swelling aspect of acute inflammation.
The vasculitis shown here demonstrates the
destruction that can accompany the acute
inflammatory process and the interplay with the
coagulation mechanism. The arterial wall is
undergoing necrosis, and there is thrombus
formation in the lumen.
Edema with inflammation is not trivial at all: Marked
laryngeal edema such that the airway is narrowed.
This is life-threatening. Thus, fluid collections can be
serious depending upon their location.
A purulent exudate is seen beneath the
meninges in the brain of this patient with acute
meningitis from Streptococcus pneumoniae
infection. The exudate obscures the sulci.
Acute bronchopneumonia of the lung
This tissue gram stain of an acute pneumonia
demonstrates gram positive cocci that have
been eaten by the numerous PMN's exuded
into the alveolar space. Opsonins such as IgG
and C3b facilitate the attachment of PMN's to
offending agents such as bacteria so that the
PMN's can phagocytose them.
Neutrophilic alveolar exudate with PMN
The patient had a "productive" cough because
of large amounts of purulent sputum.
Numerous neutrophils fill the alveoli in this case of
acute bronchopneumonia in a patient with a high
fever. Pseudomonas aeruginosa was cultured from
sputum. Dilated capillaries in the alveolar walls from
vasodilation with the acute inflammatory process.
CONSEQUENCES OF SKIN DAMAGE
INFLAMMATION IN CONNECTIVE TISSUE
THE IMMUNE RESPONSE AGAINST EXTRACELLULAR
BACTERIA
Complement-mediated lysis
T-INDEPENDENT
IgM/IgG antibody + Complement
Bacterial killing
Plasma level
plasma
B
CR1
CR3macrophage
LPS
FcR
TNF-α
IC
IL-1β
IL-6
1
2
3
4
5
INNATE IMMUNITY
hours
Helper T-cell activation
IgM  IgG switch
MECHANISMS OF PROTECTION
INNATE IMMUNITY
Complement activation
Gram (+)
Gram (-)
peptidoglycan 
LPS

Mannose + MBL 
alternative pathway
alternative pathway
lectin pathway
Phagocytosis
Antibody and complement mediated opsonization
Inflammation
LPS
Peptidoglycan


TLR macrophage activation
TLR macrophage activation
ACQUIRED IMMUNITY
Humoral immune response
Targets: cell wall antigens and toxins
T-independent
T-dependent
 cell wall polysaccharide
 bacterial protein
 isotype switch
 inflammation
 macrophage activation
ESCAPE MECHANISMS - overcome complement activation
ANTIBODY MEDIATED EFFECTOR FUNCTIONS
SPECIFIC ANTIBODY
Bacterial toxin
Bacteria in interstitium
Bacteria in plasma
Toxin
receptor
Neutralization
Opsonization
Complement activation
COMPLEMENT
Neutralization
Phagocytosis
Phagocytosis and lysis
EVASION MECHANISMS OF EXTRACELLULAR BACTERIA
Proteins to increase adhesion
Bordetella pertussis
Inhibition of phagocytosis
S.aureus, Str. pneumoniae,
Antigenic variants
Neisseria gonorrhoeae (pilin)
Inhibition of complement-dependent cell lysis
Str. pyogenes M-protein
Sialic acid rich capsule inhibits activation of the alternative complement pathway
A reaktív oxigén gyökök lekötése
Katalase pozitív staphylococci
Degradation of IgA antibodies
Neisseria, H. influenzae
GENERAL SUPPRESSION OF THE IMMUNE RESPONSE
SUBVERSION OF THE IMMUNE SYSTEM BY
EXTRACELLULAR BACTERIA
Superantigens of staphylococci – staphylococcal enterotoxins (SE)
PROFESSIONAL APC
2
2
– toxic shock syndrom toxin-1 (TSST-1)
Simultaneous binding to MHC class II and TCR -chain
irrespective of peptide binding specificity
Mimic specific antigen
1

1

Induce massive but ineffective T-cell activation and
proliferation in the absence of specific peptide
2 – 20% of CD4+ T-cells, which are not specific for
the bacteria but share V get activated and develop to
effector T-lymphocytes
Over production of cytokines – IL-1, IL-2, TNF-α
T cell
Systemic toxicity – sepsis/septicemia
Suppression of adaptive immunity by
apoptosis
Sepsis/Septicemia
TNF-α→platelet activating factor by
endothelial cells→clotting, blockage
restricts plasma leakage & spread of
infection
Infection of blood – Sepsis
Sysemic edema, decreased blood
volume, collapse of vessels
Disseminated intravascular
coagulation, multiple organ failure