SITE OF REPLICATION
EXTRACELLULAR INTRACELLULAR
Interstitial spacesBlood, lymph
Bronchial,Gastrointestinal lumen
Epithelial surfaces Cytoplasmic Vesicular
VirusesBacteriaProtozoa
FungiWorms
Neisseria gonorrhoeaeWorms
MycoplasmaStreptococcuspneumoniae
Vibrio choleraeEscherichia coli
Candida albicansHelicobacter pylori
VirusesChlamydia ssp.Richettsia ssp.
Listeria monocytogenesProtozoa
MycobacteriaSalmonella typhimurium
Seishmania spp.Listeria ssp.
Trypanosoma spp.Legionella pneumophila
Cryptococcus neoformansHistoplasma
Yersinia pestis
IgA type Antibodies Anti-microbial peptides
AntibodiesComplementPhagocytosisNeutralization
Cytotoxic T cellsNK cells
T cell and NK cell-dependent
macrophage activation
PROTECTIVE IMMUNITY
MHCI
MHCII
MHCII
MHCII
B-sejt
PATHOGEN TYPE PROCESSING RESPONSE
Extracellular
Intravesicular
Cytosolic
Acidic vesicles
MHC II binding
CD4+ T cells
ANTIBODY PRODUCTIONNeutralizationComplement activationPhagocytosis
THE SITE OF PATHOGEN DEGRADATION DETERMINES THE TYPE OF IMMUNE RESPONSES
Acidic vesicles
MHC II binding
CD4+ T cells
KILLING BACTERIA OF PARASITE IN VESICLES
Intracellular killing
Th1 NK
Cytoplasm
MHC I bindingMHC II binding
CD8+ T cellsCD4+ T cells
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
S. pneumoniae in the lung
EVASION OF THE IMMUNE RESPONSE TO STREPTOCOCCI
BB LymphoLymphocytecyte
12 h12 hrsrs
BaBaccteriumterium
6x106x101010 BaBaccteriteriaaTToxinoxin
OpsonizationOpsonization
ESCAPEESCAPE
High carbohydrate High carbohydrate variabilityvariability
Competition of Competition of strains strains
~90 serotypes~90 serotypes
Serotype-specific Serotype-specific Ab responseAb response
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.
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 PMNThe 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.
Acute bronchopneumonia of the lung
CONSEQUENCES OF SKIN DAMAGECONSEQUENCES OF SKIN DAMAGE
INFLAMMATION IN CONNECTIVE TISSUEINFLAMMATION IN CONNECTIVE TISSUE
IC
THE IMMUNE RESPONSE AGAINST EXTRACELLULAR BACTERIA
INNATE IMMUNITY
1 2 3 4 5
Pla
sma
leve
l
hours
LPS
TNF-α
IL-1βIL-6
T-INDEPENDENT
IgM/IgG antibody + Complement
Complement-mediated lysis
Bplasma
CR1CR3
Helper T-cell activation
IgM IgG switch
FcR
macrophage
Bacterial killing
MECHANISMS OF PROTECTION
INNATE IMMUNITYComplement activation
Gram (+) peptidoglycan alternative pathwayGram (-) LPS alternative pathway
Mannose + MBL lectin pathwayPhagocytosis
Antibody and complement mediated opsonization
Inflammation LPS TLR macrophage activationPeptidoglycan TLR macrophage activation
ACQUIRED IMMUNITYHumoral immune response
Targets: cell wall antigens and toxins
T-independent cell wall polysaccharideT-dependent bacterial protein isotype switch
inflammation macrophage activation
ESCAPE MECHANISMS - overcome complement activation
ANTIBODY MEDIATED EFFECTOR FUNCTIONS
SPECIFIC ANTIBODY
Bacterial toxin
Toxin receptor
Neutralization
Neutralization
Bacteria in interstitium Bacteria in plasma
Opsonization Complement activation
Phagocytosis Phagocytosis and lysis
COMPLEMENT
EVASION MECHANISMS OF EXTRACELLULAR BACTERIA
Inhibition of complement-dependent cell lysis Str. pyogenes M-proteinM-proteinSialic acid rich capsule inhibits activation of the alternative complement pathway
Antigenic variantsNeisseria gonorrhoeae (pilinpilin)
A reaktív oxigén gyökök lekötéseKatalase pozitív staphylococci
Degradation of IgA antibodiesNeisseria, H. influenzae
Proteins to increase adhesionBordetella pertussis
Inhibition of phagocytosisS.aureus, Str. pneumoniae,
GENERAL SUPPRESSION OF THE IMMUNE RESPONSEGENERAL SUPPRESSION OF THE IMMUNE RESPONSE
SUBVERSION OF THE IMMUNE SYSTEM BY EXTRACELLULAR BACTERIA
Superantigens of staphylococci – staphylococcal enterotoxins (SE)
– toxic shock syndrom toxin-1 (TSST-1)
Simultaneous binding to MHC class II and TCR -chain irrespective of peptide binding specificity
Mimic specific antigenMimic specific antigen
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
Systemic toxicity – sepsis/septicemia
Suppression of adaptive immunity by
apoptosis
PROFESSIONAL APC
11
22
T cell
Sepsis/SepticemiaSepsis/Septicemia
TNF-TNF-αα→platelet activating factor by endothelial cells→clotting, blockage restricts plasma leakage & spread of infection
Infection of blood – SepsisInfection of blood – Sepsis
Sysemic edema, decreased blood Sysemic edema, decreased blood volume, collapse of vesselsvolume, collapse of vessels
Disseminated intravascular Disseminated intravascular coagulation, multiple organ failurecoagulation, multiple organ failure