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