the immune responses to pathogens. pathogens viruses, bacteria, fungi parasites unicellular protozoa...
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THE IMMUNE RESPONSES TO PATHOGENS
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PATHOGENSViruses, Bacteria, Fungi
ParasitesUnicellular protozoaMulticellular worms
REQUIRES HIGH INITIAL DOSE FOR INFECTIONESCAPE MECHANISMS TO AVOID DEFENSE MECHANISMS
HUMAN BODY
VAST RESOURCE RICH ENVIRONMENT FOR PATHOGENSDEFENSE MECHANISMS
Physical barriers/Innate immunity – STOP MOST INFECTIONS WITHOUT CALLING Adaptive immunity
Diseases – Medical practice
DISEASEDISEASE Innate immunity fails to terminate infection
Pathogen spreading into lymphoid tissues and activation of adaptive immunity
Successful evasion and subversion of the immune Successful evasion and subversion of the immune system by pathogenssystem by pathogens
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DIRECT
EXOTOXIN ENDOTOXIN CYTOPHATHIC
Streptococcus pyogenesStaphylococcus aureus
Corynebacterium diphteriaeClostridium tetani
Vibrio cholerae
Escherichia coliHaemophylus influenzae
Salmonella typhiShigella
Pseudomonas aeruginosaYersinia pestis
VariolaVaricella zosterHepatitis B virus
Polio virusMeasles virusInfluenza virus
Herpes simplex virus
TonsilitisScarlet fever
Toxic shock syndromeFood poisoning
DiphteriaTetanusCholera
Gram (-) sepsisMeningitisPneumonia
Typhoid feverBaccillary dysentery
Wound infectionPlague
Small poxChicken pox, shingles
HepatitisPoliomyelitis
MeaslesSubacute sclerosing
panencephalitisInfluenza, cold sores
MECHANISMS OF TISSUE DEMAGE INDUCED BY PATHOGENS
DISEASE
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INDIRECT
IMMUNE COMPLEX ANTI-HOST ANTIBODY CELL-MEDIATED IMMUNITY
Hepatitis B virusMalaria
Strreptococcus pyogenesTreponema pallidumMost acute infections
Streptococcus pyogenesMycoplasma pneumoniae
Mycobacterium tuberculosisMycobacterium lepraeLymphocytic chorio-
meningitis virusBorrelia burgdorferi
Schistosoma mansoniHerpes simplex virus
Kidney diseaseVascular deposits
GlomerulonephritisKidney demage
in secondary syphilisTransient renal deposits
Rheumatic feverHemolytic anaemia
TuberculosisTuberculoid leprosyAseptic meningitis
Lyme arthritisSchistosomiasis
Herpes stromal keratitis
MECHANISMS OF TISSUE DEMAGE INDUCED BY PATHOGENS
DISEASE
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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
AntibodiesComplementPhagocytosis
Neutralization
Cytotoxic T cellsNK cells
T cell and NK cell-dependent
macrophage activation
PROTECTIVE IMMUNITY
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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 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
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S. pneumoniae in the lung
EVASION OF THE IMMUNE RESPONSE TO STREPTOCOCCI
BB LymphoLymphocytecyte
12 h12 hrsrs
BaBaccteriumterium
6x106x101010 BaBaccteriteriaaTToxinoxin
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CONSEQUENCES OF SKIN DAMAGECONSEQUENCES OF SKIN DAMAGE
INFLAMMATION IN CONNECTIVE TISSUEINFLAMMATION IN CONNECTIVE TISSUE
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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.
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IC
THE IMMUNE RESPONSE AGAINST EXTRACELLULAR BACTERIA
INNATE IMMUNITY
1 2 3 4 5
Plas
ma
leve
l
hours
LPS
TNF-α
IL-1βIL-6
T-INDEPENDENT
IgM antibody + Complement
Complement-mediated lysis
Bplasma
CR1CR3
Helper T-cell activation
IgM IgG switch
FcR
macrophage
Bacterial killing
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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
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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
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GENERAL SUPPRESSION OF THE IMMUNE RESPONSEGENERAL SUPPRESSION OF THE IMMUNE RESPONSE
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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
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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
Systemic edema, decreased blood Systemic edema, decreased blood volume, collapse of vesselsvolume, collapse of vessels
Disseminated intravascular Disseminated intravascular coagulation, multiple organ failurecoagulation, multiple organ failure
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OpsonizationOpsonization
ESCAPEESCAPE
High carbohydrate High carbohydrate variabilityvariability
Competition of strains Competition of strains
~90 serotypes~90 serotypes
Serotype-specific Ab Serotype-specific Ab responseresponse
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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)
Elimination of reactive oxygen speciesCatalase positive staphylococci
Degradation of IgA antibodiesNeisseria, H. influenzae
Proteins to increase adhesionBordetella pertussis
Inhibition of phagocytosisS.aureus, Str. pneumoniae,