INFECTION & IMMUNITY · 2016-09-06 · Immunity From Latin “immunitas” - (especially immune to...
Transcript of INFECTION & IMMUNITY · 2016-09-06 · Immunity From Latin “immunitas” - (especially immune to...
![Page 1: INFECTION & IMMUNITY · 2016-09-06 · Immunity From Latin “immunitas” - (especially immune to something) having a natural resistance to or protected by inoculation from a particular](https://reader033.fdocuments.net/reader033/viewer/2022041916/5e69bf10480d1062026dbc3f/html5/thumbnails/1.jpg)
INFECTION & IMMUNITY
Division of Infectious Diseases,
Department of Internal Medicine,
The Catholic University of Korea
Choi Jung Hyun
![Page 2: INFECTION & IMMUNITY · 2016-09-06 · Immunity From Latin “immunitas” - (especially immune to something) having a natural resistance to or protected by inoculation from a particular](https://reader033.fdocuments.net/reader033/viewer/2022041916/5e69bf10480d1062026dbc3f/html5/thumbnails/2.jpg)
Immunity
From Latin “immunitas”
- (especially immune to something) having a natural resistance to or
protected by inoculation from a particular disease.
- (especially immune from something) free, exempt or protected from it.
- (especially immune to something) unaffected by or not susceptible to it.
![Page 3: INFECTION & IMMUNITY · 2016-09-06 · Immunity From Latin “immunitas” - (especially immune to something) having a natural resistance to or protected by inoculation from a particular](https://reader033.fdocuments.net/reader033/viewer/2022041916/5e69bf10480d1062026dbc3f/html5/thumbnails/3.jpg)
Immunological recognition
Immune effector function
Immune regulation
Immunological memory
Characteristics of Immunity
![Page 4: INFECTION & IMMUNITY · 2016-09-06 · Immunity From Latin “immunitas” - (especially immune to something) having a natural resistance to or protected by inoculation from a particular](https://reader033.fdocuments.net/reader033/viewer/2022041916/5e69bf10480d1062026dbc3f/html5/thumbnails/4.jpg)
Epithelial cells vs. Blood cells
Innate immunity vs. Adaptive immunity
Antigen-presenters vs. Effectors
T cells vs. B cells
Cellular immunity vs. Humoral immunity
Composition of Immune System
![Page 5: INFECTION & IMMUNITY · 2016-09-06 · Immunity From Latin “immunitas” - (especially immune to something) having a natural resistance to or protected by inoculation from a particular](https://reader033.fdocuments.net/reader033/viewer/2022041916/5e69bf10480d1062026dbc3f/html5/thumbnails/5.jpg)
Epithelial surfaces make up the 1st line of defense against infections
Epithelial injuries (catheterization) Mucosal injury (chemotherapy)
INFECTION !
Epithelial Cells
![Page 6: INFECTION & IMMUNITY · 2016-09-06 · Immunity From Latin “immunitas” - (especially immune to something) having a natural resistance to or protected by inoculation from a particular](https://reader033.fdocuments.net/reader033/viewer/2022041916/5e69bf10480d1062026dbc3f/html5/thumbnails/6.jpg)
Blood Cells
![Page 7: INFECTION & IMMUNITY · 2016-09-06 · Immunity From Latin “immunitas” - (especially immune to something) having a natural resistance to or protected by inoculation from a particular](https://reader033.fdocuments.net/reader033/viewer/2022041916/5e69bf10480d1062026dbc3f/html5/thumbnails/7.jpg)
Others
Kupffer cells
alveolar macrophages
mesangial cells gut lymphocytes
![Page 8: INFECTION & IMMUNITY · 2016-09-06 · Immunity From Latin “immunitas” - (especially immune to something) having a natural resistance to or protected by inoculation from a particular](https://reader033.fdocuments.net/reader033/viewer/2022041916/5e69bf10480d1062026dbc3f/html5/thumbnails/8.jpg)
Invasion of Microbes
![Page 9: INFECTION & IMMUNITY · 2016-09-06 · Immunity From Latin “immunitas” - (especially immune to something) having a natural resistance to or protected by inoculation from a particular](https://reader033.fdocuments.net/reader033/viewer/2022041916/5e69bf10480d1062026dbc3f/html5/thumbnails/9.jpg)
Damages by Microbes
![Page 10: INFECTION & IMMUNITY · 2016-09-06 · Immunity From Latin “immunitas” - (especially immune to something) having a natural resistance to or protected by inoculation from a particular](https://reader033.fdocuments.net/reader033/viewer/2022041916/5e69bf10480d1062026dbc3f/html5/thumbnails/10.jpg)
Timetables of Immune Responses
![Page 11: INFECTION & IMMUNITY · 2016-09-06 · Immunity From Latin “immunitas” - (especially immune to something) having a natural resistance to or protected by inoculation from a particular](https://reader033.fdocuments.net/reader033/viewer/2022041916/5e69bf10480d1062026dbc3f/html5/thumbnails/11.jpg)
Innate Immunity
Preformed effectors ?
Recognition of molecular pattern ?
![Page 12: INFECTION & IMMUNITY · 2016-09-06 · Immunity From Latin “immunitas” - (especially immune to something) having a natural resistance to or protected by inoculation from a particular](https://reader033.fdocuments.net/reader033/viewer/2022041916/5e69bf10480d1062026dbc3f/html5/thumbnails/12.jpg)
Preformed Effectors
Complements - direct microbial lysis
- role in phagocytosis, cytokine/chemokine production, attraction of
leukocytes to infected sites
Mannose-binding lectin - pluripotent sugar-binding protien
- discriminate self and nonself sugar
- activate complement system
Fibronectin - cell-cell adhesion, enhance macrophage functions
Antibacterial proteins - -defensins, -defensins, cathelin, protegrin, granulsyin, histatin, secretory
leukoprotease inhibitor, probiotics
Phagocytes
![Page 13: INFECTION & IMMUNITY · 2016-09-06 · Immunity From Latin “immunitas” - (especially immune to something) having a natural resistance to or protected by inoculation from a particular](https://reader033.fdocuments.net/reader033/viewer/2022041916/5e69bf10480d1062026dbc3f/html5/thumbnails/13.jpg)
Phagocytes
NK cell Macrophage Dendritic cell Neutrophils Eosinophils
For innate immunity
- phagocytose and kill bacteria
- produce antimicrobial peptides
- produce cytokines/chemokines
For adaptive immunity
- antigen presentation
Preformed Effectors
![Page 14: INFECTION & IMMUNITY · 2016-09-06 · Immunity From Latin “immunitas” - (especially immune to something) having a natural resistance to or protected by inoculation from a particular](https://reader033.fdocuments.net/reader033/viewer/2022041916/5e69bf10480d1062026dbc3f/html5/thumbnails/14.jpg)
Recognition of Molecular Pattern
Toll-like receptors (TLRs)
Inflammasome
Peroxisome proliferating activator receptor (PPAR-)
More and more….
![Page 15: INFECTION & IMMUNITY · 2016-09-06 · Immunity From Latin “immunitas” - (especially immune to something) having a natural resistance to or protected by inoculation from a particular](https://reader033.fdocuments.net/reader033/viewer/2022041916/5e69bf10480d1062026dbc3f/html5/thumbnails/15.jpg)
TLRs Chronicles
![Page 16: INFECTION & IMMUNITY · 2016-09-06 · Immunity From Latin “immunitas” - (especially immune to something) having a natural resistance to or protected by inoculation from a particular](https://reader033.fdocuments.net/reader033/viewer/2022041916/5e69bf10480d1062026dbc3f/html5/thumbnails/16.jpg)
Peptidoglycan [G(+)] Lipoprotein Lipoarabinomannan LPS (Leptospira) LPS (Porphyromonas) GPI (T. cruzi) Zymosan (Yeasts)
LPS LTA HSP60 RSV F protein dsRNA Fragellin
Unmethylated CpG DNA
TLR6 TLR2 TLR1 CD14 TLR4 TLR3 TLR5 TLR9
MD2
Ligands for TLRs
TLRs
![Page 17: INFECTION & IMMUNITY · 2016-09-06 · Immunity From Latin “immunitas” - (especially immune to something) having a natural resistance to or protected by inoculation from a particular](https://reader033.fdocuments.net/reader033/viewer/2022041916/5e69bf10480d1062026dbc3f/html5/thumbnails/17.jpg)
TLRs TLR signaling: Pro-inflammatory!!
![Page 18: INFECTION & IMMUNITY · 2016-09-06 · Immunity From Latin “immunitas” - (especially immune to something) having a natural resistance to or protected by inoculation from a particular](https://reader033.fdocuments.net/reader033/viewer/2022041916/5e69bf10480d1062026dbc3f/html5/thumbnails/18.jpg)
Shock 2005;23:393 - 9
PPAR- signaling: Anti-inflammatory!!
PPAR-
![Page 19: INFECTION & IMMUNITY · 2016-09-06 · Immunity From Latin “immunitas” - (especially immune to something) having a natural resistance to or protected by inoculation from a particular](https://reader033.fdocuments.net/reader033/viewer/2022041916/5e69bf10480d1062026dbc3f/html5/thumbnails/19.jpg)
Cytokines
![Page 20: INFECTION & IMMUNITY · 2016-09-06 · Immunity From Latin “immunitas” - (especially immune to something) having a natural resistance to or protected by inoculation from a particular](https://reader033.fdocuments.net/reader033/viewer/2022041916/5e69bf10480d1062026dbc3f/html5/thumbnails/20.jpg)
Sepsis Cascades
![Page 21: INFECTION & IMMUNITY · 2016-09-06 · Immunity From Latin “immunitas” - (especially immune to something) having a natural resistance to or protected by inoculation from a particular](https://reader033.fdocuments.net/reader033/viewer/2022041916/5e69bf10480d1062026dbc3f/html5/thumbnails/21.jpg)
Classic Pathway Alternative Pathway
Ag/Ab complex Pathogen surfaces
C1 C4 C2 C3 B D
C3 convertase
C4a, C3a, C5a C3b C5b, C6, C7, C8, C9
Mediator of inflammation
Phagocyte recruitment
Opsonization of pathogen
Remove immune complex
Membrane attack complex
lysis of pathogen or cells
Tissue factor + Factor VII
Tissue factor +
Factor VII
Factor X
Factor Xa
Factor IXa
Factor II Factor IIa
Fibrinogen
Fibrin
Extrinsic
Prothrombin Thrombin
Factor V
Factor IX
Prekallikrein
Kallikrein
Factor XIa Factor XI
Factor XII
Factor XIIa
Collagen/Glass/
Platelet
Intrinsic
Factor VIII
Arachidonic Acid-Phospholipids
Arachidonic Acid
PGH2
PGG2
LTA4 LTC4
TXA2
TXB2
PGI2 PGE2 PGF2a
6-keto PGF1a
LTB4 LTD4
LTE4
Phospholipase A2
Fatty acid Cyclooxygenase
5-Lipooxygenase
+H2O +H2O
Can you see it?
![Page 22: INFECTION & IMMUNITY · 2016-09-06 · Immunity From Latin “immunitas” - (especially immune to something) having a natural resistance to or protected by inoculation from a particular](https://reader033.fdocuments.net/reader033/viewer/2022041916/5e69bf10480d1062026dbc3f/html5/thumbnails/22.jpg)
![Page 23: INFECTION & IMMUNITY · 2016-09-06 · Immunity From Latin “immunitas” - (especially immune to something) having a natural resistance to or protected by inoculation from a particular](https://reader033.fdocuments.net/reader033/viewer/2022041916/5e69bf10480d1062026dbc3f/html5/thumbnails/23.jpg)
Adaptive Immunity
Transport of antigen ?
B cell and T cells ?
Clonal expansion and differentiation ?
![Page 24: INFECTION & IMMUNITY · 2016-09-06 · Immunity From Latin “immunitas” - (especially immune to something) having a natural resistance to or protected by inoculation from a particular](https://reader033.fdocuments.net/reader033/viewer/2022041916/5e69bf10480d1062026dbc3f/html5/thumbnails/24.jpg)
Transporters of Antigen
Human leukocyte antigen (HLA)
- Human version of major
histocompatibility complex (MHC)
- Wide-ranging effects not only
because of system’s role in the
adaptive immune response, but
also because of its genetic
complexity
![Page 25: INFECTION & IMMUNITY · 2016-09-06 · Immunity From Latin “immunitas” - (especially immune to something) having a natural resistance to or protected by inoculation from a particular](https://reader033.fdocuments.net/reader033/viewer/2022041916/5e69bf10480d1062026dbc3f/html5/thumbnails/25.jpg)
MHC
Class I - HLA-A, -B, -C… - intracellular organism 처리 - naive T cell을 cytotoxic T cell (CD8)로 분화
Class II - HLA-D (-DR, -DQ…) - extracellular organism 처리 - naive T cell을 helper T cell (CD4)로 분화
![Page 26: INFECTION & IMMUNITY · 2016-09-06 · Immunity From Latin “immunitas” - (especially immune to something) having a natural resistance to or protected by inoculation from a particular](https://reader033.fdocuments.net/reader033/viewer/2022041916/5e69bf10480d1062026dbc3f/html5/thumbnails/26.jpg)
T cell receptor
![Page 27: INFECTION & IMMUNITY · 2016-09-06 · Immunity From Latin “immunitas” - (especially immune to something) having a natural resistance to or protected by inoculation from a particular](https://reader033.fdocuments.net/reader033/viewer/2022041916/5e69bf10480d1062026dbc3f/html5/thumbnails/27.jpg)
- MHC class I molecules bearing viral peptides are recognized by CD-8 bearing cytotoxic T cells, which then kill the infected cells;
- MHC class II molecule bearing peptide derived from pathogens taken up into vesicles are recognized by CD-4 bearing TH1 or TH2 cells
T cell activation
![Page 28: INFECTION & IMMUNITY · 2016-09-06 · Immunity From Latin “immunitas” - (especially immune to something) having a natural resistance to or protected by inoculation from a particular](https://reader033.fdocuments.net/reader033/viewer/2022041916/5e69bf10480d1062026dbc3f/html5/thumbnails/28.jpg)
Role of T cells
![Page 29: INFECTION & IMMUNITY · 2016-09-06 · Immunity From Latin “immunitas” - (especially immune to something) having a natural resistance to or protected by inoculation from a particular](https://reader033.fdocuments.net/reader033/viewer/2022041916/5e69bf10480d1062026dbc3f/html5/thumbnails/29.jpg)
B cells
![Page 30: INFECTION & IMMUNITY · 2016-09-06 · Immunity From Latin “immunitas” - (especially immune to something) having a natural resistance to or protected by inoculation from a particular](https://reader033.fdocuments.net/reader033/viewer/2022041916/5e69bf10480d1062026dbc3f/html5/thumbnails/30.jpg)
B cells & antibodies
![Page 31: INFECTION & IMMUNITY · 2016-09-06 · Immunity From Latin “immunitas” - (especially immune to something) having a natural resistance to or protected by inoculation from a particular](https://reader033.fdocuments.net/reader033/viewer/2022041916/5e69bf10480d1062026dbc3f/html5/thumbnails/31.jpg)
Clonal expansion
Proliferation and differentiation of effector cells
![Page 32: INFECTION & IMMUNITY · 2016-09-06 · Immunity From Latin “immunitas” - (especially immune to something) having a natural resistance to or protected by inoculation from a particular](https://reader033.fdocuments.net/reader033/viewer/2022041916/5e69bf10480d1062026dbc3f/html5/thumbnails/32.jpg)
Summary of Immune Reaction
![Page 33: INFECTION & IMMUNITY · 2016-09-06 · Immunity From Latin “immunitas” - (especially immune to something) having a natural resistance to or protected by inoculation from a particular](https://reader033.fdocuments.net/reader033/viewer/2022041916/5e69bf10480d1062026dbc3f/html5/thumbnails/33.jpg)
Summary of Immune Reaction
![Page 34: INFECTION & IMMUNITY · 2016-09-06 · Immunity From Latin “immunitas” - (especially immune to something) having a natural resistance to or protected by inoculation from a particular](https://reader033.fdocuments.net/reader033/viewer/2022041916/5e69bf10480d1062026dbc3f/html5/thumbnails/34.jpg)
Immunological Memory
![Page 35: INFECTION & IMMUNITY · 2016-09-06 · Immunity From Latin “immunitas” - (especially immune to something) having a natural resistance to or protected by inoculation from a particular](https://reader033.fdocuments.net/reader033/viewer/2022041916/5e69bf10480d1062026dbc3f/html5/thumbnails/35.jpg)
![Page 36: INFECTION & IMMUNITY · 2016-09-06 · Immunity From Latin “immunitas” - (especially immune to something) having a natural resistance to or protected by inoculation from a particular](https://reader033.fdocuments.net/reader033/viewer/2022041916/5e69bf10480d1062026dbc3f/html5/thumbnails/36.jpg)
![Page 37: INFECTION & IMMUNITY · 2016-09-06 · Immunity From Latin “immunitas” - (especially immune to something) having a natural resistance to or protected by inoculation from a particular](https://reader033.fdocuments.net/reader033/viewer/2022041916/5e69bf10480d1062026dbc3f/html5/thumbnails/37.jpg)
Definition of Sepsis
From the Greek words sepsis meaning to decay and sepein meaning to putrefy.
Represents the body’s systemic immune response to severe infection, and is the result of a complex interaction between the host and the invading organisms resulting in the release of a myriad of inflammatory mediators and resulting in host damages.
![Page 38: INFECTION & IMMUNITY · 2016-09-06 · Immunity From Latin “immunitas” - (especially immune to something) having a natural resistance to or protected by inoculation from a particular](https://reader033.fdocuments.net/reader033/viewer/2022041916/5e69bf10480d1062026dbc3f/html5/thumbnails/38.jpg)
Death by Sepsis
Nidus of infection Pneumonia, cellulitis, meningitis, UTI, cholangitis, abscess, peritonitis …
Organism proliferation & spread ; microorganism-derived mediators • Bacterial products (exotoxins) ; TSST-1, Toxin A • Structural components ; endotoxin (LPS), teichoic acid antigens
Activation of host defense systems Plasma components, neutrophil, monocyte/macrophage, endothelial cells
Endogenous mediator release Nitric oxide Arachidonic acid metabolites ;
Oxygen free radical prostaglandins, leukotrienes
Cytokines ; TNF, IL, IFN Complement : C5a
Platelet activating factor (PAF) Coagulation
Endorphins Kinins : bradykinin
Endothelial cell damage Organ dysfunction
![Page 39: INFECTION & IMMUNITY · 2016-09-06 · Immunity From Latin “immunitas” - (especially immune to something) having a natural resistance to or protected by inoculation from a particular](https://reader033.fdocuments.net/reader033/viewer/2022041916/5e69bf10480d1062026dbc3f/html5/thumbnails/39.jpg)
Mortality by Sepsis
Infection
Sepsis
Severe sepsis
Septic shock
Am J Respir Crit Care Med 2003;168:77-84
![Page 40: INFECTION & IMMUNITY · 2016-09-06 · Immunity From Latin “immunitas” - (especially immune to something) having a natural resistance to or protected by inoculation from a particular](https://reader033.fdocuments.net/reader033/viewer/2022041916/5e69bf10480d1062026dbc3f/html5/thumbnails/40.jpg)
Mortality by Sepsis
![Page 41: INFECTION & IMMUNITY · 2016-09-06 · Immunity From Latin “immunitas” - (especially immune to something) having a natural resistance to or protected by inoculation from a particular](https://reader033.fdocuments.net/reader033/viewer/2022041916/5e69bf10480d1062026dbc3f/html5/thumbnails/41.jpg)
Mortality by Severe Sepsis
![Page 42: INFECTION & IMMUNITY · 2016-09-06 · Immunity From Latin “immunitas” - (especially immune to something) having a natural resistance to or protected by inoculation from a particular](https://reader033.fdocuments.net/reader033/viewer/2022041916/5e69bf10480d1062026dbc3f/html5/thumbnails/42.jpg)
Microbiologic factors Virulence
Resistance to antimicrobials
Host factors Age
Genetic factors
Immune status
- HIV infection, cancer, transplantation, immunosuppressants…
Co-morbid illness - DM, CRF, chronic lung diseases…
Site of infection
Treatment associated
Antimicrobial factors Appropriateness
Timing
Affecting Factors to Death
![Page 43: INFECTION & IMMUNITY · 2016-09-06 · Immunity From Latin “immunitas” - (especially immune to something) having a natural resistance to or protected by inoculation from a particular](https://reader033.fdocuments.net/reader033/viewer/2022041916/5e69bf10480d1062026dbc3f/html5/thumbnails/43.jpg)
LPS and other triggers
Release of 2ndary mediators cytokines, prostaglandins PAF, kinins Activation of coagulation Complement activation
Hypotension vasodilation myocardial depression Tissue damage hypoxia neutrophil migration ROIs proteolytic enzymes
Responding cells
Prevention of activation
Inhibition of mediators
Limit organ damage
Immunotherapy of Sepsis
![Page 44: INFECTION & IMMUNITY · 2016-09-06 · Immunity From Latin “immunitas” - (especially immune to something) having a natural resistance to or protected by inoculation from a particular](https://reader033.fdocuments.net/reader033/viewer/2022041916/5e69bf10480d1062026dbc3f/html5/thumbnails/44.jpg)
![Page 45: INFECTION & IMMUNITY · 2016-09-06 · Immunity From Latin “immunitas” - (especially immune to something) having a natural resistance to or protected by inoculation from a particular](https://reader033.fdocuments.net/reader033/viewer/2022041916/5e69bf10480d1062026dbc3f/html5/thumbnails/45.jpg)
Glucocorticoid in Sepsis ?
![Page 46: INFECTION & IMMUNITY · 2016-09-06 · Immunity From Latin “immunitas” - (especially immune to something) having a natural resistance to or protected by inoculation from a particular](https://reader033.fdocuments.net/reader033/viewer/2022041916/5e69bf10480d1062026dbc3f/html5/thumbnails/46.jpg)
Br Med J, 2004;329:480-8
In conclusion, hydrocortisone (or equivalent) should be given to patients with septic shock immediately after they undergo an adrenocorticotropin hormone test, add a doe of 200-300 mg, and should be continued for 5-11 days, and only when absolute or relative adrenal insufficiency is present.
Glucocorticoid
![Page 47: INFECTION & IMMUNITY · 2016-09-06 · Immunity From Latin “immunitas” - (especially immune to something) having a natural resistance to or protected by inoculation from a particular](https://reader033.fdocuments.net/reader033/viewer/2022041916/5e69bf10480d1062026dbc3f/html5/thumbnails/47.jpg)
N Engl J Med 2008;358:111-24
Conclusions
Hydrocortisone did not improve survival or reversal of shock in patients with septic shock, either overall or in patients who did not have a response to corticotropin, although hydrocortisone hastened reversal of shock in patients in whom shock was reversed. (Clinical Trials.gov number, NCT00147004.)
Glucocorticoid
![Page 48: INFECTION & IMMUNITY · 2016-09-06 · Immunity From Latin “immunitas” - (especially immune to something) having a natural resistance to or protected by inoculation from a particular](https://reader033.fdocuments.net/reader033/viewer/2022041916/5e69bf10480d1062026dbc3f/html5/thumbnails/48.jpg)
N Engl J Med 2008;358:111-24
Survival at 28th day
![Page 49: INFECTION & IMMUNITY · 2016-09-06 · Immunity From Latin “immunitas” - (especially immune to something) having a natural resistance to or protected by inoculation from a particular](https://reader033.fdocuments.net/reader033/viewer/2022041916/5e69bf10480d1062026dbc3f/html5/thumbnails/49.jpg)
Shock reversal
N Engl J Med 2008;358:111-24
![Page 50: INFECTION & IMMUNITY · 2016-09-06 · Immunity From Latin “immunitas” - (especially immune to something) having a natural resistance to or protected by inoculation from a particular](https://reader033.fdocuments.net/reader033/viewer/2022041916/5e69bf10480d1062026dbc3f/html5/thumbnails/50.jpg)
JAMA 2010;303:341 - 8
![Page 51: INFECTION & IMMUNITY · 2016-09-06 · Immunity From Latin “immunitas” - (especially immune to something) having a natural resistance to or protected by inoculation from a particular](https://reader033.fdocuments.net/reader033/viewer/2022041916/5e69bf10480d1062026dbc3f/html5/thumbnails/51.jpg)
Possible mechanisms of IVIG
Immunoglobulin
![Page 52: INFECTION & IMMUNITY · 2016-09-06 · Immunity From Latin “immunitas” - (especially immune to something) having a natural resistance to or protected by inoculation from a particular](https://reader033.fdocuments.net/reader033/viewer/2022041916/5e69bf10480d1062026dbc3f/html5/thumbnails/52.jpg)
Immunoglobulin
![Page 53: INFECTION & IMMUNITY · 2016-09-06 · Immunity From Latin “immunitas” - (especially immune to something) having a natural resistance to or protected by inoculation from a particular](https://reader033.fdocuments.net/reader033/viewer/2022041916/5e69bf10480d1062026dbc3f/html5/thumbnails/53.jpg)
Recombinant activated protein C
Only FDA approved immunomodulatory agent
2008 Surviving Sepsis Campaign recommended for the treatment of severe sepsis in patient with more than one organ dysfunction, an APACHE II score >25, or both.
2012 Surviving Sepsis Campaign
The results of the PROWESS SHOCK trial (1,696 patients) were released in late 2011, showing no benefit of rhAPC in patients with septic shock (mortality 26.4 % for rhAPC, 24.2 % placebo) with a relative risk of 1.09 and a P value of 0.31.
The drug was withdrawn from the market and is no longer available, negating any need for an SSC recommendation regarding its use.
![Page 54: INFECTION & IMMUNITY · 2016-09-06 · Immunity From Latin “immunitas” - (especially immune to something) having a natural resistance to or protected by inoculation from a particular](https://reader033.fdocuments.net/reader033/viewer/2022041916/5e69bf10480d1062026dbc3f/html5/thumbnails/54.jpg)
Curr Opin Crit Care 2004;10:354-63
- rhGCSF, recombinant human granulocyte colony stimulating factor - MAB-T88, human monoclonal immunoglobulin M Ab directed at the enterobacterial common Ag - TFPI, tissue factor pathway inhibitor - LY315920Na/S-5960, selective inhibitor of 14-kDa group IIA secretory phospholipase A2 - rhPAF-AH, recombinant human platelet-activating factor acetylhydrolase - 546C88, nitric oxide synthase inhibitor
DSMB : data and safety monitoring board
Other Immunomodulators
![Page 55: INFECTION & IMMUNITY · 2016-09-06 · Immunity From Latin “immunitas” - (especially immune to something) having a natural resistance to or protected by inoculation from a particular](https://reader033.fdocuments.net/reader033/viewer/2022041916/5e69bf10480d1062026dbc3f/html5/thumbnails/55.jpg)
Anti-inflammatory Is Matter!
![Page 56: INFECTION & IMMUNITY · 2016-09-06 · Immunity From Latin “immunitas” - (especially immune to something) having a natural resistance to or protected by inoculation from a particular](https://reader033.fdocuments.net/reader033/viewer/2022041916/5e69bf10480d1062026dbc3f/html5/thumbnails/56.jpg)
Agent Study Outcomes
G-CSF RCT in patients with pneumonia and severe sepsis Increased WBC counts No reduction in mortality Well tolerated
G-CSF RCT in patients with multilobar pneumonia Increased WBC counts Reduction in mortality (trend) Well tolerated
GM-CSF RCT in patients with sepsis or septic shock and sepsis induced immunosuppression
Increased HLA-DR expression Restored cytokine secretion in monocytes Improved patients outcomes
GM-CSF, rIFN- (ongoing)
Effects of immunosuppression with GM-CSF or IFN- on immunoparalysis following human endotoxemia
Cytokine secretion by lymphocytes, HLA-DR expression, Monocyte/neutrophil function, Lymphocyte gene expression, volunteer responses
rIFN- RCT in trauma patients Increased HLA-DR expression Decreased severe infection (trend)
rIFN- RCT in patients with burns No improved patients outcome
rIFN- RCT in trauma patients Reduced infection related deaths
rIFN- (ongoing)
Effects of IFN- on sepsis-induced immuoparalysis Cytokine secretion by lymphocytes, HLA-DR and receptor expression (PD-1), Lymphocyte gene expression, Reversibility of monocyte dysfunction, Patients outcomes
Immunostimulation
Virulence 2013, Sep 25:5(1), Epub
![Page 57: INFECTION & IMMUNITY · 2016-09-06 · Immunity From Latin “immunitas” - (especially immune to something) having a natural resistance to or protected by inoculation from a particular](https://reader033.fdocuments.net/reader033/viewer/2022041916/5e69bf10480d1062026dbc3f/html5/thumbnails/57.jpg)
Initial resuscitation and infection
issues
Initial resuscitation Diagnosis Antimicrobial therapy Source control
Hemodynamic support and adjunctive
therapy
Fluid therapy Vasopressors Inotropic therapy Corticosteroids
Other supportive therapy
Blood product administration Mechanical ventilation Sedation, analgesics, NM blockade Glucose control Renal replacement Bicarbonate therapy DVT prophylaxis Stress ulcer prophylaxis Nutrition
Surviving Sepsis Campaign Intensive Care Med 2013;39:165-228
![Page 58: INFECTION & IMMUNITY · 2016-09-06 · Immunity From Latin “immunitas” - (especially immune to something) having a natural resistance to or protected by inoculation from a particular](https://reader033.fdocuments.net/reader033/viewer/2022041916/5e69bf10480d1062026dbc3f/html5/thumbnails/58.jpg)
Conclusion
Prevention and protection are the best way
Infection Control and Prevention
Vaccination
![Page 59: INFECTION & IMMUNITY · 2016-09-06 · Immunity From Latin “immunitas” - (especially immune to something) having a natural resistance to or protected by inoculation from a particular](https://reader033.fdocuments.net/reader033/viewer/2022041916/5e69bf10480d1062026dbc3f/html5/thumbnails/59.jpg)