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35 Cards in this Set
- Front
- Back
1st hurdle for a pathogen:
2nd hurdle: |
barriers
pattern recognition receptors |
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Neutrophil hematopoiesis:
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*Hematopoieses is coordinated by specific transcription factors --> G-CSF modulates the relative levels of transcriptional factors within myeloid cells --> influences differentiation
*G-CSF also influences proliferation, maturation, survival of myeloid cells and accelerates passage of neutrophil pre-cursors through the bone marrow *Infection: G-CSF increases *Therapeutic use: rhG-CSF (filgastrim=Neupogen; peg-filgastrim=Neulasta) |
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Neutrophil Kinetics:
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*Daily production 10^9 cells/kg BW
*During infection 10 times more *5% of the total granulocyte pool located intravascularly -Intravascular circulating cells -Marginating cells *Dynamic equilibrium: cells marginate via transient endothelial interaction, then resume rapid flow *Intravascular t1/2 6-8hrs; extravacsular t1/2 hrs-days *Steroids shift equilibrium by decreasing neutrophil adherence from marginating to circulating pool |
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Summary of steps of the inflammatory response:
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1. Recruitment
2. Ingestion 3. Intracellular disposition of ingested microbe - Oxidative burst - Degranulation 4. Resolution of inflammatory response |
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Quantitative and Qualitative Defects in neutrophil-dependent host defense:
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*Quantitative
-Neutropenia Chemotherapy Radiation Cancer related Sequestration (hypersplenism) Autoimmunity *Qualitative -Functional impairment of adhesion/chemotaxis/ingestion/microbicidal systems -Opsonization defect (complement/immunoglobulin deficiency) |
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What are infections typically like in pts with neutrophil defects?
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*Infections resulting from either defect are persistent, slowly responsive to antimicrobial therapy, and recurrent
*Quantitative defect: bacteremia with septic picture *Qualitative defect: localized infections *Predominant organisms: Staphylococci, Gram-negative bacteria, fungi an in case of opsonization defect encapsulated bacteria |
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Neutropenia:
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*Risk of infection increases progressively with duration and magnitude of neutropenia
*Relative neutropenia 500 - 1000 cells/mm3 *Absolute neutropenia <500 cells/mm3 |
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Extrinsic Chemotactic Defects:
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*Extrinsic defects
-Genetic complement deficiency C3 (prone to bacterial infections) C5 (prone to infections due to Neisseria meningitidis/gonorrhoeae) -Decreased complement production due to cirrhosis -Loss of serum proteins (burns, nephrotic syndrome) -Depression of neutrophil chemotactic response in diabetic patients -Inhibiting factors (RA, SLE, sarcoidosis, Hodgkin’s Disease) |
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What can cause opsonization defects?
What are these pts vulnerable to? How can you prevent them from getting ill? |
*Opsonization defect
-Hypogammaglobulinemia (decreased production [i.e. Multiple Myeloma; loss of serum proteins [i.e. nephrotic syndrome]) -C3 deficiency [i.e. cirrhosis] -Asplenia [Splenectomy/Congenital] -Functional asplenia [i.e. due to sickle cell anemia] *Prone to infections with encapsulated bacteria -Haemophilus influenzae type b -Streptococcus pneumoniae -Neisseria meningitidis -Salmonella typhi *Prevention -Vaccinate (streptococcal, meningococcal, Hib vaccine) prior to splenectomy -Preventive antibiotic therapy (daily vs as needed for fever) |
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How does the adaptive immune system normally deal with a viral infection?
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*MHC class I presentation of virally derived peptide antigens to CD8+ T-cells
-Cytolysis or inhibition of viral replication in host cells |
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How does the adaptive immune system normally deal with intracellular bacteria?
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How does the adaptive immune system normally deal with extracellular bacteria?
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What happens if you have damaged barrier function?
Neutropenia? Compromised/absent splenic function? |
*Damaged barrier function
Colonizing flora of skin/oral mucosa/gut mucosa *Neutropenia Gram-positive cocci Gram-negative bacilli Fungal infections *Compromised/absent splenic function Encapsulated bacteria |
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What happens if you have impaired cellular immunity?
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*Viral infections
-Reactivation of latent viruses (i.e. HSV, VZV, CMV) -Newly acquired viral infections (i.e. influenza, parainfluenza, RSV, adenovirus) *Intracellular bacterial infections -Reactivation of latent infection (tuberculosis) -Newly acquired bacterial infections (i.e. non-tuberculous mycobacteria, Listeria monocytogenes, Nocardia spp., Salmonella spp.) *Fungal infections -i.e. Pneumocystis jirovecii, Aspergillus spp., Cryptococcus spp. *Parasitic infections -i.e. Toxoplasma gondii |
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What happens if you have impaired humoral immunity?
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Bacterial infections--> Streptococcus pneumoniae, Heamophilus influenzae
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Diabetes Mellitus:
Where is the defect? What infections is the patient at risk for? How can infections be prevented? |
*Depression of neutrophil chemotactic response
*Focal bacterial infections (i.e. UTI, Fournier’s gangrene, cellulitis, osteomyelitis/diabetic foot infection) *Focal fungal infections (i.e. rhino-cerebral mucor) *Optimized glucose control *Vaccination (pneumococcal vaccine) *Podiatry care |
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Cirrhosis:
Where is the defect? What infections is the patient at risk for? How can infections be prevented? |
*Neutrophil chemotaxis and phagocytosis
*Impaired gut mucosal barrier *Focal bacterial infections, most commonly spontaneous bacterial peritonitis (SBP), followed by urinary tract infections, pneumonia and cellulitis (Vibrio vulnificus) *The most frequent causative organisms in community-acquired infections are gram-negative bacilli, mainly Escherichia coli *Vaccination (pneumococcal vaccine, HBV/HAV vaccination) *SBP prophylaxis *Education about avoidance of raw seafood (oysters) consumption and wading in salt water |
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Hematologic Malignancies:
Where is the defect? |
*Depends on the affected cell line and the drugs used for treatment
*i.e. AML disease related immune defect: neutropenia; AML treatment related immune defects: mainly neutropenia and impaired barrier(mucositis),to a lesser degree impaired cellular and humoral immunity |
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Solid Organ Transplant:
Where is the defect? |
*Impaired cellular immunity
*Degree of impairment / coexistence of other immune defects depend on -Reason for transplantation (i.e. patients transplanted for cirrhosis (especially due to autoimmune hepatitis), diabetes associated end-stage renal disease, etc. have pre-existing immune deficiencies) -Type of transplant (some organs are more immunogenic than others and require higher degree of immunosuppression) -Time after transplantation: 3-6 months post transplant is the time of most intense immunosuppression (dependent on drugs used for induction, pre-existing immunosuppression at time of transplant, taper of maintenance immunosuppression, treatment for episodes of rejection) |
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Timeline of Infections after Solid Organ Transplantation:
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Solid Organ Transplantation--How can Infections be prevented?
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*Pre-transplant
-Serologic screening of recipient and donor -Treatment of latent infectious diseases prior to transplant (i.e. strongyloides, latent TB) -Pre-transplant vaccinations -Counseling about food/travel/outdoor activity/sexual safety *Post-transplant -TMP/SMX for PCP, toxoplasmosis, nocardia, listeria, Hib, pneumococcal disease prevention -Ganciclovir/valganciclovir for CMV, HSV, VZV prevention |
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Timeline of Infections after Allogeneic Hematopoietic Stem Cell Transplantation:
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Allogeneic Hematopoietic Stem Cell Transplantation--How can Infections be prevented?
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*Acyclovir or valacyclovir for HSV/VZV prophylaxis for 1 year/until all immunosuppressive treatment discontinued
*TMP/SMX prophylaxis for 1 year/until all immunosuppressive treatment discontinued *Pre-emptive monitoring for CMV replication until day +100 or longer if GVHD treatment *Pre-emptive monitoring for EBV replication in T-cell depleted or umbilical cord blood transplant recipients *Mold prophylaxis in patients with severe GVHD *Vaccination *Counseling |
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24 yo female with AML undergoing induction chemotherapy with fever, oral pain and dysphagia.
Where is the defect? What infections is the patient at risk for? What to do? |
neutropenia
mucositis--impaired mucosal integrity *Invasive infections i.e. Viridans group streptococci and other oral bacterial flora *HSV *Candida infections *Physical exam and review of symptoms; COMPLETE skin exam (including perianal area-but don’t do a rectal exam as you could translocate bacteria) *Empiric antibiotic treatment (cefepime); If HSV seropositive: add acyclovir; Labs, blood cultures, imaging |
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46 yo male s/p kidney transplantation complicated by an
episode of acute rejection treated with pulse dose steroids a month ago. On tacrolimus, mycophenolate mofetil, and prednisone Maintenance immunosuppression. Presents with progressive shortness of breath, non-productive cough, and fever. Where is the defect? What infections is the patient at risk for? |
-CT scan of PCP
-Impaired cellular immunity -Viral infections -Intracellular bacterial infections -Fungal infections -Parasitic infections |
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What immune defect predisposes to this infection?
How could this infection have been prevented in a patient after allogeneic bone marrow transplantation? |
Impaired cellular immunity
Acyclovir or valacyclovir prophylaxis |
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65 yo m with newly diagnosed multiple myeloma not yet on treatment. Presents with fever, chills, cough productive of yellow sputum and chest pain.
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-gram pos diplococci
-pneumococcal pneumonia |
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49 yo male with liver cirrhosis secondary to alcohol abuse presents with fever and painful bullous lesions on his right leg. Ate raw oysters.
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vibrio vulnificus
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37 yo female with relapsed AML undergoing re-induction
chemotherapy. Developed nosebleeds and intraoral lesion. |
-Mucormycosis (pt is deeply neutropenic from treatment)
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47 yo m presents with sepsis and the skin findings depicted in the photograph.
What might be the patient’s underlying Immune defect? Would this infection have been preventable? |
*purpura (indicative of sepsis)
*Opsonization defect (complement or impaired splenic function) *Preventable with antibiotic prophylaxis |
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55 yo female s/p renal transplantation 7 months ago. Presents with fever, abdominal pain and non-bloody
diarrhea. |
*CMV!
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55 yo male s/p liver transplant 2 months ago for end-stage liver disease secondary to autoimmune hepatitis. Presents with fever, cough, chest pain, and confusion.
He has been compliant with his TMP/SMX and valganciclovir prophylaxis. *He has lots of pigeons around his apartment* |
*Cryptococcus infection
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22 yo f with AML undergoing induction chemotherapy treatment. Presents with fever and a skin lesion on her right calf.
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*Neutropenia
*At risk for bacterial and fungal infections *Ecthyma gangrenosum, pseudomonas, zygomycosis, aspergillus -- lots of options here. *This one is actually pseudomonas |
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29 yo female s/p allogeneic bone marrow transplantation for AML 28 days ago. Not yet engrafted. Developed progressive fever, chest pain and cough.
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-Aspergillus
-halo sign around the lesion |
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55 yo m s/p allogeneic bone marrow transplantation 150 days ago, c/b GVHD for which he remains on treatment with tacrolimus and low dose prednisone.
Presents with fever and cough productive of yellow sputum. Patient has a sulfa allergy but has been compliant with his atovaquone and acyclovir prophylaxis. |
-Nocardia
-Gram stain gives it away. -Chinese letter-like configuration on gram stain -cavitations on lung |