Test 3: Wk11: 4 Cystic Fibrosis and Tuberculosis - Yu Flashcards
— activate M1 macrophages
microbial TLR-ligands
IFN-gamma
activated M1 macrophage releases
ROS, NO, lysosomal enzymes
— activate M2 macrophage
IL-13
IL-4
Activated M2 macrophages release
IL-10
TGF-Beta
M1 macrophage actions
microbicidal actions
M2 macrophage actions
anti-inflammatory, wound repair, fibrosis
3 Functions of M1 Macrophages
- produce ROS, NO, lysosomal enzymes
- Cytokine Secretion
- Increased expression of B7 MHC molecules
— are antigen presenting cells and activate —
macrophages, T cells
Lobar pneumonia is characterized by — and is caused by what organism
Inflammatory infiltrates in alveolus
Streptococcus pneumonia
Lobar pneumonia color
red/gray hepatization and resolution
Bronchopneumonia is characterized by — and infiltrates in —
caused by what organism
patchy inflammation; inflammatory infiltrates in small airways
Staphylococcus aureus,
Interstitial pneumonia is an atypical ammonia with inflammatory infiltrates —. What organisms cause it? Why is it atypical
on alveolar walls only.
Legionella pneumophila, Mycoplasma pneumoniae and Chlamydia pneumonia.
caused by virus and bacteria
Causes of Pneumonia Neonates < 4 weeks (2)
Group B strep, E. coli
Causes of Pneumonia Children - 4 weeks to 18 yrs (3)
) Mycoplasma, Chlamydia, Strep pneumoniae
Causes of Pneumonia Adults
Strep pneumoniae
Haemophilus influenza
Atypical pneumonia bacteria
most common cause of pneumonia in adults
Strep pneumoniae
Causes of Pneumonia
Adults (hospital-acquired)
Gram-negative rods, Klebisella, E. coli, Pseudomonas, in VAP, ICU
S. aureus
Anaerobes
Gene for CF
CFTR gene chromosome 7
Most common CF mutation
F508 deletion of 3 bases, missing one aa (F) resulting in abnormal protein trafficking
what kind of channel is CFTR
chloride
CFTR Channel function
Chloride channel uses ATP to pump Cl-out of cells.
Increased Cl ion inside the cells, increased Na ion reabsorption
CFTR mutation causes
The mucus on top of the airway, small intestine (meconium ileus), and pancreatic duct become dehydrated and sticky.
Loss of CFTR in sweat glands results in
Na pump is called ENaC. Loss of CFTR makes both Na and Cl levels increased extracellularly (hypertonic luminal fluid on apical surface).
Bronchoalveolar lavage (BAL) fluid from a patient with CF
see slide 13
CF microbiology (6)
–
S. aureus including MRSA (childhood)
Haemophilus influenzae (no capsule)
P. aeruginosa including MDR-PA (adult)
Burkholderia cepacia
Achromobacter
Stenotrophomonas maltophilia
— is a poor prognosticator for lung transplant with a low 5 year survival rate.
B. cepacia
— is a poor prognosticator for lung transplant with a low 5 year survival rate.
B. cepacia
CF antibacterial therapy
Anti-Pseudomonas penicillins
4th gen cephalosporins
Combination therapy
Inhaled tobramycin
Monobactams (Aztreonam) or Carbapenems (Meropenem)
Anti-Pseudomonas penicillins (2) they have greater
Piperacillin and Ticarcillin; greater porin penetration
add — to Piperacillin and Ticarcillin
β-lactamase inhibitors. e.g, Zosyn and Timentin.
4thgen cephalosporins
cefepime
CF Combination therapy
Intravenous administration of ticarcillin or piperacillin, plus an aminoglycoside
— is resistant to many antibiotics (MDR).
P. aeruginosa
Major mechanism of antibiotic resistance in Gram-negative pathogens
β-Lactamases
It is synthesized in cytoplasm and secreted to in periplasm
β-Lactamases
Gram-positives synthesize — in cytoplasm which is then secreted extracellularly.
β-lactamases
Three types of β-lactamases
- Penicillinases inactivate penicillins
- “Extended-spectrum β-lactamases”
- Carbapenemases
agents inhibit bacterial growth while the agent is present. Rely on the immune system (of an immunocompetent person) to aid the bacteriostatic agent and clear the infection.
Bacteriostatic
agents kill bacteria but are bacteriostatic under some conditions
Bactericidal
Tuberculosis is caused by inhalation of
aerosolized Mycobacterium spp including M. tuberculosis
Mycobacterium are — aerobes
Obligate aerobes
Primary tuberculosis — intracellular, and infects —
Facultative
macrophages
Primary tuberculosis culture
Difficult to culture, slow growing, doesn’t stain well with Gram stain. Acid fast
Primary tuberculosis develops in
Develops 2 to 4 weeks after exposure
Primary tuberculosis Initial exposure causes
the formation of focal caseating necrosis in the lower lobe of lung and hilar lymph nodes
Cell mediated immune response controls TB
TH1 response, CD4+ T cells, interferon-γsecretion, macrophage activation
Secondary TB due to the reactivation of what 2 major risk factors
HIV and aging
– inhibitors is a risk factor for Secondary TB
TNF alpha Etanercept, Infliximab
is diabetes a risk factor for reactivation of TB
yes
Secondary TB due to the reactivation Occurs — and can spread to any tissue
at the apex of lung
Secondary TB due to the reactivation forms what in the lung
cavitary foci of caseous necrosis
Secondary TB due to the reactivation symptoms
fever and night sweats
cough with hemotypsis
wt loss
biopsy of TB granuloma will show
AFBpositive bacilli
Two subtypes of granuloma
Noncaseating granuloma
Necrotizing or caseating granuloma
see image on slide 24
Caseating granulomas Bacteria:
Mycobacterium tuberculosis
Treponema pallidum
Listeria monocytogenes
Caseating granulomas Fungi:
Aspergillus Blastomyces Coccidioides Cryptococcus Candida Histoplasma
Caseating granulomas Helminthic infection
Schistosoma mansoni
S. japonicum
the liver granulomas form around the parasite eggs.
Noncaseating granulomas are a reaction to what and caused by (5)
Reaction to foreign materials
Sarcoidosis
Beryllium exposure
Crohn disease
Cat scratch disease
Mycobacterium leprae
TB diagnosis
tuberculin skin test (TST), PPD
vitro IFN-γrelease assays
TB diagnosis microscopy
Acid fast bacilli
gold standard of TB dx
Culture, takes 3-4 wks
TB treatment first 2 months
RIF, INH, PZA, EMB
2 drug TB treatment 4 months
INH and RIF
— is important to ensure adherence and resistance in TB Tx
Direct observed therapy
For LTBI — is used for —
INH
9 months
