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6-year-old immigrant from Eastern Europe having difficulty breathing. Has fever, not eating or drinking. Neck swelling, palatal paralysis, and gray pharyngeal exudate. No vaccination history.

• Diphtheria (caused by Corynebacterium diphtheriae).
• Acute infection of the naso-oropharynx transmitted via respiratory droplets.
• Pseudomembranous pharyngitis (gray pharyngeal exudate)
• Sx. Sore throat, fever, LAD, upper airway dyspnea, odynophagia.
• Diphtheria toxin has tropism for neural/cardiac tissue –> can cause CNS/cardiac sequelae.
• Diphtheria infection associated with 5-10% mortality rate, esp in young patients or those with myocarditis.
• Cardiomyopathy is the most common cause of death.
• Tx. Diphtheria antitoxin (passive immunization)- inactivates all circulating toxin but ineffective against toxin that has already gained access to cardiac or neural cells.
• Rapid administration of antitoxin essential –> transfer of pre-existing neutralizing antibodies.
• Penicillin or erythromycin kills bacteria, halting release of new exotoxin into bloodstream and preventing transmission.
• TDaP vaccine (active immunization)- provides lasting immunity against future infection.


Diphtheria exotoxin

AB toxin that ADP-ribosylates and deactivates elongation factor-2, inhibiting protein synthesis. Tropism for neural and cardiac tissue.


Most common causes of viral meningitis

• Enteroviruses (eg, coxsackievirus, echovirus, poliovirus) –> cause 90% of aseptic meningitis cases
• Arboviruses
• HSV type 2
• Mumps virus, but unlikely in fully immunized child. • Meningitis caused by mumps virus accompanied by parotitis in 50% of cases.


Most common causes of bacterial meningitis

Adults: Streptococcus pneumoniae, Neisseria meningitidis
Neonates: Group B streptococcus (S. agalactiae), gram-negative bacilli


CSF profile of viral (aseptic) meningitis

• Sx. Fever, headache, vomiting, stiff neck, typically less severe sx than bacterial meningitis. No focal neurologic signs, seizures, AMS.
• CSF WBC count: less than 500, lymphocytic predominance
• CSF Glucose: normal or slightly reduced
• CSF Protein: usually less than 150 mg/dL
• CSF Gram stain/culture: No organisms identified.


CSF profile of bacterial meningitis

• CSF WBC count: greater than 1000, neutrophilic predominance
• CSF Glucose: less than 45 mg/dL
• CSF Protein: greater than 250 mg/dL
• CSF Gram stain/culture: often positive for specific organism



• Lower respiratory tract infection most commonly caused by respiratory syncytial virus (RSV) and typically in infants less than 2 years old.
• Presents with low-grade fever, cough, tachypnea, and increased work of breathing (retractions and nasal flaring).
• Apnea in high-risk patients (less than 2 months old or premature).


Disseminated mycobacterial disease in infancy or early childhood

• AR deficiencies of IFN-γ receptor (or other elements in IFN-γ signaling pathway) lead to impaired IFN-γ-mediated immunity.
• Can cause disseminated mycobacterial disease in infancy or childhood, including disseminated infection by the BCG vaccine strain if administered.
• Once identified, patients require lifelong treatment with continuous antimycobacterial agents.
• Host defense against mycobacterial infections depends on interactions btw macrophages and T cells through the IFN-γ and IL-12 signaling pathway.
• IFN-γsecreted by TH1 cells or NK cells is key to elimination of these infections.


IFN-gamma signaling pathway

• Møs infected by mycobacteria produce IL-12, which stimulates TH1 cells and NK cells to produce IFN-γ.
• IFN-γ binds to its receptor on the Mø, leading to dimerization of receptor and activation of intracellular JAK1 and 2.
• STAT1 activation by JAK1 and JAK2 leads to nuclear translocation of STAT1 and transcription of IFN-γ-regulated genes that promote intracellular killing.
• IFN-γ also enhances viral and parasitic resistance by increasing MHC expression and intrinsic defense factors.


C3 deficiency

Predisposes to recurrent infections with encapsulated organisms.


C5-C9 deficiency

Predisposes to recurrent infections with Neisseria meningitidis or N gonorrhoeae. C5-C9 = membrane attack complex (MAC).


Isotype switching

• Isotype switching to IgE induced by IL-4
• Isotype switching to IgA induced by IL-5
• Occurs in naive B lymphocytes on initial exposure to antigen.
• Primarily induced by CD40 interaction with CD40L on T-helper cells, which then secrete IL-4 and IL-5.


HBV infection

• Worldwide, countries with high rates of HBV infection have more than 85% of all hepatocellular carcinoma (HCC) cases.
• Korea, Taiwan, Mozambique, and China have the highest annual rates of HCC.
• Individuals who develop HCC in those countries usually have chronic HBV infection acquired through vertical transmission at childbirth.
• In US, HCC normally arises after age 60, while in these countries with high rates of HBV infection, HCC commonly presents in adults 20-40 years old.
• Universal vaccination of children against HBV infection would likely cause a steep decline in worldwide incidence of HCC.


HBV phases of infection

1. Proliferative phase- entire virion and related antigens of the episomal HBV DNA are present. HBsAg and HBcAg are expressed with MHC Class I molecules on hepatocyte cell surface, activating cytotoxic CD8+ T lymphocytes, which respond by destroying infected hepatocytes.
2. Integrative phase- HBV DNA is incorporated into the host genome of those hepatocytes that survived the immune response. Infectivity ceases and liver damage tapers off when the antiviral antibodies appear and viral replication stops. However, risk of HCC remains elevated due to HBV DNA integration into host genome.


Features of systemic mycoses

• Cause pneumonia and can disseminate
• Dimorphic fungi: cold=mold, heat=yeast
• Exception: coccidioidomycosis is a spherule (not yeast) in tissue.
• Tx fluconazole/itraconazole for local infection.
• Tx amphotericin B for systemic infection.
• Systemic mycoses can form granulomas (like TB) but cannot spread person-to-person (unlike TB).



• Pneumonia-like sx caused by infection with Histoplasma capsulatum
• Location: Mississippi and Ohio River valleys
• Macrophages filled with Histoplasma (organisms smaller than an RBC).
• Histo "hides" within macrophages.
• Associated with bird (eg, starlings) or bat droppings and cave exploring
• Tx fluconazole/itraconazole for local infection
• Tx amphotericin B for systemic infection



• Pneumonia-like sx caused by infection with Blastomyces dermatitidis
• Location: Eastern US and Central America
• Inflammatory lung disease and can disseminate to skin and bone, causing granulomatous nodules.
• Broad-base budding (same size as an RBC).
• Blasto buds broadly.



• Pneumonia-like sx caused by infection with Coccidioides immitis or Coccidioides posadasii
• Location: Southwest US, California
• Pneumonia and meningitis, can disseminate to skin and bone
• Case rate increases after earthquakes, b/c spores in the dust are thrown into the air and inhaled by people, forming spherules in the lungs.
• Spherule filled with endospores (much larger than RBC)
• "San Joaquin Valley Fever"
• "Desert bumps" = erythema nodosum
• "Desert rheumatism" = arthralgias associated with dissemination.



• Caused by Paracoccidioides brasiliensis
• Location: Latin America
• Budding yeast with "captain's wheel" formation (much larger than RBC)
• PARAcoccidio PARAsails with the Captain's Wheel all the way to Latin America.
• Tx with fluconazole/itraconazole (local), Amphotericin B (systemic)



• Nagging Pests Must Breathe
• Nocardia
• Pseudomonas aeruginosa
• MycoBacterium tuberculosis
• Reactivation TB ---> predilection for lung apices


India ink stain

• Cryptococcus neoformans
• Mucicarmine can also be used to stain thick polysaccharide capsule red



• Present in both gram + and gram - bacteria
• Gene for exotoxin on plasmid or bacteriophage
• Polypeptide secreted from cell
• Fatal dose on order of 1 µg
• Induces high-titer antibodies called "antitoxins"
• Toxoids used as vaccines
• Ex. tetanus toxin, botulinum toxin, diphtheria toxin



• Organized polysaccharide layer that protects against phagocytosis
• Bacillus anthracis is only bacteria to have poly-D-glutamate capsule instead of polysaccharide


Charcoal-yeast extract agar buffered with cysteine and iron

• Legionella pneumophila
• Think: "Legionnaire (soldier) with SILVER helmet sitting at a campfire (CHARCOAL) with his IRON dagger - he is no sissy! (CYSTEINE)"
• Silver stain to see legionella, doesn't gram stain


Eosin-methylene blue (EMB) agar

• E. coli colonies grow with green metallic sheen
• Other lactose fermenters grow as purple/black colonies


Ecthyma gangrenosum

Rapidly progressive necrotic cutaneous lesion caused by Pseudomonas, typically seen in immunocompromised patients.


Obligate intracellular pathogens

• "Stay inside when it's Really CHilly COld!"
• Rickettsia
• Chlamydia
• Coxiella
• These pathogens rely on host ATP to replicate/survive and thus are obligate intracellular pathogens.


Facultative intracellular pathogens

• Some Nasty Bugs May Live FacultativeLY
• Salmonella
• Neisseria
• Brucella
• Mycobacterium
• Listeria
• Francisella
• Legionella
• Yersinia pestis


Ziehl-Neelsen stain

• Aka carbol fuchsin stain
• Stains acid-fast bacteria: Mycobacteria (stains mycolic acid in cell wall), Nocardia (weakly), protozoa (eg, cryptosporidium oocysts)
• Cheaper alternative with greater sensitivity but decreased specificity: auramine-rhodamine


Hemolytic Uremic Syndrome

• E coli 0157: H7
• Triad of anemia (MAHA), thrombocytopenia (platelet consumption), and acute renal failure (decreased RBF) due to platelet microthrombi on damaged endothelium.