---

Comprehensive Microbiology & Immunology Review

---

1. HERPES VIRUSES (CMV, EBV, HSV)

HSV-1 and HSV-2

• Herpes encephalitis: most common fatal sporadic encephalitis; temporal lobe hemorrhagic necrosis; treat with IV acyclovir
• Herpes keratitis: dendritic ulcer on fluorescein staining

CMV (HHV-5)

• Transmission: saliva, urine, blood, sexual, congenital (most common congenital viral infection)
• Immunocompetent: usually asymptomatic or mononucleosis-like (heterophile-negative)
• Congenital CMV: sensorineural hearing loss, periventricular calcifications, "blueberry muffin" rash, chorioretinitis, microcephaly, jaundice
• Immunocompromised (AIDS, transplant): CMV retinitis (cotton-wool spots, pizza-pie fundus), colitis (linear ulcers), pneumonitis, esophagitis, hepatitis
• Histology: "owl-eye" intranuclear inclusions in enlarged cells
• Treat: ganciclovir, valganciclovir

EBV (HHV-4)

• Causes Infectious Mononucleosis (mono)
• Transmission: saliva ("kissing disease")
• Latency in B cells; replicates in oropharyngeal epithelium
• Manifestations:
  • Fever, severe pharyngitis/tonsillitis, posterior cervical lymphadenopathy
  • Splenomegaly (risk of rupture - avoid contact sports!)
  • Hepatitis (90% have abnormal LFTs)
  • Atypical lymphocytosis (CD8+ T cells reacting against infected B cells)
  • Maculopapular rash if given ampicillin/amoxicillin
• Heterophile antibody (Monospot test): positive IgM antibody that agglutinates sheep/horse RBCs; specificity 99%, sensitivity lower in first week
• Complications: Burkitt lymphoma (t(8;14) c-myc), nasopharyngeal carcinoma, CNS lymphoma (immunocompromised), post-transplant lymphoproliferative disorder, hairy leukoplakia, Hodgkin lymphoma

---

2. EBOLA VIRUS

• Classification: RNA virus, family Filoviridae (filamentous shape, from Latin "filo" = thread)
• Other filovirus: Marburg virus
• Reservoir: fruit bats
• Transmission: direct contact with blood/body fluids of infected individuals
• Manifestations:
  • Incubation 2-21 days
  • Sudden fever, severe headache, muscle pain, weakness
  • Vomiting, diarrhea, abdominal pain
  • Unexplained hemorrhage (DIC - diffuse intravascular coagulation)
  • Rash, impaired kidney/liver function
  • Multi-organ failure, shock
• Pathogenesis: Infects monocytes/macrophages -> suppresses innate and adaptive immunity -> cytokine storm
• Replicates in liver, spleen, lymph nodes, GI tract, lungs
• Mortality: 25-90% depending on strain
• BSL-4 pathogen

---

3. PARASITES (Names + Key Manifestations)

Protozoa

Helminths

---

4. ZIKA VIRUS COMPLICATIONS

• Family: Flaviviridae (same as dengue, West Nile, yellow fever)
• Transmission: Aedes mosquito, sexual contact, vertical (mother to fetus), blood transfusion
• Adult symptoms: Usually mild - fever, rash, joint pain, conjunctivitis; 80% asymptomatic
• Complications:
  • Congenital Zika syndrome: Microcephaly (most feared), intracranial calcifications, ventriculomegaly, eye abnormalities (macular scarring), arthrogryposis, hearing loss
  • Guillain-Barre Syndrome (GBS): ascending paralysis, weeks after infection - most important adult neurological complication
  • Neonatal neurological abnormalities

---

5. PARVOVIRUS B19

• Classification: ssDNA virus (smallest DNA virus; only pathogenic parvovirus in humans)
• Tropism: infects erythroid precursors (requires P antigen receptor)
• Transmission: respiratory droplets (viremic phase)
• Diseases:
  1. Fifth disease (Erythema infectiosum) - children: "slapped cheek" rash, then lacy reticular rash on trunk/limbs; by time rash appears, child is no longer contagious
  2. Aplastic crisis - patients with hemolytic anemias (sickle cell, spherocytosis): sudden severe anemia; can be fatal if untreated
  3. Hydrops fetalis - pregnant women in first/second trimester: fetal anemia, heart failure, death
  4. Chronic anemia - immunocompromised patients
  5. Polyarthropathy - adults, especially women; symmetric small joint arthritis mimicking RA
  6. Papular-purpuric gloves-and-socks syndrome - adults; purpuric rash on hands and feet

---

6. PAPILLOMAVIRUS (HPV) - MANIFESTATIONS

• Classification: dsDNA virus, non-enveloped; >100 types
• Low-risk types (6, 11): benign lesions
  • Condyloma acuminata (anogenital warts): soft, cauliflower-like growths
  • Laryngeal papillomatosis (recurrent respiratory papillomatosis) - types 6, 11
  • Common warts (verruca vulgaris) - type 2
  • Plantar warts (verruca plantaris) - type 1
  • Flat warts - type 3, 10
• High-risk types (16, 18): oncogenic
  • Cervical carcinoma (most important; HPV 16 = squamous cell, HPV 18 = adenocarcinoma)
  • Anal, vulvar, vaginal, penile, oropharyngeal carcinomas
  • CIN (cervical intraepithelial neoplasia)
• Mechanism of oncogenesis: E6 protein degrades p53; E7 protein inactivates Rb
• Koilocytes on Pap smear (perinuclear halo, raisin-like nucleus)

---

7. CONTAMINATED WATER BACTERIA

---

8. POX VIRUSES (Cowpox focus)

• Family: Poxviridae; largest DNA viruses; replicate in cytoplasm (unique!)
• Members:
  • Variola (Smallpox): eradicated 1980; pustular rash all at same stage, centrifugal distribution; high mortality
  • Vaccinia: used in smallpox vaccine (live attenuated)
  • Cowpox: infects cattle; causes localized pustular lesion on hands of milkmaids; Edward Jenner used cowpox to develop smallpox vaccine (1796); transmitted from infected animals
  • Monkeypox: zoonosis; similar to smallpox but milder; lymphadenopathy (distinguishes from smallpox); central Africa; 2022 outbreak (mpox)
  • Molluscum contagiosum: umbilicated papules; Henderson-Patterson bodies (molluscum bodies) on histology
  • Orf (ecthyma contagiosum): infects sheep/goats; pustular lesion on hands
• Cowpox manifestations: Painful red papule -> vesicle -> pustule -> eschar on hands; mild systemic symptoms; self-limiting in immunocompetent

---

9. HEPATITIS B, C, AND D - MANIFESTATIONS

Hepatitis B (HBV)

• dsDNA virus, Hepadnaviridae; partially double-stranded
• Transmission: blood, sexual, perinatal (vertical - most common route of chronicity)
• Acute: RUQ pain, jaundice, nausea, vomiting, elevated AST/ALT, dark urine
• Chronic (>6 months): hepatitis, cirrhosis, hepatocellular carcinoma (HCC)
• Extrahepatic manifestations:
  • Polyarteritis nodosa (PAN) - immune complex mediated
  • Membranous nephropathy, membranoproliferative GN
  • Serum sickness-like prodrome (urticaria, arthritis, fever)
  • Aplastic anemia
• Serology: HBsAg (active infection), HBeAg (high infectivity), Anti-HBs (immunity), Anti-HBc IgM (acute), window period (only Anti-HBc positive)

Hepatitis C (HCV)

• ssRNA virus (+sense), Flaviviridae; genotype 1 most common in USA
• Transmission: primarily blood (IVDU #1, transfusion pre-1992); sexual less efficient; rarely vertical
• Acute: usually asymptomatic (80%); mild jaundice
• Chronic (75-85% of acute cases become chronic): most common chronic bloodborne infection in USA
• Manifestations:
  • Cirrhosis (#1 cause of liver transplant in USA)
  • HCC
  • Essential mixed cryoglobulinemia (type II) - arthritis, purpura, peripheral neuropathy, glomerulonephritis
  • Membranoproliferative GN
  • Porphyria cutanea tarda (photosensitive blistering, fragile skin)
  • Non-Hodgkin lymphoma (B-cell)
  • Sjögren's-like syndrome
  • Lichen planus
• Treatment: Direct-acting antivirals (DAAs) - sofosbuvir/ledipasvir; >95% cure

Hepatitis D (HDV)

• RNA virus; defective/incomplete - requires HBsAg for assembly and transmission
• Can only infect patients with HBV (co-infection or superinfection)
• Transmission: same as HBV (blood, sexual)
• Co-infection (HBV+HDV simultaneously): self-limited in most; higher risk of fulminant hepatitis
• Superinfection (HDV in chronic HBV carrier): worst prognosis; rapidly accelerates to cirrhosis; high risk of fulminant hepatitis; HDV superinfection dramatically worsens HBV
• Prevention: HBV vaccination prevents HDV (since HDV requires HBV)

---

10. PRIONS

• Definition: Proteinaceous infectious particles; no DNA or RNA (only protein)
• Mechanism: Normal prion protein (PrP^C) is alpha-helical; abnormal prion (PrP^Sc) is beta-sheet rich; PrP^Sc acts as a template, converting PrP^C to PrP^Sc - exponential accumulation
• Properties: Resistant to heat, UV, proteases, formaldehyde; autoclave does NOT reliably destroy; incineration is best
• Diseases (Transmissible Spongiform Encephalopathies - TSEs):

• CJD manifestations: Rapidly progressive dementia, myoclonus, ataxia, visual disturbances, death within 1 year; EEG: periodic sharp-wave complexes; MRI: basal ganglia/cortical signal on DWI; CSF: 14-3-3 protein
• Histology: Spongiform change (vacuoles), neuronal loss, gliosis, amyloid plaques (kuru plaques in vCJD)

---

11. POLIO VACCINE - IMMUNITY

• OPV induces gut mucosal immunity (prevents viral shedding) - key for eradication
• IPV induces serum neutralizing antibodies (IgG) - prevents viremia and paralysis
• The switch to IPV in USA occurred because wild poliovirus was eliminated and VAPP risk became unacceptable

---

12. HYPERSENSITIVITY - ALL 4 TYPES

• Type I: Immediate (minutes); late phase reaction (hours) via leukotrienes
• Type III: 6-24 hrs (Arthus) or days (serum sickness)
• Type IV: 48-72 hours (delayed)

---

13. WHICH CELLS ACTIVATE CD8, Th1, Th2

CD8+ T Cell (Cytotoxic T Lymphocyte) Activation

• Activated by: MHC Class I + antigen presented by dendritic cells (and other APCs)
• Require co-stimulation: CD28-B7 interaction
• Require help from CD4+ Th1 cells: IL-2 from Th1 drives CD8 proliferation
• Kill target cells via: perforin/granzyme, Fas-FasL pathway
• Recognize endogenous/intracellular antigens (viruses, intracellular bacteria, tumor cells)

Th1 Cell Activation

• Naïve CD4+ T cell differentiated into Th1 by: IL-12 (from macrophages/dendritic cells) and IFN-γ
• Activated by: MHC Class II + antigen on APCs (dendritic cells, macrophages, B cells)
• Key transcription factor: T-bet
• Functions:
  • Secretes IFN-γ -> activates macrophages (classical activation) -> kills intracellular bacteria
  • IL-2 -> stimulates CD8+ T cell proliferation
  • Mediates Type IV hypersensitivity
  • Promotes opsonizing IgG antibodies
• Fights: intracellular pathogens (MTB, Leishmania, Listeria, viruses)
• Inhibited by: IL-4, IL-10 (Th2 cytokines)

Th2 Cell Activation

• Naïve CD4+ T cell differentiated into Th2 by: IL-4 (early source: mast cells, basophils, NKT cells)
• Key transcription factor: GATA-3
• Functions:
  • Secretes IL-4, IL-5, IL-13
  • IL-4 -> promotes IgE class switching (allergy)
  • IL-5 -> eosinophil activation/survival
  • IL-13 -> mucus production, smooth muscle contraction
  • Promotes B cell differentiation and antibody production (especially IgE, IgA)
• Fights: extracellular parasites (helminths)
• Inhibited by: IFN-γ (Th1 cytokine)

• CD8 = MHC I + IL-2 (from Th1) + DC
• Th1 = IL-12 from macrophage/DC -> fights intracellular bugs
• Th2 = IL-4 from mast cells -> fights parasites, drives allergy

---

14. GIANT CELL - RELATED CONDITIONS

---

15. HETEROPHILE ANTIBODY

• Definition: IgM antibodies that cross-react with antigens from other species (not the causative pathogen)
• Clinical significance: EBV (Infectious Mononucleosis)
• Tests:
  1. Monospot test (rapid): Patient IgM agglutinates horse RBCs; specificity 99%; sensitivity lower in first week (up to 25% false-negative in week 1), 5-10% in week 2
  2. Paul-Bunnell test: agglutination of sheep or horse RBCs; absorbed with guinea pig kidney (removes Forssman Ab) vs beef RBCs (removes serum sickness Ab); EBV mono leaves only the beef RBC-absorbed antibody positive
• EBV heterophile Ab characteristics:
  • Not directed against EBV antigens specifically
  • IgM class
  • Appear during acute infection
  • May persist weeks to months
  • False negatives in young children (<4 yrs) - use EBV-specific serology (VCA-IgM, EA, EBNA)
• Causes of heterophile-negative mono: CMV (most common!), HIV acute seroconversion, toxoplasmosis, HHV-6 (roseola), adenovirus

---