LOs: 39-40 Flashcards
39 Definitions:
Persistence
Latency
Reactivation
Carrier State
ability of a pathogen to remain long-term within the host
persistent infection in which the pathogen is quiescent, no overt disease
persistent/latent pathogen re-enters productive replication
infected individual that displays no overt disease (reservoir)
39 How Pathogens Modulate the Host Response to Establish Persistence (5)
Infection and destruction of host immune cells
Establish latency
Induction of autoimmune disease
Antigenic variation of major surface antigens
Molecular mimicry of host molecules
39 How Pathogens Modulate the Host Response to Establish Persistence:
Infection and destruction of host immune cells (5)
Establish latency (7)
Induction of autoimmune disease (1)
Antigenic variation of major surface antigens (4)
Molecular mimicry of host molecules (2)
a. HIV: T-cells
b. Mycobacteria: macrophages
c. EBV: B-cells
d. Trypanosomes: macrophages
e. CMV: T-cells and macrophages
a. EBV: B-cells
b. HSV-1: trigeminal ganglion neurons.
c. HSV-2: dorsal root ganglion neurons
d. VZV: neurons and glia
e. CMV: monocytes
f. HPV: keratinocytes
g. HIV: resting T-cells
a. Streptococci: M-protein
a. Trypanosomes: switch in major surface antigen
b. Influenza virus: antigenic shift/drift in HA and NA
c. HIV: antigenic variation in gp120/gp41
d. Neisseria: pillin switching
a. Treponema: block ADCC.
b. Neisseria: group B capsular polysaccharide
39 Herpes simplex virus (HSV):
Biological Characteristics
- Family
- Viruses (8)
- Serotypes (2)
Reservoir
Virus particle (4)
Reservoir/Transmission
Virulence Factors (4)
Pathogenesis (3)
Diagnosis (7)
- Important for…
Prevention/Treatment (6)
BC
- herpesvirus
- HSV-1, HSV-2, VZV, CMV, EBV, HHV6, HHV7, KSHV
- HSV-1 (orofacial > genital lesions) & HSV-2 (genital > orofacial lesions)
R
- Humans
VP
- envelope: acquired from host
- tegument: surrounds capsid
- capsid: icosahedral
- DNA genome: linear dsDNA
R/T
- R: humans (widespread, not seasonal)
- T: spread by intimate (STD) or direct contact (secretions, respiratory droplets, mucosal surfaces, skin abrasions)
VF
- Viral DNA synthesis: maintain nucleotide pools in quiescent cells (thymidine kinase & ribonucleotide reductase)
- Control host cell function: shut-off protein synthesis and block apoptosis (UL41 & g34.5)
- Control host cell function: toxicity/apoptosis (ICP0)
- Immune regulation: block complement, antibody and Ag recognition (gE/gI, gC, & ICP47)
P
- vesicular lesion formation: cytopathic effects, inflammation
- virus shedding: even in presence of high levels of neutralizing antibody
- CMI response: resolving lesions
D
- clinical exam
- serologic tests
- Tzanck smear stain
- direct virus isolation
- FISH
- PCR
- important for pregnant women b/c of asymptomatic shedding
P/T
- barrier methods
- ART: acyclovir, penciclovir
- drugs to block viral entry
- cesarean delivery
- vaccines not yet effective
- gene therapy
39 Herpes simplex virus (HSV):
Lytic Life Cycle (6)
Latent infection of neurons (5)
Recurrent Infection / Reactivation (5)
LLC
- attachment: heparan sulfate, HveA, & HveC
- entry: fusion at cell surface, receptor-dependent
- transcriptional cascade
- DNA replication: nuclear
- assembly: nuclear
- egress: cell death
LioN
- Spread: retrograde axonal transport to PNS
- DNA persists as an extrachromosomal circular episome
- Absence of lytic gene proteins
- Expression of Latency-Associated Transcript (LAT)
- No overt disease.
RI/R
- Stimuli: UV, surgery, stress, trauma, hormones, immune
- Virus re-enters lytic cycle
- Anterograde axonal spread from PNS to site of primary infection
- Asymptomatic virus shedding
- No apparent lysis of virus-infected neurons
39 Herpes simplex virus (HSV):
Severity of primary infection
Severity of recurrent infection
Complications Detected in Immunocompromised Patients
- Neonates (3)
- AIDS (1)
- Correlates with increased frequency of reactivation
- Correlates with increased duration of reactivation
- Correlates with increased viral load
- Usually lesions are more severe with longer duration
- Varies with serotype
- Varies with between herpesviruses
- Spread to CNS: encephalitis.
- Usually lesions are less severe with decreased duration.
- Exception: Herpetic stromal keratitis (HSK) where corneal opacity results from CMI response to virus-infected corneal stromal cells due to frequent recurrences
- Disseminated.
- CNS.
- SEM: Skin, Eye, Mouth.
- Increase in HSV-2/HIV-1 seropositive individuals
39 Definitions:
Benign tumor
Malignant tumor
Indirect tumor formation
Direct tumor formation (2)
Oncogene
Proto-oncogene
Tumor suppressor gene
Non-metastatic
Metastatic, spread to other tissues/sites within the host
Disruption of cellular processes usually involving DNA replication
- Mediated by outside source, bacterial or viral pathogen
- Direct expression of an oncogene encoded by a bacteria or virus
Gene product capable of cell transformation
Normal cellular gene that when improperly regulated is capable of cell transformation
Normal cellular gene capable of suppressing oncogene products
39 Direct Tumor Formation:
Mechanisms & Examples (3)
Examples (2)
(1) Insertional inactivation
- Mutation of a crucial cellular gene such as a tumor suppressor involved in the regulation of cell DNA synthesis/repair
- Ex. Retroviruses, HPV
(2) Integration of promoter directly upstream of proto-oncogene
- Overexpression or disregulation of normal cellular proto-oncogene by cis-activation
- Ex. Retroviruses
(3) Bacterial/viral protein activates transcription of proto-oncogene
- Overexpression or disregulation of normal cellular proto-oncogene by trans-activation
- Ex. HTLV-1
(1) Avian oncoretroviruses: express altered proto-oncogenes
- Growth factors
- Receptors
- Receptor-kinases
(2) HPV.
- E6 binds and degrades p53 tumor suppressor protein
- E7 binds and sequesters Rb tumor suppressor protein
39 Human papillomavirus (HPV):
Biological Characteristics
- Family
- Genomes
- Genes
- Isolates
Benign associated tumors (6)
Malignant associated tumors (2)
Replication (4)
Reservoir/Transmission
Virulence Factors
- Entry
- Integration
Pathogenesis
Diagnosis (4)
Prevention/Treatment
- All
- Benign (2)
- Malignant (5)
BC
- Papovaviruses (papillomaviruses)
- Circular dsDNA
- 5-7 early (transcription & replication), 2 late (capsid proteins)
- 70 benign, 40 malignant lesions
B
- Skin warts
- Anogenital warts
- Laryngeal warts
- Oral papillomatosis
M
- Cerivcal cancer
- Oropharyngeal cancer
R
- Species & tissue specific
- No cell culture system (new raft system)
- Maintained in basal cells as episome (no replication or transcription)
- As basal progresses through proliferation, early genes –> late genes –> virus
R/T
- R: humans (STI)
- T: direct contact, vertical transmission
VF
- Enter and remain in latency in keratinocytes
- Inactivation of E1 or E2 genes –> integration into host DNA –> up-regulation of E6 &E7 oncogenes –> transformation
P
- Transformation –> hypertrophy (reversible by E2 expression, depends on serotype)
- Benign & skin or mucosal lesions (90%, HPV 6 & 11)
- Metastatic disease: cervical carcinoma (80%, HPV 16 & 18), slow developing, cervical intraepithelial neoplasia
D
- Clinical exam /w biopsy
- PAP smear
- FISH
- PCR
P/T
- Barrier method
- Spontaneous regression, surgical removal if painful
- Topical agents, cryotherapy, surgery, inferferons, vaccination (quadrivalent & bivalent)
40 Definitions:
Vaccine
Immunization
Active immunization
Passive immunization
Toxoid
Adjuvant
Sterilizing immunity
Herd immunity
A suspension of microorganisms (live attenuated or killed) or fractions of
microorganisms, administered to induce immunity and prevent disease
Artificially inducing an immune response or providing protection against an infectious disease
Inducing the body to mount a protective immune response
Transferring exogenous antibody for temporary protection
Bacterial toxin rendered non-toxic and used to stimulate anti-toxin antibodies
Mixed with the vaccine components to induce a
stronger immune response (“danger signal)
An immune response that completely eliminates the infection
The resistance of a population to an infectious agent due to the immunity of a high proportion of the population
40 Types of Vaccines:
- Two characteristics
- Examples
Live attenuated microorganisms (6)
Killed/inactivated microorganisms (3)
Subunit vaccines (5)
a. microbe is rendered relatively avirulent
b. replicates in the recipient, inducing a strong immune response; protection is long-lived and only one dose is necessary
c. Examples: measles, mumps, rubella, smallpox, BCG, oral polio
a. organism is killed, requires more than one dose, and boosters are also necessary
b. induces an antibody response.
c. Examples: whole pertussis, inactivated polio vaccine, hepatitis A
a. purified components of microorganisms, such as toxoids, recombinant antigens, polysaccharides conjugated to carrier proteins.
b. repeated doses are needed, with adjuvant, and antibody responses are induced
c. Examples: hepatitis B vaccine, tetanus, diptheria, Hib, acellular pertussis
40 Required vaccines for children in the US (11)
Hepatitis B vaccine (HBV)
Diptheria, pertussis, tetanus (DTaP)
Inactivated polio vaccine (IPV)
Haemophilus influenzae type b
(Hib)
Chickenpox (varivax)
Measles, mumps, rubella (MMR)
Pneumococcal vaccine (PCV)
Hepatitis A
HPV quadrrivalent vaccine
Influenza
Rotavirus
40 Mumps:
Virus Characteristics
- Family
- Type
- Serotypes
Disease
Symptoms
Complications
Vaccine
- Type
- How many
- Given…
VC
- Paramyxoviridae
- ssRNA(-)
- 1 serotype
D
- Acute viral infection with swelling and tenderness of the parotid and salivary glands
S
- fever, malaise, headache, involvement of parotid and salivary glands (benign)
C
- meningitis and epididymo-orchitis
V
- Attenuated virus grown in chick embryo cell culture
- Single immunization
- Given at >12 months of age, to avoid maternal antibodies
40 Measles:
Virus Characteristics
- Family
- Type
- Membrane glycoproteins
Disease
Symptoms (2)
Complications
Vaccine
- Type
- Immunity
- Given…
VC
- Paramyxoviridae
- ssRNA(-)
- Hemagglutinins and the F (fusin) protein
D
- Contagious
- Respiratory transmission
S
- Malaise, fever, runny nose, respiratory symptoms (cough) precede the rash
- Rash: begins on face, proceeds down body, with extremities last. Erythematous and maculopapular
C
- Respiratory tract complications
- Neurologic (encephalitis)
- Long term immunosuppression
V
- Live attenuated virus
- Antibody and T cell-mediated, long-lasting immunity
- Given at 12-15 months of age because of maternal antibodies
40 Rubella (German Measles)
Virus Characteristics
- Family
- Type
Disease
- Transmission
- Postnatal
- Congenital
Vaccine
- Type
- Rationale
VC
- Togaviridae
- ssRNA(+)
D
- Respiratory
- Subclinical infection, rash develops in symptomatic individuals
- Infection in early gestation very dangerous, can lead to fetal death, premature delivery and congenital defects, such as deafness, myopia, heart disease, mental retardation
V
- Live attenuated
- Prevent congenital rubella by controlling postnatal rubella
