LOs: 39-40 Flashcards Preview

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Flashcards in LOs: 39-40 Deck (19):
1

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)

2

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

3

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

4

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

5

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

6

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

1. Disseminated.
2. CNS.
3. SEM: Skin, Eye, Mouth.

1. Increase in HSV-2/HIV-1 seropositive individuals

7

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

8

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

9

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)

10

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

11

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

12

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

13

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

14

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

15

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

16

40 Chickenpox (Varicella zoster virus--VZV):

Virus Characteristics
- Family
- Disease course

Disease
- Transmission
- Primary infection
- Symptoms
- Secondary bacterial infection
- Reactivation

Treatment
- Varicella
- Herpes zoster

Vaccine
- Type
- Prevents...

VC
- Herpesvirus
- Establishes latency in sensory ganglia, but is disseminated

D
- respiratory route
- Varicella (chickenpox)
- Fever headaches, malaise preceding a exanthematous rash; rash begins on the face, scalp or trunk, and the vesicular lesions are very itchy, usually self-limiting
- From scratching
- Herpes zoster (shingles): lesions are clustered & dermatomal, painful

T
- Hygiene, bathing, topical dressings, Acyclovir
- Acyclovir

V
- Live attenuated (Varivax)
- Shingles

17

40 Smallpox:

Virus Characteristics
- Family
- Type
- Replication in...
- Reservoir
- Strains

Disease Characteristics
- Vaccination
- Infects...
- Requires...
- Symptoms
- Death

Vaccine
- Virus used
- Type
- Carriers
- Reservoir

Smallpox as a Biological Weapon

VC
- Poxviridae
- dsDNA
- Cytpolasm
- Humans
- Variola major (most virulent) & minor

DC
- Vaccination caused eradication
- Upper respiratory tract, then spreads to regional lymph nodes and throughout
body
- Close contact to spread
- Uniform pattern from maculopapules to vesicles to pustules and scabs
- Caused by bleeding, cardiovascular collapse, secondary infections

V
- Vaccinia
- 1 antigenic type
- No persistent carriers
- Humans (no animal)

Highly contagious with a high fatality rate

18

40 Human Papilloma virus vaccine:

Virus Characteristics
- DNA/RNA
- Envelope
- Capsule

Causes (2)

Genotypes
- Low risk (2)
- High risk (2)

Vaccine
- Virus
- Genotypes
- Induces...
- Given...

VC
- dsDNA
- Non-enveloped
- Encapsulated

C
- Genital warts
- Cervical cancer (rare)

G
- HPV 6 & 11
- HPV 16 & 18

V
- Virus like particle (VLP) non-infectious capsid like particle, no nucleic acids
- HPV 6, 11, 16, 18
- A strong neutralizing antibody response
- Before sexually active

19

40 Bordetella pertussis:

Bacterial Characteristics
- Type
- Aerobe/Anaerobe
- Growth
- Sensitivity

Whooping Cough
- Infects...
- Reservoir
- Disease course
- Most infectious
- Complications

Pathogenesis
- Entry
- Spread
- Trapped

Virulence Factors (5)

Transcriptional regulation of virulence gene expression (4)

Vaccine
- Type
- Complications
- Alternate version
- In adults

Causes of outbreaks (4)

BC
- gram(-) coccobacillus
- strict aerobe
- fastidious
- to the environment

WC
- children worldwide
- adults (get milder version)
- tracheitis and bronchitis, with accumulation of mucus, cells, and bacteria in the airways; mucociliary elevator is impaired; hemorrhages & vomiting
- early in infection
- secondary infections (such as pneumonia), physical sequelae, CNS abnormalities

P
- enters the trachea and bronchi by inhalation and attach to large airways
- rapidly multiplies & spreads along mucosa of lower respiratory tract
- trapped in cilia & mucus, becomes inflamed, destroys epithelial cells

VF
- adhesins: fliamentous hemagglutinin, pertussin toxin, pili
- pertussis toxin: A-B exotoxin, increases cAMP
- adenylate cyclase: increases cAMP
- tracheal cytotoxin derived from peptidoglycan: kills ciliated cells
- heat-labile toxin: local damage

T
- Bvg system (bvgA, bvgS) two component regulatory system
- BvgS senses environmental signals
- BvgA: transcriptional activator of virulence genes
- Induces transcription of toxin genes

V
- purified diptheria and tetanus toxoid proteins (DPT)
- fever, malaise, pain at injection site, neurologic symptoms
- acellular version (DtaP), adverse reactions much lower
- should be boosted

C
- poor vaccination rates
- genetic changes in B. pertussis due to vaccine pressure
- better diagnosis and reporting of cases
- reduced efficacy of acellular version of vaccine