DD Viral pathogenesis and Host reponse

Question 1

Tissue Tropism

Answer 1

the likeliness of a virus to infect tissues and not others; aka tissue specificity.

Question 2

Which virus is hardier, enveloped ones, or non-enveloped ones?

Answer 2

□ Enveloped viruses: fragile and sensitive
- thus needs to be transmitted via close contact

□ Non-enveloped: hardier, can withstand stresses
- thus often transmitted via- viral associated objects or fomites ( objects) and use respiratory or fecal/ oral routes.

Question 3

acute local disease (ie: common cold)

• incubation period
• virus shedding and transmission
• host responses
• likelihood of re-infection

Answer 3

• incubation period: short
• virus shedding and transmission: many serotypes are rapidly mutating, resulting in short lived immunity
• host responses: secretory IgA
• likelihood of re-infection: common

Question 4

acute systemic disease (ie: measles)

• incubation period
• virus shedding and transmission
• host responses
• likelihood of re-infection

Answer 4

• incubation period: long
• virus shedding and transmission: primary infxn in epithelium but can result in 2nd replication sites
• host responses: secretory IgA and serum IgG
• likelihood of re-infection: low

Question 5

Types of viral diseases

Examples

Answer 5

1. Acute local: common cold
2. Acute systemic: Smallpox, measles
3. Chronic: rubella in neonate
4. Latent: VZV in nerves
5. Slow/Progressive: AIDS

Question 6

Effects of viruses on infected cells:

Answer 6

1. CPE (Cytopathic effects)
2. Syncytia
3. Growth
4. Apoptosis

Question 7

CPE (Cytopathic effects)

Answer 7

any detectable morphological changes or inclusion bodies in host cell.

• Direct cell damage: *think what things virus can interfere with in the cytoplasm
• Indirect cell damage: integration of viral genome→ induction of mutations in host genome →inflammation and host immune response.

Question 8

Explain the interferon response and “anti-viral state”.

Answer 8

When the host cell is infected (bound) with the virus, it induces IFNs (interferes with viral infection of neighboring cells) which induces the anti-viral state.

Question 9

When a host cell is infected with a virus, what factors does it induce? What does that do?

Answer 9

IFNs → antiviral state

• results in some blockade of cell division, reduction of cell metabolism, increase in NK activity including IFNg production, ­ expression of APC, and may lead to apoptosis and more.

Question 10

What two ways are IFNs activated by viruses?

Answer 10

1. facilitated by dsRNA (virus)

2. TLRs and RLHs (retinoic acid inducible gene- like helicases)

Question 11

What does innate response to viruses depend on?

Answer 11

TLRs and Helicases (RLHs)

non specific, but immediate

Question 12

Type I IFNS and Type II IFNS

• what do they each consist of?
• Are they apart of innate or adaptive responses?

Answer 12

Type I IFNS: alpha and beta

Type II IFNS: gamma

• Both are innate

Question 13

What produces:
Type I IFNS

Type II IFNS

Answer 13

Type I IFNs (IFN alpha and beta) produced by most infected cells within hours of infection

Type II IFNs (IFN gamma) produced by T cells and NK cells, (more restricted)

Question 14

IFNs induce the antiviral state how? (mechanism)

Answer 14

IFNs bind to specific receptors on cells → signal through JAK/State pathway and control Type I and Type II genes → induce transcription of genes = antiviral state.

Question 15

IFNs can involve mediators such as PKR and OAS when activating the antiviral state. What do each of them do?

Answer 15

□ PKR (protein kinase): phosphorylate and inactivate translation (tln) initiation factor to decrease protein synthesis

□ OAS: activates a cellular ribonuclease that degrades mRNA

Question 16

2 types of viral Adaptive Responses

Answer 16

1. humoral

2. cell mediated

Question 17

Humoral Response:

Answer 17

Ab produced during primary virus infections are usually of lower affinity. It is not until later that they bind with higher affinity, most Ab being IgM (unswitched).

§ BIG PICTURE: humoral response is important for recognition of virions.

Question 18

Which Ig inhibits fusion of enveloped viruses with host membranes

Answer 18

IgG

Question 19

Cell-Mediated Response:

Answer 19

CTLs lyse/clear virus-infected cells

NK and macrophages kill infected cells directly or by Ab-dependent cell-mediated cytotoxicity (ADCC)

Question 20

Between Th1 and Th2 which one “skews” toward humoral response and which towards cell-mediated?

Answer 20

Th1 differentiation skews towards cell-mediated immunity and inflammation

Th2 differentiation skews toward humoral response

Question 21

Compare antibodies produced in primary and secondary responses.

Answer 21

• 1° response: Abs are usually of lower affinity than those produced later.
  
  • 2° Response: Already has Abs of greater affinity and there is a faster increase in that AB both due to immunological memory.

Question 22

List and describe major cell types involved in anti-viral responses.

Answer 22

1. Mononuclear phagocytes: phagocytosis, release of inflammatory mediators, Ag presentation
2. DC: APC, stimulate B cell diff and prolif, modulator of development of adaptive immune response, secrete antiviral and immunoregulatory cytokines.
3. NK cells- serve to contain infection while
   CTL cells are produced by adaptive immune response which can then clear infection.
4. Granulocytes- PMNs, basophils, and eosinophils

Question 23

Which Ig inhibits virion/host attachment, neutralizes toxins and enzymes

Answer 23

IgA