Host Response To Viral Infection

Question 1

Describe the different ways hosts respond to viral infections.

Answer 1

Question 2

Describe innate immunity.

Answer 2

-no antigen specificity or memory
-first defense against viral inf bc:
>always present
>immediately after viral inf
>only immune defense for the first few says after viral inf

Question 3

Describe innate immunity - primary physical & chemical defenses.

Answer 3

1. Skin
   -keratin outer layer (mechanical barrier), low pH, FA, dry
2. Mucous membrane
   -virucidal proteins
3. GIT
   -MM of oral cavity & esophagus
   -acidity of stomach & alkalinity of intestine
   -layer of mucus in gut
   -lipolytic bile
   -proteolytic pancreatic enzymes
   -defensins (host defense peptides) antiviral
   =modulate IR
4. Respiratory tract
   -mucociliary blanket
   -temp gradient: between nasal passage (33c) & alveoli (37c) = localize inf
   >rhinoviruses inf nasopharynx (common cold) = replicate at 33c but not at 37c
   >influenza virus (LRT) = inverse temp preference

Question 4

Describe innate immunity - NK cells.

Answer 4

-death of virus via apoptosis
-syn & release cytokines like type II IFN & interleukins = stim own prolif & cytolytic activity

Question 5

Describe innate immunity - PRR.

Answer 5

-cells at portals of virus entry = surface receptors (PRR) that recog specific PAMPs
-one class of PRRs = TLRs

Question 6

Describe innate immunity - interferons.

Answer 6

-cytokines (complex glycoproteins) secreted by somatic cells in resp to viral inf & other stim
-antiviral, immunomodulation, anticancer
-no virus specificity
-RNA virus induce INF more strongly than DNA viruses
-INF orally inactive = administered via parenteral route (inj)

Question 7

Describe the different types of interferons of innate immunity.

Answer 7

based on antigenic & chemical differences
1. Type I
-INFa:
>leukocyte interferon
>made in lg quantities by plasmacytoid dendritic cells
-IFN B
>secreted by virus inf fibroblast
2. Type II
-IFNy
>immunoregulatory
>made by antigen stim T cells & NK cells
3. Type III
-IFNy1, IFNy2, IFNy3
>recent discovery
>in resp to viral inf & activation of TLRs
>immunoregulator

Question 8

Describe the roles of Type I IFNs in innate immunity.

Answer 8

1. Inhibit virus replication in host cells
2. Activate NK cells to kill inf cells
3. Inc expression of MHCI & antigen presentation
4. Stim differentiation of monocytes into dendritic cells
5. Maturation of dendritic cells
6. Stim memory T cell prolif

Question 9

Describe how type I IFNs inhibit virus replication in innate immunity.

Answer 9

-activate latent ribonuclease ‘RNAse L’ -> degrades viral RNA
-syn Mx proteins that bind & trap viral nucleocapsid & inhibit virus assembly
-syn of protein kinase R (PKR) = prevent initiation of translation of viral RNA

Question 10

Describe adaptive immunity.

Answer 10

1. Humoral & cellular immunity
2. Humoral = Ab released from B lymphocytes
3. Cellular = T lymphocytes
4. Antigen specific -> take days to develop
   >mediated by lymphocytes that have surface receptors specific to each pathogen
5. Long term memory after inf
6. Internal viral antigens -> protective cell mediated immune (CMI) response
7. Surface antigens -> protective humoral & CMI resp

Question 11

Describe antibody mediated immunity (humoral immunity) - adaptive immunity.

Answer 11

-Ab directed against viral proteins on free virions (capsid or envelope) OR against viral proteins expressed on surface of inf cells

Question 12

Describe antiviral effects of antibodies - adaptive immunity.

Answer 12

1. Virus neutralization
   -neutralizing antibodies prevent virus attachment & entry into host cells
   -bind to viral capsid or host envelope
2. Opsonization
   -coating of virions w ab
   -ab coated virion recog & phagocytosis by macrophages (sometimes neutrophils)
3. Clumping of viruses (immunocomplex formation)
4. Activation of complement system
5. Antibody dependent cell mediate cytotoxicity

Question 13

Describe cell mediated immunity of adaptive immunity.

Answer 13

Question 14

Describe evasion of the immune system.

Answer 14

1. Antigenic plasticity
   -rapid change in structure of viral ag = result of mutation, reassortment, recombination
   -change in ag structure = virus become resistant to immunity gen by prev inf
2. Antigenic multiplicity
   -antigenic variants w little to no cross reactivity
3. Neg cytokine regulation
   -virokines: virus syn proteins that are homologs of cytokines/interferons
   -viroreceptors: virus encode proteins that are homologous to the receptors for cytokines
4. Down reg MHC I
5. Inhibition of complement activation
6. Evasion of neutralizing antibodies
7. Latency
8. Cell to cell spread of viruses
9. Inhibition of apoptosis