Immunity to viruses: A Brief Review

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Immunity to virusesA Brief Review
Nancy L. Haigwood, Ph.D. haigwood_at_u.washington.edu
Innate Immunity
Acquired Immunity
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Immunity to microbes Innate
Prevent entry
Host Cell
Virus
Intact barriers
Bacterium
IFNs TNF-a
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Immunity to viruses Acquired

• Discrimination between pathogens/self
• Antigen specificity
• Diversity of responses
• Self-limiting
• Immunologic memory

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Acquired immunity the key players
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The antigen-presenting cell
Virus
Exogenous
Endogenous
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T cell Antigen Receptor
T lymphocytes Immunoglobulin shape Tetramer of
large (alpha) and small (beta) chains Variable
and constant domains Four CD3 proteins (g, d, e,
?)
CD8 or CD8
V
V
outside
V
C
C
V
C
C
T-cell receptor
inside
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Antigen Processing
Endogenous pathway Virus infection and protein
synthesis Proteasome degradation TAP transfer
to ER Affinity binding/selection to Class
I Golgi transport Complex localized in cell
membrane
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MHC Class I Antigen Processing
Internal protein expression after infection
MHC Class I
CD8
V
V
V
C
C
V
C
C
CD8 T cell Cytotoxic cell
T-cell receptor
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Antigen Processing
Exogenous pathway Endocytosis and
proteolysis Class II is expressed into the
ER Transported to Golgi, fused with
endosome Peptides complexed in the cell membrane
External protein
CD4
V
V
V
C
C
V
C
C
T-cell receptor
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MHC Class II Antigen Processing
Antigen processing without expression
APC, B cells, DCs, macroph.
MHC Class II
External protein
CD4
V
V
V
C
C
V
C
C
CD4 T cell T-helper cell
T-cell receptor
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B cells and antibody
IgM, IgD
IgM
IgG, IgA, IgE
Th
Antibody secreting cell
Antigen
Y
Y
Proliferation Isotype switch Affinity maturation
Y
Y
Enhance phagocytosis Neutralize Activate
complement
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Antibody isotype and immunity
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Humoral and CMI comparison
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Specificity, memory, self-limitation
Antigen X
Antigen X
IgG response
X-specifc Antibody titers
IgM response
2
4
6
8
10
12
Weeks
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Post-infection immune responses
Illness
Viral titers
CTL
Antibody
7
14
28
35
0
Days post-infection
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Immunological goal of vaccination
CTL
Antibody
CTL
Antibody
Illness
Vaccine
Infection
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Designing vaccines local vs. systemic responses
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Designing vaccines immunological considerations

• Correlates of protective immunity
• Location of viral entry
• Immunological status of host
• Targeting effector populations
• Cellular and/or humoral
• Composition of antigen/immunogen
• Viral latency

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Current live antiviral vaccines

• Polio (Sabin)
• Measles
• Mumps
• Rubella
• Yellow Fever
• Vaccinia (smallpox)
• Varicella (chicken pox)
• Influenza

• Antibody
• CD4 T cell
• CD8 T cell
• All viral antigens
• Months/years immunity
• Cross protection
• Disease risk

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Current dead antiviral vaccines

• Influenza
• Rabies
• Hepatitis B
• Polio (Salk)

• Antibody
• CD4 T cell
• --- CD8 T cell
• Not all viral antigens
• Months of immunity
• Cross protection
• ---Risk of disease

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Viral Immune Evasion

• Inducing immunosuppression
• Infect B or T cells
• Infect the thymus and induce tolerance
• Destroy specialized APCs
• Evading antibody responses
• Mutation or viral sequences
• Replacement of viral proteins
• Down-regulation of viral proteins
• Evading T cell responses
• Infect cells lacking Class I MHC
• Inhibit MHC function
• Down-regulate viral protein expression
• Mutation of viral protein T cell epitopes