Immune response to viruses

transcript

Yoavanit Srivaro M.D.

Outlines

• Definition and Properties of a Virus

• Viral replication

• Innate immune response to viral infection

• Adaptive immune response to viral infection

• Immune Evasion by Viruses

Outlines

Definition and Properties of a Virus

• Filterable agents

• Obligate intracellular parasites

• Can not make energy/proteins without host cell

Murray PR, Rosenthal KS, Pfaller MA, editors. Medical microbiology. 8th ed. Philadelphia: Elsevier Saunder; 2014.

Definition and Properties of a Virus

• Viral genomes may be RNA or DNA

• Viruses have a naked capsid or an envelope

morphology

• Viral components are assembled and do not

replicate by “division.”

FIGURE 36-1 Components of the basic virion.

FIGURE 36-4 Virion structure.

Outlines

FIGURE 36-8 A general scheme of viral replication

Peakman M, Vergani D, editors. Basic and Clinical Immunology. 2nd ed. Philadelphia: Elsevier Saunders; 2009.

Virus Receptor

Epstein-Barr virus Complement receptor 2 (CR2)

Influenza virus Sialic residue on cell surface glycoprotein

Rhinovirus Intracellular adhesion molecule:ICAMs

Vaccinia virus Epidermal growth factor receptor

Cellular receptor for viruses entry

Scott N. Mueller BTR. Immune responses to viruses. In: Rich RR, Fleisher TA, William T. Shearer HW, Jr. S, Frew AJ, Weyand CM, editors. Clinical immunology principle and practice. 3rd ed. Philadelphia: Mosby Elsevier 2008. p. 421-31.

Outlines

Innate immune response to viral infection

• Epithelial barrier

• Early non-specific or innate immune

– Interferon (IFN)

• Type I IFNs (IFN α and IFN β)

• Type II IFN (IFN γ)

– Natural killer cells

– Macrophages

Borrow P, Nash AA. Immunity to viruses. In: Male D, Brostoff J, Roth D, Roitt I, editors. Immunology. 8th ed. Philadelphia: Elsevier Saunders; 2013. p. 211-22.

Abbas AK, Lichtman AH, Pillai S, editors. Cellular and molecular immunology. 8th ed. Philadelphia: Elsevier Saunders;2015.

– Macrophages

FIGURE 4-5 Epithelial barriers.

– Macrophages

Type I interferons

• IFN-α is produced by

- Plasmacytoid dendritic cells

- Mononuclear phagocytes

• IFN-β is produced by many cell types

Interferon: interfere with viral infection

FIGURE 13.1 Pathways by which type I IFN production

Plasmacytoid DCs• Produce high levels

of type I IFN • Without themselves

becoming infected

FIGURE 4-16 Mechanisms of induction of type I interferons by viruses

FIGURE 4-17 Biologic actions of type I interferons

Abbas AK, Lichtman AH, Pillai S, editors. Cellular and molecular immunology. 8th ed.Philadelphia Elsevier Saunders:;2015.

– Macrophages

FIGURE 4-7 Functions of NK cells

Abbas AK, Lichtman AH, Pillai S, editors. Cellular and molecular immunology. 8th ed.Philadelphia Elsevier Saunders:;2015.

Important mechanism of immunity against viruses early in the course of infection.

– Macrophages

Macrophages

• Phagocytosis of virus and virus-infected cells;

• Killing of virus-infected cells; and

• Production of antiviral molecules

: TNFα, nitric oxide, and IFNα.

Adaptive immune response to viral infection

• Antiviral antibodies

• Cytotoxic T lymphocytes (CTLs)

• Helper T (Th) cells

Antiviral antibodies

• Secretory IgA: neutralizing antibody

- Respiratory tract

- Intestinal tract

• IgG

- ADCC

Antiviral antibodies

• Secretory IgA: neutralizing antibody

- Respiratory tract

- Intestinal tract

• IgG

- ADCC

Fig. 13.6 Effector mechanisms by which adaptive responses combat virus replication

1. Blocks binding to cell2. Blocks entry into cell

1. Activate membrane attack complex lysis2. Opsonization

Antibody bound to infected cells ADCC

FIGURE 16-7 Adaptive immune responses against viruses.

FIGURE 11-6 Mechanisms of CTL-mediated killing of target cells..

Helper T (Th) cells

• CD4+ T cell-derived IL-2: CD8+ T cell growth factor

• CD4+ T cell-derived chemokines: recruit CD8+ T to

site of infection

• CD4+ T cells secrete IFNγ and TNFα to recruit and

activate macrophages

Helper T (Th) cells

site of infection

Helper T (Th) cells

site of infection

FIGURE 16-7 Innate and adaptive immune responses against viruses.

Outlines

Mechanism of Immune Evasion Examples

Antigenic variation Influenza, rhinovirus, HIV

Inhibition of antigen processingBlockade of TAP transporterRemoval of class I moleculesfrom the ER

Herpes simplex virus (HSV)Cytomegalovirus (CMV)

Production of “decoy” MHCmolecules to inhibit NK cells

Cytomegalovirus (murine)

Production of cytokine receptorhomologues

Vaccinia, poxviruses (IL-1, IFN-γ)Cytomegalovirus (chemokine)

TABLE 16-3 Mechanisms of Immune Evasion by Viruses

Figure 11-29Biochemistry Sixth Edition

2007 W.H> Freeman and Company

Influenza Virus

Figure 11-29Biochemistry Sixth Edition

2007 W.H> Freeman and Company

Influenza Virus

FIGURE 16-8 Generation of new influenza virus strainsby genetic recombination (antigenic shift).

FIGURE16-9 Mechanisms by which viruses inhibit antigen processing & presentation.

Production of immunosuppressivecytokine

Epstein-Barr (IL-10)

Infection and death or functionalimpairment of immune cells

Inhibition of complementactivation

Recruitment of factor H Incorporation of CD59 in viral envelope

HIVHIV, vaccinia, human CMV

Inhibition of innate immunityInhibition of access to RIG-IRNA sensorInhibition of PKR (signaling byIFN receptor

Vaccinia, HIV

HIV, HCV, HSV, polio

Vaccinia, HIV

Summary

• Innate immune mechanisms restrict the early stages

of infection and delay spread of virus.

: Interferon

: NK cells

: Macrophages

Summary

• As a viral infection proceeds, the adaptive (specific) immune response unfolds.

: Ab & complement limit viral spread &

reinfection

: CD8+ CTLs destroy virus infected cells

: CD4+ T cells are a major effector cell

population

Summary

• Viruses have evolved strategies to evade the immune response.

: Virus latency & antigenic variation are the

most effective mechanisms.

: Many DNA viruses have strategies to control

expression of MHC molecules.

Immune response to viruses

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