Host Resistance to Viral Infections: Mechanisms and Immune Responses

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Host Resistance to Viral Infections

Overview of Host Resistance

Host resistance to viral infections refers to the ability of an organism to limit or prevent viral replication, spread, and disease. This resistance is achieved through a multi-layered defense system, including both innate (nonspecific) and adaptive (specific) immunity. The effectiveness of these defenses varies among individuals and species, influenced by genetic, immunological, and environmental factors.

Resistance: Reduces viral burden by eliminating or controlling the pathogen.
Tolerance: Minimizes tissue damage caused by infection, even if the virus is not cleared.

Mechanisms of Host Resistance

Innate Immunity (Nonspecific Defenses)

Innate immunity provides the first line of defense against viral infections, acting rapidly and without prior exposure to the pathogen. It includes physical barriers, chemical defenses, and cellular responses.

Physical and Chemical Barriers

Skin: Acts as a physical barrier, preventing entry of viruses, bacteria, and toxins.
Mucus and Saliva: Trap and help eliminate pathogens from mucosal surfaces.

Diagram of normal and disrupted skin barrier function, showing protection against viruses, bacteria, and toxins

Cellular and Molecular Responses

Interferons (IFNs): Signaling proteins released by infected cells to alert neighboring cells and inhibit viral replication.
Natural Killer (NK) Cells: Immune cells that identify and destroy infected cells.
Antigen-Presenting Cells (APCs): Cells such as dendritic cells and macrophages that present viral antigens to initiate adaptive immunity.

Interferons and the Antiviral State

Interferons are crucial for establishing an antiviral state in cells. They are released by infected and neighboring cells, warning the immune system and activating antiviral defenses.

Diagram showing interferon signaling to neighboring cells to induce antiviral responses

Induction of Interferon-Stimulated Genes (ISGs): IFNs signal neighboring cells to upregulate ISGs, which encode proteins that disrupt various stages of the viral life cycle.
Examples of ISG Actions: Degradation of viral RNA, inhibition of viral protein synthesis.

Diagram of interferon production and ISG induction in response to viral infection Diagram showing establishment and maintenance of the antiviral state in cells

Natural Killer (NK) Cells

NK cells are a vital component of innate immunity, providing rapid responses to virally infected cells. They kill infected cells directly and secrete cytokines to coordinate the immune response.

Cytotoxic Killing: NK cells release perforin and granzymes to induce lysis of infected cells.
Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC): NK cells recognize antibody-coated infected cells and induce apoptosis.
Cytokine Production: NK cells secrete cytokines that enhance antiviral immunity and modulate other immune cells.
Immunopathology: Excessive NK cell activity can cause tissue damage, highlighting the need for immune balance.

Diagram showing activation and lysis by NK and T helper cells Diagram of ADCC mechanism by NK cells

Antigen-Presenting Cells (APCs)

APCs, such as dendritic cells and macrophages, bridge innate and adaptive immunity. They ingest viruses, process antigens, and present them on MHC molecules to activate T cells in lymph nodes.

Dendritic Cells: Located in tissues exposed to the environment (e.g., skin, mucosa), they present antigens to T helper cells via MHC II molecules.

Diagram of dendritic cell presenting antigens to helper and cytotoxic T cells

Adaptive Immunity (Specific Defenses)

Overview of Adaptive Immunity

Adaptive immunity develops more slowly but is highly specific to the infecting virus. It involves B cells (antibody production) and T cells (cell-mediated responses), and generates immunological memory for faster responses upon re-exposure.

B Cells: Produce antibodies that neutralize viruses and mark them for destruction.
T Cells: Include helper T cells (coordinate immune responses) and cytotoxic T cells (kill infected cells).
Immunological Memory: Memory B and T cells enable rapid, robust responses to future infections by the same virus.

Time Course of Immune Responses

Innate defenses act rapidly after infection, while adaptive responses (antibodies and T cells) take days to weeks to develop.

Graph showing time course of nonspecific and specific immune responses after viral infection

Humoral Response: Antibody Production

B cells are activated by viral antigens and differentiate into plasma cells that secrete antibodies. These antibodies neutralize viruses and facilitate their clearance.

Diagram of B cell activation and differentiation into plasma and memory cells

Neutralization: Antibodies bind to viral particles, blocking their attachment and entry into host cells.
Opsonization: Antibodies coat viruses, marking them for phagocytosis by macrophages.
ADCC: Antibodies bound to infected cells recruit NK cells to induce apoptosis.

Diagram of opsonization and phagocytosis of antibody-coated viruses Diagram of ADCC mechanism involving antibodies and NK cells

Cell-Mediated Response: T Cells

T cells are essential for eliminating viruses that have already infected host cells. There are two main subtypes: cytotoxic T cells (CD8+) and helper T cells (CD4+).

Cytotoxic T Cells (CD8+): Recognize viral antigens presented on MHC I molecules of infected cells and induce apoptosis via perforin and granzymes.
Helper T Cells (CD4+): Recognize antigens on MHC II molecules of APCs, secrete cytokines to activate B cells, cytotoxic T cells, and innate immune cells.

Diagram of T cell activation and cytotoxic function Diagram of cytotoxic T cell recognizing antigen on infected cell Diagram of cytotoxic T cell binding to infected cell via TCR and MHC I Diagram of apoptosis induction by cytotoxic T cell

Helper T Cells (CD4+)

Antigen Presentation: Recognize viral antigens on MHC II molecules of APCs.
Activation of B Cells: Stimulate B cell maturation and antibody production.
Enhancement of Cytotoxic T Cells: Secrete cytokines (e.g., IFN-γ, IL-2) to promote cytotoxic T cell proliferation.
Boosting Innate Immunity: Activate macrophages and NK cells for enhanced antiviral activity.

Factors Influencing Host Resistance

Genetic Factors: Genes, especially those in the major histocompatibility complex (MHC), influence immune responses.
Physiological Factors: Age, nutrition, stress, and health status affect resistance to viral infections.
Co-evolution: Viruses evolve mechanisms to evade host defenses, leading to an evolutionary arms race.

Distinction Between Resistance and Tolerance

Resistance: Reduces the viral load by eliminating the pathogen.
Tolerance: Limits tissue damage without necessarily reducing viral burden.
Example: The body may minimize tissue damage even if the virus persists.