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What is the primary function of B cells in the adaptive immune response?
The innate immune response is responsible for the specific elimination of established infections.
False
What are small, soluble molecules secreted by immune cells called?
Cytokines
The first phase of the adaptive immune response is the ______ phase where pathogens are recognized.
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Match the following T cell types with their functions:
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Which of the following describes the decline phase of the adaptive immune response?
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What type of T cells are reduced in patients with moderate and severe COVID-19?
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Increased activation of CD4 and CD8 T cells indicates a healthy immune response during COVID-19.
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What cytokines are mentioned as potentially inhibiting T cell circulation in blood?
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In critically ill patients, CD4 T cells produce inflammatory cytokines such as __________.
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Match the following cytokines with their effects on T cell circulation:
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What is a common feature of T cells during the acute phase of an infection?
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Direct viral infection of T cells has been reported in COVID-19 patients.
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What is the relationship between CD8+ T cells and COVID-19 disease severity?
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T regulatory cells are __________ in severe COVID-19.
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What T cell responses are identified in recovering COVID patients?
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Which antibody is primarily responsible for antibody-dependent cell cytotoxicity (ADCC)?
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IgM antibodies can agglutinate viral particles.
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What is the role of lung-resident respiratory dendritic cells (rDCs) in viral infections?
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The immune response begins with direct infection of the __________ epithelium.
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Match the following immune cell types with their roles in viral infections:
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What occurs following viral clearance in terms of T cells?
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Chronic viral infections are characterized by effective suppression of adaptive immunity.
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What is meant by 'T cell exhaustion' in the context of chronic viral infections?
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What protein do the majority of SARS-CoV-2 specific CD4+ T cells primarily respond to?
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SARS-CoV-2 specific CD8+ T cells predominantly express the central memory phenotype.
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What type of T cell response is associated with less severe COVID-19 disease?
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Activated CD4+ T cells produce high amounts of _______ whether activated to the spike or non-spike protein.
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Match the T cell types to their characteristics:
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What is an observed characteristic of SARS-CoV-2 reactive CD4+ T cells found in unexposed individuals?
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Study Notes
Innate and Adaptive Immunity to Viruses
- Innate immunity is the initial response to infection, acting within the first few days after onset.
- Adaptive immunity is responsible for protection against infection and eradication of established infection.
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Characteristics of the Adaptive Immune System
- T cells recognize pathogens and destroy or eliminate foreign invaders.
- T cells produce cytokines (small, soluble signaling molecules) that activate or inhibit other immune cells.
- T cells can directly kill virally infected cells and cancer cells (cytotoxic function).
- B cells produce antibodies that bind to antigens on pathogens, leading to pathogen destruction.
- Antigens (or antigenic determinants) are specific parts of a pathogen that are targeted by antibodies.
Phases of the Adaptive Immune Response
- Recognition Phase: Pathogen is recognized by T cells and B cells.
- Activation Phase: The immune response is activated once the pathogen is recognized.
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Effector Phase: Effector B and T cells act to eliminate the pathogen, involving both:
- Cell-mediated immunity: Mediated by T cells.
- Humoral immunity: Mediated by antibodies.
- Decline (Homeostasis): Effector B and T cells die by apoptosis to prevent potential damage to the body.
- Memory: Memory B and T cells are generated to facilitate rapid immune responses in the case of reinfection. This is how the body recognizes and responds to pathogens it has encountered before.
T Cells in Viral Infection
- CD4+ T cells (Helper T cells): Help B cells produce virus-specific antibodies.
- CD8+ T cells (Cytotoxic T cells): Directly kill infected cells.
- Antibody-Dependent Cell Cytotoxicity (ADCC): Antibodies can kill infected cells by activating natural killer (NK) cells.
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Antibodies & Viral Interactions: Antibodies block virus-cell interactions, agglutinate (clump) viral particles, and opsonize (coat) viral particles for easier removal.
- IgG: Can bind to infected cells and cause ADCC.
- IgM: Agglutinates virus particles and opsonizes them.
- IgA: Blocks virus-cell interactions.
Induction of T Cell Responses to Respiratory Virus Infection
- Respiratory Dendritic Cells (rDCs) in the lungs acquire virus or antigens from infected cells.
- rDCs migrate to draining lymph nodes (DLNs) and present processed antigen to naive T cells.
- Engagement of the T cell receptor (TCR) with the antigen-MHC complex leads to T cell activation, proliferation, and migration to the site of infection (lungs) to perform their effector functions.
Immune Dysregulation during Chronic Viral Infection
- T cell-mediated adaptive immune response is crucial for clearing and suppressing viral infections.
- Viral clearance typically occurs within a week of initial infection and requires both CD8+ T cell killing of infected cells and CD4+ T cell support for CD8+ and B cell responses.
- Memory T cells are essential for long-term antiviral immunity.
- Chronic viral infections evade or suppress adaptive immunity leading to T cell "exhaustion", a non-responsive state.
- Lymphopenia (Low Lymphocyte Count) is observed in T cells during an acute phase of infection.
Changes in T Cell Phenotype in Peripheral Blood during COVID-19 Infection
- Reduced CD4+ and CD8+ T cells in moderate and severe COVID-19 during the acute phase.
- Decreased CD8+ T cells associated with disease severity and mortality in ICU patients.
- Increased activated CD4+ and CD8+ T cells exhibiting an exhausted phenotype (upregulated inhibitory markers like PD-1 and Tim-3) in persistent COVID.
- Production of inflammatory cytokines like GM-CSF by CD4+ T cells in critically ill patients.
- Reduced frequency of T regulatory cells in severe COVID-19.
Mechanisms Contributing to Reduced T Cells in Blood
- Cause of peripheral T cell loss in moderate to severe COVID-19 is still unclear.
- Cytokines like IFN-α, IL-6, and TNF-α can inhibit T cell circulation by promoting retention in lymphoid organs and attachment to endothelium.
- T cell recruitment to sites of infection can reduce their presence in the peripheral blood.
- Direct viral infection of T cells has not been reported.
CD4+ and CD8+ T Cell Responses to SARS-CoV-2
- T cell responses specific for Spike, Matrix, and Nucleocapsid proteins are found in COVID-19 patients.
- T cell reactivity to SARS-CoV-2 is also detected in non-exposed individuals.
Antiviral T Cell Responses to SARS-CoV-2
- Most individuals exhibit SARS-CoV-2 specific T cells.
- CD4+ and CD8+ T cell responses target different antigens, mainly Spike and Nucleocapsid proteins.
- CD4+ T cells primarily exhibit a central memory phenotype (CCR7+CD45-), with some effector memory cells (CCR7-CD45-).
- CD8+ T cells predominantly express the effector memory phenotype.
- SARS-CoV-2 specific CD4+ and CD8+ T cells have a Th1 profile with increased cytotoxic activity and elevated immune activation markers.
Pro-inflammatory Cytokine Secretion Profile of CD4+ T Cells
- Activated CD4+ T cells produce high amounts of cytokines, regardless of whether they are activated by Spike or non-Spike proteins.
SARS-CoV-2 Specific T Cell Responses and Disease Severity
- Early detection of SARS-CoV-2 specific CD4+ T cell response is associated with less severe disease, more so than antibody responses or CD8+ T cell responses .
- Early induction of CD4+ T cells secreting interferon gamma occurs earlier in patients with mild disease and is linked to viral clearance.
- Preliminary evidence suggests rapid induction of CD8+ T cells may explain asymptomatic disease.
- Severe COVID-19 is associated with poor polyfunctionality and proliferative capacity of T cells.
Cytokine Profile of CD4+ and CD8+ T Cells Specific to SARS-CoV-2 Proteins
- SARS-CoV-2 reactive CD4+ T cells have been found in unexposed individuals.
- Pre-existing memory CD4+ T cells cross-reactive with SARS-CoV-2 and common cold coronaviruses (HCoV-OC43, HCoV-229E, HCoV-NL63, HCoV-HKU1) contribute to responses to SARS-CoV-2 infection. This means that prior exposure to common cold coronaviruses can lead to better responses to SARS-CoV-2 infection.
Correlation between Neutralizing Antibody Titers and T Cell Responses
- Correlation between neutralizing antibody titers and the number of Nucleocapsid Protein-specific T cells: This suggests that neutralizing antibody development may be linked to the activation of antiviral T cells.
Serological Signatures and SARS-CoV-2 Survival
- Limited early differences in titers and neutralization were observed between survivors and deceased patients.
- Shift in the balance of Spike to Nucleocapsid antibodies in convalescent versus deceased groups.
- Increased Spike-specific phagocytic and complement-fixing activity in convalescent individuals.
- Increased Nucleocapsid protein-specific antibodies in individuals who passed away from SARS-CoV-2.
Immunological Similarities between COVID-19 and Recent Pandemics
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2003 SARS-CoV pandemic:
- TLR-mediated innate immune responses were activated by SARS-CoV viral particles.
- Lymphopenia was common, associated with severe disease.
- SARS significantly affected children with lymphopenia.
- Virus-specific memory T cell development was associated with disease resolution and protection.
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2009 H1N1 influenza A pandemic:
- Lymphopenia was prevalent.
- Lymphopenia and significant morbidity were observed in children.
- Elevated systemic innate inflammatory factors, including MCP-1 and IL-6, were seen. High IL-6 levels correlated with disease severity.
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2013 MERS-CoV pandemic:
- Lymphopenia occurred less frequently but was associated with disease severity.
- Recovery was associated with improved outcomes.
- Neutralizing antibodies and MERS-CoV specific CD4+ T cells correlated with disease severity.
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Description
Explore the critical differences between innate and adaptive immunity to viruses. This quiz covers the roles of T cells and B cells, the phases of the adaptive immune response, and the functions of cytokines and antibodies. Test your knowledge on how the immune system combats infections and maintains health.
