CD4+ and CD8+ T Cells in Viral Infections

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Questions and Answers

What specific T cell response is essential for controlling SARS-CoV effectively?

Th1 response (correct)

Th2 response

Th17 response

Treg response

Which viral protein is most associated with CD4 T cell specificity in SARS-CoV responses?

N protein

M protein

S protein (correct)

E protein

What cytokine levels are significantly elevated in severe COVID-19 cases compared to moderate cases?

Interferon gamma

IL-1 and IL-5

IL-4 and IL-13

IL-2R, IL-6, IL-10, TNF-α (correct)

In MERS-CoV infections, what is correlated with disease severity during the convalescent phase?

Dominance of Th1 type helper T cells Signup and view all the answers

Which of the following statements about T cell responses to SARS-CoV and MERS-CoV is accurate?

Virus-specific memory T cells are present in recovered individuals for over a decade post-infection. Signup and view all the answers

What is the primary function of CD4+ T cells?

To augment CD8+ cytotoxic T cells and recruit macrophages Signup and view all the answers

Which cytokine is responsible for the differentiation of T helper cells into Th1 cells?

IL-12 Signup and view all the answers

What is the main role of CD8+ T cells in the immune response?

To secrete molecules like perforin and gamma interferon to eradicate viruses Signup and view all the answers

Which type of T helper cell is primarily involved in mediating allergic responses?

Th2 Signup and view all the answers

Which antibody is primarily responsible for binding to infected cells and causing antibody-dependent cell cytotoxicity (ADCC)?

IgG Signup and view all the answers

What is the key characteristic of IgG antibodies in the immune system?

They are crucial for secondary immune responses and represent the majority of circulating antibodies. Signup and view all the answers

What is the primary function of IgM antibodies in the context of viral infections?

Agglutinate virus particles Signup and view all the answers

Which cytokines are involved in the differentiation of CD4+ T cells into Th17 cells?

IL-6 and IL-23 Signup and view all the answers

In the initial immune response to respiratory viral infection, what role do lung-resident respiratory dendritic cells (rDCs) play?

Present processed antigens to naive T cells Signup and view all the answers

What is required for effective viral clearance after initial infection?

CD8+ effector T cell killing and CD4+ T cell enhancement Signup and view all the answers

What is the primary function of the Fab region of an antibody?

To bind the antigen Signup and view all the answers

What characterizes chronic viral infections in terms of T cell responses?

Persistent antigenic activation leading to T cell exhaustion Signup and view all the answers

What is the role of T-reg cells in the immune system?

To promote tolerance and immune suppression Signup and view all the answers

What occurs to the majority of virus-specific T cells following viral clearance?

They undergo apoptosis Signup and view all the answers

Which two types of T cells play crucial roles in the adaptive immune response against viral infections?

CD8+ and CD4+ T cells Signup and view all the answers

What is meant by 'opsonization' in the context of viral infections?

Coating of viral particles for clearance Signup and view all the answers

What characterizes the T cell profile in patients with moderate to severe COVID-19 during the acute phase?

Decreased CD4+ and CD8+ T cells Signup and view all the answers

What does the presence of exhausted phenotype in CD4 and CD8 T cells indicate in critically ill COVID-19 patients?

High levels of PD-1 and Tim-3 inhibitory markers Signup and view all the answers

Which cytokines are believed to inhibit T cell circulation in moderate to severe COVID-19?

IFN-α, IL-6, and TNF-α Signup and view all the answers

What is the proposed mechanism for the peripheral loss of T cells in patients with severe COVID-19?

T cell recruitment to sites of infection Signup and view all the answers

What type of T cell responses are specifically found in convalescent COVID-19 patients?

Responses specific for Spike, Matrix, and Nucleocapsid proteins Signup and view all the answers

What indicates a correlation between the development of neutralizing antibodies and T cell activation?

Higher titers of Nucleocapsid Protein-specific T cells Signup and view all the answers

Which group had a shift in the balance of antibodies compared to the others?

Convalescent versus deceased group Signup and view all the answers

How did the immune response in people who passed away from SARS-CoV-2 differ?

Increased levels of Nucleocapsid protein-specific antibodies Signup and view all the answers

What common feature was observed in children affected by past pandemics?

Significant morbidity and lymphopenia Signup and view all the answers

Which factor correlated with disease severity during recent pandemics?

Elevation of systemic innate inflammatory factors Signup and view all the answers

What is the primary role of IgG antibodies in viral infections?

Causing antibody-dependent cell cytotoxicity Signup and view all the answers

IgM antibodies alone are sufficient for clearing virus particles from the body.

False Signup and view all the answers

What is opsonization in the context of viral infections?

Coating of viral particles to enhance clearance. Signup and view all the answers

Infections characterized by persistent antigenic activation of T cells can lead to T cell ______________.

exhaustion Signup and view all the answers

Match the immune cell type with its function:

CD8+ T cells = Killing of virally infected cells CD4+ T cells = Enhancing B cell responses Lung-resident dendritic cells = Presenting antigen in lymph nodes Memory T cells = Retaining long-term immunity Signup and view all the answers

What happens to the majority of virus-specific T cells after viral clearance?

They undergo apoptosis Signup and view all the answers

What was observed in individuals who passed away from SARS-CoV-2 compared to convalescent individuals?

Increased Nucleocapsid protein-specific antibodies Signup and view all the answers

T cell-mediated adaptive immune response is not essential for clearing viral infections.

False Signup and view all the answers

Lymphopenia was a common feature observed in children during previous pandemics.

True Signup and view all the answers

What initiates the immune response during a respiratory viral infection?

Direct infection of airway epithelium. Signup and view all the answers

What type of immune response was associated with the resolution of disease in previous pandemics?

Virus-specific memory T cells Signup and view all the answers

A shift in the balance of spike to nucleocapsid antibodies was noted between the convalescent group and the ______ group.

deceased Signup and view all the answers

Match the following pandemics with their associated immune response characteristics:

SARS-CoV-2 = Increased Nucleocapsid protein-specific antibodies in deceased 2009 H1N1 influenza A = Lymphopenia commonly observed 2013 MERS-CoV = Lymphopenia less frequent but severe disease association 2003 SARS = Marked activation of TLR-mediated immune responses Signup and view all the answers

Which T cell population is decreased in moderate and severe COVID-19 patients?

CD8+ T cells Signup and view all the answers

Cytokines such as IFN-α and IL-6 may promote T cell circulation in the blood.

False Signup and view all the answers

What is the effect of CD8+ T cell infiltrate in patients with severe COVID-19?

Increased presence in bronchoalveolar lavage fluid. Signup and view all the answers

In critically ill patients, CD4 T cells produce inflammatory cytokines such as ______.

GM-CSF Signup and view all the answers

Match the T cell phenotypes with their characteristics:

Exhausted phenotype = Upregulated expression of inhibitory markers Activated CD4 T cells = Production of inflammatory cytokines Reduced T regulatory cells = Loss of immune modulation Increased CD8 T cell infiltrate = Presence in bronchoalveolar lavage fluid Signup and view all the answers

What correlates with COVID-19-associated disease severity and mortality?

Decrease in CD8+ T cells Signup and view all the answers

Direct viral infection of T cells has been reported in COVID-19 cases.

False Signup and view all the answers

What remains unclear regarding T cell loss in moderate to severe COVID-19?

The mechanisms contributing to peripheral T cell loss. Signup and view all the answers

Which cytokine does NOT play a role in inhibiting T cell circulation in COVID-19?

TNF-β Signup and view all the answers

The primary T cell responses specific for SARS-CoV proteins are found in ______ patients.

convalescent Signup and view all the answers

What is the primary cytokine secreted by activated CD4+ T cells in response to SARS-CoV-2?

Interferon gamma Signup and view all the answers

SARS-CoV-2 specific CD8+ T cells predominantly exhibit a central memory phenotype.

False Signup and view all the answers

What type of T cell response is associated with less severe COVID-19 disease?

CD4+ T cell response Signup and view all the answers

Healthy individuals who have previously been exposed to __________ responded better to SARS-CoV-2 infection.

common cold coronaviruses Signup and view all the answers

Which of the following T cell types is mainly responsible for cytotoxic activity against SARS-CoV-2?

CD8+ T cells Signup and view all the answers

What T cell subset appears to be more activated in response to infections?

CD8 T cells Signup and view all the answers

Match the T cell type with its characteristic:

CD4+ T cells = Secreting interferon gamma CD8+ T cells = Displaying effector memory phenotype CCR7+CD45- = Central memory T cells CCR7-CD45- = Effector memory T cells Signup and view all the answers

SARS-CoV-2 specific T cells are entirely absent in non-exposed individuals.

False Signup and view all the answers

CD4 T cells are the primary subset involved in the exhaustion observed in critically ill COVID-19 patients.

False Signup and view all the answers

The majority of SARS-CoV-2 CD4+ T cells exhibit a __________ phenotype.

CCR7+CD45- Signup and view all the answers

What is the time frame in days when neutralizing antibodies to the Spike protein typically peak after infection?

20-30 days Signup and view all the answers

Individuals who recovered from SARS-CoV have detectable Spike-specific IgG and neutralizing antibodies after _____ months.

12 Signup and view all the answers

In patients with mild COVID-19 disease, what correlates with viral clearance?

Early induction of CD4+ T cells secreting interferon gamma Signup and view all the answers

What is a characteristic feature of severe COVID-19 cases concerning T cell function?

Poor polyfunctionality and proliferative capacity Signup and view all the answers

Match the following immune responses with their characteristics:

IgG antibodies = Appear early and correlate with neutralizing antibody titers Memory T cell responses = Detected in a majority of SARS patients even six years post infection Neutralizing antibodies = Peak at 20-30 days after infection Inhibitory markers = Common in severely ill COVID-19 patients Signup and view all the answers

Which of the following markers indicates an exhausted T cell state in severely ill patients?

PD-1 Signup and view all the answers

Antibody responses to SARS-CoV are typically lower in patients with severe outcomes compared to those with milder illnesses.

True Signup and view all the answers

What percentage of patients had memory T cell responses detected six years after SARS infection?

60% Signup and view all the answers

In recovering patients, there is an increase in follicular helper T cells and effector molecules such as Gzm A, Gzm B, and ________.

perforin Signup and view all the answers

Which T cell subset is associated with higher expression of co-stimulatory and inhibitory molecules?

Effector T cells Signup and view all the answers

Study Notes

CD4+ and CD8+ T Cell Roles in Viral Infection

CD4+ T cells produce cytokines that augment CD8+ cytotoxic T cells and macrophage recruitment.
CD8+ cytotoxic T cells (CTLs) secrete perforin, granzymes, and gamma interferon to eradicate viruses from the host.
CD4+ and CD8+ T cells collaborate with other cells to resolve acute viral infections and provide protection against reinfection.
Delineating the frequency, specificity, functionality, and durability of T cells during COVID-19 is vital for understanding their use as biomarkers and targets for immunotherapies and vaccines.

T Helper Cell Differentiation

CD4+ T helper cells differentiate into four subtypes: Th1, Th2, Th17, and T-reg.
Th1: Cellular immunity, inflammation clearance of intracellular pathogens (stimulated by IL-12).
Th2: Humoral immunity, allergic responses (stimulated by IL-4).
Th17: Tissue inflammation, autoimmunity, clearance of extracellular pathogens (stimulated by IL-6 and IL-23).
T-reg: Tolerance, immune suppression.

Antibody Function and Types

Antibodies bind antigens, neutralize or block antigen activities.
Antibodies trigger immune responses by engaging Fc receptors on immune cells.
Complement binding to the antibody-antigen complex results in pathogen lysis.
IgM is the first antibody produced in a primary immune response, comprising 10% of the total antibody pool.
IgG is the major human serum immunoglobulin (60-70% of total circulating antibodies), playing a key role in the secondary immune response.

Antibodies in Viral Infection

IgG, IgM, and IgA antibodies can neutralize extracellular viruses before infection.
Only IgG antibodies can bind to infected cells and cause antibody-dependent cell cytotoxicity (ADCC).
ADCC utilizes antibody-mediated complement lysis to kill infected cells.
IgG, IgM, and IgA antibodies block virus/cell interactions.
IgM antibodies can agglutinate viral particles.
IgM and IgG can opsonize viral particles for clearance.

T Cell Responses to Respiratory Virus Infection

The immune response begins with direct airway epithelium infection.
Lung-resident respiratory dendritic cells (rDCs) acquire the virus or antigens from infected epithelial cells, become activated, process antigen, and migrate to the draining lymph nodes (DLN).
In the DLNs, rDCs present the processed antigen as an MHC/peptide complex to naive circulating T cells.
Engagement of the T cell receptor (TCR) with the peptide–MHC complex and additional co-stimulatory signals activates T cell proliferation and migration to the site of infection (the lung) to perform their effector function.

Immune Dysregulation During Chronic Viral Infection

T cell–mediated adaptive immunity is crucial for clearing and maintaining long-term suppression of viral infections.
Effective viral clearance requires both CD8+ effector T cell–mediated killing of virally infected cells and CD4+ T cell–dependent enhancement of CD8+ and B cell responses.
Following viral clearance, most virus-specific T cells undergo apoptosis, but retaining a virus-specific memory T cell population is necessary for long-term antiviral immunity.
Chronic viral infections evade or suppress adaptive immunity.
Persistent antigenic activation of T cells drives a nonresponsive cell state or T cell “exhaustion.”

T Cell Immune Responses to SARS-CoV-2

Marked leukopenia (dramatic loss of CD4+ and CD8+ T cells).
Severe infection delays the development of the adaptive immune response and prolongs virus clearance.
T cell epitopes are found in the S, N, and M viral proteins. Most CD4+ T cells are specific for the S protein.
Th1 response is key for successful control of SARS-CoV-2.
The magnitude and frequency of CD8+ memory T cells exceed those of CD4+ memory T cells.
Virus-specific memory CD4+ and CD8+ T cells are found in individuals who recovered from the infection at least 10 years after acute infection.

T Cell Immune Response to MERS-CoV

High frequencies of MERS-CoV-reactive CD8+ T cells are observed in patients with severe/moderate illness before detection of Abs and CD4+ T cell responses.
A strong specific T-cell response against the MERS-CoV S protein is observed on day 24 after disease onset.
All deceased patients displayed rapid drops in their lymphocyte counts.
IL-12 and interferon gamma levels are lower in a fatal case than in a patient who survived the infection.
An early rise of CD8+ T cells correlates with disease severity, and at the convalescent phase, dominant Th1 type helper T cells are observed.

Plasma Cytokine Levels in Patients with COVID-19: The Cytokine Storm

Levels of interleukin 2R (IL-2R), IL-6, IL-10, and tumor necrosis factor α (TNF-α) are markedly higher in severe cases than in moderate cases.

Lymphopenia in COVID-19

Marked lymphopenia (drop in lymphocytes) is observed in T cells in patients with the acute phase of infection.

Changes in the Phenotype of T Cells in the Peripheral Blood

Reduced CD4+ and CD8+ T cells in moderate and severe COVID-19 in the acute phase.
Decreases in CD8+ T cells in patients admitted to the ICU correlate to COVID-associated disease severity and mortality.
Increases in activated CD4+ and CD8+ T cells displaying an exhausted phenotype (upregulated expression of inhibitory markers like PD-1 and Tim-3) in persistent COVID-19.
Production of inflammatory cytokines such as GM-CSF by CD4+ T cells in critically ill patients.
Reduced frequencies of T regulatory cells in severe COVID-19.

Mechanisms Contributing to Reduced T Cells in the Blood

The cause of peripheral T cell loss in moderate to severe COVID-19 remains elusive.
A similar phenomenon is observed in other viral infections.
Cytokines like IFN-α, IL-6, and TNF-α may inhibit T cell circulation in blood 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 (increased CD8+ T cell infiltrate in bronchoalveolar lavage fluid).
Direct viral infection has not been reported.

CD4+ and CD8+ T Cell Responses in Convalescent COVID-19 Patients

T cell responses specific for Spike, Matrix, and Nucleocapsid proteins are found in convalescent COVID-19 patients.
A correlation exists between the neutralizing antibody titers and the number of Nucleocapsid Protein-specific T cells, suggesting a link between neutralizing antibody development and antiviral T cell activation.

Serological Signatures Track with SARS-CoV-2 Survival

Limited early differences exist in titer and neutralization.
A shift occurs in the balance of spike to nucleocapsid antibodies in convalescent versus deceased groups.
Spike-specific phagocytic and complement-fixing activity is increased in convalescent individuals.
Individuals who passed away from SARS-CoV-2 had increased Nucleocapsid protein-specific antibodies.

Immunological Similarities between COVID-19 and Recent Pandemics

2003 SARS-CoV pandemic:
- SARS-CoV viral particles significantly activated TLR-mediated innate immune responses.
- Lymphopenia occurred in most patients and was associated with severe disease.
- SARS also significantly affected children, in whom lymphopenia was a common feature.
- Development of virus-specific memory T cells was associated with disease resolution and protection from subsequent infection.
2009 H1N1 influenza A pandemic:
- Lymphopenia occurred in the majority of patients.
- Occurred frequently and caused lymphopenia and significant morbidity in children.
- Marked elevation of systemic innate inflammatory factors, including MCP-1 and IL-6, with elevated IL-6 correlating with disease severity.
2013 MERS-CoV pandemic:
- Lymphopenia occurred less frequently but was associated with disease severity, and recovery was associated with improved outcomes.
- Neutralizing antibodies to MERS and MERS-CoV–specific CD4+ T cells correlated with disease severity.

Involvement in Viral Infection

Only IgG antibodies directly attack infected cells, using antibody-dependent cell cytotoxicity (ADCC) and complement lysis
All three types of antibodies (IgG, IgM, and IgA) prevent virus/cell interactions.
IgM antibodies agglutinate (clump) viral particles
IgM and IgG antibodies opsonize viral particles, tagging them for immune system clearance.

Immune Responses to Respiratory Virus Infection

Lung-resident respiratory dendritic cells (rDCs) are the first to encounter the virus or antigens from infected epithelial cells
rDCs become activated, process antigens, and migrate to draining lymph nodes (DLNs)
In DLNs, rDCs present processed antigens via MHC/peptide complexes to naive circulating T cells
Engagement of the T cell receptor (TCR) with the MHC/peptide complex and co-stimulatory signals activate T cell proliferation and migration to the lungs, where they perform their effector functions.

Immune Dysregulation During Chronic Viral Infection

CD8+ effector T cells kill virally infected cells, and CD4+ T cells enhance CD8+ and B cell responses, crucial for viral clearance
Most virus-specific T cells undergo apoptosis following viral clearance, but memory T cells are vital for long-term antiviral immunity
Chronic viral infections evade or suppress adaptive immunity
Persistent antigenic activation of T cells leads to T cell exhaustion, a dysfunctional state

Changes in the Phenotype of T Cells in the Peripheral Blood

Marked lymphopenia in patients with acute phase of infection
Reduced CD4+ and CD8+ T cells in Moderate and severe COVID-19 in acute phase
Decrease in CD8+ T cells in patients admitted to Intensive Care Unit (ICU) correlates with COVID-associated disease severity and mortality
Increased activated CD4 and CD8 T cells with an exhausted phenotype, characterized by upregulated expression of inhibitory markers like PD-1 and Tim-3 in persistent COVID
Production of inflammatory cytokines such as GM-CSF (Granulocyte-Macrophage Colony-Stimulating factor) by CD4 T cells in critically ill patients.
Reduced frequencies of T regulatory cells in severe COVID-19

Mechanisms Contributing to Reduced T Cells in the Blood

The cause of peripheral T cell loss in moderate to severe COVID-19 remains unclear.
This phenomenon is observed in other viral infections as well.
Cytokines like IFN-α, IL-6, and TNF-α may inhibit T cell circulation by promoting retention in lymphoid organs and attachment to endothelium
T cell recruitment to infection sites may reduce their presence in the peripheral blood, as seen by increased CD8 T cell infiltration in bronchoalveolar lavage fluid
Direct viral infection has not been reported.

CD4 and CD8 T Cell Responses

T cell responses specific to Spike, Matrix, and Nucleocapsid proteins are found in convalescent COVID patients.
T cell reactivity to SARS-CoV-2 is detectable in individuals with no prior exposure.

Anti-viral T Cell Responses

SARS-CoV-2 specific T cells are observed in most individuals
CD4 and CD8 T cell responses target different antigens, mostly Spike and Nucleocapsid proteins
The majority of SARS-CoV-2 CD4+ T cells exhibit a CCR7+CD45- phenotype (central memory - 50-60%) and some exhibit a CCR7-CD45- phenotype (effector memory - 25-40%)
SARS-CoV-2 CD8+ T cells predominantly express the effector memory phenotype
SARS-CoV-2 specific CD4 and CD8 T cells display a Th1 profile with increased cytotoxic activity and elevated expression of immune activation markers.

Pro-inflammatory Cytokine Secretion Profile

Activated CD4+ T cells produce high amounts of cytokines, whether activated by Spike or non-Spike proteins

SARS-CoV-2-Specific T Cells and Associations with Disease Severity

Detection of an early SARS-Cov2 CD4+ T cell response is associated with less severe disease than antibody response or CD8+ T cell response.
Early induction of CD4+ T cells secreting interferon gamma occurs much earlier in patients with mild disease and correlates with viral clearance
Preliminary evidence suggests very rapid induction of CD8+ T cells might lead to asymptomatic disease
Severe COVID-19 is associated with poor polyfunctionality and proliferative capacity and enhanced immune activation.

Cytokine Profile of CD4 and CD8-Specific T Cells to SARS-CoV2 Proteins

SARS-CoV-2 reactive CD4+ T cells have been detected in unexposed individuals
There's a spectrum of pre-existing memory CD4+ T cells that are cross-reactive with SARS-CoV-2 and common cold coronaviruses (HCoV-OC43, HCoV-229E, HCoV-NL63, HCoV-HKU1)
Healthy individuals previously exposed to common cold coronaviruses respond better to SARS-CoV-2 infection.

Phenotype and Function of T Cell Subsets

Increase in activated T cells, characterized by expression of HLA-DR, CD38, CD69, CD25, CD44, and Ki-67
CD8 T cells seem to be more activated than CD4 T cells
Higher expression of various co-stimulatory and inhibitory molecules like OX-40, CD137, CTLA-4, NKG2a, and TIGIT
Levels of most markers tend to increase in severe versus non-severe cases
Impaired functionality in CD4 and CD8 T cells in critically ill patients
T cells in severe COVID-19 appear to be more activated and exhausted, based on continuous expression of inhibitory markers like PD-1 and Tim-3
Increase in Follicular Helper T cells (Tfh) and effector molecules like Gzm A, Gzm B, and perforin, but a decrease in levels of inhibitory molecules in recovering patients.

B cell Immunity to SARS-CoV

IgG antibodies appear early on (day 4-45) after symptom onset
IgG antibody and neutralizing antibody (Nab) titers are highly correlated, peaking at month 4 after disease onset, with marked decrease at 2 years post-infection
Nabs to Spike protein peak at 20–30 days after infection and are sustained for over 150 days. NAb titers decrease markedly after month 16.
IgG level of mild patients is significantly higher than that of severe patients
SARS-CoV-infected patients with fatal outcomes display deficient antibody production against the S protein compared to non-severe patients.

Antibody Responses to SARS-CoV

One year after infection, Spike-specific IgG and neutralizing antibodies are detected in recovered individuals compared to high-risk healthy controls.
Healthy individuals do not have any Spike-specific antibodies

Specific Memory T and B Cell Responses to SARS-CoV

Memory T cell responses were detected in 60% of SARS patients six years after infection
T cell response is much stronger than B cell or antibody response.
No SARS-specific memory B cell responses were detected.

Correlation Between Neutralizing Antibody Titers and Anti-viral T Cell Activity

There's a correlation between neutralizing antibody titers and the number of Nucleocapsid Protein-specific T cells, suggesting that the development of neutralizing antibodies may be correlated with the activation of anti-viral T cells

Serological Signatures Track with SARS-CoV-2 Survival

Limited early differences were seen in titers and neutralization
A shift in the balance of Spike to Nucleocapsid antibodies is observed in convalescent versus deceased groups
Spike-specific phagocytic and complement-fixing activity was increased in convalescent individuals
Individuals that passed away from SARS-CoV-2 had increased Nucleocapsid protein-specific antibodies.

2003 CoV Pandemic

SARS-CoV viral particles markedly activated TLR-mediated innate immune responses
Lymphopenia occurred in the majority of patients and was associated with severe disease
Lymphopenia was a common feature in children, significantly impacting them
Development of virus-specific memory T cells was associated with disease resolution and protection from subsequent infection.

Immunological Similarities Between COVID-19 and Recent Pandemics?

Lymphopenia occurred in the majority of patients during the 2009 H1N1 influenza A pandemic and was also a frequent occurrence with significant morbidity in children.
Marked elevation of systemic innate inflammatory factors like MCP-1 and IL-6, and elevated IL-6 correlated with disease severity.
In the 2013 MERS-CoV pandemic, lymphopenia occurred less frequently, but was associated with disease severity, and recovery was associated with improved outcomes.
Neutralizing antibodies to MERS and MERS-CoV–specific CD4+ T cells correlated with disease severity.

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Explore the key roles of CD4+ and CD8+ T cells in combating viral infections. This quiz delves into their functions, interactions, and differentiation into various subtypes, highlighting their significance in immunity and immunotherapy, especially in the context of COVID-19.