Immunology Year 1: Intracellular Infections

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Questions and Answers

What is activated in the innate immune response to viruses?

Viral PRRs (correct)

Mitochondrial DNA

B cell receptors

T cell receptors

Which type of cytokines are synthesized during the innate immune response to viruses?

Neurotransmitters

Secondary messengers

Type I interferons (correct)

Anti-inflammatory cytokines

What is the primary goal of viruses in relation to the immune system?

Survive and evade immune responses (correct)

Infect host cells

Maximize replication rate

Enhance cytokine production

What characterizes the innate immune response to viruses?

Multi-faceted and rapid activation Signup and view all the answers

How have viruses adapted to face the immune system?

By evolving strategies to evade the immune response Signup and view all the answers

Which type of receptors recognize viral capsid proteins?

TLR2/6 Signup and view all the answers

What is the primary function of type I interferons (IFNs) after viral recognition?

Induce an anti-viral immune state Signup and view all the answers

Which cells are activated by type I interferons to enhance immune response?

Cytotoxic T cells and NK cells Signup and view all the answers

Which receptor is primarily responsible for recognizing viral RNA?

TLR3 Signup and view all the answers

What immune response do NK cells have against infected cells?

Directly killing infected cells Signup and view all the answers

What occurs to MHC class I molecules in response to type I interferons?

Upregulation Signup and view all the answers

Which of the following is NOT a result of type I interferon action?

Viral replication increase Signup and view all the answers

What is one of the key roles of dendritic cells (DC) upon activation by type I interferons?

Enhancing antibody production from B cells Signup and view all the answers

What is the main cytokine produced by virally-infected cells?

IFN-α/β Signup and view all the answers

Which immune cells are primarily responsible for killing virally-infected cells?

CTLs and NK cells Signup and view all the answers

What type of receptors do NK cells possess to identify infected cells?

Both inhibitory and activatory receptors Signup and view all the answers

What is the role of antibodies against viruses?

All of the above Signup and view all the answers

How do NK cells differentiate between infected and uninfected cells?

By the expression of MHC class I Signup and view all the answers

What happens to NK cells when they encounter uninfected cells?

They remain inactive Signup and view all the answers

Which of the following cytokines is least likely to be produced by virally-infected cells?

IL-2 Signup and view all the answers

What type of immune response do CTLs primarily contribute to?

Cell-mediated immune response Signup and view all the answers

What strategy do viruses use to avoid being attacked by NK cells?

They down-regulate MHC class I expression Signup and view all the answers

What is a key function of NK cells in the immune response?

To kill cells infected by pathogens Signup and view all the answers

Which immune cells also have a role in killing virally-infected cells alongside CTLs?

NK cells Signup and view all the answers

In what way do NK cells kill infected cells?

In the same way as cytotoxic T cells Signup and view all the answers

What mechanism do antibodies use to neutralize viruses?

Blocking their entry into host cells Signup and view all the answers

Which is NOT a characteristic of uninfected cells regarding NK cell activity?

Lack inhibitory receptors Signup and view all the answers

In which scenario would IL-10 be most relevant?

In chronic viral infections Signup and view all the answers

What role does the activatory receptor play for NK cells?

Recognizes virally-infected cells Signup and view all the answers

What mechanism allows viruses to evade detection by the immune system?

Mutating viral genes Signup and view all the answers

What is a consequence of down-regulating MHC class I on infected cells?

Targeting by NK cells Signup and view all the answers

What does antigenic drift in influenza refer to?

Subtle changes in surface antigens Signup and view all the answers

Which virus is specifically mentioned as having a protein that inhibits antigen processing?

Epstein Barr Virus Signup and view all the answers

What event leads to anti-viral antibodies becoming ineffective against the influenza virus?

Antigenic drift Signup and view all the answers

What kind of changes does antigenic shift refer to in viral antigens?

Major changes Signup and view all the answers

How does the herpes simplex virus (HSV) evade the immune response?

By preventing peptide generation Signup and view all the answers

What is the effect of viruses that down-regulate MHC class I?

Increased risk of being targeted by NK cells Signup and view all the answers

What is a major factor that allows influenza to frequently evade the immune response?

Frequent antigen changes Signup and view all the answers

Which immune response mechanism is directly inhibited by some viruses like Epstein Barr Virus?

Antigen presentation Signup and view all the answers

What is the primary function of Cytotoxic T Lymphocytes (CTL) in combating viral infections?

To kill virally infected cells displaying viral antigens Signup and view all the answers

Which molecule do infected cells display to signal their infection to Cytotoxic T cells?

MHC class I Signup and view all the answers

What role does perforin play in the activity of Cytotoxic T Lymphocytes?

It forms pores in the infected cell membrane Signup and view all the answers

What is the function of granzymes in the immune response?

To activate apoptosis in infected cells Signup and view all the answers

Which cytokine is released by Cytotoxic T Lymphocytes to drive Th1 responses?

IFN-γ Signup and view all the answers

Why are antibodies noted as insignificant for anti-viral immunity in certain contexts?

They do not specifically target infected cells Signup and view all the answers

What is true about the cells that Cytotoxic T Lymphocytes kill?

They are cells infected by viruses Signup and view all the answers

Which action best describes the activation of Cytotoxic T cells once they recognize an antigen on MHC class I?

They bind and release cytotoxic factors Signup and view all the answers

What mechanism allows viruses to continuously change their surface antigens to evade the immune system?

Antigenic drift Signup and view all the answers

Which virus is associated with a protein that inhibits antigen processing?

Epstein Barr Virus Signup and view all the answers

What occurs when cells down-regulate MHC class I molecules?

They are targeted by Natural Killer (NK) cells Signup and view all the answers

Which of the following best describes antigenic shift?

Major reassortments of viral genes Signup and view all the answers

What is a consequence of antigenic drift in influenza viruses?

Ineffective anti-viral antibodies Signup and view all the answers

Which method is employed by some viruses to prevent MHC class I from reaching the cell surface?

Blocking peptide generation Signup and view all the answers

What can be a major immune evasion tactic employed by influenza viruses?

Changing surface antigens drastically Signup and view all the answers

How do viruses like HSV evade the immune response?

By preventing antigen processing Signup and view all the answers

What often results from the viral genetic variations associated with immune evasion?

Failure of previous vaccines Signup and view all the answers

Which type of changes is involved in the process of antigenic drift?

Subtle alterations through mutations Signup and view all the answers

What occurs as a result of Th1 cell activation during an immune response?

Enhanced microbiocidal activity Signup and view all the answers

Which factor can lead to reactivation of Mycobacterium tuberculosis residing in granulomas?

Steroid treatment Signup and view all the answers

What is the primary role of IFN-γ in the immune response?

To activate macrophages Signup and view all the answers

What is a major consequence of Th1 induced macrophage maturation?

Granuloma formation Signup and view all the answers

How does the Th1 response affect antigen presentation?

By increasing MHC class I and II Signup and view all the answers

Which of the following best describes granulomas formed during an immune response?

Walls of immune cells sealing off infections Signup and view all the answers

What effect do Th1 cells have on macrophages?

They activate macrophages for enhanced activity Signup and view all the answers

What role do granulomas play in relation to Mycobacterium tuberculosis?

They provide a bacterial reservoir for years Signup and view all the answers

What is the effect of IL-12 in the context of Th1 cell differentiation?

Stimulates Th1 cell differentiation Signup and view all the answers

What is one key function of macrophage activation by IFN-γ?

Increase in ROS production Signup and view all the answers

What is a key challenge posed by viruses in relation to the immune system?

Viruses have developed strategies to evade the immune system. Signup and view all the answers

Which aspect of the innate immune response is primarily activated in response to viral infections?

Viral pattern recognition receptors (PRRs). Signup and view all the answers

How do Type I interferons primarily contribute to the immune response?

By inhibiting viral replication directly within host cells. Signup and view all the answers

What is a significant result of viruses developing strategies to evade the immune system?

Failure of the immune system to recognize and destroy infected cells. Signup and view all the answers

What defines the innate immune response during viral infections?

It involves a rapid and general defense mechanism. Signup and view all the answers

What is the primary goal of the immune system when dealing with extracellular pathogens?

To kill the pathogen Signup and view all the answers

Which immune cells primarily respond to helminth infections?

Eosinophils and mast cells Signup and view all the answers

What immune response is commonly associated with intracellular bacteria?

Th1 response and IFN-γ Signup and view all the answers

What immune response mechanism is crucial in combating viral infections?

Cytotoxic T cells and NK cells Signup and view all the answers

Which component is not typically involved in the immune response to extracellular bacteria?

Cytotoxic T cells Signup and view all the answers

What is the primary effect of type I interferons (IFNs) on infected cells?

Shut down infected cells and nearby cells Signup and view all the answers

Which of the following effects is NOT associated with the action of type I interferons?

Inhibition of antigen presentation Signup and view all the answers

Which immune cells are enhanced in response to type I interferons, contributing to the anti-viral response?

Natural Killer cells and macrophages Signup and view all the answers

What role do RIG-I receptors play in viral recognition?

Identify cytoplasmic viral RNA Signup and view all the answers

How do type I interferons influence the activity of dendritic cells?

They activate dendritic cells to enhance antigen presentation Signup and view all the answers

Which of the following statements about Natural Killer (NK) cells is correct?

NK cells directly kill infected cells without prior sensitization Signup and view all the answers

What is the role of MHC class I molecules in the immune response to viral infections?

Display viral antigens to cytotoxic T cells Signup and view all the answers

Which of the following is a consequence of type I interferon action on neighboring uninfected cells?

Induction of an anti-viral immune state Signup and view all the answers

What is the primary function of antibodies in fighting viral infections?

Neutralisation of viruses Signup and view all the answers

Which immune cells play a crucial role in eliminating virally-infected cells?

Cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells Signup and view all the answers

Which cytokine is primarily associated with antiviral activity in response to viral infection?

IFN-α/β Signup and view all the answers

What is the major outcome for viruses that successfully evade the host immune response?

Avoid detection by antibodies and immune cells Signup and view all the answers

What effect does antigenic drift have on the influenza virus?

Promotes the emergence of new viral strains Signup and view all the answers

How do viruses like Epstein Barr Virus inhibit the immune response?

Through down-regulating MHC class I on infected cells Signup and view all the answers

What is the role of perforin in the immune response?

To create pores in the membranes of infected cells Signup and view all the answers

What is the significance of cytokine release by Cytotoxic T Lymphocytes (CTLs)?

It drives Th1 responses and enhances the immune response Signup and view all the answers

What strategy do viruses employ to ensure their survival against the immune system?

Evolving mechanisms to evade immune recognition Signup and view all the answers

Which of the following is a characteristic of the innate immune response to viral infections?

Activation of pattern recognition receptors (PRRs) Signup and view all the answers

Which factor best explains why type I interferons are crucial in the innate immune response?

They enhance the ability of adjacent cells to resist viral infection Signup and view all the answers

What is a consequence of viruses down-regulating MHC class I molecules on infected cells?

Decreased immunogenicity to cytotoxic T lymphocytes Signup and view all the answers

Which of the following describes a method by which viruses evade the immune response?

Modifying or disguising their antigens Signup and view all the answers

What is the primary role of Natural Killer (NK) cells in antiviral immunity?

To directly kill infected cells Signup and view all the answers

Which mechanism allows viruses to effectively evade the immune system?

Antigenic drift and shift Signup and view all the answers

How do cytotoxic T lymphocytes (CTLs) identify their target cells?

By detecting viral peptides presented on MHC class I molecules Signup and view all the answers

What role do interferons play in the antiviral response?

Modulating the activity of neighboring uninfected cells to resist infection Signup and view all the answers

What describes the term 'granulomas' in the context of immune response?

Chronic inflammatory sites that contain intracellular bacteria Signup and view all the answers

What is a significant outcome of type I interferon action?

Enhancing the expression of MHC class I molecules Signup and view all the answers

Which function does perforin serve in the immune response?

Creating pores in the membrane of target cells Signup and view all the answers

What is a key characteristic of the adaptive immune response to intracellular bacteria?

Development of a memory response primarily involving T cells Signup and view all the answers

What distinguishes the immune response to viral infections from that of extracellular infections?

INTERFERONS are vital in antiviral responses Signup and view all the answers

What mechanism do viruses typically utilize to inhibit MHC class I expression?

Interfering with antigen processing and presentation Signup and view all the answers

What is one consequence of type I interferons inducing an anti-viral immune state in infected cells?

Infected cells undergo apoptosis Signup and view all the answers

Which immune cell type is primarily activated by type I interferons to target infected cells?

Natural Killer (NK) cells Signup and view all the answers

Which innate immune response mechanism directly leads to the increase of antigen presentation across all cells?

Upregulation of MHC class I molecules Signup and view all the answers

What receptors are responsible for cytoplasmic recognition of viral RNA during viral infections?

RIG-I Signup and view all the answers

How do type I interferons influence dendritic cells (DC) in the context of viral infections?

By enhancing their ability to present antigens Signup and view all the answers

Which response best describes the action of Natural Killer (NK) cells upon recognition of infected cells?

Directly inducing apoptosis in infected cells Signup and view all the answers

What is the primary function of MHC class I molecules in the context of viral infections?

To present viral antigens to Cytotoxic T cells Signup and view all the answers

What role does the activation of macrophages play in the immune response to viral infections?

They enhance the phagocytosis of infected cells Signup and view all the answers

Which cells are primarily responsible for combating extracellular bacteria in the immune response?

Neutrophils and macrophages Signup and view all the answers

Which immune mechanisms are most associated with the response to helminth infections?

Th2 responses and IgE antibodies Signup and view all the answers

What is the primary goal of the immune system in response to intracellular pathogens such as viruses?

To kill the infected host cells Signup and view all the answers

Which immune component is most important in the defense against intracellular bacteria?

Th1 cells and IFN-γ Signup and view all the answers

How do the responses of T H 2 cells differ from those of T H 17 cells in the immune response?

T H 2 cells are associated with antibody production, whereas T H 17 cells are associated with recruiting neutrophils. Signup and view all the answers

What is the primary action of granzymes released by Cytotoxic T Lymphocytes?

They induce cell apoptosis. Signup and view all the answers

What role does IFN-γ play in the immune response against viral infections?

It enhances the activity of NK cells. Signup and view all the answers

How do Cytotoxic T Lymphocytes (CTLs) recognize infected cells?

By binding to viral antigens displayed on MHC class I molecules. Signup and view all the answers

What is a key characteristic of the cell killing mechanism used by Cytotoxic T cells?

They induce apoptosis in cells presenting viral antigens. Signup and view all the answers

What is the end result of perforin activity during the CTL killing mechanism?

Formation of pores in infected cell membranes. Signup and view all the answers

Which statement most accurately reflects the immune response to intracellular infections?

Perforin and granzymes act together to eliminate infected cells. Signup and view all the answers

What results when a virally-infected cell presents antigens on MHC class I molecules?

It signals for the activation of Cytotoxic T Lymphocytes. Signup and view all the answers

What is the effect of CTLs targeting cells infected by pathogens rather than the pathogens themselves?

This directly eliminates the source of the infection. Signup and view all the answers

What is a consequence of Th1 activation on macrophages in response to intracellular bacterial infections?

Increased antigen presentation capabilities Signup and view all the answers

Which of the following accurately describes the role of granuloma formation in tuberculosis?

They help to contain the infection in immune cells Signup and view all the answers

Which cytokine is primarily produced by Th1 cells to activate macrophages?

IFN-γ Signup and view all the answers

What effect does ongoing Th1 response have on the host's health regarding Mycobacterium tuberculosis (MTb)?

It is necessary for lifelong control of the infection Signup and view all the answers

What happens to the center of a granuloma over time?

It may undergo necrosis and become hypoxic Signup and view all the answers

Which of the following is NOT a function attributed to IFN-γ in macrophage activation?

Decreases antigen presentation via MHC Signup and view all the answers

What is a potential trigger for the reactivation of Mycobacterium tuberculosis from latency?

Immunosuppression such as from HIV Signup and view all the answers

In what way do Th1 cells enhance macrophage functions?

By increasing the production of costimulatory ligands Signup and view all the answers

What best describes the overall result of Th1-mediated immune responses against Mycobacterial infections?

Formation of protective barriers limiting pathogen spread Signup and view all the answers

Which statement about the immunity developed against completely new viruses created by genetic recombination is true?

No historical immunity exists, increasing susceptibility to new strains Signup and view all the answers

Study Notes

Responses to Intracellular Infections

Topic of the lecture: Responses to Intracellular Infections
Presented by: Dr. Patrick Walsh
Class: Year 1
Module: BMF
Date: November 2024

Immunology Lectures Outline

Barrier Immunity (lecture): Physical, mechanical, and chemical barriers to infection
Innate Immunity (lecture): Cytokines, inflammation, complement, and antigen presentation
Adaptive Immunity (lecture): Response to extracellular and intracellular infection (T-cell and B-cell responses)
Timeline of Immune Response: Instant, minutes/hours, days/weeks

Lecture Learning Outcomes

Describe a typical immune response to viral infection (using influenza as an example)
Explain the role of interferons in the anti-viral response
Define the role of Natural Killer (NK) cells and cytotoxic T cells in antiviral immunity
Define the adaptive immune response to viral infection
Describe viral escape from immune detection and disease pathology
Detail the innate and adaptive responses to intracellular bacteria (using mycobacterium as an example)
Explain granuloma development and maintenance

Extracellular vs. Intracellular Infections

Extracellular: Bacteria, fungi, protozoa, helminths (interstitial spaces, blood, lymph, epithelial surfaces)
Intracellular: Viruses (cytoplasmic or vesicular), bacteria, fungi, protozoa (cytoplasmic or vesicular)
Different infections require different immune responses

Viral Pattern Recognition Receptors

Viral capsid proteins: TLR2/6 & TLR4
Viral RNA (RNA virus): TLR3
Cytoplasmic RNA receptors: RIG-I

Overview of Immune Response to Intracellular Infections

Innate immunity: NK cells, Type I IFNs, virus titer,
Adaptive immunity: Antibodies, virus-specific CTLs
Timeline of immune responses (days after viral infection)

Innate Immune Response to Viruses

Type I interferons (IFNs) are produced by infected cells
Induction of an anti-viral immune state ('shut down' nearby cells)
Increase in antigen presentation and activation of innate cells (e.g., NK cells, macrophages, dendritic cells)
Induction of adaptive immunity

Effects of Type I IFNs on Immune Cells

MHC class I upregulation
Activation of dendritic cells and macrophages
Activation of cytotoxic T cells (directly kill infected cells)
Activation of NK cells (directly kill infected cells)

NK Cells in Anti-viral Innate Immune Response

NK cells are innate immune cells
No specific antigen receptor
Detect "altered self" cells
Kill virally-infected cells and tumor cells

Mechanism of NK Cells Killing Virally Infected Cells

Uninfected cells: Express MHC class I, positive signal from inhibitory receptor, NK cells not activated
Infected cells: Viruses may down-regulate MHC class I, no positive signal from inhibitory receptor, NK cells activated
NK cells kill infected cells through cytokine production and granule release

NK Cells Mechanism of Action

Perforin: Forms pores in the target cell membrane
Granzymes: Enter the pores and trigger apoptosis (programmed cell death)
IFN-γ: Drives Th1 responses and CTL activity

Antibody Effector Mechanisms Against Viruses

Neutralization: Antibody prevents adherence (insignificant role in anti-viral immunity)
Opsonization: Antibody blocks binding and infection (insignificant role in anti-viral immunity)
Complement activation: Antibody blocks infection of adjacent cells (insignificant role in anti-viral immunity)

Cytotoxic T Lymphocytes (CTL) Activation

Virally-infected cells display viral antigens on MHC class I molecules
CTL cells recognize the antigen-MHC complex
CTL cells release perforin and granzymes to induce apoptosis in the infected cell

Cytotoxic T Lymphocyte (CTL) Killing

Virally infected cells display viral antigens on MHC class I molecules
Activated cytotoxic T cells bind the antigen on MHC class I
CTLs are packed with toxic enzymes
Perforin forms pores in the target cell membrane
Granzymes activate apoptosis in the target cell
CTLs kill infected cells, not the pathogens themselves.

Overview of Immune Response to Intracellular Infections (summary)

Innate Immunity: NK cells, Type I IFNs, virus titer
Adaptive Immunity: Antibodies, Virus-specific CTLs

Follow the Influenza Virus Signaling

Cytokine produced by virally infected cells: IFN-α/β
Immune cells responsible for killing virally infected cells: CTLs and NK cells
Role of antibodies against viruses: Neutralization, Opsonization, and Complement activation.

How can Viruses Elude the Host Immune Response?

Viral genetic variation (mutations)
Down-regulation of MHC class I molecules
Interference with antigen processing
Evasion mechanisms to avoid detection
New strains produced.

Innate Immune Response to Viruses (summary)

Viral PRRs activated.
Type I IFN production and pro-inflammatory cytokines synthesized.
Multi-faceted innate immune response.

Viruses Strike Back: Evasion Strategies

Viruses strive to survive in the host environment by evading the immune response.
Viruses have evolved significant strategies to impede the detection of the virus and IFN production, to withstand immune responses, and ultimately resist infection.

Mechanisms of How Viruses Evade the Immune Response

Viral genetic variation(Mutations)
Down-regulate MHC class I molecules.
Interference with antigen processing.

Mechanisms of Influenza Evasion

Antigenic drift: Subtle changes in surface antigens (easy adaptation, causing frequent changes in viral strain).
Antigenic shift: Major changes in viral antigens (caused through genetic recombination).

Other Factors in Immune Evasion and How Influenza Viruses Evade

Th1 cells are involved in mycobacterial and other intracellular bacterial diseases.
Th1 induced macrophage maturation results in granuloma formation.

Immune Responses Summary

Extracellular Pathogens: Goal is to kill the pathogen. Neutrophils, macrophages, Th17, Antibodies, and eosinophils, mast cells, and IgE.
Intracellular Pathogens: Goal to kill the infected cells. Viruses, NK cells, cytotoxic T cells, and antibody neutralization. Intracellular bacteria, Th1, and IFN-γ.

SGT- A healthy immune response

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Description

This quiz focuses on the immune responses to intracellular infections, especially in the context of viral infections like influenza. Students will explore the roles of interferons, Natural Killer cells, and cytotoxic T cells in antiviral immunity, alongside the mechanisms of viral escape from immune detection.