Lecture 11: Immune Response During Infection Flashcards by Katlyn Heneghan

Pathogens in extracellular environment use ___ immunity while pathogens in intracellular environment use ____ immunity

extracellular - humoral immunity
intracellular - cellular immunity

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True or False: Protective Immunity always leads to sterilizing immunity

False - protective immunity can cause sterilizing or non-sterilizing immunity (e.g herpes)

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If host survives with partial, incomplete, or temporary immunity, subsequent exposures to same pathogen will be _____. Example?

less severe
Example: influenza

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If host survives with no immunity, the immune response to subsequent exposures to same pathogen will be ___ to first. Example?

identical
Example: tetanus

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What outcomes would you expect to see in deleterious host immune response?

1) Damage to normal tissue (scarring in TB)
2) Altered immune response (e.g encouraging Th2 instead of Th1 - as in EBV, where viral IL-10 is made)
3) Autoimmune response

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Klebsiella can cause ____ and c. jejuni can cause ____, both of which are autoimmune diseases

Ankylosing spondylitis
Guillian Barre syndrome

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Which of the following immune response components are useful in combatting intracellular pathogens?
A. antibody
B. complement
C. lysozyme
D. NK cells

D. NK cells

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If pathogen is eradicated by innate immune response, what type of immunity does one have?

Sterilizing Immunity

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True or False: Once pathogen bypasses outer barriers and proliferates, insoluble adaptive factors recognize pathogen and activate cells at infection site

False - once pathogen bypasses outer barriers and proliferates, SOLUBLE and INNATE factors recognize pathogen and activate cells at infection site

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True or False: If immediate innate immune response cannot eradicate pathogen, the innate immune response continues to be induced

True

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If pathogen is not easily eradicated, additional members of innate IR are induced. Examples?

1) Resident innate immune cells
2) Effector immune cells
3) Fever
4) Acute phase response

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If after 4 days, pathogen remains, which immune response is activated?

Adaptive immune response

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In the time course of an infection, what occurs when the adaptive immune response is activated?

1) Reactive B and T cells interact
2) Antigen-specific B and T cells proliferate and become effectors cells
3) Antigen-specific antibodies and effector T cells go to infection

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Humoral or Cell Mediated Immunity depends on ___

pathogen

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If you have a staph or strep infection, what kind of immune response do you want?

If you have an intracellular pathogen, what kind of immune response do you want?

Staph/Strep = Humoral
Intracellular = CMI

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Are cytotoxic T cells, macrophages, monocytes associates with extracellular or intracellular pathogens?

Intracellular

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___ is an obligate, intracellular pathogen
___ is a facultative, intracellular pathogen

Chlamydia: is an obligate, intracellular pathogen
Salmonella: is a facultative, intracellular pathogen

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What are four methods by which Humoral Immunity combats extracellular (staph/strep) pathogens?

1) Ab
2) Ab/Phagocytosis
3) Complement
4) ADCC

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What are four methods by which Cell-Mediated Immunity combats intracellular pathogens?

1) Th1 cells - IFN-gamma
2) CD8+ T cells
3) NK cells
4) Anti-viral state

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_____ antibodies are extracellular methods that are particularly critical for getting rid of encapsulated organisms (such as: strep pneumoniae). Examples?

Opsonizing Antibodies
- IgG and C3b

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Under what two clinical situations is phagocytosis impaired?

1) Splenectomized patients - more likely to get sepsis
2) Neutropenic patients - more likely to get extracellular pathogen infections

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True or False: Staph is more likely to cause infection in person without a spleen. Why or why not?

True
- Without a spleen, one has impaired phagocytosis
- Phagocytosis is needed to rid one of extracellular bacteria - particularly strep/staph

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Which antibody interferes with binding to host cell and prevents attachment (thereby allowing for immunity to extracellular bacteria)?

Neutralizing Antibody

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In general, we can develop immunity to extracellular bacteria by activating what three pathways?

1) Complement
2) MBL
3) Alt

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True or False: Antibody Dependent Cell Cytotoxicity (ADCC) allow for immunity to extracellular pathogens. Antibodies have a Fc region that binds to Fc portion of extracellular pathogen

True

Antibody-dependent cellular cytotoxicity is utilized to provide immunity to ___ bacteria. What is the results?

Extracellular; apoptosis/lysis

___ is expressed on mucosal surfaces. allow for neutralization. Therefore: they provide immunity to extracellular pathogens.

IgA

Many extracellular bacteria try to evade immune response by colonizing or infecting only ___ surfaces. Why?

mucosal Because mucosal surface have low complement levels and few phagocytic cells

How can extracellular pathogens cause damage without enter into a cell?

Release /Elaborate a toxins once mucosal surface is colonized, which could have systemic effect

What is the best strategy we have for for combatting extracellular bacteria?

Mucosal immunity (secreting IgA at mucosal surface, so it binds to toxins)

True or False: Toxins that are produced by extracellular bacterias may be neutralized with an antibody

True

Endotoxin (LPS/LOS) is produced by ____ while exotoxins are made by either ___ or ____

Endotoxin (LPS/LOS) = gram - Exotoxin = gram - or gram +

True or False: Exotoxins: mediate septic/endotoxic shock (IL-1, TNF-a, IL-6) and activate the alternate complement pathway

False - endotoxins mediate septic/endotoxic shock (IL-1, IL-6, and TNF-a)

___ can be converted to many toxoid and have specific activity, depending on toxin

Exotoxin

____ has broad biological activity, but does not have any toxoid (inactive form of toxin) available.

Endotoxin

Only ___, a certain exotoxin, directly induces cytokine release

superantigens

In superantigens, the result is ____ activation of all T cells and APC binding to superantigen

non-specific

True or False: As a result of superantigens, MANY T cells are activated to make cytokine and systemic response

True

Example of toxic shock syndrome?

Superantigens + super antigen stimulation

True or False: In superantigen stimulation, T cells are activated depending on antigen specificity

False - in superantigen stimulation, T cells are activated regardless of antigen specificity

Capsules, toxins, and attachment factors are examples of ____

virulence factors (substances made by pathogenic organisms, enables it to cause disease in host)

Which of the following molecules is most important for immunity from infection with encapsulated bacteria? A. IFN-gamma B. IgG C. IgE D. HLA-I E. IL-12

B. IgG - important for opsonizing

IFN gamma is better at treating ___ infections

viral

HLA Class I expresses a ___ pathogen

Itnracellular

IL-12 is good for ___ response

Th1

Superantigens stimulate an immune response that is composed of: A. Polyclonal Antibody Response B. Monoclonal Antibody Response C. Polyclonal T cell Response D. Monoclonal T cell Response

C. Polyclonal T cell Response

What kind of intracellular bacteria must be inside a cell for life cycle to occur?

Obligate (chlamydia)

To have immunity to INTRACELLULAR BACTERIA, you must have activation of ___ and production of ___

Activate CD4+ Th1 Produce IFN-gamma (encourages macrophages to phagocytose)

What are the two groups of interferons?

Type 1 (IFN-alpha and IFN-beta) Type 2 (IFN-gamma)

____ and ___ produce IFN-gamma

T Lymphocytes and NK Cells

Which Type of interferons are "non immune" and made by almost every nucleated cell of the body upon infection with a VIRUS?

Type 1 (IFN-alpha and IFN-beta)

True or False: IFN-gamma encourages a Th1 response and encourages phagocytosis

True

What are some features shared by both Type 1 and 2 Interferons?

Restrict protein synthesis Decrease membrane fluidity Induce iNOS and O2 Alter metabolism Increase HLA Class I - more CTL activity

ooo

IFN-gamma activates ___ to destroy intracellular pathogens

macrophages

True or False: Activated macrophages only express HLA I

False - activated macrophages express HLA I and II

What cells secrete IFN-gamma to stimulate macrophages to kill intracellular pathogens?

Th1 cells

True or False: Endogenous cytokines and exogenous cytokines (LPS) can increase phagocytosis alone. But together, there's even greater phagocytosis!

True

____ has antibacterial effects on macrophages

IFN-gamma

What are features that make Type 2 IFN-gamma cells unique?

1) Increase respiratory burst 2) Increase expression of HLA 1 AND 2! 3) Increase Fc receptor and C3b 4) Increase metabolism 5) Induce iNOS and O2-

___ makes a monocyte derived macrophage into APC

IFN-gamma

True or False: Cytotoxic cells are important for extracellular bacterial infections

False - cytotoxic cells are important for intracellular bacterial infections

What two cell types are important in intracellular bacterial infections early in the response?

NK Cells Gamma/delta TCR T Lymphocytes

Activation of two cells are important for intracellular bacterial infections later in the response?

1) CD4+ Th1 activation (IFN-gamma and IL-2) 2) CD8+ CTL's (recognize processed antigens)

Both __ and ___ cells are cytolytic

NK cells and CD8+ T cells

True or False: Th1-mediated responses are critical for eradication of extracellular bacteria

False - Th1-mediated responses are critical for eradication of INTRACELLULAR bacteria

What types of pathogens will often drive a Th2 response? How?

Obligate intracellular pathogens - Down regulate Th1

If Th1 response predominates, how will an obligate intracellular pathogen respond?

Becomes latent until response wanes

During intracellular bacterial infections, _____ are important early on while ___ are important later in the response A. CD8+ T cells - CD4+ T cell B. NK Cells - CD8+ T cells C. NK Cells - gamma/delta T cells D. Gamma/delta T cells - NK cells

B. NK Cells - CD8+ T cells

True or False: Cytotoxic cells are involved in extracellular bacterial infections

False - cytotoxic cells are involved in intracellular infections

True or False: Only the innate response is important for immunity to fungi

False - both the innate and adaptive are important

How will the innate immune system target fungus infection?

1) Neutrophils will use PRR's to recognize fungal PAMPS and, ultimately, phagocytose the fungus 2) Mannose Binding Lectin (of complement pathway)

___ and ___ are important helping the adaptive immune system fight off fungal infections

Th-1 and Th-17

Which adaptive responses are needed to control opportunistic fungal infections?

Th-1

True or False: In Th-1 mediated responses of the adaptive immune system, IFN-gamma is needed to increase phagocytic activity

True

True or False: Viruses are facultative intracellular pathogens

False - viruses are obligate, intracellular pathogens (they are entirely dependent on host)

How are viral antigens processed?

Exogenously (HLA Class 2 on APC) Endogenously (HLA Class 1 on APC)

Virally infected cell will present using HLA ___

HLA 1

What type of immunity can be used to fight against viral infections?

Humoral Immunity

Four roles of the antibody in humoral immunity to viral infections?

1) Neutralization - of virus ligands for host cell receptor (block viral attachment) 2) Opsonization of virus or host cells expressing viral antigens in their membrane - ENHANCES phagocytosis 3) Activation of complement (virus or host cell - classical pathway) 4) ADCC (Antibody-dependent cellular cytotoxicity) of infected host cell Note: None of these mechanisms work if target is INSIDE a cell

What cell is important for EARLY stages of cellular immunity against intracellular virus particles?

NK cells (sense lack of self, HLA 1, by KIR's) Gamma/Delta T cells (PAMP's)

What cell is important for LATER stages of cellular immunity against intracellular virus particles?

CTL (Cytotoxic T Lymphocyte) - Involves HLA 1 presentation of viral peptide

Induction of anti-viral state by ___ is important for establishing cellular immunity against intracellular virus particles. Examples?

interferons - IFN alpha and beta (all nucleated cells) - IFN gamma (Th1, CTL, gamma/delta TCR+, NK)

What are four ways that IFN's effect viral infections?

1) Less membrane fluidity 2) Makes enzymes that degrade viral NA's 3) Inhibit viral protein synthesis 4) Up-regulate HLA Class 1

What are the five viral responses to host defense?

1) Block IFN - inactivates signaling pathways (hep C) 2) Block HLA - molecule expression (herpes); TAP delivery (adenovirus) 3) Block complement activation (influenza A) 4) Antigenic variation (influenza) 5) Make homologoues of immune regulatory cytokines (IL-10 made by EBV)

Extracellular protozoan parasites require what type of immune response? Intracellular protozoan parasites require what type of immune response?

Extracellular: Humoral (Th2 response) Intracellular: CMI (Th1 response)

What antibody is important for binding and recruiting eosinophils during helminthic infection?

IgE antibody (Th2 response)

What mediates septic syndrome?

Massive release of pro-inflammatory cytokines

True or False: LPS (gram negative bacteria) and peptidoglycan (gram positive bacteria) can both engage PAMP receptor, leading to large release of pro-inflammatory cytokines and, ultimately, Septic Syndrome

True

Type 1 interferons exert their antiviral effects by which of the following mechanisms? A. Increasing membrane fluidity B. Increasing endogenous antigen processing pathways C. Increasing viral protein synthesis to increase presentation

B. Increasing endogenous antigen

The host response to parasitic helminth infestations is most similar to which of the following? A. Allergies and allergic asthma B. Sepsis or the systemic inflammatory response syndrome (SIRS) C. Type 1 hereditary angioedema D. Toxic shock syndrome E. Responses to viral infections

A. Allergies and allergic asthma

True or False: In superantigen stimulation of T cells, T cells are activated regardless of antigen specificity

True