Lecture 11: Immune Response During Infection Flashcards
Pathogens in extracellular environment use ___ immunity while pathogens in intracellular environment use ____ immunity
extracellular - humoral immunity
intracellular - cellular immunity
True or False: Protective Immunity always leads to sterilizing immunity
False - protective immunity can cause sterilizing or non-sterilizing immunity (e.g herpes)
If host survives with partial, incomplete, or temporary immunity, subsequent exposures to same pathogen will be _____. Example?
less severe
Example: influenza
If host survives with no immunity, the immune response to subsequent exposures to same pathogen will be ___ to first. Example?
identical
Example: tetanus
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
Klebsiella can cause ____ and c. jejuni can cause ____, both of which are autoimmune diseases
Ankylosing spondylitis
Guillian Barre syndrome
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
If pathogen is eradicated by innate immune response, what type of immunity does one have?
Sterilizing Immunity
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
True or False: If immediate innate immune response cannot eradicate pathogen, the innate immune response continues to be induced
True
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
If after 4 days, pathogen remains, which immune response is activated?
Adaptive immune response
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
Humoral or Cell Mediated Immunity depends on ___
pathogen
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
Are cytotoxic T cells, macrophages, monocytes associates with extracellular or intracellular pathogens?
Intracellular
___ is an obligate, intracellular pathogen
___ is a facultative, intracellular pathogen
Chlamydia: is an obligate, intracellular pathogen
Salmonella: is a facultative, intracellular pathogen
What are four methods by which Humoral Immunity combats extracellular (staph/strep) pathogens?
1) Ab
2) Ab/Phagocytosis
3) Complement
4) ADCC
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
_____ antibodies are extracellular methods that are particularly critical for getting rid of encapsulated organisms (such as: strep pneumoniae). Examples?
Opsonizing Antibodies
- IgG and C3b
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
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
Which antibody interferes with binding to host cell and prevents attachment (thereby allowing for immunity to extracellular bacteria)?
Neutralizing Antibody
In general, we can develop immunity to extracellular bacteria by activating what three pathways?
1) Complement
2) MBL
3) Alt
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
