Applied Immunity Flashcards
Immunity in the Oral Cavity
The oral cavity is the port of entry for many pathogens, food, and drugs which can trigger an immune response.
___t components: __ ___, ___, ___
____ components: ___ pathogens that colonize the oral cavity
Immunity in the Oral Cavity
The oral cavity is the port of entry for many pathogens, food, and drugs which can trigger an immune response.
Transient components: Dead pathogens, allergens, food
Persistent components: Live pathogens that colonize the oral cavity
Oral Cavity
Distinct locations:
Tooth surface, tongue, oral mucosa gingival crevices have selective immune responses
Distinct inductive sites: ___ ___
Two distinct effector sites:
- ___ ___
- ___ ___ ___
Pathogens have developed mechanisms to subvert or inactivate the host immune system
Unchecked growth of pathogens can lead to deterioration or loss of oral function
Oral Cavity
Distinct locations:
Tooth surface, tongue, oral mucosa gingival crevices have selective immune responses
Distinct inductive sites: Waldeyer’s ring
Two distinct effector sites:
Salivary glands
Gingival lamina propria
Pathogens have developed mechanisms to subvert or inactivate the host immune system
Unchecked growth of pathogens can lead to deterioration or loss of oral function
NALT: Inductive and Effector Sites
Inductor Sites represented by various tonsils. You have M cells to transport Ag to be processed by dendritic cells or macrophages. When those are activated, they migrate to the lymph nodes where they activate and cause differentiation of B and T cells.
They move to effector sites.
NALT: Inductive and Effector Sites
Inductor Sites represented by various tonsils. You have M cells to transport Ag to be processed by dendritic cells or macrophages. When those are activated, they migrate to the lymph nodes where they activate and cause differentiation of B and T cells.
They move to effector sites.
NALT Tissue: Waldeyer’s Ring
Named after the nineteenth century Heinrich Wilhelm Gottfried von Waldeyer-Hartz (German anatomist)
Consists of the lymphoid tissue on the __ of the tongue (___ tonsil), ___ (____) tonsils, the ____(____ tonsil), and the ___ tonsils (located bilaterally, where each Eustachian tube opens into the nasopharynx)
___ __in the lymphatic system that ___ and ___ to airborne and alimentary antigens
Tonsillectomies and/or adenoidectomies are indicated for children with impaired breathing through the ___ (i.e. sleep apnea), chronic upper __ __ infections, or recurrent ____
Ring of lymphoid tissue that surrounds ___ and ___ ___
NALT Tissue: Waldeyer’s Ring
Named after the nineteenth century Heinrich Wilhelm Gottfried von Waldeyer-Hartz (German anatomist)
Consists of the lymphoid tissue on the base of the tongue (lingual tonsil), two (palatine) tonsils, the adenoids (nasopharyngeal tonsil), and the tubal tonsils (located bilaterally, where each Eustachian tube opens into the nasopharynx)
First organs in the lymphatic system that analyze and react to airborne and alimentary antigens
Tonsillectomies and/or adenoidectomies are indicated for children with impaired breathing through the nose (i.e. sleep apnea), chronic upper respiratory tract infections, or recurrent earaches
Ring of lymphoid tissue that surrounds respiratory and alimentary tracts
Unique Defense Mechanisms in the Oral Cavity
In addition to normal tissue responses to infections, the oral cavity has two important biologic fluids which help prevent microorganisms from entering through the oral cavity:
- ___
- ___ ____ (Ab)
- ___ Immunity
- ___ __ __
- ___ ___(Ab)
- ___ Immunity
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Unique Defense Mechanisms in the Oral Cavity
In addition to normal tissue responses to infections, the oral cavity has two important biologic fluids which help prevent microorganisms from entering through the oral cavity:Saliva
Mucosal sIgA
Mucosal Immunity
Gingival Crevicular Fluid (GCF)
Blood plasma IgG
Systemic Immunity
Anti-microbial Components in Saliva
Antibodies: ____ Defense
Bind Bacteria
Calprotectin: Innate Defense
Chelates Zn and Ca to inhibit growth
Cystatins: Innate Defense
Inhibit ___ ___
Defensins: Innate Defense
___ mediated disruption of membrane
Histatins: Innate Defense
____
Lactoferrin: Innate Defense
Binds __ to inhibit growth
Lysozyme: Innate Defense
___
Mucins: Innate Defense
___ and aggregate microbe
PRP: Innate Defense
__ Bacteria
Statherin: Innate Defense
___ Bacteria
Anti-microbial Components in Saliva
Antibodies: Acquired Defense
Bind Bacteria
Calprotectin: Innate Defense
Chelates Zn and Ca to inhibit growth
Cystatins: Innate Defense
Inhibit Cysteine proteases
Defensins: Innate Defense
Charge mediated disruption of membrane
Histatins: Innate Defense
Antifungal
Lactoferrin: Innate Defense
Binds Fe to inhibit growth
Lysozyme: Innate Defense
Lyses
Mucins: Innate Defense
Entrap and aggregate microbe
PRP: Innate Defense
Bind Bacteria
Statherin: Innate Defense
Bind Bacteria
Calprotectin
- ___ ___
- Bacterial ___ ____ depend on ___ for ___
- àSensitivity to___
- Abundant in ____
- Sucks up Mn in environment so the SODs are inactive and bacteria more sensitive to ROS
- Marker of____ in IBD
- Increase Calprotectin à_____inflammation à Increased disease activity
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Calprotectin
Metal chelator
Bacterial superoxide dismutases (SODs) depend on Mn2+ for activityàSensitivity to ROS
Abundant in neutrophils
Sucks up Mn in environment so the SODs are inactive and bacteria more sensitive to ROS
Marker of inflammation in IBD
Increase Calprotectin à Increased inflammation à Increased disease activity
Specific Immune Components in Saliva
Secretory IgA (mucosal immune system)
- Found as a dimer connected by a “J” chain
- Contains a secretory component (“Sc” protein)
- Secreted by __ ___ in ___ ____
- Acts as a specific agglutinin of bacteria or fungus
- Prevents bacterial ____ to host cells or salivary ____
- Does not bind ___ and does not ___ bacteria well
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Specific Immune Components in Saliva
Secretory IgA (mucosal immune system)
Found as a dimer connected by a “J” chain
Contains a secretory component (“Sc” protein)
Secreted by Plasma cells in Salivary Glands
Acts as a specific agglutinin of bacteria or fungus
Prevents bacterial adhesion to host cells or salivary pellicle
Does not bind complement and does not opsonize bacteria well
Gingival Crevicular Fluid (GCF)
Is a __ ___or___ ___ derived from periodontal tissues that is found in the ___ ___
GCF contains molecules found in ___, the ___ ___, and in the ___
Contains:
___ Epithelial Cells
Leukocytes (predominately ____)
Host ____ (Collagenase, Elastase)
____ Components
_____ (IL-1, IL-8, TNF)
Immunoglobulins (IgG, IgA)
____ Acid metabolites
Prostaglandins
Leukotrienes
Other host proteins
Gingival Crevicular Fluid (GCF)
Is a serum transudate or inflammatory exudate derived from periodontal tissues that is found in the gingival sulcus
GCF contains molecules found in serum, the periodontal tissues, and in the sulcus
Contains:
Shed Epithelial Cells
Leukocytes (predominately Neutrophils)
Host Enzymes (Collagenase, Elastase)
Complement Components
Cytokines (IL-1, IL-8, TNF)
Immunoglobulins (IgG, IgA)
Arachidonic Acid metabolites
Prostaglandins
Leukotrienes
Other host proteins
The Gut is Bombarded by Foreign Antigens
The Gut is Bombarded by Foreign Antigens
Host needs to have a Balance between Respond and Don’t Respond
Respond: Fight and Eradicate Pathogens
Ignore: Self, Food
Host needs to have a Balance between Respond and Don’t Respond
Respond: Fight and Eradicate Pathogens
Ignore: Self, Food
Antigenic Challenge and Immune Responses in Mucosal Immunity
The context in which peptide antigen is presented to T lymphocytes in the mucosal immune system is important.
In the absence of inflammation and co-stimulation, presentation of peptide to T cells by MHC molecules on antigen presenting cells induces ____
In the presence of inflammation and pathogenic microorganisms in the tissues, the maturation and expression of co-stimulatory molecules on antigen presenting cells is stimulated. Antigen presentation to T cells under these conditions favors development of a _____ ____ ____
Antigenic Challenge and Immune Responses in Mucosal Immunity
The context in which peptide antigen is presented to T lymphocytes in the mucosal immune system is important.
In the absence of inflammation and co-stimulation, presentation of peptide to T cells by MHC molecules on antigen presenting cells induces tolerance.
In the presence of inflammation and pathogenic microorganisms in the tissues, the maturation and expression of co-stimulatory molecules on antigen presenting cells is stimulated. Antigen presentation to T cells under these conditions favors development of a protective TH1 response.
Oral Tolerance
Oral tolerance is
A general _____ state in the oral mucosa to prevent reaction to ____ Ags such as commensals or foods
The generation of systemic immune unresponsiveness by feeding of ____
Necessary to prevent excessive response to normal flora and food antigens
Oral Tolerance
Oral tolerance is
A general immunosuppressive state in the oral mucosa to prevent reaction to harmless Ags such as commensals or foods
The generation of systemic immune unresponsiveness by feeding of antigen
Necessary to prevent excessive response to normal flora and food antigens
Biological variables that influence the immunophenotype
Many factors determine whether you have ___ ___ or __ __
Biological variables that influence the immunophenotype
Many factors determine whether you have immune response or oral tolerance
Protective Immunity Versus Tolerance
- Protective Immunity ,Oral Tolerance
- Ag:
- Invasive Pathogens
- Food, commensals
- Ig Production
- ___ ___, ___ Ab present in serum
- ____ local IgA, ___ or ___ Ab serum
- T Cell Response
- Local and systemic ___ and___ T cells
- ___ local effector T cell response
- Response to Ag Reexposure
- Enhanced (____) Response
- __or __ response
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Protective Immunity Versus Tolerance
Protective Immunity
Oral Tolerance
Ag
Invasive Pathogens
Food, commensals
Ig Production
Intestinal IgA
Specific Ab present in serum
Some local IgA
Low or no Ab serum
T Cell Response
Local and systemic effector and memory T cells
No local effector T cell response
Response to Ag Reexposure
Enhanced (memory) Response
Low or no response
Experimental Demonstration of Oral Tolerance
Humoral Response
Mice fed Ag A. They were then challenged with that Ag via an injection 7 days later. Then mice were sacrified. Response to Ag was assessed via Ab production.
Fed nothing and challenged with Aà __ ___ response to A
Fed B and then challenged with Aà __ response
Fed A and then challenged with Aà ____ Ab response
Control: fed A and challenged with Bà ___ Ab response to A
Experimental Demonstration of Oral Tolerance
Humoral Response
Mice fed Ag A. They were then challenged with that Ag via an injection 7 days later. Then mice were sacrified. Response to Ag when assessed via Ab production.
Fed nothing and challenged with Aà Distinct Ab response to A
Fed B and then challenged with Aà Ab response
Fed A and then challenged with Aà reduced Ab response
Control: fed A and challenged with Bà no Ab response to A
Experimental Demonstration of Oral Tolerance
Did same experiment but wanted to look at CD4 T cell
Fed Ovalbumin. Challenge with Ovalbumin
Mice that were fed Ovalbumin and then challenged with Ovalbumin had ____ response.
If not fed Ovalbumin, you had ___ response (CD4 T cells ___to Ovalbumin)
Experimental Demonstration of Oral Tolerance
Did same experiment but wanted to look at CD4 T cell
Fed Ovalbumin. Challenge with Ovalbumin
Mice that were fed Ovalbumin and then challenged with Ovalbumin had a low response.
If not fed Ovalbumin, you had High response (CD4 T cells specific to Ovalbumin)
Oral Tolerance can be _____
Cell Mediated Portion of Response
Fed mouse with Ag A.
Took ___ ___ from the cells and transferred it to another mouse
Wanted to see if immune response/tolerance could be transferred by immune cell
Challenged second mouse with A
Conclusion: if you transferred T cells from mouse that were previously fed the Ag, the T cell oral tolerance could be transferred along with the cells.
Oral Tolerance can be Transferred
Cell Mediated Portion of Response
Fed mouse with Ag A.
Took bone marrow from the cells and transferred it to another mouse
Wanted to see if immune response/tolerance could be transferred by immune cell
Challenged second mouse with A
Conclusion: if you transferred T cells from mouse that were previously fed the Ag, the T cell oral tolerance could be transferred along with the cells.
Oral Tolerance can be ___ / ____
Depends on microenvironment around it
Feed mouse Ag with IFN Gamma (____ ____), it would ____tolerance.
Feed mouse Ag with IL10 or TGFB (____ ___), it would ____ your tolerance
Oral Tolerance can be Enhanced/ Reduced
Depends on microenvironment around it
Feed mouse Ag with IFN Gamma (pro-inflammatory cytokine), it would reduce tolerance.
Feed mouse Ag with IL10 or TGFB (anti-inflammatory cytokine), it would increase your tolerance
Oral Tolerance Mechanism
____
Induction of ___ ___
Induction of ____ ___
Induction of ___ ___ ___ which produce_____ cytokines
Oral Tolerance Mechanism
Ignorance
Induction of clonal anergy
Induction of clonal deletion
Induction of T regulatory cells which produce suppressor cytokines
Ignorance
- There are T cells and B cells specific for _____ present in circulation.
- These cells are quite ___ of making a response but are ____ of the presence of their auto-antigen.
- Why?
- 1.Antigen____ is too ___-lymphocytes have a threshold for receptor occupancy which is required to trigger a response
- 2.Antigens are ____ from the immune system in locations which are not freely____ to surveillance- immunologically ____ sites Barriers
- a)Potential____ ramifications if barriers disrupted
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Ignorance
There are T cells and B cells specific for auto-antigens present in circulation.
These cells are quite capable of making a response but are unaware of the presence of their auto-antigen.
Why?
- Antigen concentration is too low-lymphocytes have a threshold for receptor occupancy which is required to trigger a response
- Antigens are sequestered from the immune system in locations which are not freely exposed to surveillance- immunologically privileged sites Barriers
a) Potential autoimmune ramifications if barriers disrupted
High vs. Low Dose Tolerance
That will influence how mechanism of tolerance works
High Dose: Induce ___ or ____ of T cell that recognizes that ___
Low Dose: Favor product of __ _____ (______)
High vs. Low Dose Tolerance
That will influence how mechanism of tolerance works
High Dose: Induce Anergy or deletion of T cell that recognizes that Ag
Low Dose: Favor product of T regulatory cells (immunosuppressive)
Oral Tolerance Summary
Oral tolerance is a specific mechanism
Clonal deletion and regulatory T cells are the primary mechanisms
Breakdown of tolerance can lead to _____ disorders.
Oral Tolerance Summary
Oral tolerance is a specific mechanism
Clonal deletion and regulatory T cells are the primary mechanisms
Breakdown of tolerance can lead to autoimmune disorders.
Mucosal Immunity: Commensals
- Microbiota communities affected by
- Age
- Location
- Environmental cues (i.e. antibiotics, diet)
- Therapy
- Genetics predisposition
- Disease vs. health
- Dynamic communityà Changes thruout life
- ___ ___ ___ play role in regulating response to commensals
- IECs deficient in _____ (____ regulator of ____s) show ____cytokines, ____ susceptibility to intestinal inflammation
- Immune status of host also influences makeup of commensal flora, thereby affecting immune system function
- IgA-deficient mice have different microbial spp
- Tbet KO/scid mice have increased “_____” bacteria and ___ symptoms
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Mucosal Immunity: Commensals
Microbiota communities affected by
Age
Location
Environmental cues (i.e. antibiotics, diet)
Therapy
Genetics predisposition
Disease vs. health
Dynamic communityà Changes thruout life
Intestinal epithelial cells play role in regulating response to commensals
IECs deficient in SIGGIR (negative regulator of TLRs) show increased cytokines, increased susceptibility to intestinal inflammation
Immune status of host also influences makeup of commensal flora, thereby affecting immune system function
IgA-deficient mice have different microbial spp
Tbet KO/scid mice have increased “colitogenic” bacteria and UC symptoms
