Applied Immunity Flashcards Preview

Oral Bio > Applied Immunity > Flashcards

Flashcards in Applied Immunity Deck (55)
Loading flashcards...
1

 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

 

2

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

 

3

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.

4

 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

5

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
  •  

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

 

6

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

7

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
  •  

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

 

8

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
  •  

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

 

9

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

 

 

10

The Gut is Bombarded by Foreign Antigens

The Gut is Bombarded by Foreign Antigens

11

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

 

 

12

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.

 

13

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

 

14

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

15

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
  •  

 

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

 

 

16

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 

17

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)

 

18

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. 

19

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

20

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

 

21

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
  •  

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?

1.Antigen concentration is too low-lymphocytes have a threshold for receptor occupancy which is required to trigger a response

2.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

 

22

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)

23

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. 

 

24

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
  •  

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

 

25

Microbiota changes with life stage

Normal weight, Obese, Gastric Bypass

Pregnancy

Fecal transplant to mice from pregnant women

1st trimester: mouse___ weight

3rd trimester: mouse ____ and developed ___ ___

Microbiota changes with life stage

Normal weight, Obese, Gastric Bypass

Pregnancy

Fecal transplant to mice from pregnant women

1st trimester: mouse normal weight

3rd trimester: mouse fatter and developed insulin desensitization

26

Specific commensals determine ___ vs. ____

Differentiation of lamina propria T cells into ____ vs ____cells is determined by flora

Bacterial DNA signals through TLR9 to suppress Treg conversion, acts as a “natural adjuvant” (Hall, Immunity 2008)

Specific types of flora promote Th17 vs Treg development in the intestine (Ivanov, Cell Host & Microbe, 2008)

 

Specific commensals determine inflammation vs. suppression

Differentiation of lamina propria T cells into Treg vs Th17 cells is determined by flora

Bacterial DNA signals through TLR9 to suppress Treg conversion, acts as a “natural adjuvant” (Hall, Immunity 2008)

Specific types of flora promote Th17 vs Treg development in the intestine (Ivanov, Cell Host & Microbe, 2008)

 

27

Breakdown of oral tolerance

Immune responses to food leads to__ ___

e.g. celiac disease

Immune responses to___ ___eads to ___ ___ ___

Crohn’s disease

Ulcerative colitis

 

Breakdown of oral tolerance

Immune responses to food

leads to food intolerance

e.g. celiac disease

Immune responses to commensal bacterialeads to inflammatory bowel disease (IBD)

Crohn’s disease

Ulcerative colitis

 

28

Diseases of the Intestinal Immune System

Caused by:

Failure to ____ oral tolerance or

Food Allergies

Failure to ____ oral tolerance

 

Diseases of the Intestinal Immune System

Caused by:

Failure to establish oral tolerance or

Food Allergies

Failure to maintain oral tolerance

 

29

Food Allergies

Failure to establish tolerance

Production of __ to an antigen (allergen) which is then encountered again

2-4% of children and fewer adults suffer

Sensitive patients are usually atopic

Treatment is simple; avoidance and replacement

 

Food Allergies

Failure to establish tolerance

Production of IgE to an antigen (allergen) which is then encountered again

2-4% of children and fewer adults suffer

Sensitive patients are usually atopic

Treatment is simple; avoidance and replacement

 

30

Classification of adverse reactions to foods

Non immune mediated (___ ___) and immune mediated (___ ___)

Classification of adverse reactions to foods

Non immune mediated (food intolerance) and immune mediated (food allergy)