Mucosal Immune System Flashcards
Mucosal immune system
Situated at ‘____ mucosal surfaces of body
e.g., ___, _____, ____, ___, _____
___ from systemic immune system
Mucosal immune system
Situated at ‘exposed’ mucosal surfaces of body
e.g., eyes, gastrointestinal tract, oral cavity, lungs, genitourinary tract
Distinct from systemic immune system
Challenges at mucosal surfaces
- Sites of important interaction between the _____ and the_____
- Lung epithelium: ___ ____
- Gastrointestinal epithelium: ___ ___
- Represent a vast ___ ___
- ____ and most important area exposed to the external environment
- GI surface is over____
- Most ____ site of infection by pathogens
- Heaviest ____ load
- Vulnerable to ___ and invasion
- Skin is exposed to the external environment but is____
- The mucosa is an extension of the skin and lines the digestive track from mouth to anus
Challenges at mucosal surfaces
Sites of important interaction between the organism/body and the external environment
Lung epithelium: gas exchange
Gastrointestinal epithelium: nutrient absorption
Represent a vast surface area
Largest and most important area exposed to the external environment
GI surface is over 200 m2
Most frequent site of infection by pathogens
Heaviest antigenic load
Vulnerable to colonization and invasion
Skin is exposed to the external environment but is sealed.
The mucosa is an extension of the skin and lines the digestive track from mouth to anus
Surface area exposed to the external environment
SA of Skin is very___ compared to lungs and GI.
This is due to ___ in lungs and___ in GI
Surface area exposed to the external environment
SA of Skin is very small compared to lungs and GI.
This is due to alveoli in lungs and villi in GI
___ ___ ___ ___ (MALT)
- ___-associated lymphoid tissues (GALT)
- ___ ____
- ___ lymph nodes
- ____
- ___ lymph nodes
- ____-associated lymphoid tissues (NALT) Oral Cavity
- ____ Ring: palatine, nasopharyngeal (adenoids), tubal, and lingual tonsils
- ____ tract
- ____-associated lymphoid tissue (BALT)
- ____ (or ___)-associated lymphoid tissue (CALT or EALT)
- ____ ____-associated lymphatic tissue (O-MALT)
Mucosa-associated lymphoid tissue (MALT)
Gut-associated lymphoid tissues (GALT)
Peyer’s patches (PP)
Mesenteric lymph nodes
Appendix
Solitary lymph nodes
Nasopharyngeal-associated lymphoid tissues (NALT) Oral Cavity
Waldeyer’s Ring: palatine, nasopharyngeal (adenoids), tubal, and lingual tonsils
Genitourinary tract
Bronchus-associated lymphoid tissue (BALT)
Conjunctiva (or Eye)-associated lymphoid tissue (CALT or EALT)
Organized mucosa-associated lymphatic tissue (O-MALT)
Fundamental objectives of the mucosal immune system
- Containment of the vast onslaught of environmental ____ without compromising the integrity of mucosal ___
- Protect ___ ___ from pathogens (while still allowing for efficient ___ ___ ___ from external environ into host)
- ____ infectious agents and prevent (pathogenic) microbial _____
- Barrier function
- Transport ____ across the ___ ___ (____ Sampling)
- So that immune sys can recognize and respond to pathogens
- Epithelial barrier separates the ___ immune tissue from the ____
- Transport ____ across the ___ ___ (____ Sampling)
- Protect ___ ___ from pathogens (while still allowing for efficient ___ ___ ___ from external environ into host)
- Prevent ___ _____of the ___ compartment
- Compartmentalization of ____ functions
- Tolerate ____ and____antigens (___ ___)
- Do not respond to ____ environmental antigens (like gluten)
- Do not ____ the mucosal surface
- Maintenance of mucosal homeostasis
- ____ influence on ____ immunity
- Focus of much vaccine work
Fundamental objectives of the mucosal immune system
Containment of the vast onslaught of environmental antigens without compromising the integrity of mucosal barriers
Protect mucous membranes from pathogens (while still allowing for efficient transfer of nutrients from external environ into host)
Clear infectious agents and prevent (pathogenic) microbial colonization
Barrier functionTransport antigens across the mucosal surface (Antigenic Sampling)
So that immune sys can recognize and respond to pathogens
Epithelial barrier separates the mucosal immune tissue from the lumen
Prevent over-stimulation of the systemic compartment
Compartmentalization of effector functions
Tolerate commensals and food antigens (Oral Tolerance)
Do not respond to harmless environmental antigens (like gluten)
Do not damage the mucosal surface
Maintenance of mucosal homeostasis
Regulatory influence on systemic immunity
Focus of much vaccine work
Mucosal Defense:
- Non-immunologic barriers
- Physical
- ____ barriers
- ______ ____
- ____ of epithelium
- ____
- Physiological/Chemical
- Gastric___ and ____
- _____ secretions
- Physical
- Commensal bacteria
- Immune system- innate and adaptive
- Cellular
- ___/___-___ response
- ____
- _____
- ____ factors
- C
- C
- S
- D
- P
- L
- L
- Cellular
Mucosal Defense:
Non-immunologic barriers
Physical
Epithelial barriers
Mucociliary escalator
Shedding of epithelium
Peristalsis
Physiological/Chemical
Gastric acid and bile
Mucous secretions
Commensal bacteria
Immune system- innate and adaptiveCellular
Cytotoxic/Cell-mediated response
Phagocytosis
Immunoglobulins
Soluble factors
Cytokines
Complement
Surfactant proteins
Defensins
Proteases
Lactoferrin
Lysozyme
Mucosal Defense: Epithelium as a Physical Barrier
Epithelial ___ junctions, ___ junctions, and_____ form a _____ (structural) barrier to prevent _____ passage
Don’t want free flow of stuff from external environment to underside of mucosa
Mucosal Defense: Epithelium as a Physical Barrier
Epithelial tight junctions, adherens junctions, and desmosomes form a paracellular (structural) barrier to prevent macromolecule passage
Don’t want free flow of stuff from external environment to underside of mucosa
Mucosal Defense: Physiological/Chemical Barriers
- ____
- Low __ of ____ and ___
- Molecular defenses
- ____/____ secretions
- ____, ____ enzymes, ____
- C____
- C___
- M____
- ____/____ secretions
Mucosal Defense: Physiological/Chemical Barriers
Biochemical
Low pH of stomach and vagina
Molecular defensesAntibacterial/antimicrobial secretions
Defensins, Hydrolytic enzymes, Lysozyme
Complement
Cytokines
Mucus
Mucosal Defense: Secretions
- Mucins- form a ___ layer to ____ pathogens; ___of mucosal surface for passage of nutrients
- Secreted from ____ cells in the epithelial layer
- ____ peptides- promote epithelial ____
- Antimicrobials (___, ___, & ____)- ____ effects on bacteria and fungi
- Excreted into the ___
- Cytokines- immune _____ effects
- Antibodies/Immunoglobulins: _____and ___ foreign objects
Mucosal Defense: Secretions
Mucins- form a mucus layer to trap pathogens; lubrication of mucosal surface for passage of nutrients
Secreted from goblet cells in the epithelial layer
Trefoil peptides- promote epithelial healing
Antimicrobials (defensins, cathelicidins, & RegIII)- microbicidal effects on bacteria and fungi
Excreted into the lumen
Cytokines- immune modulatory effects
Antibodies/Immunoglobulins- identify and neutralize foreign objects
Mucosal Defense: Microbiota
- They outnumber human cells at least 10-100:1 (“you are only ____% human”)
- Weight ~_ kg
- Normal commensal flora maintain ____
- Help ___ ____, etc.
- Fill niches to prevent pathogenic bacteria from___
- Secret ___ substances
- ____ with pathogenic bacteria for nutrients or attachment to cell surfaces
- Required for immune____
- Germ-free rodents have reduced lymphoid __, low __, reduced immune ____ of all types
- Help maintain ____
Mucosal Defense: Microbiota
They outnumber human cells at least 10-100:1 (“you are only 1-10% human”)
Weight ~1 kg
Normal commensal flora maintain health
Help metabolize cellulose, etc.
Fill niches to prevent pathogenic bacteria from colonizing
Secret toxic substances
Compete with pathogenic bacteria for nutrients or attachment to cell surfaces
Required for immune development
Germ-free rodents have reduced lymphoid organs, low Ig, reduced immune responses of all types
Help maintain tolerance
Detox: If we eat xenobiotic, they can convert it to ___ ___
Biosynthesis: secrete into the lumen for uptake by host ___ ___ or ____ that host can’t make
Immune maturation
Metabolic: Help digest ___ into __ __ ___, which have ___ and ____(_______) activities for the host
Protective: compete with pathogenic bacteria to exclude them
Detox: If we eat xenobiotic, they can convert it to harmless metabolite
Biosynthesis: secrete into the lumen for uptake by host essential aa or vitamins that host can’t make
Immune maturation
Metabolic: Help digest fiber into short chain fa, which have catabolic and immunological (anti-inflammatory) activities for the host
Protective: compete with pathogenic bacteria to exclude them
Mice with knocked out genes have changes in the ____
Genes influence___ and microbiota influence the ___
Mice with knocked out genes have changes in the microbiota
Genes influence microbiota and microbiota influence the host
Mucosal Defense: Cellular Barriers
Primary Functions:
- Phagocytosis:
- ____ and _____
- Goble it up and destroy it
- Macrophages also ____ it to adaptive immune cells
- Cytokines
- ____ cells and _____ secrete cytokines that will ____/____ immune response
- Mucus
- _____ cells secrete ___ that form ____ layer to prevent pathogens from ____ the host
- Antigen Presentation
- APC= ___ ___ involved in processing Ag from pathogens and presenting them to the immune system for identification and possible response
- Antimicrobials
- ____ Cells
- Antibodies
- B cells, plasma cells
- Cytotoxic effects
- ____ the ___ ___ itself
- _____ ___ (mainly CD_)
Mucosal Defense: Cellular Barriers
Primary Functions:
Phagocytosis:
Neutrophils and macrophages
Goble it up and destroy it
Macrophages also present it to adaptive immune cells
Cytokines
CD4 T cells and macrophages secrete cytokines that will enhance/suppress immune response
Mucus
Goblet cells secrete mucins that form mucous layer to prevent pathogens from colonizing the host
Antigen Presentation
APC= Dendritic Cell involved in processing Ag from pathogens and presenting them to the immune system for identification and possible response
Antimicrobials
Paneth Cells
Antibodies
B cells, plasma cells
Cytotoxic effects
Within the epithelial layer itself
Interepithelial lymphocyte (mainly CD8)
Nomenclature of immune cells
Green mediates cross talk bw the two
___
___ ____
____ ___ __
Nomenclature of immune cells
Green mediates cross talk bw the two
NK
Gamma delta T cells
Innate Lymphoid Cells
Mucosal Defense: Epithelium as Orchestrators of Immune Response
In addition to the physical ____ function, the epithelial cells interact with innate and adaptive cells, via ___ ___ (i.e., cytokines, TSLP) and ___ ____, to regulate __ ___ and ___ ___
Epithelium provides the barrier fcn so you keep out pathogens
In addition, when epithelium encounters a pathogen, it can ___ ___ itself that will interact with underlying innate and adaptive immune cells to regulate the barrier fcn and initiate an immune response
Mucosal Defense: Epithelium as Orchestrators of Immune Response
In addition to the physical barrier function, the epithelial cells interact with innate and adaptive cells, via chemical messengers (i.e., cytokines, TSLP) and antigen presentation, to regulate barrier function and immune response.
Epithelium provides the barrier fcn so you keep out pathogens
In addition, when epithelium encounters a pathogen, it can secrete cytokines itself that will interact with underlying innate and adaptive immune cells to regulate the barrier fcn and initiate an immune response
