Lecture 26: Cutaneous & Mucosal-Associated Lymphoid Tissues Flashcards
what are barrier immune tissues?
any tissues that separate our “insides” from the outside world
t/f there are some differences in barrier immune tissues, but the basic barriers are consistent
t
what are the 3 layered barriers?
- commensal microflora
- Epithelial & associated cells
- Sentinel Cells
what are the 3 functions of the commensal microflora?
- maintain balance
- help digestion
- crowd out pathogens
what is the function of epithelial and associated cells?
produce mucous or antimicrobial peptides/chemicals
what are the 3 functions of sentinel cells?
- tolerance to commensals
- first line of detection
- differ based on the location
commensal microfloral is also called ___
the microbiome
what is the commensal microbiome?
the friendly viruses, bacteria, fungi, protozoa and worms that exist in equilibrium and sometimes also symbiosis
commensal microflora is present at each barrier surface, but the ____ is different
composition
barriers and sentinel immune cells calibrate immunity at barriers by producing ____ and inducing ____
immune regulatory factors; regulatory immune populations
commensal entry is regulated by ___, ___, and ___ barriers
chemical, physical and cellular
In healthy barrier tissues, what immunologic features generate a tolerizing response?
TGFB, IL-10, Treg cells, and IgA-producing B cells
damage or invading stimulate innate & adaptive immune cells to generate ___ and ___ immune responses
Type 1 and Typ2
what are examples of innate immune cells?
- epithelial cells (enterocytes, goblet cells, paneth cells, M cells)
- macrophages, DCs (including pDCs) and innate lymphoid cells (ILCs)
what are some examples of adaptive immune cells?
B cells, T cells, NKT cells
barriers must simultaneously convey ___ and ___ to protect against dangerous invaders
regulation and immunity
t/f immune CONTEXT is important
t
local lymph nodes generate ____ responses to antigen from barrier tissues
systemic
____ and ___ direct activated lymphocytes to infected barrier tissues
adhesion molecules & chemokines
GALT contains well organized ____ and loosely organized ____
Peyer’s patches; isolated lymphoid follicles
in GALT, what are the major source of IgA-secreting B cells?
Peyer’s patches and isolated lymphoid follicles
____ lymphoid tissue broadly describes barrier organ-associate lymphoid tissues of the entire mucosal
mucosal associated lymphoid tissue (MALT)
B cells activated by T-dependent or T-independent antigens go on to differentiate into ____ and ____ cells
IgA synthesizing plasma cells; IgA-committed memory B cells
In T-independent activation of B cells, there is generally ____ (higher or lower) affinity and is dependent on ___ and ___
lower; BAFF and APRIL
innate lymphoid cells are lymphoid cells that mirror the functions of ___ cells
T cells
innate lymphoid cells reside in the ___ and are ____(fast or slow) acting
tissues; fast
what is the major role of innate lymphoid cells?
cytokine secretion
what are the 2 functions of mucous membranes?
- mechanical barrier of tight junctions btwn epithelial cells
- makes it difficult for pathogens to get in
the mucous in mucous membranes is secreted by ____ cells in the intestine, respiratory and GI tracts
goblet cells
what are 2 properties of the mucous secreted by mucous membrane?
- viscous fluid that traps and washes away potential pathogens
- contains antimicrobial substances like lysozymes
the lysozymes found in the mucous are made by ____ cells in the intestine
Paneth
some mucous membrane contain ___ cells that mechanically remove foreign substances (ex: lung muco-ciliary elevator)
ciliated
what is the function of enterocytes in mucosal immunity?
transport nutrients across the epithelial barrier and make cytokines in response to microbes that signal to immune cells
enterocytes realize there are pathogens bc the pathogens stimulate the ____
PRRs
enterocytes signal to immune cells in the ____
lamina propria
what 3 things does the intestinal microbiome provide?
- competitive protection
- metabolites from food
- help establish a balance btwn immune responsiveness & tolerance
mucosa is in contact with ___
intestinal lumen
what is the intestinal mucosa?
a single layer of epithelia cells and connective tissue
the intestinal mucosa is also called the ___
lamina propria
what is the site in teh intestinal mucosa with the most immune cell activity?
lamina propria
what is the function of M (microfold cells)?
transport antigen from the lumen to DC
where are M (microfold) cells located?
above Peyer’s patches and isolated lymphoid follicles
M (microfold) cells transport antigens within ___ from teh luminal membrane to the ___ membrane
vesicles; pocket membrane
what happens to the antigen-containign vesicles once microfold cells transport them to the pocket membrane?
vesicles fuse and deliver their contents to antigen-presenting cells
t/f multiple mechanisms exist to transport antigen from the intestinal lumen to underlying antigen-presenting cells
t
in addition to M cells, ____ cells transport small soluble antigens
goblet
___ on epithelial cells allow for the transport of IgA-antigen complexes
Fc receptors
some resident antigen-presenting cells directly sample the ____ contents
intestinal lumen
Intraepithelial lymphocytes are called
IELs
CD8+ T cells participate in ___ and ___
regulation and inflammation
what are 3 ways in which CD8+ intraepithelial lymphocytes have less stringent requirements for activation?
- some TCR interact w/ microbial phospholipids w/o any need for MHC presentation
- some recognize stress-induced MCH-like molecules
- NKT cells are activated by glycolipid antigens presented by CD1 molecules
cytokines secreted by activated intraepithelial lymphocytes shape the _____ immune response so that is the correct type to eliminate the invading pathogen
adaptive
cytotoxic IELs kill what two types of cells?
cancerous and virus-infected
lymphocytes that were initially activated in MALT recirculate in the ___ and preferentially home to ____
blood; mucosal tissues
the homing of lymphocytes is mediated by ____ found in Peyer’s patches
vascular addressins such as MadCAM-1
what is Mad-CAM-1?
mucosal addressin cell adhesion molecule-1
what is the most abundantly produced Ig?
secretatory IgA
what Ig is an important line of defense for mucosal surfaces against bacteria (ex: salmonella) and viruses (ex; polio)?
secretatory IgA
what is a benefit of the polymeric structure of secretory IgA?
allows for the cross-linking of large antigens, making them easily trapped in mucus
once IgA cross-links antigens and they are trapped in mucos, what happens to them?
antigens are eliminated by the action of cilia in the respiratory tract or perstalsis in the gut
how does secretory IgA binding to bacteria & viruses affect infection?
prevents the receptor-mediated attachment to mucosal epithelial cells, which inhibits the infection & colonization by pathogens
IgA from ___ cells is transported across the epithelial barrier
plasma
the J-chain of dimeric IgA binds to a ____ receptor and this complex will cross to the lumen
poly-Ig
what happens to the poly-Ig receptor to form the secretory component of secretory IgA/
the poly-Ig is cleaved by an enzyme
what is a non-immune feature of the skin that acts as a barrier?
keratinocytes
what are keratinocytes?
skin epithelial cells
what are the functions of keratinocytes?
form a waterproof protective layer of keratin and secrete cytokines & antimicrobial factors
what is an antimicrobial factor secreted by keratinocytes?
psoriasin
the keratin layer is continuously replenished in what direction (from top down or from bottom up)?
from the bottom up
____ secreted by sebaceous glands creates an acidic environment that inhibits microbial growth
sebum
how does sweat have antibacterial activity?
contains lysozymes
keratinocytes and skin mast cells express ____, resulting in proinflammatory and polarizing cytokine secretion in response to pathogens
PRRs
what is the first immune defense in skin immunity?
intraepithelial lymphocytes
what 2 cell types in the epidermis contribute to skin immunity?
- CD8+ Trm cells
2. y0 T cells with limited antigen receptor diversity
what cells in the dermis contribute to skin immunity (2)
- CD4+ memory cells that circulate
2. y0 T cells that secrete IL-17 in response to IL-23 secreted by dermal APCs
Y0 cells produce ___ in response to ___ release from dermal APcs
IL-17; IL-23
unlike in mucosal tissues, the ____ does not have dedicated, organized lymphoid structures
skin
what are langerhams cells in the skin?
specialized DCs in the skin
what is the function of langerhans cells in the skin?
act as sentinels by extending processes between keratinocytes and transport antigen via lymphatic vessel to regional lymph nodes
langerhans cells can assist in generating _____ or ____
tolerance or immunity
t/f local skin responses can have systemic effects
t
what is an example of local skin responses having a systemic effect?
vaccination
T reg cells are plentiful in what parts of the skin?
dermis and epidermis
T reg cells are mostly primed in what stage of life?
early
