Chapter 13 Flashcards
The main regional
immune systems are where?
in the gastrointestinal tract
and skin, which together protect against microbial
invasion across an enormous surface area of exposure to the environment.
The gastrointestinal immune system must cope
with the presence of trillions of commensal bacteria in the gut lumen how?
by preventing their invasion
and tolerating their presence in the lumen, while
also identifying and responding to numerically
rare pathogenic organisms
Innate immunity in the gastrointestinal system is
mediated in part by the mucosal epithelial lining
cells, which does what?
impede microbial invasion by tight
intercellular junctions, secretion of mucus which
prevents microbial attachment to the lining cells,
and the production of antimicrobial molecules,
such as defensins
Innate immune effector cells in
the lamina propria include what?
macrophages, DCs, and
mast cells. Intraepithelial lymphocytes, including
γδ T cells, also provide innate defense against commonly a encountered microbes at the intestinal
epithelial barrier
Specialized anatomic features of
adaptive immunity in the intestinal tract include what?
collections of lymphoid tissues just below the epithelial lining that comprise the gut-associated lymphoid tissues (GALT), including oropharyngeal
tonsils, Peyer’s patches in the ileum, and similar
collections in the colon
M cells in the epithelial
lining do what?
sample lumen antigens and transport them
to antigen-presenting cells in the GALT
Lamina
propria DCs extend processes through what?
intestinal
epithelial lining cells to sample lumenal antigens.
There are also diffuse effector lymphocytes in the
lamina propria of the gut and in mesenteric lymph
nodes, where many of the adaptive immune
responses in the bowel wall are initiated
Effector B and T lymphocytes that differentiate
from naive T cells in the GALT or mesenteric
lymph nodes enter where and do what?
enter the circulation, and selectively
migrate back to the intestinal lamina propria. This
tissue-specific homing is due to signals the naive
T cells receive from DCs in the GALT and mesenteric nodes, including retinoic acid derived from
dietary Vitamin A, which induce expression of
chemokine receptors and adhesion molecules on
the differentiated effector cells that favor homing
back to the gut
Humoral immunity in the gastrointestinal tract is
dominated by IgA secretion into the lumen, where
the antibodies do what?
neutralize potentially invading
pathogens
B cells in the GALT and mesenteric
lymph nodes differentiate into what?
IgA-secreting
plasma cells under the influence of TGFβ, BAFF,
and other cytokines, through both T-dependentand T-independent mechanisms, and the plasma
cells migrate to the lamina propria beneath the
epithelial barrier and secrete IgA
Dimerized IgA is
transported across the epithelium by who?
the poly-Igreceptor and released into the lumen. IgA is also
secreted into breast milk, and mediates passive
immunity in the gut of breastfeeding infants
TH17 cells play a dominant role in what?
n T cell–mediated
immunity in the intestinal tract, in part because
IL-17 and IL-22, which they secrete, enhance epithelial barrier function
TH2 cells are important in
defense against what?
against intestinal parasites. Changes in
bacterial flora can influence the balance between
different helper T cell subset responses, both in the
gut and systemically throughout the adaptive
immune system
Immune reposes to commensal organisms and
food antigens in the lumen of the intestinal tract
are minimized by a variety of mechanisms, including what?
selective expression of pattern recognition
receptors in the cytoplasm and basolateral surfaces
of the epithelial lining cells, and sampling of
luminal microbial antigen by DCs which are specialized to induce Treg that suppress adaptive
immune responses
Several cytokines are essential
to maintain immune homeostasis is the bowel
wall, including which ones?
TGFβ, IL-10, and IL-2. Systemic
tolerance to some antigens can be induced by
feeding the antigens to mice, a phenomenon called
oral tolerance.
Several intestinal diseases are related to abnormal
immune responses, including inflammatory bowel
diseases (Crohn’s disease and ulcerative colitis), in
which what happens?
innate and adaptive immune responses to
normal gut flora are not adequately regulated, and
celiac disease, in which humoral and cell-mediated
responses to dietary wheat glutens occur
Mucosal immunity in the respiratory system
defends against what?
against airborne pathogens, and is the
cause of allergic airway diseases, such as asthma
Innate immunity in the bronchial tree depends on
the ciliated epithelial lining, which secretes what?
mucus
and defensins and moves the mucus with entrapped
microbes out of the lungs.
As in the intestines, regulatory mechanisms, including Treg and
immunosuppressive cytokines are important for what?
prevention harmful responses to nonpathogenic
organisms or other inhaled antigens inhaled
antigens.
The cutaneous immune system defends against
microbial invasion how?
through the skin, and suppresses responses against numerous commensal
organisms. The outer multilayered keratinized
squamous epithelial layer, called the epidermis,
performs innate immune defense functions, providing a physical barrier to microbial invasion
what do keratinocytes do?
Keratinocytes secrete defensins as well as inflammatory cytokines in response to various PAMPs
and DAMPs. The dermis contains a mixed population of mast cells, macrophages, and DCs
that respond to microbes and injury and mediate
inflammatory responses.
DCs are abundant in the skin and mediate innate
immune responses. These DCs also do what?
transport
microbial and environmental antigens that enter
through the skin to draining lymph nodes where
they initiate T cells responses
Skin-derived
DCs provide signals, including Vitamin D, to who?
the
naive T cells they activate in draining lymph,
which induce chemokines and adhesion molecules
that favor homing of the effector T cells back to
the skin
A significant fraction of the body’s T cells are
present in the skin. Most of these T cells are what?
CD4+
or CD8+
effectors or memory T cells in the dermis
TH1, TH2, and TH17 cells are important for defense
against what?
different types of skin-invading pathogens,
while TH1 and TH17 cells contribute to inflammatory dermatoses such as psoriasis.
Immune privileged sites, which are tissues where
immune responses are not readily initiated, include what?
the brain, anterior chamber of the eye, and testis
The mechanisms of immune privilege include what?
the
tight junctions of endothelial cells in blood vessels
at these sites, local production of immunosuppressive cytokines, and expression of cell surface molecules that inactivate or kill lymphocytes
Mammals have evolved mechanisms that prevent what?
maternal immunologic rejection of the developing
fetus, which invariably expresses paternal antigens
that are allogeneic to the mother. These mechanisms appear to act locally at the placental maternal-fetal interface, since systemic maternal
tolerance to paternal alloantigens does not occur
what are some examples of the mechanisms used to prevent maternal immunologic rejection of the developing fetus?
include lack of MHC expression on fetal trophoblasts, expression of immunosuppressive cytokines, the actions of Treg, and
local indolamine 2,3-dioxygenase mediated depletion of tryptophan needed for lymphocyte growth.
