Innate lymphoid cells

Along with the skin, the gut mucosa represents the first line of defense against environmental factors. In the gut mucosa, a recently discovered type of lymphocytes called innate lymphoid cells (ILCs) maintain tissue homeostasis, orchestrate tolerance to food or commensal bacteria and contribute to immune responses to pathogens.

The Immune Response

Th17 Cells and Innate Lymphoid Cells

Shaping of Immune Responses

Immunology in the skin

The skin is the body’s main barrier against physical insults and microbial pathogens. Diverse and functionally specialized subsets of immune cells in the skin sense and respond to infection or various barrier breaches to activate an immune response and eventually, return to homeostasis. However, deregulated immune responses can also cause skin disorders, such as psoriasis. This Nature Video introduces the environment and key participants in skin immunity during steady-state and disease.

00:31
the skin is the body’s primary barrier
00:34
against physical insults and microbial
00:36
pathogens it represents a unique
00:39
environment in which immune cells
00:41
interact with skin cells to maintain
00:43
tissue homeostasis and induce immune
00:46
responses the skin is composed of
00:49
epidermis dermis and a subcutaneous
00:52
fatty region commensal bacteria fungi
00:56
and viruses living on the skin have
00:58
beneficial effects in the protection
00:59
against pathogens and in wound healing
01:02
the epidermis is composed of highly
01:05
specialized epithelial cells known as
01:07
keratinocytes they are continuously
01:10
replenished from just one layer of basal
01:12
keratinocytes which divide frequently
01:16
dead cells called cornea sites form the
01:19
outermost layer and are largely
01:21
responsible for the barrier function of
01:23
the skin in the dermis cells known as
01:27
fibroblasts secrete elastin and collagen
01:29
fibres that form a dense extracellular
01:32
matrix blood capillaries irrigate the
01:35
dermis while lymph fluid is drained
01:37
through lymphatic vessels to lymph nodes
01:39
specialized immune structures in which
01:41
immune cells are activated after
01:43
pathogen encounter diverse and
01:48
functionally specialized immune cells
01:50
populate the skin in the epidermis a
01:53
specialized subset of dendritic cells
01:55
called Langerhans cells sample antigen
01:58
they project dendrites upward towards
02:01
the qualified epithelial layer and
02:02
sample bacterial antigens such as toxins
02:06
Langerhans cells appear to be both
02:08
anti-inflammatory and activator ii
02:10
depending on
02:13
dendritic cells in the dermis are highly
02:16
efficient at capturing dead cells and
02:18
presenting antigen such as viruses other
02:21
intracellular pathogens or skin
02:23
associated self antigen to t-cells if
02:26
dendritic cells are the immune Sentinels
02:29
T cells are the immune effectors healthy
02:33
skin contains more than twice the number
02:34
of t-cells found in the blood most of
02:37
them are memory t-cells that have
02:39
previously encountered antigen and can
02:41
be rapidly reactivated T cells in the
02:44
epidermis are mostly cd8 t-cells a
02:47
subset that becomes cytotoxic and kill
02:50
target cells upon activation their
02:53
long-term residence in the epidermis
02:55
mostly disconnected from the circulation
02:58
T cells in the dermis are mostly helper
03:01
cd4 T cells which have a more modulatory
03:04
role in the immune response a variety of
03:07
other immune cells such as natural
03:09
killer cells
03:10
eosinophils and mast cells are present
03:13
in the dermis and might be involved in
03:15
allergic reactions in the skin dendritic
03:19
cells and keratinocytes sense tissue
03:21
damage such as wounds or cold sore
03:24
lesions that occur when latent herpes
03:26
virus reactivates and they do that
03:28
through evolutionarily conserved
03:29
receptors that recognize pathogen
03:32
derived molecular patterns or host
03:34
derived molecules that are exposed by
03:36
cell death such as DNA keratinocytes
03:39
produce antimicrobial peptides which can
03:42
kill bacteria directly inflammatory
03:45
mediators such as interleukin 1 or il-1
03:48
which activate dendritic cells and
03:50
chemokines which recruit neutrophils
03:52
macrophages and T cells activated
03:57
dendritic cells migrate to the lymph
03:59
nodes where they present antigen from
04:01
the site of infection to naive t-cells
04:03
priming them to activate and
04:05
differentiate into effector T cells
04:09
activated t-cells return to the skin and
04:12
kill infected keratinocytes to control
04:14
viral infection or secrete signals that
04:17
recruit additional immune effector cells
04:20
following viral clearance memory cd8
04:23
t-cells persist in the epidermis to
04:26
provide immunity for future encounters
04:28
with the same virus immune responses can
04:32
become dysregulated and cause skin
04:34
disorders such as psoriasis or atopic
04:37
dermatitis psoriasis is a lifelong
04:40
inflammatory skin disease characterized
04:42
by scaly reddish plaques a combination
04:45
of environmental and genetic factors
04:47
confers susceptibility to the disease
04:51
physical injury or inflammation can
04:53
trigger the formation of an acute lesion
04:55
the antigenic trigger is unknown but
04:58
current models propose that stressed
05:00
keratinocytes might release self DNA
05:02
which in complex with an antimicrobial
05:04
peptide activates dermal plasma site or
05:07
dendritic cells to secrete high amounts
05:10
of the antiviral mediator interferon
05:12
together with pro-inflammatory il-1
05:15
alpha released by stressed keratinocytes
05:17
interferon activates dermal dendritic
05:20
cells to promote T cell differentiation
05:23
the earliest recognisable change in the
05:26
affected skin is the accumulation of T
05:29
cells and dendritic cells around blood
05:31
vessels in the dermis an overt lesion
05:35
occurs when cd8 t-cells dendritic cells
05:38
and neutrophils infiltrate the epidermis
05:43
specialized subsets of T cells secrete
05:45
soluble mediators like interferon gamma
05:48
and il-17 which stimulate the
05:50
proliferation of keratinocytes and this
05:53
produces a marked thickening of the
05:54
epidermis signals from the proliferating
05:58
keratinocytes act as chemo attractants
06:01
for infiltrating neutrophils crosstalk
06:05
between immune cells keratinocytes and
06:07
dermal cells thus contributes to tissue
06:10
remodeling and amplification of this
06:12
dysregulated immune response without
06:15
treatment
06:16
acute psoriatic lesions become
06:18
chronically jhin’s genetic studies have
06:20
identified psoriasis associated
06:22
susceptibility genes some of them
06:24
linking th17 cells the subset of T cells
06:27
that produce il-17 to psoriasis
06:30
pathogenesis thus immune cells in the
06:33
skin exert important roles in
06:35
maintaining the barrier function against
06:37
pathogens but can also become activated
06:39
by self antigen or harmless antigen to
06:42
cause autoimmunity or allergies

 

Our lungs bring in vital oxygen and expel carbon dioxide. But they’re also an important immune site. They filter the air we breathe, repulsing invaders and repairing injury. But sometimes these powerful immune responses overreact, causing diseases such as asthma.

00:40
the lungs are where the body draws in
00:42
vital oxygen and exchanges it for carbon
00:45
dioxide but every breath we take is
00:48
accompanied by potentially harmful
00:50
microbes as well as particulates which
00:52
can damage delicate lung tissue to
00:55
counter these threats the lungs are
00:57
enriched in immune cells that repulse
00:59
invaders and repair injury but this
01:02
potent Arsenal comes at a heavy cost
01:04
over reactions or inappropriate
01:06
responses resulting diseases such as
01:09
asthma the lungs are spongy organs
01:12
composed of increasingly finer tubules
01:14
first comes the truck here and the
01:17
bronchi these are then divided into the
01:20
bronchioles which are wrapped in a
01:22
muscular sheath at the ends of the
01:24
bronchioles a microscopic air filled
01:27
sacs called alveoli in the case of
01:30
asthma most of the harmful immunological
01:32
events occur within the bronchi and
01:34
bronchioles the bronchial wall is made
01:37
up of an epithelium covered in tiny
01:39
hairlike structures called cilia and
01:41
interstitial and muscle cells goblet
01:45
cells scattered along the epithelium
01:47
discharge a thin layer of mucus into the
01:49
bronchial lumen the mucus is continually
01:52
swept back up through the lungs by the
01:54
action of the cilia this system is known
01:57
as the mucus escalator and is important
01:59
for removing inhaled particles trapped
02:02
within the mucus embedded throughout the
02:04
bronchial wall our immune cells such as
02:06
dendritic cells which sample antigens
02:09
from the lumen mast cells which are
02:11
packed with granules tiny packages rich
02:13
in histamine and innate lymphoid cells
02:16
or ILCs individuals with asthma need to
02:20
have been previously sensitized to a
02:22
specific environmental antigen the most
02:25
common is found in the feces of house
02:27
dust mites but symptoms can also be
02:30
worsened by respiratory virus infections
02:32
smoke or pollutants
02:35
when inhaled antigens contact the
02:37
epithelium they trigger the release of
02:39
two chemicals il 25 and TS LP which
02:43
simulate nearby dendritic cells and
02:45
innate lymphoid cells those il seeds the
02:49
dendritic cells leave the epithelium for
02:51
the lymph nodes where they activate T
02:53
cells and initiate an adaptive immune
02:55
response antigen can also pass through
02:58
the epithelium especially in conjunction
03:00
with damaging particles such as those
03:03
found within tobacco smoke or diesel
03:05
fumes some of this antigen can reach the
03:08
mast cells housed in smooth muscle
03:10
tissue the mast cells of asthmatic
03:13
individuals are unusual they have more
03:15
of an immune molecule called IgE stuck
03:18
to their surface the attached I GE then
03:21
binds the relevant antigen in this case
03:23
from house dust mites in a highly
03:25
specific manner when an antigen gets
03:28
bound to two IgE molecules it signals
03:31
the mast cell to D granulate and spill
03:33
out the contents of the granules the
03:36
granules innards then exert their
03:37
effects on surrounding cells and tissues
03:40
in asthma the granule contents cause
03:42
smooth muscle contraction and mucosal
03:45
edema leading to narrowing of the
03:47
bronchioles many anti-allergy drugs
03:49
target this key process of degranulation
03:54
back to those T cells in the lymph nodes
03:57
once activated T cells enter the
03:59
interstitial and team up with ILCs to
04:02
escalate the asthmatic response they
04:05
secrete chemical signals that recruit
04:07
other immune cells most critical of
04:09
these being eosinophils these cells play
04:12
central roles in almost all allergic
04:14
diseases
04:15
eosinophils squeeze through the
04:17
epithelium into the lumen and begin
04:19
releasing their own inflammatory signals
04:21
including il-5 il-13 and platelet
04:25
activating factor together these act on
04:28
goblet cells causing them to ramp up
04:30
production of mucus in a process known
04:32
as goblet hyperplasia by now the victim
04:36
is in the midst of an asthma attack as
04:38
the attack proceeds more and more
04:40
eosinophils are recruited into the lumen
04:42
and a mucus layer progressively thickens
04:45
the collective effects of smooth muscle
04:47
contraction and mucus overproduction
04:49
restrict air flow and result in the
04:52
classic symptoms of asthma including
04:54
difficulty breathing coughing and
04:56
wheezing multiple attacks can over time
04:59
lead to fibrosis and permanent injury of
05:01
the lung