Primary Organs of the Immune System

Primary Organs of the Immune System
Bone Marrow:
Location of HSCs
1
, myeloid cell
production, and initial division of
lymphoid cells
NK cells rise from here and B cells
divide and rearrange their genes here.
T cells undergo initial commitment
here, but then leave for the thymus to
finish rearranging genes and
determining their specific roles.
Marrow of femur, humerus, hip bones
and sternum are major sites.

The two types of bone marrow are medulla ossium rubra (red marrow), which
consists mainly of hematopoietic tissue, and medulla ossium flava (yellow
marrow), which is mainly made up of fat cells. Red blood cells, platelets, and
most white blood cells arise in red marrow. In cases of severe blood loss, the body
can convert yellow marrow back to red
marrow to increase blood cell
production.
Bone marrow contains two types of stem
cells: hemopoietic (which can produce
blood cells) and stromal (which can
produce fat, cartilage and bone).
The fat of the bone marrow is a cell type
that sends out a lot of the signals that
regulate hematopoiesis, or the
development of blood cells.





1
Hematopoietic stem cells
Thymus
The thymus is a speciali
2
zed organ of theimmune system.
Within the thymus, T-cells, critical to the adaptive immune
system, mature
Located above the heart, below the thyroid and behind the
upper part of the sternum
a) cortex ( general word meaning outer layer) - Immature
T cells (thymocytes) start here.
b) medulla – (general word meaning interior) – Final
Quality check.
Site of T-cell maturation (details of the process later)
a. Cells rearrange genes for TCR (the T-cell receptor) in cortex.
b. Cells are checked for the ability to recognize antigen on MHC with
the correct affinity (positive selection) in cortex.
c. Cells that survive selection travel through the medulla and undergo
selection to remove self-reactive cells (negative selection).
d. Cells that survive enter the circulation.
e. Cells that do not (over 95%) undergo apoptosis.

The thymus is made up of two lobes that join in front
of the trachea. Each lobe is made of lymphoid
tissue, consisting of tightly packed white blood cells
and fat.
Its function is to transform lymphocytes (white blood
cells developed in the bone marrow) into T-cells
(cells developed in the thymus). These cells are then
transported to various lymph glands, where they play
an important part in fighting infections and disease.
Swelling of lymph glands and fever are a signal that
immune cells are multiplying to fight off invaders of the body: bacteria, fungi,
viruses or parasites.
In addition to immune function, the thymus also produces hormones that promote
growth and maturation.
http://www.healthline.com/human-body-maps/thymus#4/1

2
Concretamente, la función del timo es la de madurar y diferenciar los linfocitos T provenientes de la médula
ósea (estas células son un tipo de leucocito o glóbulo blanco, cuya cometido general es reconocer y destruir
sustancias extrañas o agentes infecciosos). Desde la corteza hasta la médula existe un gradiente de
diferenciación, de modo que en la corteza se encuentran los timocitos más inmaduros, mientras que en la
médula se localizan los timocitos en fases madurativas más avanzadas.
Secondary Organs of the Immune System
An interconnected surveillance system
3
, where the immune cells gather and
exchange information
Circulation among the organs: lymph makes a one-way trip, while blood makes a
round trip.
Blood moves immune cells throughout the body (along with
erythrocytes)
The lining of vessels (endothelium) responds to infections with
inflammation and this directs neutrophils and other immune
cells to the infected site.
Proteins in blood plasma include antibodies, clotting proteins
and complement proteins that attack foreign cells.
Blood filtered by spleen, which recycles aged erythrocyte and
picks of antigen and other detritus.
The lymph system is a network of organs, lymph nodes,
lymph ducts, and lymph vessels that make and move
lymph
4
from tissues to the bloodstream. The lymph
system is a major part of the body's immune system.
Lymph is the fluid that circulates throughout
the lymphatic system. The lymph is formed when
the interstitial fluid is collected through lymph
capillaries. Lymph is a clear-to-white fluid made of:
 White blood cells, especially lymphocytes, the
cells that attack bacteria in the blood
 Fluid from the intestines called chyle, which
contains proteins and fats


3
órganos linfoides primarios o centrales, que proporcionan el entorno para la maduración de linfocitos (linfopoyesis), de
modo que los linfocitos adquieren su repertorio de receptores específicos para cada tipo de antígeno; los linfocitos se
seleccionan de modo que poseen autotolerancia (evitación de la autoinmunidad).
 Órganos linfoides secundarios o periféricos, que proporcionan el entorno para que los linfocitos interaccionen entre sí, o
con las APC y otras células accesorias, y para que entren en contacto con el antígeno;diseminan la respuesta inmune al
resto del cuerpo.
4 La linfa es un líquido incoloro compuesto de glóbulos blancos, proteínas, grasas y sales. Se transporta desde los tejidos
hasta la sangre a través de los vasos linfáticos.
En el sistema linfático no existe una bomba que impulse la linfa, a diferencia de lo que ocurre en el aparato circulatorio sino
que se mueve, aprovechando las contracciones musculares. El sistema linfático es la estructura anatómica que transporta
la linfa unidireccionalmente hacia el corazón, y es parte del aparato circulatorio.


 Lymph also provides transport of immune cells,
primarily lymphocytes, but no erythrocytes
 Drains interstitial fluid from tissues, picking up
antigens and white cells
 Lymph (fluid) filtered through lymph nodes, where
antigen is trapped and acted on.
 Vessels join into larger ones that empty into the
thoracic duct, which in turn empties into left subclavian
vein and then enters heart.

Lymph nodes
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: Trap antigen and provides sites for the
lymphocytes to interact with antigen. The lymph nodes act as
filters along the lymphatic system. These nodes trap germs
like bacteria, viruses, toxins as well as cancer cells and
ensure that these are removed from the body.
Basic structure
a) cortex receives incoming lymph (afferent)
b) follicles embedded in cortex receive and hold B cells
c) paracortex (immediately inside) hold T cells
d) mature B cells leave through this
e) exit out the efferent vessels

Cell interactions
 B cells activated by antigen migrate
to the paracortex to alert T cells. Some
get instruction to go forth and make
antibodies.
 Secondary follicle develops after antigen exposure. Has active
germinal center where B cells develop in response to signal from
follicular dendritic cells, TH cells and macrophages.
 B cells that have spent time in a secondary follicle learn to
make more effective antibodies. Undergo affinity maturation

5
Los nódulos linfáticos son acumulos de linfocitos bien definidos contenidos en una malla de fibras reticulares, que no
presentan cápsula.
El sistema linfático es una compleja red de vasos angostos, válvulas, conductos, nódulos y órganos. Ayuda a proteger y a
mantener el ambiente de fluidos del organismo produciendo, filtrando y transportando linfa, y produciendo diversos glóbulos.
Los nódulos linfáticos cumplen una importante función en la defensa del cuerpo contra las infecciones.
Los vasos linfáticos aferentes llevan fluidos no filtrados al nódulo linfático para que sean filtrados, mientras que los vasos
eferentes sacan fluidos limpios del nódulo linfático y al sistema cardiovascular, en donde ayudan a formar el plasma de la
sangre. Cuando el cuerpo resulta invadido por organismos foráneos, la dolorosa inflamación que se siente a veces en el cuello,
las axilas, la ingle o las amígdalas es causada cuando los microorganismos resultan atrapados dentro de colecciones de células
o nódulos linfáticos. Al final, estos organismos son destruidos y eliminados por células que recubren las paredes de los nódulos
linfáticos y el dolor y la inflamación disminuyen.
Spleen:
The spleen
6
plays multiple supporting roles in
the body. It acts as a filter for blood as part of
the immune system. Old red blood cells are
recycled in the spleen, and platelets and white
blood cells are stored there. The spleen also
helps fight certain kinds of bacteria that cause
pneumonia and meningitis.

I. in abdomen, next to pancreas
II. filters blood, not lymph
III. red pulp with macrophages that recycle old red blood cells
IV. white pulp (PALS) has T cells
V. marginal zone with B cells in follicles - system works like the lymph
nodes:
VI. Removing the spleen can increase a person's risk for bacterial
infections, but there does seem to be some redundancy in the system
as a whole.



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Bazo, Su función principal es la destrucción de células sanguíneas rojasviejas, producir algunas
nuevas y mantener una reserva de sangre.
La pulpa roja se compone de células sanguíneas tales como plaquetas, granulocitos, y los corpúsculos rojos de
la sangre. Actúa como un filtro y limpia la sangre mediante la eliminación de los antígenos y los glóbulos
rojos dañados.
La pulpa blanca actúa como una fuente de anticuerpos y linfocitos para el sistema inmunológico de defensa.
Area Function Composition
red pulp
Mechanical filtration
of red blood cells. In
mice: Reserve
of monocytes
[4]

 "sinuses" (or "sinusoids"), which are filled with
blood
 "splenic cords" of reticular fibers
 "marginal zone" bordering on white pulp
white pulp
Active immune
response through
humoral and cell-
mediated pathways.
Composed of nodules, called Malpighian corpuscles.
These are composed of:
"lymphoid follicles" (or "follicles"), rich in B-lymphocytes
"periarteriolar lymphoid sheaths" (PALS), rich in T-
lymphocytes
Mucosal-Associated Lymphoid Tissue – MALT
7

Also gut associated – GALT, and
bronchial (lung epithelia) – BALT, nasal –
NALT, CALT (conjunctival-associated
lymphoid tissue)
Constitutes the most extensive component
of human lymphoid tissue, these surfaces
protect the body from an enormous
quantity and variety of antigens.
The mucosa of the digestive, respiratory,
and urogenital systems represents the
major site of entry of most pathogens. The epithelia of these systems contain
defensive lymphoid tissues.
Organized structures present include tonsils, appendix, and Peyr's patches
8
in the
intestine
Tonsils
9
are collections of lymphoid tissuefacing into the aerodigestive tract.
These immunocompetent tissues are the immune system's first line of defense against ingested or
inhaled foreign pathogens.
Peyer's patches (or Peyer patches) are round or ovoid bundles of lymphatic tissue
made up of unencapsulated lymphatic cells that protect the mucous membranes of
the small intestines (the ileum) from infection.
Epithelial cells of the mucosa deliver antigen samples from the lumen
10
(spaces
inside of tubular-shaped structures within the body.), delivering them via M cells
M cells are large epithelial cells, each with a number of smaller immune cells
residing in the basolateral pocket it makes.
Antigen crosses the plasma membrane to these. The B cell then migrates to
inductive sites.


7
tejido linfoide asociado a las mucosas: es un tipo de agrupación de células linfoides sin
organización o estructura,Tejido linfoide asociado a los bronquios o BALT,se encuentra en la
mucosa que recubre las vías respiratorias. Contiene linfocitos B y T. Tejido linfoide asociado al tubo
digestivo o GALT, Se compone de folículos linfoides a todo lo largo del tubo gastrointestinal casi
todos están aislados entre si.
Tejido linfoide asociado a la nariz o NALT (nose-associated lymphoid tissue).
Tejido linfoide asociado a la conjuntiva o CALT (conjunctiva-associated lymphoide tissue)

8
placas de Peyer son unos cúmulos de tejido linfático (nódulo linfático) que recubren interiormente
las mucosas como las del intestino.
9
Las amígdalas son extensiones de tejido linfoide situados en la faringe y que constituyen el anillo
de Waldeyer, protegiendo la entrada de las vías respiratorias de la invasión bacteriana.
10
es el espacio interior de una estructura tubular, como en una arteria ointestino
Skin
The largest organ of the body, not technically a
Secondary Lymphoid Organ ( we can consider it as a
tertiary organ)
1. Important in innate defenses
Keratinocyte
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is the predominant cell type in
the epidermis, the outermost layer of the skin,
constituting 90% of the cells found there. The primary
function of keratinocytes is the formation of a barrier
against environmental damage such as pathogens, heat, UV radiation and water
loss. Epithelial cells (keratinocytes) of the outer layer secrete cytokines. Also die,
leaving behind keratin intermediate filament as a protective barrier
2. Important in adaptive defenses
a. Keratinocytes can express class II MHC and present antigen.
b .Langerhans cells are dendritic cells (antigen-presenting immune cells) of
the skin and mucosa. They are present in all layers of the epidermis, but are most
prominent in the stratum spinosum.
Langerhans (dendritic) cell phagocytize antigen and carry it to lymph
nodes.
Also carry class II MHC and activate TH cells.
c. Intraepidermal (a form of intraepithelial) lymphocyte, or IELs, many
with specialized T cell receptors) - activated or memory cells








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queratinocitos , Los queratinocitos son las células que producen queratina y además producen
citocinas que son moléculas solubles con funciones de regulación de las células epiteliales y
células dérmicas
A. Apoptosis
One aspect of the immune system that makes it so energetically expensive is
that it produces huge numbers of cells and then gets rid of the great majority
of cells before they are even used.
1. Analogous to imploding a building.
a. Cell shrinks
b. Chromatin condenses
c. Membrane blebs
d. Cell fragments into intact pieces, easily phagocytized

2. Necrosis – analogous to blowing up a building (figure)
a. Organelles swell and break down
b. Cell disintegrates
c. Contents released where they can cause tissue damage and inflammation
d. Much harder to clean up after








Evolution

Ancestral chordates, which gave rise to the vertebrate members of the
phylum
Chordata, do not have an adaptive immune system.

1. The first fish to evolve were jawless and we have only a few remaining
examples
of this type, among them the lamprey eel. These eels have B cells, GALT and
some thymic tissue with T cells at the tips of their gills.

2. Other fish have immune tissue around the gut, as well as spleens and
defined
thymic tissue. (figure)

3. Amphibians, reptiles, birds and mammals all have bone marrow, but their
B cells
mature in a variety of places.
Immunology L2, Survey of Cells and Organs- 5
4. So, while it’s true that reptiles, bird and mammals have B cells and T cell
along
with their innate defenses, there is a lot of variety in what gets made where
and
when.

5. Happily rodents and humans have reasonably similar immune systems,
making
mice and rats good lab models for the study of the immune response.





































Complejo mayor de histocompatibilidad
Presenta antigenos a los linfositos, permiten que el sistema inmune
reconosca sus celular como propias y no como antígenos
Clase I,en la membrana de todas las células, prsentan antígeno a linfocitos
cd8, citotoxicos
Clase II, solo en células inmune, presentan antígeno a los linfositos t
colaboradsores


Elepitelioes eltejidoformado por una o varias capas decélulasunidas entre sí, que puestas
recubren todas las superficies libres del organismo, y constituyen el revestimiento interno de las
cavidades, órganos huecos, conductos del cuerpo, así como forman lasmucosas y las glándulas.