The Anatomy of the Immune System

The bodys immune system is made up of individual parts which work together to find and
destroy bacteria, viruses and disease. Each part of the immune system must be functioning
properly in order to detect and differentiate the unhealthy organisms from healthy tissues.
Together, each of the six individual parts of the immune system work to keep the person healthy
and free from disease, bacteria and viruses. The immune system is an inherent self-defense
system consisting of cells that helps the body distinguish between self and non-self molecules.
Different pathways regulate different immune cells to help the body differentiate the bodies own
healthy cells from disease-causing agents including bacteria, viruses, fungi, parasites, cancerous
cells, and many more.
All the components of the immune system have to continuously modify to keep the bodies
defense up against the ever-evolving organisms that constantly are on a quest to find a new way
to attack the host. This continuously evolving system sometimes reacts against the bodies own
cells, identifying it as foreign, which leads to healthy tissue destruction and causes autoimmune
diseases and cancers. Also, weakened defenses of the body by the immune system due to genetic,
acquired causes precipitate an inherent state of anergy (unresponsiveness) that can lead to
immunodeficiency diseases.
Central lymphoid tissues
The bone marrow contains stem cells that give rise to all blood cells, including red blood cells,
immune cells (lymphocytes and monocytes), and platelets, in a process called hematopoeisis. In
humans and other mammals, the bone marrow is also the site of B cell development, during
which they undergo selection to retain only those B cells that produce antibodies that recognize
foreign antigens and not "self" antigens. The bone marrow is also the source of stem cells that

give rise to T cells upon migration to thE thymus. The thymus, a lymphoid organ situated in the
upper chest, is where T cell progenitors undergo maturation prior to release into the circulation.
Like B cells in the bone marrow, immature T cells are "educated" in the thymus to recognize
foreign antigens as part of the adaptive immune response, while ignoring " self " antigens.
Peripheral lymphoid tissues
Adaptive immune responses by T and B cells are initiated in peripheral lymphoid tissues. The
spleen, located in the upper left quadrant of the abdomen, is involved in immune responses to
blood-borne pathogens. In contrast, lymph nodes are sites where T and B cells encounter antigen
carried via lymphatics, and are aggregated in sites such as the neck, arm and axillary region.

Because most pathogens enter the body through mucosal surfaces, these surfaces are protected
by the extensive mucosa-associated lymphoid tissue (MALT). Gut associated lymphoid tissue
(GALT) is a subset of MALT and comprises tonsils, adenoids (Waldeyer's ring), Peyer's patches
in the small intestine, lymphoid aggregates in the appendix and large intestine, lymphoid tissue
that accumulates with age in the stomach, small lymphoid aggregates in the esophagus, and
diffusely distributed lymphoid cells and plasma cells in the lamina propria of the gut.

1. Bone Marrow
The primary point of production of the cells of the immune system, bone marrow is a substance
found inside the bones primarily in the hips and thighs. Bone marrow is made up of white blood
cells, red blood cells and platelets.

Information about Bone Marrow Donation from Mayo Clinic

National Library of Medicine information on bone marrow diseases.
American Cancer Society guide to Stem Cell Transplant.
National Cancer Institute provides information on bone marrow transplantation & peripheral
blood stem cell transplants.
University of Maryland Medical Center information on Myeloproliferative disorders.
2. Thymus
The thymus is the organ responsible for T-cell maturity and release. This is where the T-cells
which are critical to the adaptive immune system develop self-tolerance before being released
into the bodys system.
a) Anatomy: The thymus is responsible for producing a particular type of white blood cell known
as the T-cell. It can be found just below the chest bone.
b) Histology: the thymus consists of lymphoid tissues and lymphocytes. Two distinct structures,
the cortex and the medulla work to push lymphoid cells from maturity into circulation within the
body.

University of Washington provides information on how T-cells recognize nerve fiber insulators.

University of Michigan Medical School learning resources on Lymphatic System and thymus
histology.
Georgetown Hospital System anatomy of the thymus.
Perelman School of Medicine information on T-Cell therapy for Leukemia treatment.
University of Arizona Biology Project on cell biology.
3. Lymph nodes
Lymph nodes are part of the lymphatic system that can be found widely distributed throughout
the entire body. They are responsible for trapping foreign particles and filtering pathogens found
within the body.
a) Structure: A fibrous capsule extends from outside the lymph node to the inner substance
which includes the cortex and medulla to make up the lymph node.
b) Cortex: B cells arranged as follicles make up the outer cortex and the inner cortex is made up
of t-cells.
c) Medulla: the medullary cords are made up of plasma, macrophages and B cells. The medullary
sinuses separate the medullary cords and contain histiocytes and reticular cells. The large blood
vessels, sinuses and medullary cords make up the medulla.
d) Passage of lymph: lymphatic circulation begins in the nodes and passes through the marginal
sinus into the cortical sinuses. The passage of lymph continues until the lymph reaches the
medullary sinuses and then exits the efferent lymphatic.

Foundation Press overview of the lymph nodes.

The Structure of the Lymphatic System an overview and closer look at lymph nodes.
Stanford School of Medicine video overview of lymph node examination.
Harvard Medical School details on lymph node biopsy.
Lymph node examination step by step guide.

4. Spleen
Located in the upper left abdominal section, the spleen is structured similar to an oversize lymph
node and works as a blood filter.
a) Structure: made up of two distinct parts known as the red pulp and the white pulp, the spleen
filters foreign bodies out of the blood keeping the person healthy.
b) Red pulp: this is where the filtration of red blood cells takes place removing damaged cells
from the body.
c) White pulp: responsible for immune response, white pulp includes T cells and B cells which
fight antigens in the blood stream for improved health.

Monroe General Surgery data on spleen injury.

Boston Childrens Hospital guide to spleen injuries in children.
Radiology Journal nonsurgical management of blunt splenic injury.
Better Health Channel guide to the spleen and its functions in the immune system.
Clinical Trials outcome after conservative surgical treatment of splenic injuries following blunt
abdominal trauma.

5. Mucosa-associated lymphoid tissue (MALT)

A diffusion system made up of small amounts of lymphoid tissue located in the bodys mucosal
linings, the mucosa-associated lymphoid tissue is the largest part of lymphatic tissue. The MALT
protects the body from various antigens and has a differential naming structure which refers to
various locations of the tissue within the body such as:

Gut Associated Lymphoid Tissue

Nasal Associated Lymphoid Tissue
Bronchial or Tracheal-Associated Lymphoid Tissue
Histology of the lymphoid tissues Information on the immune system.
University of Western Australia blue histology on lymphoid tissues.
Union County College guide to lymphoid system, tissue and lymph nodes.
The Journal of Nutrition distribution of lymphocyte subsets in small intestine.

6. Lymphocyte recirculation
The cycle in which lymphocytes circulate throughout the body, in both lymphoid and nonlymphoid tissues, to remove antigens from the body and keep the person free from disease,
viruses and bacteria.

Slide show representation of lymphocyte recirculation and how it works to keep the body
healthy.
USC Med on the immune cells and protection from pathogens.
Harvard PDF on lymphocyte recirculation and leukocyte emigration.
University of Iowa on physiology of lymphocyte migration.
Leukocyte migration and inflammation information.

Immunity
Humans have three types of immunity innate, adaptive, and passive:
Innate Immunity
Everyone is born with innate (or natural) immunity, a type of general
protection. Many of the germs that affect other species don't harm us. For
example, the viruses that cause leukemia in cats or distemper in dogs don't
affect humans. Innate immunity works both ways because some viruses that
make humans ill such as the virus that causes HIV/AIDS don't make cats
or dogs sick. Innate immunity also includes the external barriers of the body,
like the skin and mucous membranes (like those that line the nose, throat, and
gastrointestinal tract), which are the first line of defense in preventing diseases
from entering the body. If this outer defensive wall is broken (as through a cut),
the skin attempts to heal the break quickly and special immune cells on the
skin attack invading germs.
Adaptive Immunity
The second kind of protection is adaptive (or active) immunity, which
develops throughout our lives. Adaptive immunity involves the lymphocytes and
develops as people are exposed to diseases or immunized against diseases
through vaccination. Vaccines are used for health purposes to expose our
bodies to a particular antigen. These antigens are usually killed or severely
weakened to decrease their potency. After destroying these pathogens, the
body stores some T cells as memory cells, due to the fact they code for a
particular antigen and can be when needed. This memory in T cells can be a
means of artificially acquiring immunity while a genuine attack by a pathogen is
a naturally acquired type of immunity.

Passive Immunity
Passive immunity is "borrowed" from another source and it lasts for a
short time. For example, antibodies in a mother's breast milk provide a baby
with temporary immunity to diseases the mother has been exposed to. This can
help protect the baby against infection during the early years of childhood.

Everyone's immune system is different. Some people never seem to get

infections, whereas others seem to be sick all the time. As people get older,
they usually become immune to more germs as the immune system comes into
contact with more and more of them. That's why adults and teens tend to get
fewer colds than kids their bodies have learned to recognize and
immediately attack many of the viruses that cause colds. This is where
immunity to particular antigens as a result of genetic traits passed on from
parents rendering the offspring immune to a particular pathogenic threat.

http://www.cabrillo.edu/~jtice/HSERV%20162/Immune%20System.pdf
http://www.biology-online.org/1/10_cell_defense.htm

STAGES of immune response

Surface coverage - the first line of defense

The body is protected from pathogens by the skin and mucous membranes
o Skin - dead cellular layer - dry, low pH
o Mucous membranes contain lysozymes (enzymes which break down bacteria)
o Other cells contain cilia which filter pathogens and particulates
Breaks in the protective barrier
o Digestive openings
o Reproductive openings
o Respiratory openings
o Sensory Organs

Non-specific responses - the second line of defense

Non-specific responses are generalized responses to pathogen infection - they do not

target a specific cell type
The non-specific response consist of some WBC's and plasma proteins
Phagocytes - cells which "eat" foreign material to destroy them

Phagocytes are formed from stem cells in bone marrow (stem cells are
undifferentiated WBC's)
Neutrophil - phagocytize bacteria
Eosinophils - secrete enzymes to kill parasitic worms among other
pathogins
Macrophage - "big eaters" phagocytize just about anything

Macrophage destroying bacterial cells

Non-phagocytic leucocytes o Basophil - contain granules of toxic chemicals that can digest foreign
microorganisms. These are cells involved in an allergic response
o Mast Cells - similar to basophils, mast cells contain a variety of inflammatory
chemicals including histamine and seratonin. Cause blood vessels near wound to
constrict.
Complement proteins - plasma proteins which have a role in nonspecific and specific
defenses

Form a cascade effect - if only a few are activated, they will trigger others to
become active in great numbers
Some punch holes in bacterial walls (forms holes where cellular
components leak out)
Some promote inflammation
Concentration gradients attract phagocytes to irritated or damaged
tissue
Encourage phagocytosis in phagocytes (promotes "eating")
Some bind to the surface of invading organisms
Chemokines - create a chemical gradient to attract neutrophils and other leucocytes to
the wound site
Inflammation

Causes localized redness, swelling, heat, and pain

Changes in capillary wall structure allow interstitial fluid and WBC's to leak out in tissue
Promotes macrophage (phagocytic WBC's) activity
Macrophages secrete Interleukins (communication proteins among WBC's)
o Interleukin-1: increases body temperature (i.e. causes a fever)
This enhances the WBC's ability to protect the body
Causes drowsiness - reduces the body's energy usage and stress

The Immune System (Specific Responses) - the third line of defense

Called into action when nonspecific methods are not enough and infection becomes
widespread

Types of cells involved in the immune system:

Macrophages - engulf foreign objects

o Inform T lymphocytes at a specific antigen is present
Helper T cells - produce and secrete chemicals which promote large numbers of effector
and memory cells
Cytotoxic T cells - T lymphocytes that eliminate infected body cells and tumor cells
B cells - produce antibodies (secrete them in the blood or position them on their cell
surfaces)

Each type of virus, bacteria, or other foreign body has molecular markers which make it unique

Host lymphocytes (i.e. those in your body) can recognize self proteins (i.e. those which
are not foreign)
When a nonself (foreign) body is detected, mitotic activity in B and T lymphocytes is
stimulated
o While mitosis is occurring, the daughter populations become subdivided
Effector cells - when fully differentiated, they will seek and destroy
foreign
Memory cells - become dormant, but can be triggered to rapid mitosis if
pathogen encountered again

Thus, immunological specificity and memory involve three events:

(1) Recognition of a specific invader
(2) Repeated cell divisions that form huge lymphocyte populations
(3) Differentiation into subpopulations of effector and memory cells

Antigen - a nonself marker that triggers the formation of lymphocyte armies

Antibodies - molecules which bind to antigens and are recognized by lymphocytes

Antigen-presenting cell - a macrophage which digests a foreign cell, but leaves the antigens
intact. It then binds these antigens to MHC molecules on its cell membrane. The antigen-MHC
complexes are noticed by certain lymphocytes (recognition) which promotes cell division
(repeated cell divisions)

Molecular cues that stimulate lypmphocytes to create an immune response

T cells (Helper T cells and Cytotoxic T cells)

T cells arise from stem cells in the bone marrow - they then travel to the thymus where
the differentiate and mature. At maturity, they acquire receptors for self markers (MHC
molecules) and for antigen-specific receptors. They are then released into the blood as
"virgin" T cells.
T cells ignore other cells with MHC molecules and they ignore free-floating antigens.
However, they will bind with a antigen-presenting macrophage (a macrophage possessing
a MHC-antigen complex). This binding promotes rapid cell division and differentiation
into effector and memory cells (all with receptors for the antigen)
Effector helper T cells secrete interlukins (stimulate both T and B cells to divide and
differentiate)
Effector cytotoxic T cells recognize infected cells with the MHC-antigen complex. They
then destroy the cell with perforans (enzymes which perforate the cell membrane,
allowing cytoplasm to leak out) and other toxins which attack organelles and DNA

B cells and Antibodies

B cells also arise from stem cells in the bone marrow. As they develop and mature, they
start synthesizing a single type of antibody
Antibodies are proteins which recognize antigens
The virgin B cell produces antibodies which move to the cell surface and stick out

The B cell floats in the blood - when it encounters the specific antigen it becomes primed
for replication
The B cell must receive an interleukin signal from a helper T cell which has already
become activated by a macrophage with a MHC-antigen complex. This promotes rapid
cell division.
The B cell population then differentiates into effector and memory B cells
The effector B cells then produce a staggering amount of free-floating antibodies
o When these free-floating antibodies encounter an antigen, they tag it for
destruction by phagocytes and complementary proteins
o These types of responses are only good for extracellular toxins and pathogens they cannot detect pathogens or toxins located inside of a cell

Antibody-mediated immune response