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The Anatomy of the Immune System

The body’s 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

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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.

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1. Bone Marrow

The primary point of production of the cells of the immune system, bone marrow is a substancefound 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-cellswhich are critical to the adaptive immune system develop self-tolerance before being released

into the body’s system. 

a) Anatomy: The thymus is responsible for producing a particular type of white blood cell knownas 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.

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  University of Michigan Medical School learning resources on Lymphatic System and thymushistology.

  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 nodesLymph 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 bloodvessels, sinuses and medullary cords make up the medulla.

d) Passage of lymph: lymphatic circulation begins in the nodes and passes through the marginalsinus 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 lymphnode 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 cellsfrom the body.

c) White pulp: responsible for immune response, white pulp includes T cells and B cells whichfight antigens in the blood stream for improved health.

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  Monroe General Surgery data on spleen injury.

  Boston Children’s 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 body’s 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 non-lymphoid 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 bodyhealthy.

  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.

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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 diseasesfrom 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 diseasesthrough 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.

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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

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o  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 foreignmicroorganisms. These are cells involved in an allergic response

o  Mast Cells - similar to basophils, mast cells contain a variety of inflammatorychemicals including histamine and seratonin. Cause blood vessels near wound toconstrict.

  Complement proteins - plasma proteins which have a role in nonspecific and specificdefenses

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o 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 cellularcomponents leak out)

  Some promote inflammation

  Concentration gradients attract phagocytes to irritated or damagedtissue

  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 tothe wound site

  Inflammation 

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  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 becomeswidespread

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 effectorand 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 cellsurfaces)

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

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  Host lymphocytes (i.e. those in your body) can recognize  self   proteins (i.e. those whichare not foreign)

  When a nonself  (foreign) body is detected, mitotic activity in B and T lymphocytes isstimulated

o  While mitosis is occurring, the daughter populations become subdivided

 Effector cells

 - when fully differentiated, they will seek and destroyforeign

  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 antigensintact. 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)

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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 possessinga 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 anddifferentiate)

  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

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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

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  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 rapidcell 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