By Dr. Shamanthakamani

Narendran

Immune System

THE MECHANISMS OF DEFENSEAll living beings have evolved methods by

which they can protect themselves against microorganisms in their environment.

Some operate on the body surface and the mucous membranes, while others come into play when the deeper tissues are in danger.

Surface defensesSkin – so long as it is intact – acts as a

mechanical barrier, preventing organisms reaching the tissue beneath.

Mucous membranes – like skin, mucous membranes also act as a mechanical barrier, protecting the deeper tissues. Some of the secretions (saliva, nasal mucus, and tears) contain enzymes (lysozyme) which can rapidly kill an invading organism.

Inner defenses In case organisms do pass through the surface

defenses, and reach the tissues underneath, there are still other powerful defense mechanisms.

Immunity Defined as the ability of the body to recognize,

destroy, and eliminate material foreign to itself. This response to an invader occurs as two phases,

a primary and the secondary response. The primary response is the way the body’s

defense (immune) system behaves when it encounters an intruder for the first time.

After a gap of about 3-10 days, specific cells are activated.

Depending on the type of intruder the cells either produce substances to destroy it, or rush to the defense themselves.

If the alien organism is present in small amounts, the response does not last more than a week.

Large amounts of the intruder result in production of ‘defense weapons’ called ‘antibodies,’ which remain in the bloodstream for several weeks.

It is now known that both the lymphocytes which go to the defense themselves (T lymphocytes) and those which produce antibodies (B lymphocytes) are able to ‘remember’ an invader, sometimes for a number of years after the first contact.

These memory cells thus recognize the invader when it enters the body the next time.

This secondary immune response takes place more rapidly than the primary response.

The system is already prepared, thus producing a more extensive response, as well.

This fact is made use of in immunization programmes, in which booster doses of weakened forms of the organism are given at specified intervals.

In this way, the body is ‘ready’ to deal with large amounts of the organism if they enter on their own.

Host Defenses

Complement system

Leuco/ Lymph Macro phage

Allergy

Autoimmunity

Rejection of organ transplant

An immune cell undergoing an allergic reaction

Protects against infectious agents

The two types of lymphocytes differ in their defense strategy.

There are the T lymphocytes which undergo further ‘processing’ in the thymus.

Some T lymphocytes are called ‘effecter’ cells, they directly kill the intruding organism.

Others are called ‘controller’ cells, as they regulate the activities of the other lymphocytes which are involved in defense responses.

Examples of ‘effecter’ cells include – Cytotoxic T cells, and Natural killer cells.

The ways in which these cells destroy an alien organism are many – sometimes they may release substances which break up the cell membrane of the organism, leading to death.

Alternatively, other substances may be released which activate other, migratory cells – macrophages.

These cells engulf and destroy the organism by phagocytosis.

The effector T cells defend the body against viruses, they also attack abnormal or cancerous cells.

An example of an unwanted response is fighting the tissues of a transplanted organ.

This leads to rejection of the transplant.Effecter T cells may inactivate and remove an

invader the very first time they are exposed to it.

There are also ‘memory’ cells, which can ‘remember’ an invader and ‘recognize’ it, when it next enters the body.

This ‘memory’ may last for some years.The second response is always more extensive

and occurs more quickly than the first response.

Controller T cells include – Helper T cells and Suppressor T cells.

These controller cells influence the activity of other T cells.

These controller cells influence the activity of other T cells, as well as the other category of lymphocytes, called B lymphocytes.

These controls are very necessary. It is essential that unwanted organisms should

be destroyed and removed without any damage to the body.

Themectomy

TT given

1. Thymosin fraction V (Calf thymus)

2. Synthetic polypeptides

Thymus

Ontogeny of Immune System

Fetus T cells Functions at 7-1/2 wks

Thymus functions at 12 wks

B cells Functions at 13 wks

IgM First to develop.

Rises in intrauterine infection

Reaches adult levels by 1 yr

IgG Develops at 4 years

IgA At adolescence

T cell subpopulation Helper cells (IgA & IgG)

Suppressor (Homeostasis)

Killer cells (Kills invading organisms)

B cell subpopulation IgM, IgG, IgA, IgD, & IgE

Hay fever, Asthma, Autoimmune disorder (Hemolytic anemia)

In case these controls do not function properly, serious problems arise.

One extreme may be immune incompetence, whereas the other extreme is autoimmunity.

In autoimmune disorders the immune system has started to fight against the body’s tissues.

Eosinophil Neutrophil

The B lymphocytes are the second type of lymphocytes.

They are also produced in the bone marrow. Unlike the T lymphocytes, their subsequent

processing occurs in lymphoid tissue other than the thymus.

In birds this occurs in a structure called the Bursa of Fabricus.

In man the exact site of processing is not certain – it may occur in lymphoid tissue in the intestine or in the bone marrow.

When these cells come in contact with an intruder, they get activated and divide to form cells called plasma cells.

Lymphoid Precursor CellsLiver

Bone marrow

Differentiation of lymphoid stem cells

T cells

(associated with thymus)

B cells (associated with bone marrow)

Peripheral Lymphoid organs

Spleen

GI tract tissue

These cells secrete proteins called antibodies or immunoglobulins.

This defense strategy is used to combat many infections.

Some B lymphocytes survive for many years and ‘remember’ the intruder, to recognize it later on.

The antibodies are specific.That is they reach with the same organism

which provoked their production.As a result of this specificity, the protection

offered is limited.

Very often, both T and B lymphocyte immune responses are seen.

This helper T cells are necessary for the B lymphocytes to be active.

Interferon is another important factor in the body’s defense mechanisms.

Interferons are small glycoproteins (protein molecules in combination with carbohydrate molecules).

Various agents such as viruses, bacteria, and certain single cellular organisms trigger the interferon response.

This mechanism comes into operation before the appearance of specific antibodies.

Circulating substances In addition to lymphocytes and interferon, there

are circulating substances in the tissue fluids – properdin and complement.

These substances cause the wall of the microorganism to break up, which eventually leads to death of the organism.

Allergic responsesLike autoimmune disorders, are conditions in

which the property of the immune system as a ‘defense system’ is modified.

These defenses are activated by substances which are not actually harmful.

These allergy producing substances are all around us.

Harmless substances in the air we breathe – dust, pollen; in our food and drink, in the clothes we wear, and the things we touch.

THE ALLERGIC RESPONSE

allergen

IgE

release of histamine

ALLERGIC REACTION

Mastcell

PSYCHONEUROIMMUNOLOGY(BRAIN + IMMUNE SYSTEM)

In recent years there has been a growing awareness that the way we feel can influence out body’s immune mechanisms.

This suggests that there are connections between the nervous and the immune system.

This was apparent from an observation that just before an exam a larger number of school children were likely to suffer from (genuine!) sore throats compared to the rest of the year.

Another observation was that just a period of extreme grief (e.g. the death of a close relative) there was a greater incidence of developing one of the most severe diseases – cancer.

This can also be linked with the immune system – an efficient immune system should be able to detect a cancer cell and eliminate it before it has the chance to spread.

These observations lead to a great deal of interest and speculations.

PSYCHONEUROIMMUNOLOGY(BRAIN + IMMUNE SYSTEM)

killer cells

sudden stress

increased killer cells

reduced killer cells

repeated stress

Diseases due to Immunologic deficiency

Primary

Secondary

AIDSAcquired immunodeficiency syndrome

Pathophysiology

Clinical diagnosis

Treatment

PreventionHIV, the virus that causes AIDS,

is shown budding out of a human immune cell.

HIVTreating HIV infected woman during pregnancy

Natural history of HIV infection

Transmission

Signs and symptoms of AIDS in new born

How does pediatric AIDS differ from adult AIDS

Management & Specific retroviral therapies

AZT (3’ Azido, 2’ 3’ deoxythymdine)

DDI (2’ 3’ Dideoxyinosine)

Immunotherapy (Hyposensitization)