LECTURE 4: OVERVIEW OF THE IMMUNE SYSTEM

4.0. INTRODUCTION

The Acquired Immunodeficiency Syndrome (AIDS ) is the advanced stage of HIV infection which occurs
when the body’s defences in the infected person have collapsed to a point at which the body becomes
vulnerable to serious multiple infections. This unit will help you to gain an understanding of how the
body defends itself against invasion by the various microorganisms ( germs) in our environment. The
various components of these defences are discussed and how the immune functions are coordinated.
With this understanding it will be easier to appreciate what leads to the immune-deficient state and its
consequences.

4.1. OBJECTIVES

At the end of this unit you should be able to:

 Define immunology
 Identify the organs, tissues, cells and molecules of the immune system
 Discuss the various ways in which the body defends itself from infection using general
measures, cellular and humoral immunity
 Recognize the role of CD4 cells in the replication cycle of the HIV virus and the
outcome of this role.

4.2. The Study of the Immune System- Immunology

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Tissues of the Immune System account for about 2% of the total body weight in a person. These tissues are divided
into primary and secondary tissues and are as shown in the diagram below.
Primary lymphoid organs and tissues are:

 The bone marrow- specifically the red bone marrow, a tissues which is part of the bone
 The liver –an organ with many functions
 The thymus gland an organ with an important role in immune function.

These structures play an important role in the production and maturation of the cells of the immune system.

Secondary lymphoid tissues are the lymph nodes, spleen, tonsils and Payer’s patches of the small intestines.
These are areas where different cells of the immune system interact such as the –macrophages, antigen presenting
cells, mature T and B lymphocytes.

Broadly speaking there are two main components of the immune system- the innate and the adaptive. These types
of immunity will be discussed later in this lecture. However before that it is necessary to first look at the various ways
in which the body protects itself in a more general way..

4.2.1. The General body defences

The Skin as a protective structure of the body

The intact skin is a very effective barrier against infection and as long as it is not damaged is not penetrated by the
HIV virus. The following characteristics make the skin well designed to prevent infection:

 The skin has a “horny layer” containing a substance called keratin which is resistant to digestion by
bacteria.
 The skin has different types of glands that secrete different substances that have some antiseptic
properties. These include sweat and sebum that contain salt, amino acids, ammonia, uric acid and so forth
that fight off bacteria.
 The skin maintains itself in a mildly acidic state of pH 5.5 which prevents growth of some microorganism
 Normal flora bacteria which live on the skin prevent disease causing microorganism to flourish by producing
antibiotic substances and competing against them for food.
 Maintains a state of relative dryness (dehydration) which also helps to prevent overgrowth of
microorganism.

Note: The value of relative dryness of the skin can be demonstrated in hot weather when one finds
that areas which remain moist such as armpits, between the toes and under the breasts in females
are more likely to get infected especially by fungi and yeasts.

Mucous Membranes

Mucous membranes line the spaces of the body in the alimentary canal, the airways, the genital tract and the eyes.
These membranes produce fluid or secretions such as saliva, tears, mucous, and genital discharges. These
watery substances help to wash away foreign particles that fall on these membranes. They also contain antiseptic
substances such as lysozymes which attack microorganism thereby preventing them from causing infection. Some
mucous membranes such as in the airways are lined with hair-like structures called cilia which help to sweep away
foreign particles. Mucous membranes also have types of antibodies called immunoglobulin A which help to fight
infection.
Protective reflexes

Other ways of defending the body include reflex actions which help to keep foreign particles out. Such reflexes
include:

 sneezing
 coughing
 vomiting
 Blinking reflex
 Withdrawal reflex.

Types of Immunity

Immunity is the ability of the body to respond to encroachment by external agents and defend itself against
infection or other potentially harmful substances such as toxins. There are different types of immunity as
discussed below.

Natural Passive Immunity- This is the type of immunity that a baby gets through inheritance of maternal antibodies
and which is important in protecting the baby in the early life after being born.

Natural active Immunity- This is immunity that develops after an individual is exposed to an antigen such as a
bacteria or a virus. This occurs for example when an individual suffers from a disease like chicken pox and he or she
becomes able to resist that infection in the future.

Artificial Passive immunity- This is immunity that one gets after being administered with antibodies against a
disease which have been prepared artificially. For example an individual bitten by a rabid dog may receive antirabies
antibodies as part of the treatment.

Artificial Active Immunity- This is immunity that one develops after the body is administered a vaccine containing
an antigen such as a weakened virus. This provokes the immune system of such a person to develop an immune
response that protects the body.

Herd Immunity- this is used to describe a situation where the majority members of a community is immune to a
disease so that a contagious disease is not able to spread in the community. This is usually obtained through mass
vaccination.

This brings us to the other way of looking at the immune system by considering what is used to fight an infecting
agent. The body can use cells of the immune system or chemical substances- When cells fight to defend the body
this is referred to as Cellullar immunity while use of chemical substances is referred to as Humoral immunity.

Innate immunity

When using humoral immunity it uses substances such as interferons which fight off viruses, lysozymes found on
areas such as mucous membranes and also cytokines which are chemicals produced by the cells of the immune
system and serve as chemical signals to alert cells of the immune system of injury to tissues thus raising the alarm
and “calling for reinforcement”.

Adaptive Immunity

This is the type of immunity that acts against specific attacks by microorganism or other invading agent.
It is developed actively by the body either after suffering an infection or through vaccination. It is
therefore specific to a particular infective agent such as the HIV virus and just like the innate type it
utilises both the cellular component as well as the humoral component.

Cellular Immunity

Cellular type of immunity depends on the various cells that are produced in the immune system from stem cells in
the bone marrow after which they are released into the circulation and secondary tissues of the immune system.
Some also migrate into the tissues where they perform various functions relating to defending the body.

4.2.2. Identification of the cells

These cells can be distinguished in the following ways:

 The appearance of the cells (morphology),

 The staining characteristics in the laboratory
 Through their surface proteins or markers.
The identification of cells by their surface markers or proteins is done by use of membrane molecule
antibodies which makes it possible to group the various cell into “clusters of differentiation” or CD
markers.

Some of the clusters into which cells of the immune system are grouped include:

CD2- all T- lymphocytes cells are positive for this marker

CD3 –All mature peripheral T- lymphocytes

CD4 – 60% of circulating T- lymphocytes fall in this cluster

CD 8- 35% of circulating T- lymphocytes

CD 20 – on all human B- lymphocyte cells

CD 21- similar as in CD 20 – used to classify malignant tissues (cancers)

Note : Cells with CD4 receptor sites cells are the main target of the HIV virus and it is these cells that the HIV
virus uses to multiply.

Immune Cells in the Blood Stream

In the blood stream there are different types of immune cells called White Blood Cells as indicated below:
Neutrophils Polymorphs( cells that don’t take up stains in laboratory staining techniques, their nucleus have
many lobes hence polymorphs)

This is a type of white blood cell which is formed from haemopoetic stem cells in the bone marrow. They are
concentrated in the blood stream and can respond to chemical signals from other immune system cells that indicate
that there is tissue injury. These cells increase in numbers when there is infection and they destroy bacteria that
invade the body through phagocytosis or “eating” the bacteria.

Eosinophils (cells that take up red stains(eosin) in laboratory cell-staining techniques)These cells are
deployed in fighting parasites such as worms and are increased in a person who has intestinal worm infestation.

Basophils(cells that take up blue stains(haematoxylins) in laboratory cell staining techniques)These produce
chemical substances such as chemokines which help to coordinate the activity of the cells of the immune system.

Monocytes( so called because they have a single non-lobulated nucleus)These are large cells that are also
good at eating foreign particles. They also migrate to the tissues where they are called “macrophages” meaning” big
eaters”

Lymphocytes- These are a subgroup of white blood cells that make up about twenty to forty percent of circulating
white cells. They come in two main types- the T-lymphocytes and the B- Lymphocytes.

T- lymphocytes- develop in the bone marrow and mature in the Thymus gland under the influence of ahormone
called Thymosin. They can differentiate into a range of the subsets as indicated below.

T –helper cells – perform immune-regulation by getting other cells of the immune system to act against foreign
invaders

T- Suppressor cells- Have a suppressing effect on immune function

T- Effector cytotoxic cells- important protection in viral, protozoa or fungal infections

T- Delayed Type Hypersensitivity cells- involved in delayed-type hypersensitivity a type of allergic reaction

B-Lymphocytes Called “B” lymphocytes because they develop in the Bursa of Fabricius in birds. Though humans
do not have this bursa they have bursa cell equivalents in their immune systems where these cells develop. As they
develop they also differentiate to form plasma cells which produce immunoglobulins. Other B- Lymphocytes
specialise into Memory Cells which are important in long-term protection of the body. Because of them the body can
sometimes develop lifelong immunity to some infections like measles and other child hood illnesses.

Natural killer cells (NK cells)

They identify infected cells whose surface molecules have changed and destroy them. They use a cytolytic protein
called ‘perforin’ to puncture other cells. They are important in fighting viral infections and also cancerous cells. NK
cells have receptors to immunoglobulin’s, have higher cell killing tendencies in the presence of specific antibodies
virus called ‘antibody dependent cell-mediated cytotoxicity’.
Mast cells

They are bone marrow derived and have cytoplasmic granules with basophilic characteristic- have inflammatory and
chemotactic mediators. An example of this type of cells are the basophils, the connective tissue type mast cells which
have immunoglobulin receptors,

4.2.3: Humoral Immunity

Uses chemical substances to fight infections.

Immunoglobulins -also referred to as Antibodies

These are the main factors in humoral immunity. Immunoglobulins are produced by Plasma cells which are a
specialized variety of B- lymphocytes. These substances are glycoproteins (ie carbohydrate-carrying protein
molecules). They have molecules with subunits held together by disulphide bonds which can be broken by reducing
agents into light and heavy chains.

Examples of Immunoglobulin:

Immunoglobulin G are important in anti-bacterial immunity and can neutralize toxins such as those of tetanus and
diphtheria.

Immunoglobulin M (Macroglobulin) activate complements to produce immune lysis (breakdown) of foreign cells.
Also links particulate antigens for agglutination and phagocytosis (eating those foreign particles such as bacteria,
infected cells, or foreign proteins.

Immunoglobulin A

They are synthesized in the mucosa ( gut and respiratory mucosa) .Found in saliva, tears ,intestinal juices,
respiratory secretions and other body fluids.

Immunoglobulin D –found on the surface of immature B lymphocytes may be involved in their maturation.

Immunoglobulin E

Binds to mast cells and basophils and are important in immediate hypersensitivity or allergic reactions such as hay
fever and other allergic reactions. Other important factors in defending the body include the substances such as the ,
complement ,interferons, cytokines including the subgroup referred to as chemokines. The chemokines are
important in HIV Infection because two of them called by their code names CCR5 and CXCR4 serve as co-receptors
in the replication cycle of the virus which will be discussed later.

Antigen- Antibody Complex

When antibodies encounter an antigen it binds to it. Then a substance called Complement attaches itself to them to
form an immune complex. This then leads to the destruction of the antigen through breakdown or being engulfed by
the phagocytes.
4.2.4. HIV and The Immune Cells

The main effect of the HIV Virus in the human body is the destruction of the Immune functions
rendering the body susceptible to many other infections that take advantage of this weakened state.
The virus targets the T- lymphocytes which have a CD4 classification which also means that they
have a receptor site to which the virus attaches itself and gains entry into the cell. The virus then
converts the CD4 cells into a virus manufacturing unit eventually destroying the CD4 cell. This
destruction will eventually lead to CD4 cell depletion and subsequently a collapse of immune
function or “immunodeficiency” .

The virus also triggers production of antibodies against it by the body. It is these antibodies that are
detected in laboratory tests. There will be further discussion of this later in the topic of Life cycle of
the virus and the one on disease progression in the patient.

SUMMARY

This chapter has introduced you to the various ways in which the body fights off
microorganism that may attempt to enter the body as well as how it deals with those that do
manage to invade the body. The first role is played by mechanisms such as the skin acting as
a mechanical barrier, the action of secretions that wash away infective agents as well as that
of reflex actions such as cough, blinking and sneezing. Once microorganisms invade the
body they are contained and destroyed by the action of the humoral as well as the cellular
components of the immune system. The chapter has covered the various cells of the immune
system such as neutrophils and lymphocytes among others that play a role in fighting off
microorganisms. The CD4 designation of some cells of the immune system has been
explained and the importance of such cells in HIV infection demonstrated. Components of
the humoral part of the immune system especially the immunoglobulins and chemokines
have also been discussed.
NOTE

. It is quite unfortunate for the human community and even ironical that one of the
characteristic of the HIV Virus is that it invades the cells of the immune systems, the CD4 cells
-the same cells that are supposed to be protecting the body- and converts them to its own
purposes- much like a criminal gang invading an army garrison and recruiting its members
into the gang thereafter using them to destroy their host country.

SELF-TEST QUESTIONS

1. Define Immunology and identify the primary and secondary tissues of the immune system.

2. Distinguish between innate and adaptive immunity.

3. Discuss Cellular and Humoral immunity

4. Discuss the importance of CD4 cells in HIV infection

5. Discuss what is implied by the term “Immunodeficiency”

Place here the self-test questions for this unit.

FURTHER READINGS

1. Maranga, R.O., Muya S.M., Ogila K.O., 2008. Fundamentals of HIV/AIDS Education.
Nairobi. Fragrancia.

2. Ministry of Health (NASCOP, KENYA),2005. National Training Curriculum ART- Comprehensive

HIV/AIDS Care. Nairobi.

3. Pratt.,R.,J. 5th Ed.2003 HIV and AIDS- A Foundation for Nursing and Health care practice. London.
Bookpower.

Place here key references forming for this unit