The Immune System

and Psychoneuroimmunology
Stress and the immune system
 Stress contributes to the development of various infectious diseases.
 The theoretical and clinical implications of the idea that stress intensifies the
susceptibility to infection led to the development of a new field of biopsychological
research, psychoneuroimmunology.
 Psychoneuroimmunology - The study deals with the association of psychological
factors, the nervous system, and the immune system.

How does stress influence immune function?

 Stress affects both the pituitary-adrenal cortical system and sympathetic adrenal
medullary system, and these systems, in turn, influence immunity.
 From various studies, we can understand that there is a correlation between stress
and immunity. i.e., during a period of stress, the person experiences illness.
 Human beings get attacked by dreadful organisms such as bacteria, viruses, fungi,
protozoans, worms, etc.
 However, the body is bestowed with a defense mechanism in the form of the
immune system to shield us from the dangerous impact of these agents.
 The human body can resist the invasion of pathogens and their toxic products. This
resistance forms the foundation of the subject known as immunology.
 Immunology is a branch of biology concerned with the body's immunity or inborn
or acquired resistance against infections caused by pathogens.
 It studies the processes by which the body defends itself from the invasion and
attack of foreign organisms.
 The resistance to infection is achieved through recognizing and disposing of non-
self or foreign material (antigens) that enters the body.

Antigens
 The foreign substance or a toxin that elicits an immune response in the body,
specifically the production of antibodies, is known as an antigen.
 Antigens can be any substance that causes the immune system to produce
antibodies against it.
 Foreign substances such as chemicals, bacteria, viruses, or pollen enter the body
from the environment.
 An antigen can be defined as any substance (as an immunogen or a hapten)
foreign to the body that evokes an immune response either alone or after
developing a complex with a larger molecule (as a protein), and that is capable of
binding with a product (as an antibody or T cell) of the immune response.
 The ability of an antigen to produce an immune response and to react with the
products is known as antigenicity.
 The ability of a material to induce an immune response is referred to as
immunogenicity, and such materials are known as immunogens.
 The most vital immunogens are proteins and polysaccharides, but lipids, nucleic
acids, and synthetic polypeptides can also be immunogenic.
 An antigen is said to be complete when it can both induce an immune response
and can react with the products of that immune response.
 An incomplete antigen or hapten is a substance that can combine with an
antibody but does not initiate an immune response (it is not immunogenic) by itself
unless it is bound to a carrier before
entering the body.
 Antigens are conjugated proteins
like lipoproteins, glycoproteins, and
nucleoproteins.
 The part of the antigen with which
the antibody reacts is known as the
antigenic determinant or
epitope. The portion of the
antibody molecule that binds to the
epitope is called a paratope.

Immunoglobulins
 The chief molecules involved in the process of the recognization of foreign antigens
are the antibodies and T-cell antigen receptors.
 Globulins are a group of blood proteins insoluble in water but dissolve in dilute salt
solutions.
 The serum globulins which are immunologically active are termed
immunoglobulins.
 Immunoglobulins are a group of glycoproteins in all vertebrate species' serum
and tissue fluids.
 Immunoglobulins process antibodies and activity
I.e., when an immunoglobin reacts with a specific antigen, it is
called an antibody
 All Antibodies are immunoglobins, but all immunoglobulins are not antibodies.
 The primary function of immunoglobulins is to protect the body against invading
microorganisms.
 A direct attack on the invader carries out the protective role, and the other
mechanism is activating a complement system that destroys the invader.
 Five distance classes of immunoglobulins are -
1. Gamma immunoglobulin (IgG)
IgG is present in the most significant amount of internal body fluids and is a
relatively stable molecule.
It is produced mainly during the secondary immune response.
The half-life of IgG is 25 days.
Under an electron microscope, IgG looks like a "Y.”
IgG is the only immunoglobulin that crosses the human placenta and thus provides
passive protection to the newborn for about 6-9 months.

2. Alpha immunoglobulin (IgA)

 In serum, IgA is found to be very little and is observed abundantly in the external
seromucous secretions of the respiratory, gastrointestinal, and urinogenital tracts
(secretory IgA).
IgA is present in the colostrum (first breast milk) and protects the baby from
intestinal pathogens. Hence breastfeeding has significant importance in preventing
gastrointestinal infections in infants.
IgA has a half-life of 6-8 days.

3. Mu immunoglobulin (IgM)
IgM is the most significant immunoglobulin, often denoted as a macroglobulin.
It has a short half-life of about 5 days. Hence the serum level of IgM is very low.
It is the earliest immunoglobulin to be synthesized by the fetus about the 5th
month of fetal life.
Because of its large size and high molecular weight (950,000 daltons), it is chiefly
localized in blood and thus protects against blood serum infections.

4. Delta immunoglobulin (IgD)

IgD is a conjugated protein.
The half-life of IgD is 2-3 days.
It is found to be associated with the surface of B lymphocytes.
It is found to act as an antigen receptor.
5. Epsilon immunoglobulin (IgE)
IgE is found only in trace amounts in the serum because it is synthesized by very
few plasma cells in the body.
in patients with allergic conditions, the level of IgE may be significantly higher than
that of ordinary persons.
Half-life of IgE is 2-3 days.
IgE is also known as a skin-sensitizing antibody.

Immunity
Immunity is broadly classified into two types -
innate immunity
acquired immunity.

INNATE IMMUNITY:
It is the first line of defense - All living organisms are naturally gifted with resistance
to specific infections from birth.
So it is also known as inborn immunity/ native immunity or natural immunity.
It does not offer any reaction against any specific microorganism. Hence it is also
known as nonspecific immunity.
The protective mechanism is effective against a wide range of infectious agents, and
it operates through several factors such as,
 physical and mechanical factors
 biochemical factors
 cellular factors
 genetic factors
  other factors

 Physical and mechanical factors

Skin:
 Skin is an excellent mechanical barrier to infection.
 In the case of damage or loss of skin due to burns or any other injury, infections
occur quickly as the microorganisms easily enter the body through this region of
injury or damage.

Mucous membrane:
 It lines the various openings and passages of the body, secretes mucus, and is
sticky.
 The secreted mucus traps the microorganisms and acts as a protective barrier.

Cilia:
The epithelial cells of the respiratory passage are lined with cilia which sweep away
the microorganisms trapped in the mucus of the respiratory passage by its constant
movement.

Coughing and sneezing:

It helps drive out the foreign particles that enter the digestive and respiratory tracts.

Peristalsis:
The microorganism that enters the intestine is pushed away by the peristaltic
movement of the intestine, thus preventing its invasion and growth inside the gut.

Tears, saliva, and urine:

 The eye's conjunctiva is freed of foreign particles by flushing the lacrimal secretion
(tear).
 The mouth is constantly bathed in saliva, and the particles that enter the mouth
are swallowed by salivary secretion.
 Tears and saliva contain a bactericidal enzyme, lysozyme, which kills pathogens.
 Some pathogens may also be eliminated through urine.

 Biochemical factor
Secretions of the skin:
 Healthy skin possesses bactericidal activity due to high salt concentrations in the
drying sweat.
 The secretions of both sweat and sebaceous glands act as antiseptics as they
contain lactic acid and fatty acids, which have bactericidal and fungicidal
properties.

Secretions of the digestive tract:

 The stomach acidity has a microbial effect due to the presence of HCl in the gastric
juice, which is secreted by oxyntic cells lining the stomach.
 HCI kills the pathogens which enter the stomach.

Breast milk:
 It is a rich source of antibacterial substances- lactoferricin and neuraminic acid and
protects against some pathogens like Coli and staphylococcus.
 The first breast milk colostrum is rich in IgA antibodies, which provide passive
immunity to infants.

Nasal secretion and saliva:

The mucopolysaccharides present in such secretions inactivate certain viruses.

Lysozyme:
Saliva, nasal secretions, tears, certain WBCs, breast milk, sweat, urine, and most
tissue fluids contain a mucolytic enzyme called the lysozyme.

Interferons (IFN):
 These are a group of soluble, non-toxic glycoproteins produced in small amounts
by all body cells.
 These antiviral agents inhibit intracellular viral replication in cells infected with
different viruses thereby preventing infection.

 Cellular factors
Phagocytosis:
 This is a process of cell eating; two cells are involved in phagocytosis –
microphages and macrophages.
 The microphages are the polymorphonuclear leucocytes (PMN) (WBCs -
neutrophils, basophils, and eosinophils).
 The macrophages are the cells of the mononuclear phagocytic system. They are
also known as the reticuloendothelial system.
 The process of phagocytosis includes the following stages-
1. Chemotaxis - involves the movement of phagocytes to the site of infection or
inflammation in response to the chemotactic factors produced by the foreign
substances or dead or damaged tissues.

2. Attachment of phagocytes to these particles by opsonins (like antibodies) layer

or coating around the
particles.
3. Then, ingestion occurs, in
which the cell membrane of
the phagocytes produces
pseudopodia around the
foreign substance. Thus the
particle is completely enclosed
in the vacuole, known as a
phagosome.
4. The phagosome then fuses
with the lysosome of the
phagocytic cell, and the fusion results in the formation of a phagolysosome, also
known as the secondary lysosome.
5. After this, the intracellular killing is made by the antimicrobial substances
produced by the lysosomes of the phagocytes.
6. Finally, the killed organisms and cells are digested by the hydrolytic enzymes of
the lysozyme, followed by the elimination of the products to the exterior.
Natural killer cells (NK cells):
 Non- phagocytic lymphoid cells, also known as large granular lymphocytes, consist
of large granules.
 Their natural cytotoxicity can kill a range of tumor cells and cells infected with
viruses without any antigen-specificity.

 Genetic factors
Species immunity:
The resistance to a pathogen exhibited by all members of a species is referred to as
species immunity.

Racial immunity:
It is known as racial immunity when different races show a difference in susceptibility
to infections within a species.
Individual immunity:
The differences in innate immunity shown by different individuals of the same race
are known as individual immunity.

 Other factors
Temperature:
 It plays an integral part in determining innate immunity.
 Some microbes pathogenic to mammals (warm-blooded animals) will not be in
cold-blooded animals.
 They can be infected if their body temperature is lowered.

Inflammation:
 Injury or irritation of tissues via the entry of pathogens leads to cellular and
vascular changes known as inflammation.
 It is characterized by four significant features heat, pain, redness, and swelling.
 Changes that occur in the site of inflammation are-
1. arterioles constrict first and then dilate, thereby increasing the blood flow
2. permeability of the walls of the capillaries increases. Thereby fluid exudation
occurs, which results in swelling.
3. the macrophages escape from the blood into the tissues and accumulate at the
injury site, followed by phagocytosis of the microorganisms and the damaged
tissues.

Fever:
 A rise in body temperature is also known as pyrexia.
 It is a natural defense mechanism that accelerates the destruction of pathogens by
enhancing the physiological processes to defend them.
 Fever stimulates the production of interferon and facilitates recovery from
virus infections.

ACQUIRED IMMUNITY:
 The resistance against pathogens or the immunity an individual acquires during life
is known as acquired immunity or adaptive immunity.
 The acquired immunity is due to specific antibodies that respond to particular
antigens or pathogens.
 Therefore, this immunity is also known as specific immunity.
 Acquired specific immunity is of two types -
a. ACTIVE IMMUNITY
b. PASSIVE IMMUNITY
 Both active and passive immunity may be natural or artificial.

 Active immunity:
It is the resistance an individual develops in response to an antigenic stimulus, either
by natural infection or other sources, such as artificial immunization by vaccination.

Humoral immunity:
 The immunity is mediated by antibodies produced in the humor or body fluids such
as plasma or lymph.
 Active humoral immunity sets in only after a period known as the latent period or
lag period, during which the immunologic machinery prepares to produce
antibodies.

Cell-mediated immunity:
 It is the immunity produced by the sensitized lymphocytes.
 In cell-mediated immunity, antibodies are not produced.

Q What is a secondary response of the immune system?

When an individual is exposed to a particular antigen for the second time,
both humoral and cell-mediated immune response occurs more quickly.
It is associated with immunologic memory, that is, the ability of the immune
system to retain the memory of the first pathologic or antigenic exposure
and which in turn leads to a quick response during the second similar
exposure
 Active immunity can be of two types natural or artificial.

Natural active immunity:

 It is the immunity developed by the host in response to the antigen that enters the
body through natural infections.
 The immunity acquired from infections is long-lasting or lifetime immunity.
 In some bacterial diseases - the immunity caused is only short-lived because the
person can be reattached by the same antigen a month or a year after the first
attack due to the antigenic variation.
 Immunity acquired after a viral infection is comparatively more permanent than
the immunity attained after a bacterial infection.

Artificial active immunity:

 This is the type of immunity where vaccinations come into action.
 The affected individual attains immunity by vaccination.
 Vaccines are the preparations for live, attenuated, or killed microorganisms or their
products (toxoids).
 a) Live Vaccine (attenuated):
 This is the preparation where different methods attenuate live organisms.
 Attenuation results in the loss of pathogenicity without the loss of antigenicity of
the microorganisms.
 Therefore, the vaccine produces an infection but does not result in disease or
injury.
 The immunity that results in the last several years, but a booster dose
may be necessary.
b) Toxoid:
These are preparations of toxins inactivated by formalin but retain the antigenic
potency and thus induce antitoxin formation.

Killed Viral Vaccine:

 Vaccines of this type are formed by inactivating a pathogen, typically using heat or
chemicals such as formaldehyde or formalin.
 This may destroy the pathogen's ability to replicate but keeps it intact so the
immune system can still recognize it.

Killed Bacterial Vaccine:

Inactivated vaccines are made from bacteria that have been killed through physical or
chemical processes, and they cannot cause disease.

Passive immunity:
 It is known as passive immunity when a non-immune individual acquires immunity
by receiving antibodies or sensitized white blood cells from an immune individual.
 Immunity through passive immunization is less effective than active immunization.
 Passive immunization produces immunity immediately; hence, this method is more
reliable when immediate resistance is needed.
 There are two types of passive immunity; natural passive immunity and
artificial passive immunity.

Natural passive immunity:

 The immunity transferred from the mother to the child passively is called natural
passive immunity.
 In humans, immunity is mainly by the passage of antibodies from the mother to
her unborn child through the placenta during the advanced pregnancy period.
 The antibodies that are transferred are mainly IgG.
 In human beings, the transfer of antibodies from the mother to the young one
occurs mainly orally through colostrum.

Artificial passive immunity:

The transfer of immunity from an immunized donor to a non-immune recipient by
transferring antibodies or immunized lymphocytes (WBCs) is known as artificial
passive immunity.

Adoptive immunity:
This passive immunity is produced by injecting immunologically competent
lymphocytes, not antibodies.
Combined immunization:
A combination of both active and passive methods of immunization employed
simultaneously is known as combined immunization and is used in an emergency
when immediate protection is needed.

Cells involved in immunity

 The immune system can distinguish the body’s tissue from the foreign tissues.
 The dead and faulty cells are also recognized and cleared away by the immune
system.
 When foreign elements enter the Organism crossing all the barriers, the immune
system comes to the rescue.
 It produces different kinds of cells developed from the same groups of pluripotent
stem cells of the bone marrow in adults.
 White blood cells or leucocytes are also known as the soldiers of the body as they
play a major role in immunity.
 when they find a target, and in antigen, a pathogen, or any foreign substances, they
multiply and send signals to the nearby cells to elicit the needed response.
 The WBCs are stored in lymphoid Organs in the body, such as the thymus, spleen,
bone marrow, and lymph nodes.
 The two lines of development for pluripotent stem cells are-
Lymphoid lineage
 It produces various lymphocytes (B lymphocytes and T lymphocytes) and null
cells.
 Lymphocytes help the body remember and recognize the previous invaders
during the second attack.
 Lymphocytes develop into B lymphocytes, enter the thymus, and become T-
lymphocytes
 B lymphocytes produce antibodies and alert the T- lymphocytes.
 T- lymphocytes in the body and help to alert other leucocytes

Myeloid lineage.
It produces Monocytes, polymorphonuclear leucocytes, PMN and antigen-presenting
cells, platelets, and mast cells similar to basophils.

HYPERSENSITIVITY REACTIONS
 Hypersensitivity is the harmful exaggerated reaction of the immune system.
  It occurs when it is re-exposed to the same antigen for the second time.
 Though the immune system is developed by nature primarily to protect the body
against pathogens, sometimes the system becomes over-enthusiastic and brings
discomfort.
 The immune response becomes a self-destructive process in hypersensitivity.
 In hypersensitivity reactions, the cells of the self are killed, or the host itself is
damaged or killed.
 Hypersensitivity is a changed reactivity of the immune system.

Factors causing hypersensitivity

The factors that induce hypersensitivity are called allergens/allergies.
Extrinsic and intrinsic factors cause hypersensitivity, and the effect may vary from
individual to individual.
Some of the factors which cause hypersensitivity are-
 Certain drugs, such as penicillin, sulphamide, aspirin, etc.
 Airborne particles like pollen grains, house dust mites, spores, animal dander, etc.
 Specific foodstuffs include shellfish, coffee, chocolate, wheat, berries, brinjal, etc.
 Infectious organisms like bacteria, viruses, fungi, parasites, etc.
 Blood transfusion of mismatched blood.
Common hypersensitivity reactions:
Based on the area where the reaction occurs, hypersensitivity is of
two types-
Local reactions: when the symptoms appear in a restricted area.
Systemic reactions: when the symptom affects all the organ systems of the
body
Based on the time taken for the reaction, hypersensitivity is of two
types-
Immediate hypersensitivity: When the immune responses manifest quickly
or in a short duration.
1. The immune responses appear and disappear rapidly
2. An inflammatory response occurs in a few minutes
3. It involves the interaction of antigens and antibody
4. It is managed by B-cells by the production of antibodies.
5. It can be passively transferred from one host to another by the transfer of
serum
6. It can be repressed by an antihistamine drug.

Delayed hypersensitivity: Immune reactions manifest slowly from 24 - 72

hours
1. The immune response appears slowly but lasts longer.
2. Inflammatory response manifests only after 24-48 hours.
3. There occurs the reaction between antigens and T-cells.
 4. It cannot be transferred from one
sensitized host to another, but the
transfer T cells can transfer it.
5. it is repressed by corticosteroid
Hypersensitivity disorder
 Anaphylactic hypersensitivity:
 It is an exaggerated reaction of an
organism to a foreign substance.
 It is an immediate-type hypersensitivity.
 Anaphylactic responses are caused
when the sensitized animals receive allergens for the second time.
 The factors causing are certain drugs, feces from bugs or insects, animal danders,
pollen grains, food allergens, etc.
 The symptoms of the reactions include death caused by drug allergies, diarrhea
and vomiting caused by food allergens, and urticaria caused by certain foods or
drugs.

 Transfusion reactions:
 Introduction of the blood from the donor into a recipient’s bloodstream.
 If the blood of the donor and the recipient are not properly matched, blood cell
agglutination occurs.
 It occurs in both ABO blood groups and the Rh blood group
 It can be both immediate and delayed.

 Erythroblastosis foetalis:
 The reaction of Rh antigen and Rh antibody causes it.
 It develops in the Rh-positive (Rh+) baby developing in Rh-negative (Rh-) mother.
 It is a delayed-type hypersensitivity reaction.
 Some human beings possess this antigen on the surface of their RBC, and others
do not.
 The individuals containing antigen D on their RBC are called Rh-positive (Rh +).
-
 The person who does not contain antigen tD is called Rh negative (Rh ).
 This means an individual’s Rh(D) status is usually described with a positive or
negative suffix after the ABO type.
- + +
 When an (Rh ) lady marries a (Rh ) man and if their fetus will be (Rh ).
+
 The (Rh ) baby develops in the uterus of the mother.
+
 The RBC of (Rh ) baby contains antigen D.
 During delivery, the placenta breaks with the rupture of some blood vessels
connecting the fetus and the mother.
 As a result, if some antigen D present in the blood of the baby mixes with the blood
of the mother.
-
 The blood of the (Rh ) mother responds and produces the anti-D.
 The anti-D form now persists in their blood throughout her life.
 The first baby will be safe.
 The complication emerges when she conceives for the second time.
 when the fetus makes contact with the mother through the placenta, the anti-D
from her blood passes into the fetus’s blood, and anti-D combines with the Rh
antigen present on the RBC of the fetus.
 This binding causes the lysis of the RBC of the fetus.
 This hemolytic disease of the fetus is called Erythroblastosis foetalis.
 The lysis of RBC leads to jaundice, and anemia causes the death of the baby.
 All subsequent babies will meet the same consequences.

 Transplant rejection reactions:

 Immediately after a foreign substance enters, our immune system recognizes that
they are not self-substance and attacks them.
 Through transplant rejection, the recipient's immune system attacks the
transplanted organ or tissue when the recipient's immune system recognizes it as
foreign and attempts to eliminate it.
 It often occurs when the immune system detects anything like bacteria or viruses.
 To prevent such rejection of the transplant, the doctor uses medicines -
immunosuppressive agents to suppress a recipient’s immune system.
 This reduces the risk of rejection of the foreign bodies.
 It is a delay type of hypersensitivity as the reaction takes 2 to 3 days to develop.

Immunosuppression
 Immunosuppression is the process by which an individual’s immune response is
partially or entirely suppressed. Thereby its ability to fight infection.
 Immunosuppression can also be provoked by certain diseases such as AIDS and
lymphoma, and often it is triggered by medications such as chemotherapy.
 It can also be intentionally induced with drugs and immunosuppressants to prevent
transplant rejection. This is also known as immunodepression.
 Immunosuppressive drugs make the immune system less able to detect and
destroy cancer cells or fight off infections that cause cancer.
 A person undergoing immunosuppression or if an individual's immune system is
weak for other reasons such as chemotherapy or HIV infection is referred to as
immunocompromised.
 Chronic stress can suppress immunity by restricting various functions and the
number of cells that provide immunity or by enhancing immunosuppressive
mechanisms.
 Some minor side effects include gastrointestinal problems, increased hair growth,
and hand trembling.

AUTOIMMUNITY
 Antigens present in one’s cell are called autoantigens or self-antigens.
 autoantigens do not elicit an immune response modification of these antigens
  The immune response where antibodies are formed against self-antigen is called
autoimmunity.
 Whenever the immune system recognizes a self-antigen as non-self, the
autoimmune response is produced.

Autoimmune diseases
A group of disorders in which humoral or self-mediated immune responses to self or
auto antigens cause tissue injury.
Characteristic
 The autoimmune response causes autoimmune diseases.
 It can be passively transferred by the transfer of autoantibodies for sensitized
lymphocytes.
 An elevated amount of immunoglobulin formation is observed in autoimmune
diseases.
 Autoimmune diseases are broadly classified into 3 groups-
 Hemolytic autoimmune diseases
This disease is related to blood, in which the destruction of blood components occurs
by forming autoantibodies against one's erythrocytes, leukocytes, and platelets.
Examples are-
Autoimmune hemolytic anemia: occurs as a reduction in the number of
RBCs or quantity of hemoglobin below the normal range.
 The destruction of RBC causes this, and the process is called hemolysis.
 This happens due to the production of autoantibodies against antigens on the
surface of RBCs.
 This is an antibody-mediated autoimmune disease.
 The half-life of normal RBC is about 21 days but in autoimmune hemolytic anemia,
the half-life of RBC is less than 7 days.
Thrombocytopenia: characterized by low platelet count due to the production
of antiplatelet antibodies of the type IgG.

 Localized autoimmune diseases

a particular organ is affected due to autoantibodies; hence, it is also called organ-
specific autoimmune disease.
Myasthenia grave: affects the skeletal muscle and is characterized by
gradually increasing weakness of muscles and caused by the antibody
against muscle antigen.

 Systemic autoimmune diseases

affects the whole body or many organs.
Lupus erythematosus is a skin disease that mainly affects women—the
appearance of a red spot over the bridge of the nose and cheeks in the form of a
butterfly.
Rheumatoid Arthritis: effects the joins with remarkable inflammatory
changes.