INTRODUCTION TO IMMUNE SYSTEM

Historically, immunity meant protection infectious diseases. Later on, found that
immune system protects the body not only from infectious agent but also from foreign
macromolecules such as protein and from abnormal cell such as tumor cells.

Definitions:
1. Immunology: Is the science that study of our protection from foreign macromolecules
or invading organisms present in the environment and our responses to them.
2. Immune System: Group of molecules, cells, tissues and organs which provide non-
specific and specific protection against Microorganisms, Microbial toxins, Tumor cells.
3. Immune response: The collective and coordinated reaction between the immune cells
and molecules to get rid of microbes
4. Immunity: Defense capacity of the body to combat diseases. Specific definition
Immunity is a reaction to foreign substances.

Immunology lingo
1. Host: e.g. me!!!!
2. Antigen: Foreign or toxic to the body (macromolecule) e.g. virus protein, worm,
parasite (Everything that should not be in my body)
3. Antibody (Immunoglobulin (Ig)): Is a large Y-shape protein produced by plasma
cells that is used by the immune system to identify and neutralize foreign objects such
as bacteria and viruses
4. Pathogen: Microorganism that can cause disease(anything that can produce disease).

Role of the immune system:

1. Defense against microbes

2. Defense against the growth of tumor cells (kills the growth of tumor cells)

3. Homeostasis ( regulation)

4. Destruction of abnormal or dead cells (e.g. dead red or white blood cells, antigen-
antibody complex)
The body's immune mechanism consist of:
I. NATURALLY ACQUIRED IMMUNITY:
1. Active
a. Antigens enter body naturally with response (MEMORY)
b. Provides long term protection
2. Passive
a. Antibodies pass from mother to
i. Fetus across placenta
ii. Infant in breast milk
b. Provides immediate short term protection
II. ARTIFICIALLY ACQUIRED IMMUNITY
1. Active
a. Antigens enter body through vaccination with response
b. Provides long term protection
2. Passive
a. Antibodies from immune individuals injected into body
b. Referred to as
i. Immune serum globulins (ISG)
ii. Immune globulins (IG)
iii. Gamma globulins
3. Provides immediate short term protection
4. Use in treatment or prevent recurrent infection in person with low antibody level.

The body's IMMUNE system can be divided into

1. Innate immunity:

Is first line of defense against antigen. non-specific, includes natural mechanical,

chemical, and biological barriers to infection, which have no degree of specificity or memory.
Immediate onset.

2. Acquired immunity ( adaptive):

Is Second line of defense. Specific and Delay onset. Is refers to developed resistance by
individual only after exposure to foreign substance ( is not inborn). Although these two arms
of immune system have distinct function both interact to develop a complete defense against
foreign substance.
Innate immunity:
Is first line of defense against antigen. non-specific, includes natural mechanical,
chemical, and biological barriers to infection, which have no degree of specificity or memory.
Immediate onset.

Innate is not only provide rapid defense against microbes but also plays several
important role in induction of adaptive immunity (send warning signals that trigger adaptive
immune responses.

Component of Innate Immunity:

I. First line:

1) Mechanical barriers.

2) Chemical & biochemical inhibitors

3) Normal flora

II. Second line ( biological factors):

1) cells

a. Natural killer

b. Phagocytes

2) Soluble factors

3)Inflammatory

First line in innate immunity:

1) Mechanical barriers
Also called physiological barrier.

a. Skin:

Skin is composed of two layer Thinner outer layer (epidermise) and thicker underlying
layer (dermis). Epidermise consist of keratinocytes which produce a waterproofing protein
called keratin. Keratinocytes respond to pathogen by produce antimicrobial peptide and
cytokine such as Tumor Necrosis Factor (TNF) (( these cytokine promote inflammation))
b. Mucosal surface:
i. Epithelial cells:
Is line of mucosal surface of intestinal, respiratory, and genitourinary tracts. Which
separate the host from environment.
ii. Mucus layer:
Composed of mucins which helps prevent pathogen attachment and invasion.
iii. Cilia:
Cilia movement propels microbes out of the respiratory tract.
c. Coughing and Sneezing:
Expel antigens that enter into the respiratory tract.
d. The flushing action of tears:
Help to prevent eye infection.
e. Flushing action of urine:
flow washes the urethra.
f. Diarrhea and Vomiting:
help to eliminate pathogens from the gastrointestinal tract.

2) Chemical & biochemical inhibitors:

Body secretions contain substances that exert bactericidal, fungicidal and viricidal
actions. These include:

a. Gastric HCL and Digestive enzymes:

Prevent growth bacteria in stomach.
b. Sweat and sebaceous secretions:
Which contain bactericidal, fungicidal substances. Sweat cantains lactic acide, urice
acids and ammonia. sebaceous secretions consist of free fatty acids, triglycerides and
wax alcohols. These substance are responsible for low skin acidity.

3) Normal flora:
Prevent colonization of pathogenic bacteria by competing with bacteria for nutrient and
attachment site. Also by secreting toxic substance.

Second line:
1) cells:
FIRST we must know All immune cells. All immune cells arise from hematopoietic stem
cell in bone marrow. All immune cells are leukocytes (white blood cell). All immune cells
follow two cell lineages; Myeliod and Lymphoid.
I. Myeliod cells:
1. Granulocytes:
Are three types: Neutrophils, Eosinophils and Basophils.
a. Neutrophils (polymorphnuclear cells, PMNs, Microphage:
Neutrophils are Polymorphoniclear leucocytes. Constitute the majority of leukocytes.
PMNs cells are very active phagocytic cells; however they are short lived cells and they
increases in response to infection or inflammation (first cells arrive to site of inflammation).
b. Eosinophils:
They are play major role in allergic disorders also they have ability to kill large
extracellular parasites such as Schistosoma species.
c. Basophils:
Also they are play role in allergic disorders also they have ability to kill large
extracellular parasites. Their granules contain histamine and heparin.
2. Monoblastes:
a. Monocytes/ Macrophages(mononuclear phagocytes):
They circulate in the blood for a day as Monocytes and then enter the tissue as
Histocytes where they live for months. Monocytes when enter tissue became larger and
termed macrophage (mature form). macrophages are Mononuclear cells.
They function are engulfment of antigens (phagocytosis), body cleaning by ingestion of
dead host cells, tissue repair by stimulating new blood vessel growth and play role in
antigen presentation cells (acquired immunity).
 b. Dendritic cell:
They are very important for activation of T cell, provide immediate cellular defense against
viral infection and produce interferon type I.
3. Mast cells:
Can found in tissue of skin and mucosal epithelia. They are play role in allergic reaction
type I and help induce inflammation. Their granules contain histamine and heparin.
II. Lymphoid cells:
1. Large granular lymphocytes (LGL):
Also called natural killer cells.
2. Small lymphocytes:
Acquired immunity cell divided into B and T lymphocytes.
i. B lymphocytes:
Only cell produce antibodies.
ii. T lymphocytes:
They have two type T cytotoxic and T helper.

Second line in innate immunity:

1) cells:
1- Natural killer (NK):

Definition: are lymphocytes typically immune cells. They capable of causing direct
damage to tissue cell infected with viruses. The development and cytotoxic effect of NK
cells is influenced by interferon which is substance secreted by virus infected cells. NK
lymphocytes are also able to attack tumor cells. However, as they have the ability to
recognize stressed cells in the absence of antibodies, allowing for a much faster immune
reaction.

Source: Bone marrow precursors

Function:NK cells play a major role in the rejection of tumours and cells infected by
viruses.

2- Phagocytes:

Are cells that protect the body by ingesting Such as neutrophils, monocytes, macrophages,
and mast cells.

Phagocytosis

The engulfment, digestion, and subsequent processing of microorganisms by macrophages

and neutrophils. Killing by

a- Oxygen depended system

 Oxygen converted to superoxide, anion, hydrogen peroxide, activated oxygen and
hydroxyl radicals.

b- Oxygen-independent system (anaerobic conditions)

Digestion and killing by lysozyme. Lactoferrin, low pH, cationic proteins and
hydrolytic and proteolytic enzymes.

B- Soluble factors (humoral innate immunity)

1- Acute phase protein (binding protein, Plasma protein, Fibrin.):
Best example is C-reactive protiens (CRP). They are synthesized by liver cells in
response to macrophage in presence of bacteria. They cannot directly kill pathogen but
they mark it for destruction by phagocytes or Complement system.
2- Interferons (Proteins against viral infections):
Definition: are proteins made and released by host cells in response to the presence
of pathogens such as viruses, bacteria, parasites or tumor cells.
They synthesized by cell after viral infection. Their major function limit viral growth in
side cell by degrade the viral genome. A viral infected cell secret interferon to act on
and protect neighbor cells that are not yet infected. Also increase the capacity of NK
cells and T cell to kill viral infected cells. So All interferons share several common
effects they are antiviral agents and can fight tumors.
Protective action of interferons are:
1) Activate T-cells
2) Activate macrophages
3) Activate NK
Types of interferons are Alpha interferon which Secreted by Macrophages Induced by
Viruses or Polynucleotide, Beta interferon Secreted by Fibroblasts, Viruses (Alpha-
interferon and Betainterferon are very important in the response to viral infections) and
Gamma interferon T- lymphocytes which is involved in the activation of macrophages
and has much less antiviral activity than alpha and beta
3- Lysozyme (Hydrolyze cell wall):
Found in secretion such as tears, nasal secretions and saliva. It degrades the
peptidoglycan layer in bacterial cell wall. More effective in gram positive bacteria.
Gram negative are protected from lysozyme by their outer membrane.
4- Lactoferrrin,Transferrin (Iron binding protein):
Stored iron and release it in controlled fashion.
5- Beta lysine :
Antibacterial protein from Platelets
6- Lactoperoxidase:
Found in Saliva & Milk
 7- Complement:
Complement is a series of plasma proteins that has many functions in the innate
immunity. Their functions include:
 lysing Gram-negative bacteria.
 enhancing the phagocytosis of foreign particles (opsonization).
 clearance of immune complexes by phagocytes.
 contributing to several aspects of the inflammatory response, including promoting
chemotaxis of lymphoid cells, Induction of inflammation, attraction of inflammatory
cells to site of infection.
 Many of the complement proteins are produced as proenzymes, which require
proteolytic cleavage to become active.
 Components exist in the plasma in their inactive form.
 Once activated, the product of one reaction is the trigger for the next reaction, and
hence the overall process can be thought of as a cascade.
 This cascade can be activated by micro-organisms, immunoglobulins, and a variety of
polysaccharides.
 Initial activation can occur in two ways either via the classical or the alternative
pathways.
8. Properdin:
Complement activation.
C) Inflammatory Barriers:
Tissue damage by a wound or by invading pathogen lead to Inflammatory response by
Release of chemical mediators from Tissue damage, Leukocytes (Histamine, fibrin, kinins,
cytokines), Invading microbe. Vasodilatation of capillaries, Redness of tissue, Tissue
temperatur, Capillary permeability, Influx of fluids, Influx of phagocytes into tissues.
The major purpose of the inflammatory response is to aid in eradicating the infection and in
repairing damaged tissue.
The major events occur:
1. The blood supply to the site is increased.
2. Capillary permeability is increased to allow soluble mediators of the immune system
(complement and antibodies) to reach the site.
3. White blood cells migrate from the capillaries into the affected tissues.
4. Neutrophils are the earliest cells to arrive, followed by monocytes/macrophages and
lymphocytes.
5. The inflammatory reaction is controlled by a cytokines. These are soluble proteins,
usually glycoproteins, which mediate interactions between cells.
6. Vasoactive mediators released from mast cells, basophils, and platelets, together with
by-products of plasma enzyme systems are also involved.
7. The initial inflammation is a result of the fast-acting vasoactive amines histamine and
products of the kinin system such as bradykinin.
8. These are followed by the leukotrienes produced by the lipo-oxygenase pathway and
mediators released from leucocytes once they accumulate.