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Immunity, antigen and antibody- Introduction
1. Immunity, Antigen and Antibody:
What is immunology?
• Immunology is the branch of biology that covers the study of immune
system in all organisms. Positive and negative consequences of immune
system, use of immune system in the applied medical science is also
studied under immunology.
What is immunity?
• Immunity is defined as the resistance offered by the host against any
foreign substances e.g. microorganisms. To offer immunity, body has a
system called immune system. Immune system is the collection of
organs, cells and proteins that function to protect the body from harmful
agents such as bacteria, fungi, parasites, viruses, cancer cells and
toxins.
2. Types of immunity:
Immunity can be broadly classified into two
classes:
1. innate (by birth) immunity and
2. Adaptive (acquired) immunity.
3. Innate immunity Adaptive / acquired immunity
It is the resistance to infection that an individual possesses
from birth
Resistance to infection that an individual acquires during
lifetime
Immune response occurs in minutes Immune response occurs in days
This is nonspecific immunity This is specific immunity
Immunological memory is absent Immunological memory is present
Innate immunity is provided by:
Anatomical barriers- skin
Physiological barriers-mucous present in respiratory
tract, gastrointestinal tract, conjunctional secretion,
genitourinary tract, body temperature
Phagocytes- neutrophils, macrophages, monocytes
Natural killer cells, mast cell, dendritic cell
Fever, inflammatory response, normal bacterial flora
Acquired immunity is provided by:
T cells (T-Lymphocytes)
B cells (B-Lymphocytes)
Innate immunity depends on:
Species
Race
Individual (age, hormonal level,
nutrition)
Acquired immunity are of following types:
Active (natural or artificial)
Natural active- immunity gained due to natural infection
Artificial active- immunity gained due to vaccination
Passive (natural or artificial)
Natural passive- immunity passively transferred from mother
to foetus through placenta & milk
Artificial passive- immunity transferred to a recipient by
parental administration of antibodies
4. Cells & organs of the immune system:
Organs of immune system:
The organs of the immune system are called lymphoid
organs
Lymphoid organs are the organs where lymphocytes
develop, congregate. These organs include the bone
marrow, thymus, lymph node, spleen & various other
clusters of lymphoid tissue.
There are two different types of lymphoid organs in body:
Primary lymphoid organs & secondary organs
5. Primary lymphoid organ:
• Also called central lymphoid organ
• It is where immature lymphocytes develop
• Organs where differentiation, proliferation and
maturation of stem cells into immune competent cells
take place
• Include thymus and bone marrow
6. Thymus:
• a bilateral organ located in the mediastinum
• attains its peak development during youth
Function : the progenitor T cells formed during hematopoiesis in bone marrow
enter into the thymus. Here they multilply, differentiate and get matured.
Finally from thymus, matured T cells enter into circulation and protect the
body from infection
Bone marrow:
• Bone marrow is the soft tissue in the hollow shafts of the flat bones
Function: all the cells of the immune system are initially derived from the bone
marrow hrough a process called hematopoiesis
Immature B cells proliferate & differentiate with in the bone marrow
Responsible for the production of important immune system cells like B cells,
granulocytes, natural killer cells and immature thymocytes. Also produces
platelets and RBC
7. Secondary lymphoid organs:
• Also called peripheral lymphoid organs
• They maintain mature naïve lymphocytes and initiate
an adaptive immune response
• The peripheral lymphoid organs are the sites of
lymphocyte activation by antigens
• Secondary lymphoid organs are:
Spleen, lymph nodes, tonsils, appendix, payer’s
patches
8. Spleen:
The spleen is a large, ovoid filtering organ situated in the left
abdminal cavity. This organ is composed of T-cell, B-cell, natural
killer cells, macrophages, dendritic cells & red blood cells. It is a
production site of antibodies and activated lymphocytes. Spleen
filters blood and traps blood borne antigen and thus respond to
systemic infection
Lymph nodes:
Bean-shaped, encapsulated structures distributed throughout the
body along the course of lymphatic vessel. They are made up of
mostly B-cells, T-cells, macrophages and dendritic cells. They act as
immunologic filters and drain the lymph from most of the body
tissues and filter out the antigens present in them, before allowing
the lymph to return to circulation
9. Tonsils: Two masses of soft glandular tissue on either side or the back of
the mouth
Function: Traps bacteria and viruses from inhaled air
Appendix: Thin, dead-end tube measuring about three-to-four inches in
length and hangs from the cecum
Functions: Help tell the lymphocytes exactly where they have to head
over to attack infection and it also enhances the massive intestines
defences to a range of drugs and foods
Peyer’s patches: The nodules of lymphatic cells that combine to make
patches or bundles and appear generally only within the lowest part of
intestine (ileum)
Functions: Detect antigens such as bacteria and toxins and mobilize
highly specialized white blood cells termed B-cells to produce an
antibody
10.
11. Cells of immune system:
The response to pathogens is managed by the complex interactions
and activities of the large number of diverse cell types involved in the
immune response
The innate immune response is the first line of defense and occurs
soon after pathogen exposure. It is carried out by phagocytic cells
such as neutrophils and macrophages, cytotoxic natural killer (NK)
cells, and granulocytes
The subsequent adaptive immune response includes antigen-specific
defense mechanisms and may take days to develop. Cell types with
critical roles in adaptive immunity are antigen-presenting cells
including macrophages and dendritic cells. Antigen-dependent
stimulation of various cell types including T cell subsets, B cells, and
macrophages
12. Defense Mechanism:
It is the way in which the body protects itself from invasion of
pathogens
The body has developed defense mechanisms to control and
to cope with the constant attack of microorganisms
The body has three lines of defense
1. First line of defense: Physical Barriers and chemical
barrier
2. Second line of defense: Defensive Cells & Proteins,
Inflammation, and Fever
3. Third line of defense: Humoral and cell mediated
response
13. The First Line of Defense:
•These are a combination of physical and chemical
barriers that prevent all types of foreign agents from
penetrating the outer layer of the body
•No specific foreign agent is targeted at this level
14. Physical Barriers:
• Skin
• Cells filled with keratin, making skin impenetrable,
waterproof, and resistant to disruptive toxins and most
invaders
• Dead cells are shed and replaced (1 million every 40
min), taking microbes with them
• Mucous Membranes
• The inner surfaces of the body are guarded by mucous
membranes that line the respiratory, digestive, urinary,
and reproductive systems and protect the internal lining
• But, mucous membranes are more vulnerable than skin
• Hair in the nose act as a coarse filter
15. Chemical barrier:
• Sweat produced by glands in the skin wash away microbes
and their acidity slows bacterial growth.
•Mucous membranes produce sticky mucous that traps
many microbes
• Saliva and tears contain an enzyme called lysozyme that
kills bacteria by rupturing their cell walls
• Cerumen (ear wax) – produced in the ear canal and protects
the canal by trapping dirt and dust particles
16.
17. The Second Line of Defense:
Defensive Cells
• If a pathogen penetrates the first line of defense, these cells play a role
in inhibiting or destroying the pathogen before it harms the body. They
are non-specific and react to the presence of any foreign organism or
substance
• Phagocytes
• Engulf pathogens, damaged tissue, or dead cells
• Neutrophils
• Macrophages
• Eosinophils
• Discharge destructive enzymes to destroy pathogens too big for
phagocytes (e.g., parasitic worms)
• Natural Killer Cells
• Seek out abnormal cells (e.g., cancer cells)
18. Defensive Proteins
• Interferon Protein
• A virus enters a cell
• The infected cell produces interferon
• The interferon binds with other cells that become infected with
a virus, and protects it by stimulating the cell to produce
antiviral proteins that prevent the virus from making copies of
itself
• The interferon attracts and stimulates natural killer cells and
macrophages to kill cells infected with the virus
19. Complement System
-Destruction of pathogen (Cell lysis)
-Enhancement of phagocytosis (Opsonization)
-Stimulation of inflammation
-Chemotaxis - attracting macrophages and
neutrophils
20. Inflammation
When body tissues are injured or damaged, a series of
events called the inflammatory response occurs
Redness: caused by increased blood flow to the
damaged area
Heat: increased blood flow elevates the temperature in
the area of injury, increasing metabolic rate of the body
cells
Swelling: histamine makes capillaries more permeable
than usual
Pain: causes person to protect the area and prevent
additional injury
21. Fever
• A fever is an abnormally high body temperature
caused by pyrogens (chemicals that set the
“thermostat” in the brain to a higher set point)
• A mild or moderate fever helps the body fight bacterial
infections by slowing the growth of bacteria and
stimulating body defense responses
22. The Third Line of Defense:
• When the first two line of defense of the body can not prevent the
infection, the immune system acts to eliminate the infectious agent
and prevent the body from infection
• Specific resistance is a third line of defense
• Forms the immune response and targets specific pathogens
• Cells of third line of defense or specific immunity are called
lymphocytes
• Types of lymphocytes:
B- lymphocytes: produce specific proteins called antibodies,
which are produced against specific antigens
T-lymphocytes: target pathogens directly
• Third line of defense works by two mechanisms: Antibody
mediated & cell mediated immune response
23. • Antibody mediated immune response:
This type of defense is provided by B lymphocyte cells that produce antibody
against the non-self substance, i.e. antigen
When B cells interact with an antigen, they are differentiated into antibody
producing plasma cells, which produce and release specific antibodies into
the blood circulation
These secreted antibodies bind to the antigen specifically and facilitate its
clearance from the body by various mechanisms:
Antitoxin (antibody against toxin) inactivates toxin
Neutralizing antibodies coat viruses, coated viruses cannot penetrate cells in
the body
Antibodies that combine with antigen on the surface of bacteria attract
macrophages and are phagocytosed
24. •Cell mediated immune response:
The principle role of cell mediated immune response is
to detect and eliminate cells that harbor intracellular
pathogens
The defense is provided by both antigen specific and
non-specific cells
Antigen specific cells include CD8 cytotoxic T
lymphocytes and cytokine secreting CD4 Th cells
Non-specific cells include NK cells, macrophages,
neutrophils and eosinophils
25. Antigen:
Definition: antigen is a substance which when introduced
parentally into the body stimulates the production of an
antibody with which it reacts specifically and in an observable
manner.
•Example: Foreign protein, Nucleic acids, Large CHO, Some
lipids, Pollen grains, microorganisms
Epitope or antigenic determinant: An epitope, also known as
antigenic determinant, is the part of an antigen that is
recognized by the immune system, specifically by antibodies,
Bcells, or Tcells. An antigen may have several epitopes. Each
epitope is recognised by a different antibody
26. Characteristics of antigens:
• Foreignness: antigen must be a foreign substance to elicit an
immune response. Molecules recognised as “self” are not
immunogenic
• Molecular size: larger molecules are highly antigenic. Substance
having molecular weight less than 10,000Dalton are either non-
antigenic or weakly antigenic
• Chemical nature: antigens are mainly proteins or polysaccharides;
lipids & nucleic acids are less antigenic on their own but do so when
combined with proteins
• Susceptibility to tissue enzymes: substance that can be
metabolised & are able to be digested by the action of tissue
enzyme behave as antigen
27. Types of antigen
1. Based on the immunogenicity:
• Complete antigen-A complete antigen can induce antibody formation
and produce a specific and observable reaction with the antibody so
produced. They are high molecular weight proteins but some are
polysaccharides also
• Incomplete antigen or Hapten- haptens are substances that are
incapable of inducing antibody formation by themselves but can react
specifically with antibodies. Hapten becomes immunogenic (capable
of inducing antibodies) on combining with a larger carrier molecule
e.g. serum protein such as albumin, globulin or polypeptide.
28. 2. Based on origin:
• Exogenous antigen: exogenous antigens are antigens, that have
entered the body from the outside for example by inhalation,
ingestion or injection.
• Endogenous antigen: endogenous antigens are antigens that have
been generated within previously normal cells as a result of normal
cell metabolism or because of viral or intracellular bacterial infection
• Autoantigen: an auto antigen is usually a normal protein or complex
of proteins (and sometime DNA or RNA) that is recognised by the
immune system of patients suffering from autoimmune diseases.
These antigens, under normal conditions, should not be the target of
the immune system, but due to genetic or environmental factors, the
normal immunological tolerance for such an antigen is lost
29. Antibody:
•Definition: antibody or immunoglobulin is a
specialised glycoprotein produced from activated
B lymphocytes (plasma cells) in response to an
antigen and react specifically with that antigen.
Chemically antibodies are globulins and hence
are also called immunoglobulins.
30. Structure of antibody:
• Antibody molecules are globular proteins. They are Y-shaped
structures, made up of two identical heavy (H) and two
identical light (L) polypeptide chains. The longer chains are
called heavy (H) chains and the shorter ones are called light
(L) chains
• Each L- chain is attached to H-chain by a disulphide (S-S)
bond and the two symmetrical H-chains are held together by
one to five S-S bonds, depending upon the type of
immunoglobulin
• Light chain consists polypeptides of around 22,000 dalton
and heavy chain consists larger polypeptide of around 50,000
dalton or more.
31. • There are five types of immunoglobulin, based on the structure of constant region
of heavy chains, denoted by Greek letters – gamma (), mu (µ), alpha (), delta (δ)
& epsilon (ε).
• The light chains exist in two forms- lambda (λ) and kappa (κ). Each
immunoglobulin molecule shows either two kappa or two lambda light chains but
they are never found in combination.
• All chains of antibody have two ends- an amino terminal end (NH3) and a carboxy
terminal end (COOH)
• An antibody is made up of a variable region and a constant region
• Variable region is the region that changes to various structure depending on
differences in antigen. It is the part near amino terminal end of both light and
heavy chain. Variable region represents the antigen binding site of antibody.
• Constant region is the remaining structure in antibody towards the carboxy
terminal end.
• Hinge region is the junction formed between constant regions of heavy chains of
IgG, IgA and IgD. It is absent in IgE & IgM. This region is rich in proline & cysteine
amino acids. The hinge region is quite flexible, thus helps the antibody in reaching
towards the antigen
32.
33. Classes of immunoglobulins / antibodies:
On the basis of nature of heavy chain, immunoglobulins
are classified as below:
• Immunoglobulin G (IgG) – contains gamma () chain
• Immunoglobulin A (IgA) – contains alpha () chain
• Immunoglobulin M (IgM) – contains mu (µ) chain
• Immunoglobulin D (IgD) – contains delta (δ) chain
• Immunoglobulin E (IgE) – contains epsilon (ε) chain
34. •Immunoglobulin G: IgG molecule consists of two heavy and
two light chains linked by disulphide bonds. IgG has two
identical antigen binding sites so that they are called divalent.
IgG appears generally two weeks after infection but persist for
long period of time. IgG is the predominant antibody in
secondary immune response. It is the only immunoglobulin
that passes through placenta and provides natural passive
immunity to newborn
•Immunoglobulin A: it is the major immunoglobulin that
appears in the sero-mucous secretions such as milk, saliva,
tears, nasal fluids, colostrum & secretions of respiratory,
intestinal and genital tracts. It protects the exposed mucous
membrane against attack by microorganisms
35. • Immunoglobulin M: it consists of 10 heavy chains and 10 light chains. IgM
appears early in response to infection and its presence in serum indicates
recent infection. It cannot cross placenta, hence presence of IgM in the
serum of newborn indicates intrauterine infection. IgM remains largely to
blood stream and offers protection against bacteraemia. Its deficiency
may lead to septicaemia.
• Immunoglobulin D: it is structurally similar to IgG. They occur on the
surface of unstimulated B-lymphocytes and serve as recognition receptors
for antigen. Combination of cell membrane bound IgD with corresponding
antigen leads to specific stimulation of the B cell to produce antibody.
• Immunoglobulin E: these antibodies are also called regains and
inactivated by heat at 56oC for 1 hour. It does not pass the placenta. It is
mostly extravascular in distribution and found in insignificant amount in
normal serum but found higher amount in allergy and intestinal parasitic
infection.