IMMUNITY

Content:

1. Immunity
- Definitions
- Components of Immune system
- Types
- Innate immunity and
Mechanism
- Adaptive immunity and Mechanism
2. Antigen
- Origin of Antigen
- Immunogen
3. Antibody- Immunoglobulin
- Structure
- Classification
- Function of each antibody
IMMUNITY
DEFINITION

• Resistance acquired by a host towards injury caused by

microorganisms and their products.

• Protection against the infectious diseases is only one of the

consequences of the immune response, which entirely is concerned
with the reaction of the body against any foreign antigen.
TYPES OF
IMMUNITY:
Innate
immunity :
a. Nonspecifi Specie
c s
b. Specific Racial
Indi
Adaptive
vidu
Immunity:
a. Active Natural
al
:
Artifici
b. al
Passive:
Natural
Artifici
al
Innate immunity:
Resistance to infection which an individual possesses by virtue of his genetic
and constitutional makeup
Not affected by prior contact with microorganisms or immunization
a. Non specific :
Indicate a degree of resistance to infections in general
b. Specific:
Resistance to a particular pathogen is concerned.
Innate Immunity:
1. Species immunity:
Resistance to pathogen, shown by all members of a particular species.
E.g. anthracis infects human beings but not chickens
2. Racial Immunity:
Within a species, different races may show difference in susceptibility
to infections.
E.g. Genetic resistance Plasmodium falciparum malaria resistance in Africa
3. Individual – immunity
Resistance to infection varies with different individuals of same race
and species
E.g.. Homozygous twins exhibit similar resistance susceptibility to leprosy and
Tuberculosis such correction is not seen in heterozygous twins.
Factors influencing innate immunity
1. Age :
In foetus immune system is immature, in old age there is gradual waning of
immune system
E.g. Polio infection , and Chickenpox highly severe in adult than children.
2. Hormonal :
Enhance suseptability to infection such as
E.g. Diabetes mellitus
• Hypothyroidism in adults
• Adrenal dysfunction
3. Nutrition
E.g. Malnutrition predisposes to bacterial infection.
• Both humoral and cell mediated immune responses are reduced in malnutrition.
Mechanism of innate immunity:
1. Epithelial surface:
a. Skin:
• It acts as a machanical barrier to microorganisms and provide bactericidal
secretions
• Resident microflora of skin and mucous membrane suface help to prevent
colonisation by pathogens
• Altertation of normal resident flora may lead to invasion by extraneous microbes
and thus causing serious disease.
• e.g Clostridial enterocoloitis fallowing oral antibiotics
b. Resiratory tract:
• Inhaled particals are arrested in the nasal passage on the moist mucous
membrane surface.
• Mucous membrane acts as a trapping mechanism hair like cilia propels
the
particals towards pharynx where its swallowed or coughed out.
• Cough reflex acts as a defence mechanism
c. Intestinal tract:
• Mouth possesses saliva which has a inhibitory effect on many microorganisms
some bacteria are destroyed by acidic pH of gastric juices
• Normal bacterial flora of intestine exerts a protective colonisation of
pathogenic
bacteria
d. conjunctiva:
• Tears ( contain lysosyme which has anti bacterial property) helps in flusing
away
bacteria and other dust particals.
e. Genitourinary tract:
• Flusing action of urine eliminates bacteria from uretar
2. Antibacterial substance:
• Nonspecific antibacterial substance present in the blood and tissue
• Substance like properiden, complement, lysosyme, betalysin, basic polypeptide and
interferon which have antiviral activity.
• Complement system plays an important role in destruction of pathogenic
microorganisms that invade blood and tissue.
3. Cellular factor :
• When infection cross the barrier of epithelial suface, tissue factor come into play
for defence.
• Exudate inflammatory reaction occurs by accumulation of phagocytes at the site
of infection and deposition of fibrin which entangles the organisms to act as a
barrier to spread of infection. Phagocytic cells ingest these organisms and
destroy them.
Phagocytic cells are classified as:
i) Microphages e.g. polymorphomuclera leucocytes ( neutrophils)
ii) Macrophages e.g mononuclear phagocytic cells
Phagocytic action are divided into 4 stages:
i) Chemotaxis:
Phagocytes reach the site of infection attracted by chemotactic substances
ii) Attachment:
Infective agent gets attached to phagocytic membrane
iii) Ingestion:
Phagoctes engulf the infective material into vacule
Membrane of phagosome fuses with lysosomes to form a phagolysosome.
iv) Intracellular killing:
Most bacteria are destroyed by phagolysosomes by hydrocytic enzymes of lysosomes
Natural killer cells play a important role in non specific defence against viral infections
and tumour.
4. Inflammation:
Inflammation occurs as a result of tissue injury or irritation, initiated by
entry of pathogens or other irritants.
It’s a nonspecific defence mechanism.
Inflammtion leads to vasodilatation, increased vascular permeability
and cellular infiltration.
Microorganisms are phagocytosed and destroyed due to increased
vascular permeability, which helps to dilute the toxic products present.
Fibrin barrier is laid to wall off site of infection
5. Fever:
Rise of temperature fallowing infection is a natural defence mechanism. It
destroyes the infecting organisms.
Fewer also stimulates the production of interferon which helps in recovery
from
viral infection.
6. Acute phase protein:
Fallowing infection or injury, there is a sudden increase in plasma
concentration of certain proteins, called acute phase proteins
This include c-reactive protein, mannose binding protein etc
CRP and acute phase protein activate alternative pathway of complement.
This is caused to prevent tissue injury and promote repair of inflammtion
lesions.
ADAPTIVE
IMMUNITY
• This is inducible and develops slowly than the innate response.
• This is specific kind of immunity and has memory, therefore providing
long term protection.
• This occurs with contact of foreign particle
Adaptive immunity is often sub-divided into two major types depending
on how the immunity was introduced.
I. Naturally acquired immunity occurs through contact with a
disease causing agent, when the contact was not deliberate
II. Artificially acquired immunity develops only through
deliberate actions such as vaccination
Mechanism:
Active immunity response stimulates both humoral and cell mediated
immunity usually parallel
i) Humoral immunity:
It’s a antibody mediated immunity
It depends on the synthesis of antibodies by plasma cells, the cells
produce specific circulating antibody which combine specifically with the
antigens and modify their activity.
Modified activity is done by lysis of antigen molecules their toxin may be
neutralised or in the form of removal of antigen by phagocytosis.
ii) Cell mediated immunity:
Depends on T- lymohocytes
Cell mediated immunity by sensitised T lymphocytes helps in resistance
to chronic bacterial infections in chronic infection, organisms can multiply
and survive in phagolysosomes and In viral infections.
 TYPES OF ADAPTIVE
IMMUNITY
Active immunity :
a. Naturally acquired active immunity occurs when the person is exposed to a live
pathogen, develops the disease, and becomes immune as a result of the primary
immune response.
b. Artificially acquired active immunity can be induced by a vaccine, a substance that
contains the antigen. A vaccine stimulates a primary response against the antigen
without causing symptoms of the disease.
Vaccine :
Live vaccine: BCG for tuberculosis, Sabin vaccine for
poliomylitis Killed vaccine: Hepatitis B vaccine, non-neural
vaccine for rabies
Bacterial product: Tetanus toxoid vaccine, Deptheria toxoid for
deptheria
Passive immunity:

a. Artificially acquired passive immunity is a short-term immunization

by the injection of antibodies, such as gamma globulin, that are not
produced by the recipient's cells.

a. Naturally acquired passive immunity occurs during pregnancy, in

which certain antibodies are passed from the maternal into the
fetal bloodstream
Active immunity Passive immunity

 Induced by infection  Conferred by administration of

ready made antibodies.
 Long lasting and effective
 Short lived and less effective
protection
 Effective immediately
 Effective only after lag period
 Lag time between exposure and
 Exposureleads to immediate
maximal response
maximal response
 No immunological memory
 Immunological memeory present
 No negative phase
 Negative phase may occur
 Applicable to immunodeficient
 Notapplicable to
immunodeficient person person

 Usedfor prophylaxis to increase  Used for treatment of acute

body resistance e.g BCG vaccine infection
 ANTIGEN

An antigen is a molecule that induces

an immune response in the body.

2
4
Origin of antigen
Exogenous antigens
• Antigens that have entered the body from the outside.
E.g. By inhalation, ingestion, or injection.

Endogenous antigens
• Antigens that have been generated within previously normal cells
as a result of normal cell metabolism, or because of viral or
intracellular bacterial infection
• An autoantigen is usually a normal protein or complex of proteins (and
sometimes DNA or RNA) that is recognized by the immune system of
patients suffering from a specific autoimmune disease.
• These antigens should, under normal conditions, not be the target of the
immune system, but, due to mainly genetic and environmental factors, the
normal immunological tolerance for such an antigen has been lost in these
patients.
Immunogen
• An immunogen is in analogy to the antigen,
• It is a substance (or a mixture of substances) that is able to
provoke an immune response if injected to the body.
• An immunogen is able to initiate an innate immune response
first, later leading to the activation of the adaptive immune
response, whereas an antigen is able to bind the highly variable
immunoreceptor products (b-cell receptor or t-cell receptor) once
these have been produced.
• Immunogenicity is the ability to induce a humoral and/or cell-mediated
immune response
• Antigenicity is the ability to combine specifically with the final products
of the immune response (i.e. Secreted antibodies and/or surface
receptors on t-cells). Although all molecules that have the property of
immunogenicity also have the property of antigenicity, the reverse is not
true
Antigen(ic) specificity
Is the ability of the host cells to recognize an antigen specifically
as a unique molecular entity and distinguish it from another with exquisite
precision. Antigen specificity is primarily due to the side-chain
conformations of the antigen.
Hapten
Is a small molecule that can elicit an immune response only when attached
to a large carrier such as a protein; the carrier may be one that also does
not elicit an immune response by itself.
Epitope:
The portion of an antigen that recognize and bound by antibody and also
called antigenic determinant.
.
• An antigen-presenting cell (APC) or accessory cell is a cell that displays
foreign antigens complexed with major histocompatibility complexes (MHC's)
on their surfaces; this process is known as antigen presentation.
• T-cells may recognize these complexes using their T-cellreceptors
(TCRs). These cells process antigens and present them to T-cells.
Eg.
• Dendritic cell,
• Macrophages,
• B cell,
• Epithelial cells,
• Fibroblast
Antibody : immunoglobulin
Immunoglobulin is a glycoprotein that is made in response to an antigen and can
recognize and bind to the antigen that caused its production.

• Are gamma globulins

• Synthesized by plasma cells
• Constitute 25-30 % of total serum proteins
• Antibodies are present in serum, tissue fluids and mucosal surfaces.
• All antibodies are immunoglobulins, but all immunoglobulins may not be
antibodies
 ANTIBODY
STRUCTURE
An antibody (Ab), also known as an
immunoglobulin (Ig)

It’s a large Y-shape protein produced by

B cells that is used by the immune
system to identify and neutralize foreign
objects such as bacteria and viruses.

The antibody recognizes a unique part of

the foreign target, called an antigen.
 Basic structure
• Composed of 4 polypeptide chains.
• 2 identical light and 2 identical heavy chains
• Linked by disulphide bonds
• Light chains similar in all immunoglobulins
• Light chains occur in 2 varieties kappa and lambda
• Light and Heavy chains are subdivided into
variable and constant region.
• Each heavy and light chain contains amino
terminal in variable region, carboxyl terminal in
constant region
• Heavy chains are structurally and antigenically
distinct for each class
• Each immunoglobulin peptide chain has intra
chain disulphide bonds- form loops
• Each loop is compactly folded to form a globular
structure-domain
• Light chain contains a single variable domain
(VL) and a single constant domain (CL).
• Heavy chain contains one variable domain (VH)
and 3 constant domains (CH1, CH2, CH3)
• Hinge region is the segment in heavy chain -
between CH1, CH2
• Each tip of the "Y" of an antibody contains a
paratope that is specific for one particular
epitope on an antigen, allowing these two
structures to bind together with precision.
• Using this binding mechanism, an antibody
can tag a microbe or an infected cell for
attack by other parts of the immune system,
or can neutralize its target directly.

• The of antibodies is the main

production
function of the humoral immune system.
• Antibodiesaresecretedbyatypeofwhite
blood cell called a plasma cell.
• Antibodies can occur in two physical forms
1. Soluble form that is secreted from the cell,
2. Membrane-bound form
That is attached to the surface of a B cell and is referred to as the B cell
receptor (BCR).
The BCR is only found on the surface of B cells
Facilitates the activation of these cells and their subsequent
differentiationinto eitherantibodyfactoriescalledplasma
cells or memory B cells
That will survive in the body and remember that same antigen so the B
cells can respond faster upon future exposure.
Classificati
on
• Based on structure and antigenic nature of H chain the immunoglobulins
are classified into 5 classes.
• Ig G- (gamma)
• Ig A- (alpha)
• Ig M- (mu)
• Ig D- (delta)
• Ig E - (epsilon)
Functions of Different Antibodies

1.IgA plays a role in localized defense mechanism in external secretions

like tear
2. IgD is involved in recognition of the antigen by B lymphocytes
3. IgE is involved in allergic reactions
4. IgG is responsible for complement fixation
5. IgM is also responsible for complement fixation.
Immunoglobulin G (Ig G)
• Most abundant class in serum

• Constitutes 80% total immunoglobulin

• Present in blood, plasma and tissue fluids

• Contains less carbohydrate than other

immunoglobulins

• It has a half life of 23 days: the longest of all

of the immunoglobulin isotopes
• Crosses placenta and provide natural
immunity to fetus and neonate at birth

• Acts against bacteria and viruses by

opsonizing

• Neutralize toxin

• Activate complement by classical

pathway

• Catabolism of IgG is unique in that it varies

with its serum concentration
Sub classes of Ig G

Ig G1, Ig G2, Ig G3, Ig

G4.
Biological function of subclasses

• IgG1, IgG3, IgG4 – cross placenta and protect fetus

• IgG3 activates complement

• IgG1 and IgG3 binds to Fc receptor on phagocytic cells, monocytes

and macrophages and mediate opsinization.
Immunoglobulin A (Ig
A)
• Constitutes 10-15 % of total immunoglobulins
• Present in milk, saliva, tears, mucous of
respiratory tract, digestive tract and genitourinary
tract.
• In serum exist as monomer
• In external secretions exist as dimer called
secretory Immunoglobulin.
• Has ‘J’ chain and secretory piece.
• Half life: 6-8 days
 Formation of secretory Ig A

• Dimeric Ig A binds to the receptor on the surface

of the epithelial cells -endocytosed and
transported across the cell to the luminal surface
• After reaching the surface, the poly-Ig receptor is
cleaved
• The portion of the receptor that remains attached
to the Ig A dimer – secretory component
• Secretory piece protects Ig A from digestive
enzymes and denaturation by bacterial proteases
 Functions

• Provides local immunity.

• Secretory Ig A binds to surface antigens of microorganism and prevent its
attachment and invasion of the mucosal surfaces of respiratory and digestive
tract- immune elimination.
• Secretory IgA provides important line of defense against salmonella,
Vibrio cholerae, N. gonorrhoeae, influenza virus and poliovirus.
• Secretory IgA present in breast milk protects newborn during first months of
life.
• Activates complement by the alternative pathway
• Promotes phagocytosis and intracellular killing of microorganisms
Immunoglobulin M (Ig
M)
• Accounts for 5-10% of total serum proteins
• Polymer of five monomeric units (pentamer)
• Held together by disulfide bonds and ‘J’
chain
• Mol. Wt. of 900,000-10,00,000 (millionaire
molecule)
• Half life: 5 days
• Most of IgM (80%) present intravascularly
• Present in low concentration in intercellular tissue fluids
• Cannot cross placenta
• Presence of IgM antibody in serum of newborn indicate congenital infection.
• Earliest immunoglobulin to be synthesized by fetus (20 weeks)
• First immunoglobulin to be produced in primary response to antigen
• Relatively short-lived hence it’s demonstration in the serum indicates recent
infection
• Monomeric IgM appears on the surface of unstimulated B lymphocytes
and act as receptors for antigens
Functions

• It agglutinates bacteria
• Activates complement by classical pathway
• Causes opsonization and immune hemolysis
• Believed to be responsible for protection against
blood invasion by microorganisms
Immunoglobulin E (Ig E)

• Structure is similar to Ig G
• Has 4 constant region domains.
• Mol. Wt. 1,90,000
• Half life: 2 days
• Heat labile (inactivated at 560C in 1 hour)
• Normal serum concentration 0.3 ug/ml
• Mostly present extra cellularly
• Does not cross placenta
• Produced in the lining of respiratory and intestinal tract
• Known as regain antibody
• Does not activate complement nor agglutinate antigens
• Binds to the Fc receptors on the membranes of blood basophils and tissue
mast cells
• Mediates immediate hypersensitivity reaction and P.K. reaction
• Responsible for symptoms of anaphylactic shock, hay fever and asthma.
• Play a role in immunity against helminthic parasites
• IgE binds to Fc receptors on the membrane of
blood basophils and tissue mast cells.
• When two IgE molecules on the surface of
these cells are cross linked by binding of the
same antigen- cells degranulates.
• Release histamine and
pharmacological mediators of
anaphylaxis from cell.
• The physiological role of IgE appears to be
protection against pathogens by mast cell
degranulation and release of inflammatory
mediators
Immunoglobulin D (Ig D)

• Structure is similar to IgG

• Serum concentration 30 micrograms per ml
• Constitutes 0.2% of total immunoglobulins
• Half life: 3 days
• IgD together with IgM is major membrane bound
immunoglobulin on unstimulated B lymphocytes-
acts as recognition receptors for antigens
Thank you