PPT 3

ANTIGEN
Any agent that BINDS to components of the immune response like lymphocytes and their receptors
or antibodies.
They’re usually peptides (proteins), polysaccharides(complex carbs) or lipids (nucleic acids) only
ANTIGENS & ANTIBODIES

when combined with proteins and polysaccharides

ANTIGENICITY
The ability to combine with the final products of the humoral and/or cell mediated immune response
It’s not activating the immune response rather it combines with the final products of the immune
system

CLASSIFICATION OF ANTIGENS

ENDOGENOUS
EXOGENOUS
Are generated within normal cells as a result of
Have entered the body from outside
metabolism or intracellular infection
Inhalation, ingestion, injection
They can be proteins from one part of the body to
They can be chemicals, bacteria, viruses, pollen
another in the same person or tumor antigens
or dust

NONINFECTIOUS MATERIALS
INFECTIOUS MATERIALS
ALLERGENS (dust, pollen, hair, foods, drugs, bee venom)
Microbial STRUCTURES (cell wall, capsules, flagella,
FOREIGN TISSUES AND CELLS (transplants and
pili, viral capsids, glycoproteins)
transfusions)
Microbial TOXINS
THE BODY’S OWN CELLS
Cancer cells, infected cells involved in autoimmune
diseases)

T-INDEPENDENT
THYMUS DEPENDENT (T-DEPENDENT)
Can directly interact with B-cells without memory
Require APC, MHC, T-cells and PROTEIN antigens
POLYSACCHARIDES ANTIGENS

AUTOantigens
Molecules on SELF TISSUES for
ALLOantigens
which tolerance is inadequate
Antigens found in different members of the
(cancer cells)
SAME SPECIES (blood type)
Also called ISOantigen

HETEROPHILE antigens
Identical antigens found in the cells of ALLERGEN
DIFFERENT BIOLOGICAL SPECIES The antigen that provokes allergy
Type I hypersensitivity reaction

MAJOR CLASSES OF ANTIGENS

SUPERantigens
Cause non-specific activation of a LARGE NUMBER OF T- SEQUESTERED antigens
HELPER CELLS (in contrast to the usual antigen which Tissue antigens sequestered behind anatomical
activates one or a few) barriers.
Release LARGE AMOUNTS OF CYTOKINES which could Found in tissues such as LENS OF THE EYE, TESTIS
lead to cell death, toxic shock syndrome and autoimmune and IVD (nucleus pulposus)
diseases They DO NOT contact T-cells
Typically associated with some infections Come into contact with the immune system
FOLLOWING TRAUMA to an organ
When they contact immunocompetent cells, induction
of an AUTOIMMUNE DISEASE RESULTS
 IMMUNOGEN
An immunogen is ANY ANTIGEN that is capable of inducing HUMORAL AND CELL MEDIATED IMMUNE RESPONSE
Proteins are significantly more immunogenic than polysaccharides
Lipids and nucleic acids ARE NOT immunogenic

IMMUNOGENICITY
The ability to induce a HUMORAL AND CELL MEDIATED immune response
Although all molecules that have this property also have the property of ANTIGENICITY the reverse is NOT TRUE
ALL IMMUNOGENS ARE ANTIGENS BUT NOT ALL ANTIGENS ARE IMMUNOGENS

FOREIGNESS
The molecule must be recognized as “NON SELF”
DONT CONFUSE WITH AUTOANTIGEN (which is a component of an individual behaving as non-self

MOLECULAR SIZE
Most potent immunogens are PROTEINS and POLYSACCHARIDES with HIGH MOLECULAR WEIGHT
(above 100,000)
Molecules of less than 10,00 molecular weight are WEAKLY IMMUNOGENIC (insulin, glucagon)
AMINO ACIDS ARE NOT IMMUNOGENIC

CHEMICAL STRUCTURAL COMPLEXITY

A certain amount of complexity is required
REQUIREMENTS FOR IMMUNOGENICITY

HETERO-POLYMERS
Proteins
Nucleoproteins (strong immunogens)
Glycoproteins (A and B blood group, Rh antigens)
Lipoproteins and Lipopolysaccharides
HOMO-POLYMERS
Weakly immunogenic
Insulin
ANTIGENIC DETERMINANT (EPITOPE)
An epitope is 5 or 6 amino acids or a monosaccharide in length
An antigen (full-length protein) has ONE OR MANY DIFFERENT EPITOPES against which antibodies can bind
(are multivalent)

Epitopes are divided into two categories:

CONFORMATIONAL EPITOPES (linear sequences)
DISCONTINUOUS EPITOPES (protein is folded into a particular conformation)

DOSE
Very small dosage might not induce immune response however might induce tolerance

ROUTE
Route of injection influences immune response (epitope of the antigen molecule may be destroyed if given orally)

TIMING
Interval between doses

GENETIC
Alloantigen is an antigen present in NON_IDENTICAL INDIVIDUALS of the same species (blood group antigens)

ADJUVANT
A substance (chemically UNRELATED to the immunogen) that HELPS (accelerate/prolong) and/or ENHANCE the
immune response to antigen
Some human’s vaccines contain adjuvants such as aluminum hydroxide or aluminum phosphate
HAPTENS
Small biological or non-biologic molecule that can binds to
THEY’RE NOT IMMUNOGENIC BUT ANTIGENIC
SPECIFIC ANTIBODIES, but can’t by themselves induce a specific
Can’t activate T-helper cells
immune response
Unable to bind to MHC proteins
Usually are small molecules, but some HIGH-WEIGHT molecular
Univalent hence can’t activate B cells
NUCLEIC ACIDS are haptens as well
by themselves

EXAMPLES OF HAPTEN HOWEVER THEY CAN BE IMMUNOGENIC IF

Penicillin, Hydralazine BONDED TO A CARRIER PROTEIN (inducing an
Urushiol (in plant oils and causes poison oak and immune response)
poison ivy)
When urushiol is absorbed through the skin, it
HAPTEN-CARRIER COMPLEX
undergoes oxidation in the skin cells to generate the actual
Can stimulate antibody
hapten, which then reacts with skin proteins to form
production and reactive B and T-
hapten adducts
cells

First exposure- SENSITIZATION (proliferation of They have been used to study ALLERGIC
effector T-cells) CONTACT DERMATITIS and the mechanisms
Second exposure- proliferated T-cells can of INFLAMMATORY BOWEL DISEASE to
become activated, generating an IMMUNE induce autoimmune-like responses.
REACTION (blisters)

ANTIBODIES (IMMUNOGLOBULINS)
Can occur as SOLUBLE PROTEINS in the circulation or be displayed on the surface of B-cells
Blood proteins can be detected by SERUM PROTEIN ELECTROPHORESIS where they can be divided to:
albumins, a-globulins, B-globulins and y-globulins
Immunoglobulins are represented by y-fraction of globulins (total of 20% of proteins in the blood)

Each tip of the “Y” of an antibody contains a PARATOPE (structure analogous to a lock) that is
SPECIFIC for one particular EPITOPE (analogous to a key) on an ANTIGEN
This allows these two structures (paratope and epitop e) to bind together with precision
With this binding mechanism, an antibody can tag a pathogen or an infected cell for attack by other parts
of the IMMUNE SYSTEM or it can neutralize its target DIRECTLY

Binding between antibody and antigen is REVERSIBLE or WEAK

It’s possible for an antibody to CROSS-REACT with different antigens
In most cases an antibody can bind one specific antigen, but sometimes they
may bind MORE THAN ONE

CROSS-REACTIVITY
Antibodies raised against a HETEROPHILE ANTIGEN from one organis, will cross-
react with a similar or identical antigen from another source
 FUNCTIONS OF ANTIBODIES
To bind foreign and non-self molecules
Diffferent components of antibodies are used for different more
specific functions

Fab FRAGMENT Fc FRAGMENT

Determines antigen specificity Determines the antibody’s class effect
Neutralizes bacterial cell, virus or toxins Complement fixation
Opsonize microbes Opsonized particles
Agglutination (antibpdies bind to pathogens to link Placental transfer
them together and be targets for phagocytosis) Attach to various cells to activate them
Prevent attachment of microbes to mucosal macrophages, neutrophils, eosinophils, lymphocytes,
surfaces NK cells)
Complement activation Can bind to certain receptors of MAST CELL and
BASOPHILS leading to their DEGRANULATION, mediating
inflammation and allergy
 TYPES ON ANTIBODIES
IgG
Main type (75-80%) of antibody found in all body fluids like BLOOD AND EXTRACELLULAR FLUID allowing it to GOOD OPSONIZER
control INFECTION of body tissues Activates PHAGOCYTOSIS by binding to their Fc receptor
Created and released by plasma cells NATURAL KILLER CELLS
Exist in MONOMERIC form (small in size and easily perfuses tissues) CLASSIC PATHWAY OF COMPLEMENT
Has FLEXIBLE HINGE REGION AGGLUTINATION
Fc portion can cross PLACENTA and enter fetal circulation providing the fetus with HUMORAL IMMUNITY ANTI-Rh ANTIBODIES
before his owns immune system develops (after 3 months an infant starts to make this type of antibody)
MOSTLY SECONDARY IMMUNE RESPONSE

IgM “Natural Antibody”

PENTAMER when secreted and in serum FIRST TO APPEAR IN RESPONSE TO INITIAL EXPOSURE
Forms POLYMERS where multiple immunoglobulins are covalently linked together, held together by J-CHAINS FIRST TO BE EXPRESSED IN FETUS (20 weeks/5months)
Has 10 binding sites MOST EFFICIENT AT AGGLUTINATION
LARGEST ANTIBODY Bacteria- infection
Heavy chain is composed of ONE VARIABLE AND FOUR RBC- blood transfusion
CONSTANT REGIONS (extra domain each) Neonatal’s serum- intrauterine infection
Expressed in naive B lymphocytes surface MOST EFFICIENT AT ACTIVATING CLASSIC PATHWAY OF COMPLEMENT

PRIMARY IMMUNE RESPONSE

IgA
10-15 % of circulating antibodies
FOUND IN EPITHELIAL CELL SURFACES (mucosal secretions) Most prevalent antibody defect is IgA deficiency
Exists MONOMERIC and POLYMERIC (held together by J-chains) Patients are more prone to AUTOIMMUNE DISORDERS
Two types of IgA rheumatoid arthritis, lupus, allergies, asthma
SERUM IgA mainly monomeric and dimeric, function is to absorb vitamin B12 recurring infections
SECRETORY IgA (most common) is polymeric, defense against local mechanisms- not to destroy but to prevent ALSO, bacteria that causes ghonorrea produces an enzyme that splices
passage of foreign substances into circulatory system IgA antibodies into Fc and Fab fragments which doesn’t allow the Fc
ASSOCIATED WITH MALT-cells fragment to attach to phagocyte
MUCOSAL IMMUNITY (works with lysozymes, which hydrolyze poly and liposaccharides)

IgE
HIGH AFFINITY TO BIND TO MAST CELLS AND BASOPHILS
Found in lungs, skin and submucosal membranes of GI
LOW AFFINITY to macrophages and eosinophils
MONOMERIC
Increased concentration of IgE indicates
ONLY IN MAMMALS
parasitic infection, protozoan parasites, inflammatory
Most IgE produced by plasma cells is bound to mast cells or basophils
diseases, infections, type I hypersensitivity, malignancies
Heavy chains of IgE could have extra-domain each

IgD
Expressed on surface of B CELLS Can bind to
Co-expressed with antibody IgM (also on surface) in B cell development BASOPHILS AND MAST CELLS (activate to produce
Very low serum levels (0.2%) antimicrobial factors- respiratory immune defense and
MONOMERIC and LONG HINGE REGION allergies)
IgD signals B-cells to be ACTIVATED BACTERIA nonspecifically through Fc
Trigger for MEMORY B-cells to become active plasma cells

Anti-Idiotypic Antibodies
An antibody created against the extra antibodies that the
Specifically binds to the antigen binding site of another antibody when the
response stymulated
immune system is trying to slow down the mediated response