Lecture 4-4

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University of Juba

School of Veterinary Medicine


Course: -32 - Immunology Class: 3rd Year

Adaptive Immunity

Lecture 4 Date: 8th Nov. 2023


Adaptive (Acquired) Immunity

• Adaptive immunity is also called acquired


immunity, since the potency of immune
response is acquired by experience only.
Cont.
• Acquired immunity against a microbe may be
induced by the host’s response to the microbe
or by transfer of antibodies or

• lymphocytes specific for the microbes. It is of


two types: active immunity and passive
immunity.
Types of Acquired Immunity
It is of two types:

• Active immunity

• Passive immunity
Active Immunity
• This is the immunity induced by exposure to a
foreign antigen.

• Active immunity is the resistance developed


by an individual after contact with foreign
antigens, e.g., microorganisms.
Cont.
This contact may be in the form of;

• Clinical or subclinical infection

• •
Immunization with live or killed infectious
agents or their antigens

• E•xposure to microbial products, such as toxins


and toxoids
Types of Active Immunity
Two types:

• Natural active immunity

• Artificial active immunity


Natural active immunity
• It is acquired by natural clinical or subclinical
infections.

• Natural immunity is long lasting. For example,


individuals suffering from smallpox become
immune to second attack of the disease.
Artificial active immunity
• It is induced in individuals by vaccines.

• There is a wide range of vaccines available


against many microbial pathogens.

• These may be live vaccines, killed vaccines, or


vaccines containing bacterial products.
Mediators of active immunity
• Active immunity is mediated by humoral
immunity and cell-mediated immunity.
Humoral immunity
• It is mediated by the antibodies are secreted
by a subset of lymphocytes known as B cells.

• The antibodies recognize microbial antigens,


combine specifically with the antigens,
neutralize the infectivity of microbes, and
target microbes for elimination by various
effector mechanisms.
Cont.

• Humoral immunity is the principal defense


mechanism against extracellular microbes.
Cell-mediated immunity
• It is mediated by both activated TH cells and CTLs.

• Cytokines secreted by TH cells activate various


phagocytic cells, enabling them to phagocytose
and kill microorganisms.

• This type of cell-mediated immune response is


especially important against a host of bacterial
and protozoal pathogens.
Cont.
• CTLs play an important role in killing virus-
infected cells and tumor cells.

• They act by killing altered self-cells.


Antigens
• Antigen (Ag): A molecule which elicits a
specific immune response when introduced
into the body of a host (human, animal,).

• Antigens, or immunogens, are usually large


organic molecules that are proteins or large
polysaccharides.
Cont.
• Proteins are excellent antigens because of their
high molecular weight and structural
complexity.

• Lipids are inferior antigens because of their


relative simplicity and lack of structural stability.

• However, when lipids are linked to proteins or


polysaccharides, they may function as antigens.
Cont.
• Nucleic acids are poor antigens because of
relative simplicity, molecular flexibility, and
rapid degradation.
• Haptens are antigens that are not immunogenic
but can take part in immune reactions.
• Haptens are univalent hence cannot activate B
cells by themselves.
Cont.
• The haptens, however, can activate B cells
when covalently bound to a “carrier” protein.
When bound with a carrier molecule, they
form an immunogenic hapten - carrier
conjugate.

Hapten-carrier conjugate
Cont.

• Immunogenicity means the ability of an antigen


to elicit an immune reaction in the form of a B-
cell or T-cell response
Cont.
• Antigenicity means just the ability to combine
specifically with the products of the immune
responses.

• All molecules that are immunogenic are


antigenic too, but all antigenic molecules
cannot be considered immunogenic.
Physical Nature of the Antigens
Important factors in the effective functioning of
antigens include;
• Foreignness
• Degradability
• Molecular weight (MW)
• Structural stability
• Complexity
Foreignness
• Foreignness is the degree to which antigenic
determinants are recognized as nonself by an
individual’s immune system.
• The immunogenicity of a molecule depends to a
great extent on its degree of foreignness. For
example, if a transplant recipient receives a
donor organ with several major HLA differences,
the organ is perceived as foreign and is
subsequently rejected by the recipient.
Cont.
• For an antigen to be recognized as foreign by an
individual’s immune system, sufficient antigens to
stimulate an immune response must be present.
Foreign molecules are rapidly destroyed and thus
cannot provide adequate antigenic exposure.
• In the case of vaccination, an adequate dose of
vaccine at appropriate intervals must be
administered for an immune response to be
stimulated.
Molecular Weight
• The higher the MW, the better the molecule
will function as an antigen.

• The number of antigenic determinants on a


molecule is directly related to its size. For
example, proteins are effective antigens
because of a large MW.
Cont.
• Although large foreign molecules (MW 10,000
daltons [Da]) are better antigens, haptens,
which are tiny molecules, can bind to a larger
carrier molecule and behave as antigens
Structural Stability
• Structural stability is important for a molecule to
be effective antigen.

• If a structure is unstable (e.g., gelatin), the


molecule will be a poor antigen.

• Structural stability of an antigen is important in


cases where the goal is to elicit a patient antibody
response when administering a vaccine.
Complexity
• Complex molecules are effective antigen.

• Complex proteins are better antigens than


large repeating polymers such as lipids,
carbohydrates, and nucleic acids, which are
relatively poor antigens.
Other factors
Biological Systems

• Biological system also plays an important role


in determining the immunological efficiency of
an antigen. Some substances are
immunogenic in one individual but not in
others (i.e., responders and nonresponders).
Cont.
Dosage and route of the antigen
• The dose of antigen and the route by which it
comes into contact with the immune system also
influence immunogenicity of the antigen.
• Very low doses of antigen do not stimulate
immune response, either because too few
lymphocytes are contacted or because a
nonresponsive state is elicited.
Adjuvants
• Adjuvants are the substances that when mixed
with an antigen and injected with it boost the
immunogenicity of the antigen.

• Adjuvants increase both the strength and the


duration of immune response.
Antigenic Specificity
• Antigenic specificity of the antigen depends
on antigenic determinants or epitopes.
Epitope
• An epitope is defined as the immunologically
active region of an immunogen that binds to
antigen-specific membrane receptors on
lymphocytes or secreted antibodies.
Types of Epitope
There are two types of epitopes:
• B-cell epitopes
• T-cell epitopes
• B-cell epitopes are antigenic determinants
recognized by B cells and it can combine with
its receptor only if the antigen molecule is in
its native state.
T-cell epitope
• T cells recognize amino acids in proteins but do
not recognize polysaccharide or nucleic acid
antigens.

• This is the reason why polysaccharides are


considered as T-independent antigens and
proteins as T-dependent antigens.
Cont.
• Free peptides are not recognized by T cells,
while the complex of MHC molecules and
peptide are recognized by T cells.

• Thus for a T-cell response, it should recognize


both the antigenic determinant and also the
MHC, and therefore it is said to be MHC
restricted
Antigen-antibody interaction
• The ability of a particular antibody to combine with a
particular antigen is referred to as its specificity.
• Antigen may bind to larger, or even separate, parts of
the variable region.
• The closer the fit between this site and the antigen
determinant, the stronger are the non-covalent forces
(e.g., hydrophobic or electrostatic bonds) between
them, and the higher is the affinity between the antigen
and antibody.
Cont.
• Antigen-antibody reactions can show a high
level of specificity.

• Specificity exists when the binding sites of


antibodies directed against determinants of
one antigen are not complementary to
determinants of another dissimilar antigen.
Cross-reactivity
• This is the situation when some of the
determinants of an antigen are shared by
similar antigenic determinants on the surface
of apparently unrelated molecules, a
proportion of the antibodies directed against
one type of antigen will also react with the
other type of antigen.
Antibody Affinity
• Affinity is the initial force of attraction that
exists between a single Fab site on an
antibody molecule and a single epitope or
determinant site on the corresponding
antigen.
Superantigens
• Superantigens are a class of molecules that
can interact with APCs and T lymphocytes in a
nonspecific way.
• The superantigens act differently by
interacting with MHC class II molecules of the
APC and the Vb domain of the T-lymphocyte
receptor.
Cont.
• This interaction results in the activation of a
larger number of T cells (10%) than
conventional antigens (1%), leading to massive
cytokine expression and immunomodulation.

• Examples of superantigens are staphylococcal


enterotoxins, toxic shock syndrome toxin,
exfoliative toxins, and also some viral proteins.
Types of Bonding
• Bonding of an antigen to an antibody results from
the formation of multiple, reversible,
intermolecular attractions between an antigen and
amino acids of the binding site.
• These forces require proximity of the interacting
groups.
• The optimum distance separating the interacting
groups varies for different.
Cont.
• The bonding of antigen to antibody is
exclusively non-covalent.
• The attractive force of non-covalent bonds is
weak compared with that of covalent bonds,
but the formation of multiple non-covalent
bonds produces considerable total binding
energy.
Types of non-covalent bonds
The four types of non-covalent bonds involved
in antigen-antibody reactions are;

• Hydrophobic bonds

• Hydrogen bonds

• Van der Waals forces

• Electrostatic forces
Detection of Antigen-Antibody Reactions
• Agglutination test is the process whereby
particulate antigens (e.g., cells) aggregate to
form larger complexes in the presence of a
specific antibody.
• Precipitation reactions combine soluble
antigen with soluble antibody to produce
insoluble complexes that are visible.
Cont.
• Hemolysis testing involves the reaction of
antigen and antibody with a cellular indicator
(e.g., lysed RBCs).

• The enzyme-linked immunosorbent assay


(ELISA) measures immune complexes formed
in an in vitro system
ABO Blood Grouping (Forward Antigen
Typing)
• The ABO blood groups (A, B, AB, and O)
represent the antigens expressed on the
erythrocytes (red blood cells, RBCs) of each
group.

• Reagent typing sera contains specific


antibodies to A antigen and B antigen.
Cont.
• When an unknown patient’s RBCs are mixed
with known antibody A or antibody B,
agglutination of the RBCs will occur if a
specific antigen-antibody reaction occurs.

• This is called direct blood typing.


Agglutination Reaction
Anti-A Anti-B Blood group

Positive Negative A
Negative Positive B
Positive Positive AB
Negative Negative O

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