BASIC IMMUNOLOGY

LECTURE 2
SPECIFIC ACQUIRED (ADAPTIVE) IMMUNITY

N. Gachechiladzde
2020 East European University (EEU)
 LEVELS OF IMMUNE DEFENSE
The innate immune system is composed of a conglomeration of soluble factors and cells
that detect and respond to infectious agents through binding to relatively invariant
structures (PAMPs) common to many pathogens;
 the neutrophils, eosinophils, basophils, mast cells, monocytes,
macrophages, dendritic cells, and natural killer (NK) cells are all
cellular components of the innate response;
 acute phase proteins and complement are soluble (humoral)
components of innate immunity
The adaptive immune system is composed of T‐ and B‐lymphocytes that recognize
highly specific structures (antigens) on microorganisms via highly diverse membrane
receptors that are generated randomly and are uniquely tailored to individual pathogens
 ADAPTIVE IMMUNE SYSTEM
All immunocompetent individuals have many distinct
lymphocytes, each of which is specific for a different foreign
substance called antigen. When an antigen is introduced into an
individual, lymphocytes with receptors for this antigen seek out
and bind it and are triggered to proliferate and differentiate,
giving rise to clones of cells specific for the antigen. These cells or
their products specifically react with the antigen to neutralize or
eliminate it. The much larger number of antigen-specific cells late
in the immune response is responsible for the ‘memory’ involved
in adaptive immunity – this is general scenario how adaptive
immune system works.
 CELLS OF ACQUIRED IMMUNITY 1/2
T‐ and B‐cells - both are highly
antigen specific and they both
exhibit immunological memory
whereby they respond more
vigorously upon re‐encounter
with specific antigen.
All lymphocytes arise from stem
cells in the bone marrow
 CELLS OF ACQUIRED IMMUNITY 2/2
T‐cells get their name from the fact that they develop
(from bone marrow precursors) in the thymus.
On stimulation by antigen, they give rise to cellular
immunity
B‐cells develop fully within the bone marrow. They give
rise to lymphoid populations which, on contact with
antigen, proliferate and differentiate into plasma cells.
These plasma cells make a humoral factor (antibody –
immunoglobulin) which is specific for the antigen and
able to neutralize and/or eliminate it.
 LYMPHOCYTE DEVELOPMENT
Sites in which mature lymphocytes are produced are called the
generative lymphoid organs.
Mature lymphocytes leave lymphoid
organs and enter the circulation
and the peripheral lymphoid
organs, where they may
encounter antigen for which
they express specific receptors.
 TISSUES OF IMMUNE SYSTEM
The tissues of the immune system consist of the generative (also
called primary, or central) lymphoid organs, in which T and B
lymphocytes mature and become competent to respond to
antigens, and the peripheral (or secondary) lymphoid organs, in
which adaptive immune responses to microbes are initiated.
 Generative organs are – Bone marrow and Thymus

 Peripheral organs are - lymph nodes, the spleen, and the

mucosal and cutaneous immune systems
 LEARNING “SELF” AND “FOREIGN”
T cell progenitors migrate from the bone marrow to the thymus, where the
entire process of maturation occurs, B cell differentiate in the bone marrow.
The peripheral lymphoid organs are organized to optimize interactions of
antigens, APCs, and lymphocytes in a way that promotes the development of
adaptive immune responses.
Within the peripheral lymphoid organs, T lymphocytes and B lymphocytes are
segregated into different anatomic compartments
 Naive lymphocytes constantly recirculate between the blood and peripheral
lymphoid organs, where they may be activated by antigens to become effector
cells, and the effector lymphocytes migrate to sites of infection, where microbes
are eliminated
 TYPES OF THE CELLS BY FUNCTION
When naive lymphocytes recognize microbial antigens and also receive
additional signals induced by microbes, the antigen-specific
lymphocytes proliferate and differentiate into effector cells and
memory cells.
Effector cells are the differentiated from naive cells which have
the ability to produce molecules that function to eliminate
antigens
Memory cells, which also are generated from of antigen-
stimulated lymphocytes, do survive for long periods of time in
the absence of antigen.
 FUNCTION OF THE CELLS
T cells - are more responsible for cell mediated adaptive response:
• Treg - regulatory T‐cells, limit excessive
or undesired immune responses; (CD8)

• Tc - cytotoxic T‐cells, kill cells

infected with pathogens; (CD8)

• Th - helper T‐cells, provide

assistance to other cells in the immune
response; (CD4)
CLONAL SELECTION 1/3
 CLONAL SELECTION 2/3
Because body can make huge amount of
different antibody molecules, it impossible
to keep all those lymphocytes producing
each type of antibody; there just would not
be enough room in the body.
Instead, lymphocytes that are
triggered by contact with
antigen undergo successive waves
of proliferation to build up a large
clone of plasma cells that will be
making antibody of the kind for
which the parent lymphocyte was programmed.
 CLONAL SELECTION 3/3
By this system of clonal selection, large
enough concentrations of specific
antibody can be produced to
combat infection effectively

Clonal selection of T‐lymphocytes

similarly ensures that only cells of
the appropriate specificity are
induced to proliferate.
 ANTIGEN 1/4
T and B cells are activated by antigen!
Antigen - is any foreign substance, which causes immune system
activation and since immune system does not recognize the substance, it is
trying to fight it off. An antigen may be a substance from the environment,
such as chemicals, bacteria, viruses, toxins or pollen. An antigen may also
form inside the body.
• Chemical nature – proteins, carbohydrates, lipids, nucleic acids,
LPS.
• Size – hapten, immunogen
• Shape – 3D
 ANTIGEN 2/4
On the structural level, an antigen must be sufficiently unique for
the immune system to make an immune response to it. It is usual
that an antigen, a molecule which is antigenic, possesses several
unique molecular structures, each of which can elicit an immune
response.
But, antibodies or cells produced against an antigen are not directed
against the whole molecule but against different parts of the
molecule. These ‘antigenic determinants’ or ‘epitopes’ are the
smallest unit of an antigen to which an antibody or cell can bind
Antigens may contain a number of different antigenic determinants
to which individual antibodies or T cell responses are made.
 ANTIGEN 3/4
For different chemical nature of antigens the epitopes could be
different – e.g. for protein, an antibody binds to a unit which is about
three to six amino acids, whilst for a carbohydrate it is about five to six
sugar residues.
Therefore, most large molecules possess many antigenic determinants
per molecule, i.e. they are ‘multideterminant’. However, these
determinants may be identical or different from each other on the
same molecule.
Antibodies bind to conformational antigenic determinants (dependent
on folding of the molecule) while T cell receptors recognize linear
amino acid sequences.
 ANTIGEN4/4
Very small molecules which can be viewed as single antigenic
determinants are incapable of eliciting an antibody response. They
are called haptens, and they can be attached covalently to larger
molecules (carriers) and in this physical form can, with the help of
T cells, induce the formation of antibodies.
Therefore, one can distinguish between molecules which can
stimulate an immune response (immunogens) and those which
react with antibodies but cannot initiate an immune response -
haptens
 ANTIGEN PRESENTATION AND CAPTURING
Protein antigens of microbes that enter the
body are captured mainly by
dendritic cells and concentrated
in the peripheral lymphoid organs,
where immune responses are initiated

Epithelia – APC (dendric cells) – cytokines

– migration to lymph nodes – presentation
to T lymphocytes
 MHC – MAJOR HISTOCOMPATIBILITY COMPLEX 1/3
MHC locus contains two sets of highly polymorphic genes, called the
class I and class II MHC genes. These genes encode the class I and class
II MHC molecules that display peptides to T cells.
 HUMAN LEUKOCYTE ANTIGENS - HLA
The collection of genes that make up the MHC locus is found in all
mammals and includes genes that encode MHC and other proteins. Human
MHC proteins are called human leukocyte antigens (HLAs) because these
proteins were discovered as antigens of leukocytes that could be identified
with specific antibodies.

In all species, the MHC locus contains two sets of highly polymorphic
genes, called the class I and class II MHC genes. These genes encode the
class I and class II MHC molecules that display peptides to T cells.
 MHC – MAJOR HISTOCOMPATIBILITY COMPLEX 2/3
Class I and class II MHC molecules are membrane proteins that each
contains a peptide-binding cleft at the amino-terminal end.
 MHC – MAJOR HISTOCOMPATIBILITY COMPLEX 3/3
MHC genes are co -dominantly expressed, meaning that the alleles inherited from
both parents are expressed equally
Class I molecules are expressed on all nucleated cells, but class II molecules are
expressed mainly on dendritic cells, macrophages and B lymphocytes.
The peptide-binding clefts of MHC molecules bind peptides derived from protein
antigens and display these peptides for recognition by T cells. Each MHC molecule
can present only one peptide at a time, because there is only one cleft, but each
MHC molecule is capable of presenting many different peptides
In each individual, the MHC molecules can display peptides derived from foreign
extracellular proteins that are internalized by specialized APCs (dendritic cells,
macrophages, and B cells) are processed in vesicles and displayed by class II MHC
molecules, whereas proteins in the cytosol of any nucleated cell are processed in the
cytoplasm and displayed by class I MHC molecules
 SIGNIFICANCE OF MHC
The role of MHC molecules in antigen display ensures that T cells only see cell-
associated protein antigens, and the correct type of T cell (helper or cytotoxic cell)
responds to the type of microbe that T cell is best for – MHC restriction
By segregating the class I and class II pathways of antigen processing, the immune
system is able to respond to extracellular and intracellular microbes in different
ways
Microbes activate APCs to express membrane proteins (called co-stimulators) and
to secrete cytokines that provide signals that function in concert with antigens to
stimulate specific T cells.
B lymphocytes recognize proteins as well as nonprotein antigens, even in their
native conformations. It is not known if a specialized system of antigen display is
essential for the induction of B cell responses
 REFERENCES
Abul K. Abbas, Andrew Lichtman – Basic Immunology (3rd edition)
P. 18-21
Summary p.21

Roit’s Essential Immunology (13th Edition)

P. 56-58
P. 23-24
P.48-50