This document discusses antigens, immunogens, and factors affecting immunogenicity. It then covers the cellular basis of the immune response, including the origin and differentiation of T cells, B cells, natural killer cells, and other immune cells from stem cells in the bone marrow and thymus. It describes the roles of macrophages, dendritic cells, and other immune cells in phagocytosis, antigen presentation, and immune responses.

1. Antigen & Cellular basis of
Immunity
Aman Ullah

2. ANTIGENS
• Antigens are molecules that react with antibodies
• immunogens are molecules that induce an immune
response
• In most cases, antigens are immunogens
• However, there are certain important exceptions, e.g.,
haptens
• Haptens are not immunogenic because they cannot
activate helper T cells
• The failure of haptens to activate is due to their inability to
bind to MHC proteins; because they are not polypeptides
and only polypeptides can be presented by MHC proteins
• Haptens are also univalent and therefore cannot activate B
cells by themselves

3. Factor affecting immunogenicity
1. Foreignness: To be immunogenic, molecules must be
recognized as "nonself," i.e., foreign
2. Molecular size: Molecule with different size have different
immunogenicity
3. Chemical-structural complexity: A certain amount of
chemical complexity is required
4. Antigenic determinants (epitopes): Epitopes are small
chemical groups on the antigen molecule that can elicit
and react with antibody. An antigen can have one or more
determinants (epitopes). Most antigens have many
determinants; i.e., they are multivalent
5. Dosage, route, and timing of antigen administration
6. Adjuvants: Enhance the immune response to an
immunogen

4. Cellular Basis of the Immune Response
Origin of immune cells
• The capability of responding to immunologic
stimuli rests mainly with lymphoid cells
• During embryonic development, blood cell
precursors originate mainly in the fetal liver and
yolk sac; in postnatal life, the stem cells reside in
the bone marrow
• Stem cells differentiate into cells of the erythroid,
myeloid, or lymphoid series
• Lymphoid series evolve into two main
lymphocyte populations: T cells and B cells

5. Origin of T and B cells
• Stem cells in the bone marrow (or fetal liver) are the
precursors of both T and B lymphocytes
• Stem cells differentiate into T cells in the thymus,
whereas they differentiate into B cells in the bone
marrow
• Within the thymus, T cells become either CD4-
• positive (helper) cells or CD8-positive (cytotoxic) cells
• B cells can differentiate into plasma cells that produce
large amounts of antibodies (immunoglobulins)
• T-cell precursors differentiate into immunocompetent
T cells within the thymus

6. Origin of T and B cells
• Stem cells lack antigen receptors and lack CD3,
CD4, and CD8 proteins on their surface
• During passage through the thymus they
differentiate into T cells that can express both
antigen receptors and the various CD proteins
• The stem cells, which initially express neither CD4
nor CD8 (double-negatives), first differentiate to
express both CD4 and CD8 (double-positives) and
then proceed to express either CD4 or CD8

7. Thymus education
1. CD4-positive, CD8-positive cells bearing antigen receptors
for "self" proteins are killed (clonal deletion) by a process
of "programmed cell death" called Apoptosis. The
removal of these self-reactive cells, a process called
negative selection, results in tolerance to our own
proteins, i.e., self-tolerance, and prevents autoimmune
reactions
2. CD4-positive, CD8-positive cells bearing antigen receptors
that do not react with self MHC protein are also killed.
This results in a positive selection for T cells that react
well with self MHC proteins
• During their passage through the thymus, each double-
positive T cell synthesizes a different, highly specific antigen
receptor called the T-cell receptor (TCR)

9. Origin of T and B cells
• B-cell precursors differentiate into
immunocompetent B cells in the bone marrow
• B cells also undergo clonal deletion of those
cells bearing antigen receptors for self
proteins, a process that induces tolerance and
reduces the occurrence of autoimmune
diseases
• The site of clonal deletion of B cells is
uncertain

11. Natural Killer cell
• Natural killer (NK) cells are large granular lymphocytes that
do not pass through the thymus, do not have an antigen
receptor, and do not bear CD4 or CD8 proteins
• They recognize and kill target cells, such as virus-infected
cells and tumor cells, without the requirement that the
antigens be presented in association with class I or class II
MHC proteins
• NK cells target those cells to be killed by detecting that they
do not display class I MHC proteins on the cell surface
• This detection process is effective because many cells lose
their ability to synthesize class I MHC proteins after they
have been infected by a virus

12. Natural Killer cell
• NK cells play an important role in the innate host defenses
• They are called "natural" killer cells because they are active without
prior exposure to the virus, are not enhanced by exposure, and are
not specific for any virus
• They can kill without antibody, but antibody (IgG) enhances their
effectiveness, a process called antibody-dependent cellular
cytotoxicity (ADCC)
• IL-12 and gamma interferon are potent activators of NK cells
• Approximately 5–10% of peripheral lymphocytes are NK cells
• NK cells detect the presence of cancer cells by recognizing a protein
called MICA that is found on the surface of many cancer cells but
not normal cells
• Interaction of MICA with a receptor on NK cells triggers the
production of cytotoxins by the NK cell and death of the tumor cell

15. Polymorphonuclear neutrophils
• Neutrophils are a very important component of our
innate host defenses, and severe bacterial infections
occur if they are too few in number (neutropenia) or
are deficient in function
• They have cytoplasmic granules
• These granules are lysosomes, which contain a variety
of degradative enzymes that are important in the
bactericidal action of these cells
• The perform phagocytosis
• Neutrophils have receptors for IgG on their surface so
IgG is the only immunoglobulin that opsonizes, i.e.,
makes bacteria more easily phagocytosed

16. Eosinophil
• Eosinophils are white blood cells with cytoplasmic granules
• The function of eosinophils has not been clearly established
• It seems likely that their main function is to defend against the migratory
larvae of nematodes, such as Strongyloide
• They attach to the surface of the larvae and discharge
• the contents of their granules, which in turn damages the cuticle of the
larvae
• Attachment to the larvae is mediated by receptors on the eosinophil
surface for the Fc portion of the heavy chain of IgG and IgE
• Another function of eosinophils may be to mitigate the effects of
immediate hypersensitivity reactions because the granules of eosinophils
contain histaminase, an enzyme that degrades histamine, which is an
important mediator of immediate reactions
• Eosinophils can phagocytose bacteria but they do so weakly and are not
sufficient to protect against pyogenic bacterial infections in neutropenic
patients

17. Basophils & Mast cells
• Basophils are white blood cells with cytoplasmic granules and circulate in
the bloodstream
• Whereas mast cells, which are similar to basophils in many ways, are fixed
in tissue, especially under the skin and in the mucosa of the respiratory
and gastrointestinal tracts
• Basophils and mast cells have receptors on their surface for the Fc portion
of the heavy chain of IgE
• When adjacent IgE molecules are cross-linked by antigen, immunologically
active mediators, such as histamine, and enzymes, such as peroxidases
and hydrolases, are released
• These cause inflammation and, when produced in large amounts, cause
severe immediate hypersensitivity reactions such as systemic
anaphylaxis
• Mast cells also play an important role in the innate response to bacteria
and viruses
• The surface of mast cells contain Toll-like receptors that recognize bacteria
and viruses and respond by releasing cytokines and enzymes from their
granules that mediate inflammation and attract neutrophils and dendritic
cells to the site of infection

18. Antigen-presenting cells
Macrophages:
• Have three main
functions:
1. Phagocytosis
2. Antigen
presentation
3. Cytokine
production

19. Macrophages
• These three functions are greatly enhanced when a process
called macrophage activation occurs
• Macrophages are activated initially by substances such as
bacterial lipopolysaccharide (LPS, endotoxin), by bacterial
peptidoglycan, and by bacterial DNA (Human DNA is
methylated, whereas bacterial DNA is unmethylated and
therefore is perceived as foreign.) These substances
interact with "toll-like receptors" on the macrophage
surface and signal the cell to produce certain cytokines
• Macrophages are also activated by gamma interferon
produced by helper T cells
• Gamma interferon increases the synthesis of class II MHC
proteins, which enhances antigen presentation and
increases the microbicidal activity of macrophages

20. Macrophages
• Macrophages are derived from bone marrow
histiocytes
• Exist both free, e.g., monocytes, and fixed in
tissues, e.g., Kupffer cells of the liver
• Macrophages migrate to the site of
inflammation, attracted by certain mediators,
especially C5a, an anaphylatoxin released in
the complement cascade

21. Dendritic Cells
• Dendritic cells are a third type of cell that function as
"professional" antigen presenting cells (macrophages and B
cells are the other two)
• They express class II MHC proteins and present antigen to
CD4-positive T cells
• They are particularly important because they are the main
inducers of the primary antibody response
• The name "dendritic" describes their many long, narrow
processes (that resemble neuronal dendrites), which make
them very efficient at making contact with foreign material
• Dendritic cells are primarily located under the skin and the
mucosa, e.g., Langerhans' cells in the skin
• Dendritic cells migrate from their peripheral location under
the skin and mucosa to local lymph nodes, where they
present antigen to helper T cells