Molecular Immunology

Sry Suryani W
Biochemistry Department
2019
 Immune System
• Physiologic function : defense against
microbes infections.
• Vaccination.
• Defense against microbes is mediated by :
– Innate immunity ( natural or native immunity--
early reactions)
– Adaptive immunity ( late response)
• Principals component of innate immunity :
– Physical and chemical barriers ( epithelial barriers)
– Phagocytic cells ( neutrophils and macrophages)
– NK cells
– Cytokines ( complement)
• Adaptive immunity ( spesific immunity)
– Lymphocytes and their products :
• B lymphocytes---- antibodies ( humoral immunity)
• T lymphocytes----- Effector T cells ( cellular immunity)
Active immunity : immunity induced by
exposure to a foreign antigen is called active
immunity.
Naive : individuals and lymphocytes that have
not encountered a particular antigen.
Passive immunity
 Cellular components of the adaptive immune
system
• Lymphocytes
– B lymphocytes : the only cells that capable producing
antibodies.
– T lymphocyes : recognize the antigens of intracellular microbes
and destroy, do not produce antibody molecules. They
recognize only peptide antigen attached to host proteins that
are encoded by genes in the major histocompatibility complex
( MHC), expressed on the surfaces of other cells.
• Helper T cells
• Cytolytic ( cytotoxic T Lymphocytes / CTLs)
• Regulatory T cells ( function mainly to inhibit immune
response)
– NK cells --- involved in innate immunity.
• Phagocytes and lymphocytes are key
mediators of immunity.
• Phagocytes internalize pathogens and
degrade them.
• Lymphocytes (B and T cells) have receptors
that recognize specific molecular components
of pathogens and have specialized functions.
• B cells make antibodies (effective against
extracellular pathogens)
• cytotoxic T lymphocytes (CTLs) kill virally
infected cells
• helper T cells coordinate the immune
response by direct cell–cell interactions and
the release of cytokines.
Cells and soluble mediators of the immune system
• B cells and T cells are responsible for the
specific recognition of antigens.
• B cells express specific antigen receptors
(immunoglobulin molecules) on their cell
surface during their development and, when
mature, secrete soluble immunoglobulin
molecules (also known as antibodies) into the
extracellular fluids.
• If a B cell binds to its specific antigen, it will
multiply and differentiate into plasma cells,
which produce large amounts of the antibody,
but in a secreted form.
• Antibodies are an essential component of an
immune response, and, when bound to their
cognate antigens, they help phagocytes to
take up antigens, a process called
opsonization (from the Latin, opsono, ‘to
prepare victuals for’).
• There are several different types of T cell :
– TH1 cells : interacts with mononuclear phagocytes
and helps them destroy intracellular pathogens
– TH2 : interacts with B cells and helps them to
divide, differentiate, and make antibody.
– cytotoxic T lymphocytes (CTLs) : responsible for
the destruction of host cells that have become
infected by viruses or other intracellular
pathogens.
– regulatory T cells or Tregs, help to control the
development of immune responses, and limit
reactions against self tissues.

– T cell antigen receptor (TCR) T cells recognize

antigens present on the surface of other cells.

– T cells generate their effects either by releasing

soluble proteins, called cytokines, which signal to
other cells, or by direct cell–cell interaction
 Soluble mediators of immunity
• A wide variety of molecules are involved in the
development of immune responses, including
antibodies, opsonins and complement system
molecules.
• The serum concentration of a number of these
proteins increases rapidly during infection and
they are therefore called acute phase proteins.
– C reactive protein (CRP)
• Complement proteins mediate phagocytosis,
control inflammation and interact with
antibodies in immune defense.
• The complement system, a key component of
innate immunity,is a group of about 20 serum
proteins whose overall function is the control
of inflammation.
• Cytokines signal between lymphocytes,
phagocytes and other cells of the body.
• Cytokine is the general term for a large group
of secreted molecules involved in signaling
between cells during immune responses.
• All cytokines are proteins or glycoproteins.
• Interferons (IFNs) are cytokines that are
particularly important in limiting the spread of
certain viral infections.
• one group of interferons (IFNα and IFNβ or
type-1 interferons) is produced by cells that
have become infected by a virus;
• another type, IFN gamma, is released by
activated TH1 cells.
• The interleukins (ILs) are a large group of
cytokines produced mainly by T cells, though
some are also produced by mononuclear
phagocytes or by tissue cells.
• Many interleukins cause other cells to divide
and differentiate
• Colony stimulating factors (CSFs) are cytokines
primarily involved in directing the division and
differentiation of bone marrow stem cells, and
the precursors of blood leukocytes.
• Chemokines are a large group of chemotactic
cytokines that direct the movement of
leukocytes around the body.
• Tumor necrosis factors, TNFa and TNFb, have
a variety of functions, but are particularly
important in mediating inflammation and
cytotoxic reactions.
• Transforming growth factors (e.g. TGFb) are
important in controlling cell division and
tissue repair
• a cell infected with a virus will present fragments of
viral proteins (peptides) on its surface that are
recognizable by T cells.
• The antigenic peptides are transported to the cell
surface and presented to the T cells by MHC
molecules (a group of molecules encoded with the
Major Histocompatibility Complex)
• T cells use their antigen-specific receptors (T cell
receptors – TCRs) to recognize the antigenic peptide–
MHC molecule complex.
• T cell responses require proper presentation of
antigen by MHC molecules (antigen presentation).
• To activate T cell responses this must occur on the
surface of specialized antigen-presenting cells (APCs),
which internalize antigens by phagocytosis or
endocytosis.
• Several different types of leukocyte can act as APCs,
including dendritic cells, macrophages, and B cells.
• APCs not only display antigenic peptide–MHC
complexes on their surface, but also express
co-stimulatory molecules that are essential for
initiating immune responses.
• The two major phases of any immune
response are antigen recognition and a
reaction to eradicate the antigen.
 Major Histocompatibility Complex

• MHC antigens have been divided into two

classes.
• The Class I MHC antigens, also termed the
classic histocompatibility antigens
• include the HLA – A; HLA – B; HLA – C series.
• The Class II MHC antigens, analogous to the
Ia antigens in the mouse include the HLA
• – DR; HLA – DQ; HLA– DP antigens.
• MHC Class I molecules are constitutively
expressed on virtually all nucleated cells,
whereas class II molecules are expressed only
on dendritic cells, B lymphocytes, macrophages
• The effector function of class I–restricted CD8+
CTLs is to kill cells infected with intracellular
microbes, such as viruses, as well as tumors
that express tumor antigens.
• class II–restricted CD4+ helper T lymphocytes
have a set of functions that require
recognizing antigen presented by a more
limited number of cell types.
• In particular, naive CD4+ T cells need to
recognize antigens that are captured and
presented by dendritic cells in lymphoid
organs.
• Differentiated CD4+ helper T lymphocytes
function mainly to activate (or help)
macrophages to eliminate extracellular
microbes that have been phagocytosed and to
activate B lymphocytes to make antibodies
that also eliminate extracellular microbes.
• Immune receptor and signal transducer
• Inflammation : reponse to tissue damage.
• Three principal changes occur in the tissue
• during an acute inflammatory response?
– increased blood supply to the affected area,
– increase in capillary permeability allowing larger
serum molecules to enter the tissue
– increase in leukocyte migration into the tissue.
• sites of acute inflammation tend to have
higher numbers of neutrophils and activated
helper T cells
• sites of chronic inflammation have a higher
proportion of macrophages, cytotoxic T cells,
and even B cells.
• References
• Cellular and molecular Immunology . Abul K.
Abbas 7th ed
• Immunology. 8ed David Male. Elsevier