Leerdoelen Immunologie
1. Describe the principles, function, similarities and differences between the specific
and non-specific immune systems
The specific immune system (adaptive) develops after exposure to or immunization with a given
substance or antigen. The cells responsible for the immune response are the B and T cells which
express somatically generated antigen-specific receptors. The so called BCR and TCR (B and T cell
receptor, respectively) are translational products of multiple genes that are pieced together by gene
rearrangements.
➢ Differentiates between self and nonself → usually only a immune response against foreign
material.
➢ Memory → Recognizes previously met molecules and is able to have a faster and better
immune response (the second time).
➢ Humoral immunity: B cells that secrete antibody (IgG, IgM, IgA, IgE and IgD) into the
bloodstream.
➢ Cell-mediated immunity or cellular immunity: T subcells and cytokines
- T cells recognize and bind to antigen peptides that are being presented to them by APCs
(antigen presenting cells) such as macrophages and dendritic cells.
- These APCs display processed MHC (major histocompatibility complex I and II) bound
peptides derived from antigen.
• MHC I + CD8 cytotoxic T cell
• MHC II + CD4 helper T cell
- Two signals are required to activate T cells, 1: T-cell expression of peptide(epiptope)-
specific TCRs and 2: ligation of T-cell expressed co-stimulatory molecules with
complementary membrane molecules expressed by APCs.
- T cell activation facilitates the activation and differentiation of B cells responding to
antigen by T-cell-derived cytokines that bind to specific cytokine receptors on B cells.
Functional consequences include B-cell proliferation, generation of memory B cells and
diversification of the kinds of immunoglobulins produced (class switching).
➢ Lymphatic system includes organs in which lymphocyte maturation, differentiation and
proliferation take place,
- 1) primary (In which the maturation of B and T lymphocytes into antigen-recognizing
lymphocytes occurs, so where the gene rearrangement takes place to create functional
and different BCRs and TCRs. T cells only partially differentiate within the bone marrow,
precursor T cells undergo final maturation within the thymus gland.)
• Thymus and bone marrow
- 2) secondary organs (The mature B and T cells migrate through the bloodstream and
lymphatic system to the peripheral lymphoid tissues, including lymph nodes and spleen.
This is where antigen-driven activation of B and T cells takes place.)
• Spleen, lymph nodes, appendix, Peyer’s patches
➢ The migration of lymphocytes between various lymphoid and nonlymphoid tissue and their
homing to a particular site is highly regulated by means of various cell-surface adhesion
molecules (CAM) and receptors to these molecules.
➢ Blood lymphocytes must generally cross the endothelial vascular lining of postcapillary
vascular sites, termed high endothelial venules (HEVs) to enter tissues = extravasation.
➢ The reticuloendothelial system (RES) is designed to trap foreign antigens that have
penetrated the body and to subject them to ingestion and degradation by the phagocytic
cells of the system. Three major routes may be followed by an antigen after it has penetrated
the interior of the body: (1) Antigens may enter the body through the bloodstream, through
the circulatory system to the spleen where they interact with APCs such as macrophages and
dendritic cells. These cells take up, process and then present components of the antigen to
, the T cells that express the appropriate antigen-specific TCR. Splenic B cells expressing
antigen-specific BCRs are also activated following exposure to antigen, a process facilitated
by the cytokines produced by antigen-activated T cells. (2) Antigens may lodge in the
epidermal, dermal or subcutaneous tissues to stimulate inflammatory responses. From these
tissues, the antigen, either free or trapped by APCs, is transported through the afferent
lymphatic channels into the regional draining lymph node. Eventually antigen-specific T cells
and antibodies, which have been synthesized in the lymph node, enter the circulation (also
via the thoracic duct) and are transported to the various tissues. (3) Antigens may enter the
gastrointestinal or respiratory tract, where it lodges in the MALT (mucosa-associated
lymphoid tissue) and BALT (bronchus-associated lymphoid tissue), respectively. There it will
interact with the macrophages and lymphocytes, antibodies synthesized in these organs are
deposited in local tissue. In addition, lymphocytes entering the efferent lymphatics are
carried through the thoracic duct to the circulation and are thereby redistributed to various
tissue.
➢ Clonal selection theory
- Self-antigen-binding lymphocytes are eliminated after being produced.
- B-cell clones, leading to the synthesis of antibodies having the same specificity. The
antigen stimulating the response is complex and contains many different epitopes, each
capable of activating a clone of epitope-specific B cells. Collectively, the clonally secreted
antibodies constitute → a polyclonal antiserum capable of interacting with multiple
epitopes expressed by an antigen.
- T cells will be activated to divide and produce clones of the same specificity, which will
synthesize and release various cytokines. Subsequent exposure to the same antigen will
results in the activation of clones of that specificity. The cytokines are soluble mediators,
exert their effect on other cells to grow or become activated facilitating elimination of
the antigen.
The nonspecific immune system (innate) is the primordial immune defense system that is present
rom birth. The major role is to provide a rapid, first line of defense against pathogens.
➢ Physical and chemical barriers. Most organisms and foreign substances cannot penetrate
intact skin. Some microorganisms can enter through sebaceous glands and hair follicles,
however the acid pH of sweat and sebaceous secretions and the presence of various fatty
acids and hydrolytic enzymes (lysozymes) all have some antimicrobial effects. In addition,
some soluble proteins, including the interferons (made by cells in response to viral infection)
and certain members of the complement system (controlled enzymatic cascade, which
targets the membrane and leads to their destruction) found in serum, contribute. The
respiratory and gastrointestinal tracts are covered with mucous which traps the
microorganisms and are swept away by ciliated epithelial cells toward the external openings.
The hairs in the nostrils and the cough reflex are also helpful in preventing organisms from
infecting the respiratory tract. The elimination of microorganisms from the respiratory tract
is aided by pulmonary or alveolar macrophages, which, as we shall see later, are phagocytic
cells able to engulf and destroy some microorganisms. Within the central nervous system
these phagocytic cells are called microglial cells. Other mechanisms include the hydrolytic
enzymes in saliva, the low pH of the stomach, and the proteolytic enzymes and bile in the
small intestine. The low pH of the vagina serves a similar function.
➢ Cells of the innate immune system derive from myeloid precursors whereas cells associated
with the adaptive immune system derive from the lymphoid precursors. These myeloid and
lymphoid precursors derive from their common hematopoietic ancestor the pluripotent
stem cell.
➢ Next line of defense: Polymorphonuclear (PMN) leukocytes (eosinophils, basophils and
neutrophils, mast cells), monocytes and macrophages.
, - PMN leukocytes are a population of cells also referred to as granulocytes. They contain
enzyme-rich lysosomes which facilitate destruction of infectious miroorganisms. They
also produce peroxide, superoxide radicals and nitric oxide which are toxic. Some
lysosomes contain bacterial proteins like lactoferrin.
• Neutrophil: Phagocytosis and activation of bactericidal mechanisms.
• Eosinophil: Killing of antibody-coated parasites.
• Basophil: Promotion of allergic responses and augmentation of anti-parasitic
immunity.
• Mast cell: Release of granules containing histamine and active agents.
- Macrophages are phagocytes derived from blood monocytes. The latter undergoes
further differentiation following their migration from the blood to various tissue:
• Kupffer cells: in the liver, large cells with many cytoplasmic projections
• Alveolar macrophages: in the lung
• Splenic macrophages: in the red pulp
• Peritoneal macrophages: free-floating in peritoneal fluid
• Microglial cells: in the central nervous system
Each of these macrophage populations constitutes part of the cellular members of the
reticuloendothelial system (RES), the main function is to phagocytize microorganisms
and foreign substances. It also functions in the destruction of aged and imperfect cells,
such as erythrocytes. (1) They engulf and with the aid of degradative enzymes in their
lysosomal granules, break down trapped materials into simple amino acids, sugars and
other substances for excretion or reuse. (2) They take up antigens, process them by
denaturation or partial digestion and present them on their surfaces.
- Dendritic cells (DCs) trigger adaptive immune responses by T cells due to their efficient
APC properties.
• Recognize and phagocytize pathogens
• Migrating dendritic cells in blood
• Nonmigrating in primary and secondary follicles of the B cell areas of lymph
nodes and the spleen → follicular dendritic cells (fDCs)
• Interdigitating cells of the thymus
• Langerhans cells in the skin
• Plasmacystoid DC (pDC) differ in the fact that theyre derived from lymphoid
precursors and their ability to produce large amounts alpha/beta inferferons
(IFN-α/β) in response to viral and bacterial stimuli.
- Natural killer (NK) cells recognize altered features of the membranes of abnormal cells
(virus-infected and cancer cells).
• Role in early viral infection or tumorgenesis before cytotoxic T lymphocytes are
generated.
• Lack antigen-specific receptors.
• Using cell-cell contact to determine whether the cell has lost a particular self-
antigen, MHC I which is expressed on nucleated cells. The killer-cell inhibitory
receptors (KIR) bind to MHC I molecules and so inhibit downstream events of the
NK cells that would otherwise cause degradation and destruction of the cell.
Virus-infected or transformed (tumor) cells have a reduced number of MHC I,
thus when encountered by NK cells fail to engage KIRs and therefore become
susceptible to NK cell-mediated cytotoxicity.
• Intracellular granules containing preformed biologically potent molecules →
released when in contact with target cells without prior stimulation.
o Forming pores in the membranes of target cells leading to lysis.
o Entering the target cell causing apoptosis by enhanced fragmentation of
its nuclear DNA.
1. Describe the principles, function, similarities and differences between the specific
and non-specific immune systems
The specific immune system (adaptive) develops after exposure to or immunization with a given
substance or antigen. The cells responsible for the immune response are the B and T cells which
express somatically generated antigen-specific receptors. The so called BCR and TCR (B and T cell
receptor, respectively) are translational products of multiple genes that are pieced together by gene
rearrangements.
➢ Differentiates between self and nonself → usually only a immune response against foreign
material.
➢ Memory → Recognizes previously met molecules and is able to have a faster and better
immune response (the second time).
➢ Humoral immunity: B cells that secrete antibody (IgG, IgM, IgA, IgE and IgD) into the
bloodstream.
➢ Cell-mediated immunity or cellular immunity: T subcells and cytokines
- T cells recognize and bind to antigen peptides that are being presented to them by APCs
(antigen presenting cells) such as macrophages and dendritic cells.
- These APCs display processed MHC (major histocompatibility complex I and II) bound
peptides derived from antigen.
• MHC I + CD8 cytotoxic T cell
• MHC II + CD4 helper T cell
- Two signals are required to activate T cells, 1: T-cell expression of peptide(epiptope)-
specific TCRs and 2: ligation of T-cell expressed co-stimulatory molecules with
complementary membrane molecules expressed by APCs.
- T cell activation facilitates the activation and differentiation of B cells responding to
antigen by T-cell-derived cytokines that bind to specific cytokine receptors on B cells.
Functional consequences include B-cell proliferation, generation of memory B cells and
diversification of the kinds of immunoglobulins produced (class switching).
➢ Lymphatic system includes organs in which lymphocyte maturation, differentiation and
proliferation take place,
- 1) primary (In which the maturation of B and T lymphocytes into antigen-recognizing
lymphocytes occurs, so where the gene rearrangement takes place to create functional
and different BCRs and TCRs. T cells only partially differentiate within the bone marrow,
precursor T cells undergo final maturation within the thymus gland.)
• Thymus and bone marrow
- 2) secondary organs (The mature B and T cells migrate through the bloodstream and
lymphatic system to the peripheral lymphoid tissues, including lymph nodes and spleen.
This is where antigen-driven activation of B and T cells takes place.)
• Spleen, lymph nodes, appendix, Peyer’s patches
➢ The migration of lymphocytes between various lymphoid and nonlymphoid tissue and their
homing to a particular site is highly regulated by means of various cell-surface adhesion
molecules (CAM) and receptors to these molecules.
➢ Blood lymphocytes must generally cross the endothelial vascular lining of postcapillary
vascular sites, termed high endothelial venules (HEVs) to enter tissues = extravasation.
➢ The reticuloendothelial system (RES) is designed to trap foreign antigens that have
penetrated the body and to subject them to ingestion and degradation by the phagocytic
cells of the system. Three major routes may be followed by an antigen after it has penetrated
the interior of the body: (1) Antigens may enter the body through the bloodstream, through
the circulatory system to the spleen where they interact with APCs such as macrophages and
dendritic cells. These cells take up, process and then present components of the antigen to
, the T cells that express the appropriate antigen-specific TCR. Splenic B cells expressing
antigen-specific BCRs are also activated following exposure to antigen, a process facilitated
by the cytokines produced by antigen-activated T cells. (2) Antigens may lodge in the
epidermal, dermal or subcutaneous tissues to stimulate inflammatory responses. From these
tissues, the antigen, either free or trapped by APCs, is transported through the afferent
lymphatic channels into the regional draining lymph node. Eventually antigen-specific T cells
and antibodies, which have been synthesized in the lymph node, enter the circulation (also
via the thoracic duct) and are transported to the various tissues. (3) Antigens may enter the
gastrointestinal or respiratory tract, where it lodges in the MALT (mucosa-associated
lymphoid tissue) and BALT (bronchus-associated lymphoid tissue), respectively. There it will
interact with the macrophages and lymphocytes, antibodies synthesized in these organs are
deposited in local tissue. In addition, lymphocytes entering the efferent lymphatics are
carried through the thoracic duct to the circulation and are thereby redistributed to various
tissue.
➢ Clonal selection theory
- Self-antigen-binding lymphocytes are eliminated after being produced.
- B-cell clones, leading to the synthesis of antibodies having the same specificity. The
antigen stimulating the response is complex and contains many different epitopes, each
capable of activating a clone of epitope-specific B cells. Collectively, the clonally secreted
antibodies constitute → a polyclonal antiserum capable of interacting with multiple
epitopes expressed by an antigen.
- T cells will be activated to divide and produce clones of the same specificity, which will
synthesize and release various cytokines. Subsequent exposure to the same antigen will
results in the activation of clones of that specificity. The cytokines are soluble mediators,
exert their effect on other cells to grow or become activated facilitating elimination of
the antigen.
The nonspecific immune system (innate) is the primordial immune defense system that is present
rom birth. The major role is to provide a rapid, first line of defense against pathogens.
➢ Physical and chemical barriers. Most organisms and foreign substances cannot penetrate
intact skin. Some microorganisms can enter through sebaceous glands and hair follicles,
however the acid pH of sweat and sebaceous secretions and the presence of various fatty
acids and hydrolytic enzymes (lysozymes) all have some antimicrobial effects. In addition,
some soluble proteins, including the interferons (made by cells in response to viral infection)
and certain members of the complement system (controlled enzymatic cascade, which
targets the membrane and leads to their destruction) found in serum, contribute. The
respiratory and gastrointestinal tracts are covered with mucous which traps the
microorganisms and are swept away by ciliated epithelial cells toward the external openings.
The hairs in the nostrils and the cough reflex are also helpful in preventing organisms from
infecting the respiratory tract. The elimination of microorganisms from the respiratory tract
is aided by pulmonary or alveolar macrophages, which, as we shall see later, are phagocytic
cells able to engulf and destroy some microorganisms. Within the central nervous system
these phagocytic cells are called microglial cells. Other mechanisms include the hydrolytic
enzymes in saliva, the low pH of the stomach, and the proteolytic enzymes and bile in the
small intestine. The low pH of the vagina serves a similar function.
➢ Cells of the innate immune system derive from myeloid precursors whereas cells associated
with the adaptive immune system derive from the lymphoid precursors. These myeloid and
lymphoid precursors derive from their common hematopoietic ancestor the pluripotent
stem cell.
➢ Next line of defense: Polymorphonuclear (PMN) leukocytes (eosinophils, basophils and
neutrophils, mast cells), monocytes and macrophages.
, - PMN leukocytes are a population of cells also referred to as granulocytes. They contain
enzyme-rich lysosomes which facilitate destruction of infectious miroorganisms. They
also produce peroxide, superoxide radicals and nitric oxide which are toxic. Some
lysosomes contain bacterial proteins like lactoferrin.
• Neutrophil: Phagocytosis and activation of bactericidal mechanisms.
• Eosinophil: Killing of antibody-coated parasites.
• Basophil: Promotion of allergic responses and augmentation of anti-parasitic
immunity.
• Mast cell: Release of granules containing histamine and active agents.
- Macrophages are phagocytes derived from blood monocytes. The latter undergoes
further differentiation following their migration from the blood to various tissue:
• Kupffer cells: in the liver, large cells with many cytoplasmic projections
• Alveolar macrophages: in the lung
• Splenic macrophages: in the red pulp
• Peritoneal macrophages: free-floating in peritoneal fluid
• Microglial cells: in the central nervous system
Each of these macrophage populations constitutes part of the cellular members of the
reticuloendothelial system (RES), the main function is to phagocytize microorganisms
and foreign substances. It also functions in the destruction of aged and imperfect cells,
such as erythrocytes. (1) They engulf and with the aid of degradative enzymes in their
lysosomal granules, break down trapped materials into simple amino acids, sugars and
other substances for excretion or reuse. (2) They take up antigens, process them by
denaturation or partial digestion and present them on their surfaces.
- Dendritic cells (DCs) trigger adaptive immune responses by T cells due to their efficient
APC properties.
• Recognize and phagocytize pathogens
• Migrating dendritic cells in blood
• Nonmigrating in primary and secondary follicles of the B cell areas of lymph
nodes and the spleen → follicular dendritic cells (fDCs)
• Interdigitating cells of the thymus
• Langerhans cells in the skin
• Plasmacystoid DC (pDC) differ in the fact that theyre derived from lymphoid
precursors and their ability to produce large amounts alpha/beta inferferons
(IFN-α/β) in response to viral and bacterial stimuli.
- Natural killer (NK) cells recognize altered features of the membranes of abnormal cells
(virus-infected and cancer cells).
• Role in early viral infection or tumorgenesis before cytotoxic T lymphocytes are
generated.
• Lack antigen-specific receptors.
• Using cell-cell contact to determine whether the cell has lost a particular self-
antigen, MHC I which is expressed on nucleated cells. The killer-cell inhibitory
receptors (KIR) bind to MHC I molecules and so inhibit downstream events of the
NK cells that would otherwise cause degradation and destruction of the cell.
Virus-infected or transformed (tumor) cells have a reduced number of MHC I,
thus when encountered by NK cells fail to engage KIRs and therefore become
susceptible to NK cell-mediated cytotoxicity.
• Intracellular granules containing preformed biologically potent molecules →
released when in contact with target cells without prior stimulation.
o Forming pores in the membranes of target cells leading to lysis.
o Entering the target cell causing apoptosis by enhanced fragmentation of
its nuclear DNA.
