01/10
Immunology: the study of immune responses.
Function of cells and tissues of the immune system:
● The physiologic function of the immune system is defense against infectious
microbes.
● The immune response can be activated also by mono infectious foreign substances
and products of our own damaged and malignant cells.
● The mechanisms that usually protect from infections and eliminate foreign
substances can themselves cause tissue damage and diseases → autoimmune
diseases. The activation of an immune response in general is a reaction to microbes
and molecules (agents) regardless of the physiologic pathologic consequence of the
reaction. For the functions there are implications.
● Allergy symptoms are due to the activation of the immune system.
● Autoimmune diseases: multifactorial disorders some individuals respond against self
antigens giving rise to autoimmune disorders which are pathologies due to the
activation of the immune system. Results in increased susceptibility to infection.
● Defense against tumors: potential for immunotherapy of cancer.
● Involved in the control of tissue regeneration and repair. Immune cells are mediators
of the repair of damaged tissue.
● The immune system recognizes and responds to tissue grafts and newly introduced
proteins. Immune responses are barriers to transplantation and gene therapy.
The immune system is divided into INNATE IMMUNITY and ADAPTIVE IMMUNITY. Innate
and adaptive immune responses cooperate to eliminate the foreign or infectious agents but
both don’t react against self molecules and tissues.
Innate immune response: essential for defending in the first hours after infection before the
adaptive immune response has developed so it is crucial to give time for the activation of the
adaptive immune system in order to control the spreading of infection. Mediated by
mechanisms that are in place even before an infection to prevent and quickly/immediately
respond to infection or tissue damage. It is non-specific.
- Immediately available, no need for an adaptation phase to the specific pathogen.
- Rapidly contributes with the activation of inflammatory response.
- Does not change or ameliorate in each successive exposure to a foreign agent.
- Remains virtually identical. Can be overwhelmed by high bacterial load.
- Recognizes structures that are common to groups of related molecules.
- DO NOT have MEMORY, therefore they are not capable of eliciting a faster and
- Stronger response when encountering an antigen frequently.
Innate Immune system is constituted by:
1. Physical barriers: cutaneous, mucosal epithelial, secretions such as
tears/saliva/sweat and microbiota.
2. Cellular responses: phagocytes (macrophages, neutrophils and dendritic cells),
natural killer cells and mast cells and the inflammatory response.
3. Blood proteins: including components of the complement system and other
factors involved in the inflammatory reaction.
,Adaptive immune response: stimulated by the exposure to infectious agents. Comes after
the innate immune response. Adaptive immunity is a more specialized mechanism of
defense and is only present in vertebrates.
- Increases in magnitude and defensive capability with each successive exposure to a
microbe.
- Needs to be activated and requires an adaptation phase to the specific pathogen.
- T cells and B cells specifically recognize a large number of microbial and non
microbial substances called antigens.
- They have MEMORY, meaning they can elicit a faster and more powerful response
when encountering an antigen for the second (or more) time.
- Adaptive immune responses expand exponentially after coming into contact with a
foreign agent, generating a population of cells identical to the original one (clonal
expansion).
- The cells of the adaptive immune system do not respond against self (tolerance);
when tolerance is lost, autoimmune diseases develop
Hematopoiesis: All immune cells are produced in the bone marrow. Immune cells are
derived from hematopoietic stem cells (HSCs). HSCs differentiate into lymphoid and myeloid
progenitors that further branch out to the more specific cell types associated with adaptive
and innate immunity.
Innate immune cells: From a common myeloid progenitor (CMPs) derived mast cells and
myeloblasts (as well as red blood cells and megakaryocytes). Mast cells are tissue resident
cells in connective tissues and myeloblast which give rise to monocytes, eosinophils,
basophils and neutrophils (granulocytes E,B,N). Neutrophils have a particular nucleus which
is composed of 2 or 3 lobes (polymorphonuclear cells). Monocytes and neutrophils are
circulating cells and are the most abundant innate immune cells in the blood and are the first
to arrive at a damaged tissue. Macrophages and dendritic cells are not circulating and these
are the cells that are sentinels (residents, ex. microglia of the CNS) in the tissue in order to
quickly respond to an injury. If macrophages are the sentinel response, dendritic cells
resident within the tissue are responsible for the activation of the adaptive immune response.
Innate immune cells and NK cells lack antigen specificity. Macrophages are resident in
almost all tissues and they arise during embryonic development although some arise in the
adult from the bone marrow. They are relatively long-lived cells with different functions such
as phagocytosis and also disposal of pathogens and cells that are targets of the adaptive
immune system and help induce inflammation.
,Adaptive immune cells: derived from a lymphoid progenitor that gives rise to T cells and B
cells. B cells when activated become plasma cells and produce antibodies. T cells can be
CD8 T cells which have cytotoxic activity and can directly recognize and kill targets while
CD4 T cells can recognize the target but can't directly kill the target. CD4 T cells are also
called T helper cells since they cooperate with other cells to eliminate the target. T and B
lymphocytes are distinguished from the other leukocytes by having antigen receptors and
from each other by their sites of differentiation (thymus of T cells and bone marrow for B
cells). After the encounter with an antigen, B cells differentiate into antibody-secreting
plasma cells while T cells (naive) become effector T cells.
Natural killer cells: belong to the lymphoid lineage (derive from the same progenitor as T
cells and B cells) but they are not specific. Natural killer cells can be found resident in
tissues and act as innate immune cells.
All the cellular elements of blood including red blood cells, platelets, and white cells derive
from the hematopoietic stem cells (HSCs) of the bone marrow. Since these cells can give
rise to all the different types of blood cells they are known as pluripotent cells.
Commensal organisms: cause little host damage. Not all microbes are pathogens, many
tissues like the skin, oral mucosa, conjunctiva, and the GI tract are constantly colonized by
microbial communities called the microbiome and cause no damage to the host. They are
called commensal organisms since they can have a symbiotic relationship with the host and
perform functions like aiding cellulose digestion in the stomach of ruminants. Commensal
organisms can’t penetrate the epithelia for example in the GI tract and only stay in the lumen
while pathogens are able to cross this barrier and cause damage.
Pathogens: damage host tissues by a variety of mechanisms. Include viruses, bacteria,
archaea, fungi and parasites.
The innate immune response: involves inflammation, complement system activation,
phagocytosis and destruction of the pathogen while the adaptive immune response is more
complex and has a much later/longer start and duration of response. However, the adaptive
immune system is capable of eliminating infections more efficiently due to specificity.
Phagocytes: macrophages + granulocytes (neutrophils, basophils, eosinophils) +
DCs.
, Local inflammation and phagocytosis of invading bacteria can also be triggered by the
activation of the complement system. Bacterial surfaces can activate the complement
system, inducing a cascade of proteolytic reactions that coat the microbes with fragments of
specific proteins of the complement system.
● Dendritic cells: when they are immature they can take up
pathogens through phagocytosis and when they are mature
they present pathogen antigens to naive T cells to make them
effectors. Immature DCs migrate through the bloodstream from
the bone marrow to enter tissues. They take up particulate
matter by phagocytosis and also continually ingest large
amounts of the extracellular fluid and its content by a process
called macropinocytosis.
● Macrophages: can also present antigens to T cells and activate
them. Macrophages are more long-lived and rely more on
induced gene transcription and protein expression.
● Granulocytes: release their contents during activation of the
adaptive immune response. (E,B,N)
● Eosinophils: involved in attacking large antibody-coated
parasites like worms.
● Basophils: involved in anti-parasite immunity.
● Mast cells: can trigger a local inflammatory response to
antigens by releasing substances that act on local blood
vessels. They begin development in the bone marrow but
migrate as immature precursors that mature in peripheral
tissues, like the skin and intestines. Their granules contain
many inflammatory mediators such as histamine.
● Neutrophils: phagocytosis, mainly use cytoskeletal
rearrangements and enzyme activation to mount rapid, transient
responses (short life-span). In tissues differentiate into
macrophages. Most abundant circulating leukocyte.
Eosinophils and basophils are less abundant than neutrophils but they
still contain granules with a variety of enzymes and toxic proteins which
are released when they are activated.
Macrophages, neutrophils, and DCs are important classes of sensor
cells that detect infection and initiate immune response by producing
inflammatory mediators. These cells express a limited number of
invariant innate recognition receptors as a means of detecting
pathogens or the damage induced by them. Also called pattern
recognition receptors (PRRs), they recognize simple molecules and
regular patterns of molecular structure known as pathogen-associated
molecular patterns (PAMPs) and damage associated molecular
patterns (DAMPs). Some PRRs are transmembrane proteins like
Toll-like receptors (TLRs) that detect PAMPs derived from extracellular
bacteria or phagocytized bacteria. On the other hand, NOD-like
receptors (NLRs) are cytoplasmic proteins that sense intracellular
bacterial invasion.
Immunology: the study of immune responses.
Function of cells and tissues of the immune system:
● The physiologic function of the immune system is defense against infectious
microbes.
● The immune response can be activated also by mono infectious foreign substances
and products of our own damaged and malignant cells.
● The mechanisms that usually protect from infections and eliminate foreign
substances can themselves cause tissue damage and diseases → autoimmune
diseases. The activation of an immune response in general is a reaction to microbes
and molecules (agents) regardless of the physiologic pathologic consequence of the
reaction. For the functions there are implications.
● Allergy symptoms are due to the activation of the immune system.
● Autoimmune diseases: multifactorial disorders some individuals respond against self
antigens giving rise to autoimmune disorders which are pathologies due to the
activation of the immune system. Results in increased susceptibility to infection.
● Defense against tumors: potential for immunotherapy of cancer.
● Involved in the control of tissue regeneration and repair. Immune cells are mediators
of the repair of damaged tissue.
● The immune system recognizes and responds to tissue grafts and newly introduced
proteins. Immune responses are barriers to transplantation and gene therapy.
The immune system is divided into INNATE IMMUNITY and ADAPTIVE IMMUNITY. Innate
and adaptive immune responses cooperate to eliminate the foreign or infectious agents but
both don’t react against self molecules and tissues.
Innate immune response: essential for defending in the first hours after infection before the
adaptive immune response has developed so it is crucial to give time for the activation of the
adaptive immune system in order to control the spreading of infection. Mediated by
mechanisms that are in place even before an infection to prevent and quickly/immediately
respond to infection or tissue damage. It is non-specific.
- Immediately available, no need for an adaptation phase to the specific pathogen.
- Rapidly contributes with the activation of inflammatory response.
- Does not change or ameliorate in each successive exposure to a foreign agent.
- Remains virtually identical. Can be overwhelmed by high bacterial load.
- Recognizes structures that are common to groups of related molecules.
- DO NOT have MEMORY, therefore they are not capable of eliciting a faster and
- Stronger response when encountering an antigen frequently.
Innate Immune system is constituted by:
1. Physical barriers: cutaneous, mucosal epithelial, secretions such as
tears/saliva/sweat and microbiota.
2. Cellular responses: phagocytes (macrophages, neutrophils and dendritic cells),
natural killer cells and mast cells and the inflammatory response.
3. Blood proteins: including components of the complement system and other
factors involved in the inflammatory reaction.
,Adaptive immune response: stimulated by the exposure to infectious agents. Comes after
the innate immune response. Adaptive immunity is a more specialized mechanism of
defense and is only present in vertebrates.
- Increases in magnitude and defensive capability with each successive exposure to a
microbe.
- Needs to be activated and requires an adaptation phase to the specific pathogen.
- T cells and B cells specifically recognize a large number of microbial and non
microbial substances called antigens.
- They have MEMORY, meaning they can elicit a faster and more powerful response
when encountering an antigen for the second (or more) time.
- Adaptive immune responses expand exponentially after coming into contact with a
foreign agent, generating a population of cells identical to the original one (clonal
expansion).
- The cells of the adaptive immune system do not respond against self (tolerance);
when tolerance is lost, autoimmune diseases develop
Hematopoiesis: All immune cells are produced in the bone marrow. Immune cells are
derived from hematopoietic stem cells (HSCs). HSCs differentiate into lymphoid and myeloid
progenitors that further branch out to the more specific cell types associated with adaptive
and innate immunity.
Innate immune cells: From a common myeloid progenitor (CMPs) derived mast cells and
myeloblasts (as well as red blood cells and megakaryocytes). Mast cells are tissue resident
cells in connective tissues and myeloblast which give rise to monocytes, eosinophils,
basophils and neutrophils (granulocytes E,B,N). Neutrophils have a particular nucleus which
is composed of 2 or 3 lobes (polymorphonuclear cells). Monocytes and neutrophils are
circulating cells and are the most abundant innate immune cells in the blood and are the first
to arrive at a damaged tissue. Macrophages and dendritic cells are not circulating and these
are the cells that are sentinels (residents, ex. microglia of the CNS) in the tissue in order to
quickly respond to an injury. If macrophages are the sentinel response, dendritic cells
resident within the tissue are responsible for the activation of the adaptive immune response.
Innate immune cells and NK cells lack antigen specificity. Macrophages are resident in
almost all tissues and they arise during embryonic development although some arise in the
adult from the bone marrow. They are relatively long-lived cells with different functions such
as phagocytosis and also disposal of pathogens and cells that are targets of the adaptive
immune system and help induce inflammation.
,Adaptive immune cells: derived from a lymphoid progenitor that gives rise to T cells and B
cells. B cells when activated become plasma cells and produce antibodies. T cells can be
CD8 T cells which have cytotoxic activity and can directly recognize and kill targets while
CD4 T cells can recognize the target but can't directly kill the target. CD4 T cells are also
called T helper cells since they cooperate with other cells to eliminate the target. T and B
lymphocytes are distinguished from the other leukocytes by having antigen receptors and
from each other by their sites of differentiation (thymus of T cells and bone marrow for B
cells). After the encounter with an antigen, B cells differentiate into antibody-secreting
plasma cells while T cells (naive) become effector T cells.
Natural killer cells: belong to the lymphoid lineage (derive from the same progenitor as T
cells and B cells) but they are not specific. Natural killer cells can be found resident in
tissues and act as innate immune cells.
All the cellular elements of blood including red blood cells, platelets, and white cells derive
from the hematopoietic stem cells (HSCs) of the bone marrow. Since these cells can give
rise to all the different types of blood cells they are known as pluripotent cells.
Commensal organisms: cause little host damage. Not all microbes are pathogens, many
tissues like the skin, oral mucosa, conjunctiva, and the GI tract are constantly colonized by
microbial communities called the microbiome and cause no damage to the host. They are
called commensal organisms since they can have a symbiotic relationship with the host and
perform functions like aiding cellulose digestion in the stomach of ruminants. Commensal
organisms can’t penetrate the epithelia for example in the GI tract and only stay in the lumen
while pathogens are able to cross this barrier and cause damage.
Pathogens: damage host tissues by a variety of mechanisms. Include viruses, bacteria,
archaea, fungi and parasites.
The innate immune response: involves inflammation, complement system activation,
phagocytosis and destruction of the pathogen while the adaptive immune response is more
complex and has a much later/longer start and duration of response. However, the adaptive
immune system is capable of eliminating infections more efficiently due to specificity.
Phagocytes: macrophages + granulocytes (neutrophils, basophils, eosinophils) +
DCs.
, Local inflammation and phagocytosis of invading bacteria can also be triggered by the
activation of the complement system. Bacterial surfaces can activate the complement
system, inducing a cascade of proteolytic reactions that coat the microbes with fragments of
specific proteins of the complement system.
● Dendritic cells: when they are immature they can take up
pathogens through phagocytosis and when they are mature
they present pathogen antigens to naive T cells to make them
effectors. Immature DCs migrate through the bloodstream from
the bone marrow to enter tissues. They take up particulate
matter by phagocytosis and also continually ingest large
amounts of the extracellular fluid and its content by a process
called macropinocytosis.
● Macrophages: can also present antigens to T cells and activate
them. Macrophages are more long-lived and rely more on
induced gene transcription and protein expression.
● Granulocytes: release their contents during activation of the
adaptive immune response. (E,B,N)
● Eosinophils: involved in attacking large antibody-coated
parasites like worms.
● Basophils: involved in anti-parasite immunity.
● Mast cells: can trigger a local inflammatory response to
antigens by releasing substances that act on local blood
vessels. They begin development in the bone marrow but
migrate as immature precursors that mature in peripheral
tissues, like the skin and intestines. Their granules contain
many inflammatory mediators such as histamine.
● Neutrophils: phagocytosis, mainly use cytoskeletal
rearrangements and enzyme activation to mount rapid, transient
responses (short life-span). In tissues differentiate into
macrophages. Most abundant circulating leukocyte.
Eosinophils and basophils are less abundant than neutrophils but they
still contain granules with a variety of enzymes and toxic proteins which
are released when they are activated.
Macrophages, neutrophils, and DCs are important classes of sensor
cells that detect infection and initiate immune response by producing
inflammatory mediators. These cells express a limited number of
invariant innate recognition receptors as a means of detecting
pathogens or the damage induced by them. Also called pattern
recognition receptors (PRRs), they recognize simple molecules and
regular patterns of molecular structure known as pathogen-associated
molecular patterns (PAMPs) and damage associated molecular
patterns (DAMPs). Some PRRs are transmembrane proteins like
Toll-like receptors (TLRs) that detect PAMPs derived from extracellular
bacteria or phagocytized bacteria. On the other hand, NOD-like
receptors (NLRs) are cytoplasmic proteins that sense intracellular
bacterial invasion.
