Cases immune responses in health and disease
Case 1: Neutrophils and macrophages in infection, inflammation and disease
1. What is the origin of immune cells in humans (focus on innate immune system)?
These cells are almost all derived from hematopoietic stem cells (HSCs) in the
bone marrow of flat bones (ribs, sternum, iliac and vertebrate) which
differentiate along branching lineages.
, Based on their common precursors, immune cells are broadly classified as
either myeloid cells (innate) , which include phagocytes and most DCs,
or lymphoid cells (adaptive) , which include all lymphocytes.
Cytokine induce certain conversions
White blood cells formation = leukopoiesis
• This is stimulated by chemical messengers: interleukins and colony-
stimulating factors (CSF) which are released by the mature WBC and
supporting cells of the red bone marrow. These factors also improve
the protective potency of mature leukocytes.
Hematopoietic stem cells divide into myeloid stem cells and lymphoid stem
cells.
• Myeloid stem cells produce eosinophils, basophils and neutrophils
• Lymphoid stem cells produce macrophages and lymphocytes
2. What is the function of the innate immune system (broad, 4 functions)?
Two major types of reactions of the innate immune system are inflammation
and antiviral defense.
• Inflammation is the process by which circulating leukocytes and
plasma proteins are brought into sites of infection in tissues and are
activated to destroy and eliminate the offending agents. Inflammation
is also the major reaction to damaged or dead cells unrelated to
, infection and to accumulations of abnormal substances in cells and
tissues.
• Antiviral defense mechanisms prevent virus replication and promote
killing of infected cells, thus eliminating reservoirs of viral infection
without an inflammatory reaction (although inflammation also may
contribute to defense against viruses).
4 functions of innate immune system:
1) Physical and chemical defenses at epithelial barriers: such as the skin
and lining of the gastrointestinal and respiratory tracts, they block
microbial entry. → Microbes are able to colonize tissues only if they
are capable of crossing epithelia. If these barriers are damaged or
microbes are able to penetrate them, innate and adaptive immune
responses are activated to provide the next lines of defense.
2) First response to microbes → prevents, controls or eliminates the
infection (inflammation, antiviral defense)
3) Recognize damaged or dead host cells → eliminates damaged cells
and initiates the process of tissue repair
4) stimulate adaptive immune responses and can influence the nature
of the adaptive responses to make them optimally effective against
different types of microbes.
Innate immune cells express various PRR and after recognizing PAMPs and
DAMPs they respond by producing inflammatory cytokines and antiviral
protein and kill microbes or infected host cells
3. What are the components of the innate immune system & what are their function?
(divided in circulating and cellular components, just list them)?
- barrier epithelia: block the entry of microbes;
- tissue-resident sentinel cells → macrophages, mast cells, and dendritic cells (DCs):
detect microbes that have breached epithelia and initiate host responses;
, - white blood cells (leukocytes)→ including neutrophils, monocytes that become
macrophages in tissues, natural killer (NK) cells, and other cells: enter the tissues
from the blood and eliminate microbes that have invaded through epithelia and also
remove damaged host cells;
- Several types of plasma proteins that combat microbes within and outside the
circulation. → including components of the complement system and other mediator
of inflammation.
Principal components of innate immunity
1) Physical and chemical barriers (epithelia and antimicrobial chemicals at epithelial
surfaces)
2) phagocytic cells (neutrophils, macrophages), DCs, mast cells, NK cells and other innate
lymphoid cells
3) blood proteins (components of complement system and other mediators of
inflammation)
4) cytokines (cells of immune system interact with one another through these secreted
proteins) → regulate and coordinate many activities of cells of innate and adaptive immunity
All immune system cells secrete some cytokines and express specific signaling receptors for
several cytokines
1) Epithelial Barriers
• Block the entry of microbes
• such as the skin and lining of the gastrointestinal and respiratory tracts
• These interfaces are lined by continuous layers of specialized epithelial
cells that serve many physiologic functions, including preventing the
entry of microbes. Loss of the integrity of these epithelial layers by
trauma or other reasons predisposes an individual to infections.
Case 1: Neutrophils and macrophages in infection, inflammation and disease
1. What is the origin of immune cells in humans (focus on innate immune system)?
These cells are almost all derived from hematopoietic stem cells (HSCs) in the
bone marrow of flat bones (ribs, sternum, iliac and vertebrate) which
differentiate along branching lineages.
, Based on their common precursors, immune cells are broadly classified as
either myeloid cells (innate) , which include phagocytes and most DCs,
or lymphoid cells (adaptive) , which include all lymphocytes.
Cytokine induce certain conversions
White blood cells formation = leukopoiesis
• This is stimulated by chemical messengers: interleukins and colony-
stimulating factors (CSF) which are released by the mature WBC and
supporting cells of the red bone marrow. These factors also improve
the protective potency of mature leukocytes.
Hematopoietic stem cells divide into myeloid stem cells and lymphoid stem
cells.
• Myeloid stem cells produce eosinophils, basophils and neutrophils
• Lymphoid stem cells produce macrophages and lymphocytes
2. What is the function of the innate immune system (broad, 4 functions)?
Two major types of reactions of the innate immune system are inflammation
and antiviral defense.
• Inflammation is the process by which circulating leukocytes and
plasma proteins are brought into sites of infection in tissues and are
activated to destroy and eliminate the offending agents. Inflammation
is also the major reaction to damaged or dead cells unrelated to
, infection and to accumulations of abnormal substances in cells and
tissues.
• Antiviral defense mechanisms prevent virus replication and promote
killing of infected cells, thus eliminating reservoirs of viral infection
without an inflammatory reaction (although inflammation also may
contribute to defense against viruses).
4 functions of innate immune system:
1) Physical and chemical defenses at epithelial barriers: such as the skin
and lining of the gastrointestinal and respiratory tracts, they block
microbial entry. → Microbes are able to colonize tissues only if they
are capable of crossing epithelia. If these barriers are damaged or
microbes are able to penetrate them, innate and adaptive immune
responses are activated to provide the next lines of defense.
2) First response to microbes → prevents, controls or eliminates the
infection (inflammation, antiviral defense)
3) Recognize damaged or dead host cells → eliminates damaged cells
and initiates the process of tissue repair
4) stimulate adaptive immune responses and can influence the nature
of the adaptive responses to make them optimally effective against
different types of microbes.
Innate immune cells express various PRR and after recognizing PAMPs and
DAMPs they respond by producing inflammatory cytokines and antiviral
protein and kill microbes or infected host cells
3. What are the components of the innate immune system & what are their function?
(divided in circulating and cellular components, just list them)?
- barrier epithelia: block the entry of microbes;
- tissue-resident sentinel cells → macrophages, mast cells, and dendritic cells (DCs):
detect microbes that have breached epithelia and initiate host responses;
, - white blood cells (leukocytes)→ including neutrophils, monocytes that become
macrophages in tissues, natural killer (NK) cells, and other cells: enter the tissues
from the blood and eliminate microbes that have invaded through epithelia and also
remove damaged host cells;
- Several types of plasma proteins that combat microbes within and outside the
circulation. → including components of the complement system and other mediator
of inflammation.
Principal components of innate immunity
1) Physical and chemical barriers (epithelia and antimicrobial chemicals at epithelial
surfaces)
2) phagocytic cells (neutrophils, macrophages), DCs, mast cells, NK cells and other innate
lymphoid cells
3) blood proteins (components of complement system and other mediators of
inflammation)
4) cytokines (cells of immune system interact with one another through these secreted
proteins) → regulate and coordinate many activities of cells of innate and adaptive immunity
All immune system cells secrete some cytokines and express specific signaling receptors for
several cytokines
1) Epithelial Barriers
• Block the entry of microbes
• such as the skin and lining of the gastrointestinal and respiratory tracts
• These interfaces are lined by continuous layers of specialized epithelial
cells that serve many physiologic functions, including preventing the
entry of microbes. Loss of the integrity of these epithelial layers by
trauma or other reasons predisposes an individual to infections.
