Medic_Summaries (IMS) Topic 11
Immunology
The immune system: this is a complex orchestration of molecules, cells, tissues and organs that
provide protection (immunity) from microbial pathogens (bacteria, viruses, parasites, fungi) and
tumour cells
Immunity to infection in the body involves:
- Innate mechanisms: innate immunity
- First line of defence
- Non-specific response
- Adaptive mechanisms: adaptive immunity
- Second line of defence
- Highly specific with memory
Active immunity: antigens enter the body and trigger the innate and adaptive immune systems,
this provides long term protection
Passive immunity: antibodies pass from mother to foetus across the placenta and from the
mother to the infant in breast milk, this provides short-term protection
Origins of cells in the immune system:
- A number of cells with different functions coordinate and effect the immune response
- Cells are derived from common pluripotent haematopoietic stem cells in bone marrow
- Myeloid lineage generates:
- Polymorphonuclear leukocytes (neutrophil, eosinophil, basophil)
- Monocytes/macrophages
- Dendritic cells
- Mast cells
- Lymphoid lineage:
- B- and T- and natural killer (NK) lymphocytes
Key cells of the immune system: polymorphonuclear leukocytes or granulocytes - characterised
by multi lobed (2-5) nuclei and cytoplasmic granules; includes:
- Neutrophils: principal phagocytic cell of innate immunity. Rapidly migrate to
sites of infection, ingest microbes by phagocytosis, release oxygen free
radicals, degranulate releasing proteins with microbicidal properties e.g.
lysosomes.
- Eosinophils: important defender against multicellular parasites and have a
role in allergy and asthma.
- Basophils: involved in inflammatory allergic reactions. Releases the potent
vasodilator, histamine.
- Monocytes: circulate in the blood, bean-shaped nuclei, precursors of tissue
macrophages. Effectors of the inflammatory response to microbes. Kills
pathogens via phagocytosis, free radical production, myeloperoxidase and
inflammatory.
- Macrophages: derived from blood monocytes. Participate in innate and
adaptive immunity. Phagocytosis, microbicidal mechanisms, antigen
presentation to other cells.
- Dendritic cells: process and present antigens (antigen presenting cell (APC))
on their cell surface to T-lymphocytes to initiate specific immune response.
- Mast cells: similarities with basophils, release histamine, close association
with allergy and inflammation.
1 Adapted from Lectures at the University of Leeds Medical School
,Medic_Summaries (IMS) Topic 11
Lymphocytes:
- Small lymphocytes: involved with specific immunity
- B-lymphocytes (B-cells):
- Produce antibodies, present antigens to other cells (APC), can produce
long-lived memory cells
- T-lymphocytes (T-cells):
- Plays critical role in development and regulation of cell-mediated immunity
- Influences the activities of other cells (eg. B-cells), able to kill virally infected
and tumour cells, generate long-lived memory cells
- Large granular lymphocytes:
- Natural killer (NK) cells:
- Generally considered part of the innate immune response
- Release performs and granzymes and trigger apoptosis in target cell
- Kill infected cells that do not express foreign surface antigen, respond
rapidly, involved in tumour immunosurveillance
Key immunological sites in the body:
- Primary lymphoid tissue: development and maturation of lymphocytes
- Bone marrow (B lymphocytes)
- Thymus glands (T lymphocytes)
- Secondary lymphoid tissue: mature lymphocytes encounter antigens/pathogens
- Lymph nodes
- Spleen
- Lymphoid tissue at other sites: tonsils, appendix, adenoids, Peyer’s patches (in
ileum), bronchial associated lymphoid tissue (BALT)
Lymph nodes:
- Found at specific sites in the body
- Virgin B- and T-lymphocytes come from bone marrow and thymus to specific sites in the
lymph nodes
- During infection, the architecture and size of nodes change in response to activation and
proliferation of lymphocytes
The spleen:
- Lymphoid organ in the abdomen
- Removes damaged or old erythrocytes
- Key site of activation of lymphocytes from blood-
borne pathogens
Architecture of the spleen:
- Red pulp: erythrocytes removed
- White pulp: lymphocytes stimulated
Key components of the innate immune system:
- Mechanical barriers: provided by skin and mucous membranes, competition with normal
flora, mucous entraps and cilia propel microbes out of the body
- Physiological: stomach pH kill some pathogens; fever response inhibits pathogen growth
- Chemical mediators: including circulating plasma proteins; lysozyme cleaves bacterial
cell wall, interferon induces antiviral defences in uninfected cells and complement lyses
microbes directly or facilitates phagocytosis
- Phagocytic leukocytes: cells that are specialised in the process of phagocytosis
- Macrophages: reside in tissues and recruit neutrophils, become activated and
release cytokines (TNF, IL1)
- Neutrophils: enter infected tissues in large numbers, become activated, release
cytokines (TNF), phagocytose bacteria
- Natural killer (NK) cells: summoned from the blood, release cytokines (IFN-
gamma, IL2), kill infected cells (trigger apoptosis)
2 Adapted from Lectures at the University of Leeds Medical School
, Medic_Summaries (IMS) Topic 11
The adaptive immune system:
- Called into action against pathogens that overcome innate immune defences
- This system adapts to the presence of an infectious agent by activating, proliferating, and
creating specific responses to eliminate the microbe
- There are two types of adaptive immune response:
- Humoral immunity: mediated by antibodies produced by B lymphocytes
- Cell-mediated immunity: effected by T lymphocytes
Non-infected tissue contains:
- Resident macrophages: eating up dead/dying cells in tissue (general ‘gardening’ duties)
- Dendritic cells: on sentry duty, waiting for the first sign of a pathogen
Infected tissue:
- Wave 1:
- DENDRITIC CELLS exit infected tissue to inform lymphocytes in lymph nodes
about the invading pathogen
- NEUTROPHILS from the bloodstream into the infected tissue to kill the pathogen
- Wave 2:
- MONOCYTES flood in from blood and become inflammatory macrophages
- NEUTROPHILS killed pathogen, but have destroyed themselves in the effort
- MACROPHAGES clear away debris, while some also migrate to lymph nodes to
inform lymphocytes
- Resolution:
- INFLAMMATORY MACROPHAGES change properties as infection resolves and
help to repair damage to tissue
Macrophages:
- Very good at eating, but to avoid wholesale destruction must be told what they can eat
- Among things they recognise as food, they eat dying cells
- Membrane plasma lipid profile changes when cell dies (macrophages can recognise this)
- They eat opsonised cells and pathogens
- Surface is coated either with complement proteins or with antibodies
- If cell/pathogen is coated with antibodies, it can be efficiently taken up by the Fc receptor
Dendritic cells:
- Migrate to lymph nodes to recruit lymphocytes and presents antigen to naive T-cell
- Have specialised receptors on surface that allow recognition of foreign molecules
- This can kick start the adaptive immune response
- Naive T-cell can now proliferate and daughter T-cells can help B-cells
- Following help, B-cells proliferate and produce antibodies
- The antibodies coat pathogens so that macrophages phagocytose them
- Although macrophages cant present to naive T-cells, they can present to primed daughter
cells of a T-cell activated by a dendritic cell
- The body can produce lots more antibody now if the infection continues
Antibodies and B-cells:
- Immunity to a virus is conferred by proteins that circulate
in the bloodstream of immunised people (antibodies, or
immunoglobins (Ig))
- Antigens recognise antibodies and causes an immune
response (immunogenicity)
- There are different classes of immunoglobulin:
- IgA, IgD, IgE, IgG, and IgM
- IgG is made up of two pairs of two different proteins, heavy chain (Hc) and light chain (Lc)
- There are two identical antigen binding regions (Fab)
- Specificity of the antibody binding to its antigen is due to the folding of the Fab region,
which matches the shape of the antigen molecule very precisely
- The tail region (Fc) can bind to Fc receptors on the surface of immune system cells such
as macrophages
3 Adapted from Lectures at the University of Leeds Medical School
Immunology
The immune system: this is a complex orchestration of molecules, cells, tissues and organs that
provide protection (immunity) from microbial pathogens (bacteria, viruses, parasites, fungi) and
tumour cells
Immunity to infection in the body involves:
- Innate mechanisms: innate immunity
- First line of defence
- Non-specific response
- Adaptive mechanisms: adaptive immunity
- Second line of defence
- Highly specific with memory
Active immunity: antigens enter the body and trigger the innate and adaptive immune systems,
this provides long term protection
Passive immunity: antibodies pass from mother to foetus across the placenta and from the
mother to the infant in breast milk, this provides short-term protection
Origins of cells in the immune system:
- A number of cells with different functions coordinate and effect the immune response
- Cells are derived from common pluripotent haematopoietic stem cells in bone marrow
- Myeloid lineage generates:
- Polymorphonuclear leukocytes (neutrophil, eosinophil, basophil)
- Monocytes/macrophages
- Dendritic cells
- Mast cells
- Lymphoid lineage:
- B- and T- and natural killer (NK) lymphocytes
Key cells of the immune system: polymorphonuclear leukocytes or granulocytes - characterised
by multi lobed (2-5) nuclei and cytoplasmic granules; includes:
- Neutrophils: principal phagocytic cell of innate immunity. Rapidly migrate to
sites of infection, ingest microbes by phagocytosis, release oxygen free
radicals, degranulate releasing proteins with microbicidal properties e.g.
lysosomes.
- Eosinophils: important defender against multicellular parasites and have a
role in allergy and asthma.
- Basophils: involved in inflammatory allergic reactions. Releases the potent
vasodilator, histamine.
- Monocytes: circulate in the blood, bean-shaped nuclei, precursors of tissue
macrophages. Effectors of the inflammatory response to microbes. Kills
pathogens via phagocytosis, free radical production, myeloperoxidase and
inflammatory.
- Macrophages: derived from blood monocytes. Participate in innate and
adaptive immunity. Phagocytosis, microbicidal mechanisms, antigen
presentation to other cells.
- Dendritic cells: process and present antigens (antigen presenting cell (APC))
on their cell surface to T-lymphocytes to initiate specific immune response.
- Mast cells: similarities with basophils, release histamine, close association
with allergy and inflammation.
1 Adapted from Lectures at the University of Leeds Medical School
,Medic_Summaries (IMS) Topic 11
Lymphocytes:
- Small lymphocytes: involved with specific immunity
- B-lymphocytes (B-cells):
- Produce antibodies, present antigens to other cells (APC), can produce
long-lived memory cells
- T-lymphocytes (T-cells):
- Plays critical role in development and regulation of cell-mediated immunity
- Influences the activities of other cells (eg. B-cells), able to kill virally infected
and tumour cells, generate long-lived memory cells
- Large granular lymphocytes:
- Natural killer (NK) cells:
- Generally considered part of the innate immune response
- Release performs and granzymes and trigger apoptosis in target cell
- Kill infected cells that do not express foreign surface antigen, respond
rapidly, involved in tumour immunosurveillance
Key immunological sites in the body:
- Primary lymphoid tissue: development and maturation of lymphocytes
- Bone marrow (B lymphocytes)
- Thymus glands (T lymphocytes)
- Secondary lymphoid tissue: mature lymphocytes encounter antigens/pathogens
- Lymph nodes
- Spleen
- Lymphoid tissue at other sites: tonsils, appendix, adenoids, Peyer’s patches (in
ileum), bronchial associated lymphoid tissue (BALT)
Lymph nodes:
- Found at specific sites in the body
- Virgin B- and T-lymphocytes come from bone marrow and thymus to specific sites in the
lymph nodes
- During infection, the architecture and size of nodes change in response to activation and
proliferation of lymphocytes
The spleen:
- Lymphoid organ in the abdomen
- Removes damaged or old erythrocytes
- Key site of activation of lymphocytes from blood-
borne pathogens
Architecture of the spleen:
- Red pulp: erythrocytes removed
- White pulp: lymphocytes stimulated
Key components of the innate immune system:
- Mechanical barriers: provided by skin and mucous membranes, competition with normal
flora, mucous entraps and cilia propel microbes out of the body
- Physiological: stomach pH kill some pathogens; fever response inhibits pathogen growth
- Chemical mediators: including circulating plasma proteins; lysozyme cleaves bacterial
cell wall, interferon induces antiviral defences in uninfected cells and complement lyses
microbes directly or facilitates phagocytosis
- Phagocytic leukocytes: cells that are specialised in the process of phagocytosis
- Macrophages: reside in tissues and recruit neutrophils, become activated and
release cytokines (TNF, IL1)
- Neutrophils: enter infected tissues in large numbers, become activated, release
cytokines (TNF), phagocytose bacteria
- Natural killer (NK) cells: summoned from the blood, release cytokines (IFN-
gamma, IL2), kill infected cells (trigger apoptosis)
2 Adapted from Lectures at the University of Leeds Medical School
, Medic_Summaries (IMS) Topic 11
The adaptive immune system:
- Called into action against pathogens that overcome innate immune defences
- This system adapts to the presence of an infectious agent by activating, proliferating, and
creating specific responses to eliminate the microbe
- There are two types of adaptive immune response:
- Humoral immunity: mediated by antibodies produced by B lymphocytes
- Cell-mediated immunity: effected by T lymphocytes
Non-infected tissue contains:
- Resident macrophages: eating up dead/dying cells in tissue (general ‘gardening’ duties)
- Dendritic cells: on sentry duty, waiting for the first sign of a pathogen
Infected tissue:
- Wave 1:
- DENDRITIC CELLS exit infected tissue to inform lymphocytes in lymph nodes
about the invading pathogen
- NEUTROPHILS from the bloodstream into the infected tissue to kill the pathogen
- Wave 2:
- MONOCYTES flood in from blood and become inflammatory macrophages
- NEUTROPHILS killed pathogen, but have destroyed themselves in the effort
- MACROPHAGES clear away debris, while some also migrate to lymph nodes to
inform lymphocytes
- Resolution:
- INFLAMMATORY MACROPHAGES change properties as infection resolves and
help to repair damage to tissue
Macrophages:
- Very good at eating, but to avoid wholesale destruction must be told what they can eat
- Among things they recognise as food, they eat dying cells
- Membrane plasma lipid profile changes when cell dies (macrophages can recognise this)
- They eat opsonised cells and pathogens
- Surface is coated either with complement proteins or with antibodies
- If cell/pathogen is coated with antibodies, it can be efficiently taken up by the Fc receptor
Dendritic cells:
- Migrate to lymph nodes to recruit lymphocytes and presents antigen to naive T-cell
- Have specialised receptors on surface that allow recognition of foreign molecules
- This can kick start the adaptive immune response
- Naive T-cell can now proliferate and daughter T-cells can help B-cells
- Following help, B-cells proliferate and produce antibodies
- The antibodies coat pathogens so that macrophages phagocytose them
- Although macrophages cant present to naive T-cells, they can present to primed daughter
cells of a T-cell activated by a dendritic cell
- The body can produce lots more antibody now if the infection continues
Antibodies and B-cells:
- Immunity to a virus is conferred by proteins that circulate
in the bloodstream of immunised people (antibodies, or
immunoglobins (Ig))
- Antigens recognise antibodies and causes an immune
response (immunogenicity)
- There are different classes of immunoglobulin:
- IgA, IgD, IgE, IgG, and IgM
- IgG is made up of two pairs of two different proteins, heavy chain (Hc) and light chain (Lc)
- There are two identical antigen binding regions (Fab)
- Specificity of the antibody binding to its antigen is due to the folding of the Fab region,
which matches the shape of the antigen molecule very precisely
- The tail region (Fc) can bind to Fc receptors on the surface of immune system cells such
as macrophages
3 Adapted from Lectures at the University of Leeds Medical School
