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Summary BBS2001 - Threats and Defense Mechanisms
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This document contains all 7 cases, including the consolidation cases, of BBS2001. All the important information from the lectures are included!
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1Case 1
Types of Blood cells
The Multipotential Hematopoietic stem cell (aka Hemocytoblast) is the precursor of all blood cells.
From here, it subdivides into (1) Common Myeloid Progenitor cells, and (2) Common Lymphoid
progenitors.
Common Myeloid Progenitor cells:
Thrombocytes/ platelets: a platelet is a
small cell fragment without a nucleus of
about 2-3μm. They can respond to a large
variety of triggers and change shape,
whereas they can also adhere to various
surfaces and spread to aggregate and close
sites of damage to a blood vessel/ bleeding.
Platelets look like sponges, with open
structural canals. They contain lots of
granules with active biomolecules.
Erythrocytes/ red blood cells: red blood
cells do not contain most organelles, such as
a nucleus or mitochondria, they have maximum carrying capacity for haemoglobin and can thus carry
oxygen from the lungs to different tissues in the body. They take up carbon dioxide from these tissues.
The haemoglobin consists of 2x alpha- and 2x beta-chains, and has several functions: (1) to maintain
the equilibrium of oxygen and carbon dioxide high environments, and (2) when a red blood cell is lysed
by a bacteria, haemoglobin is released which itself releases free radicals to kill the pathogen.
Mast cells: are not found in the bloodstream, but in tissues, such as skin, blood vessels, nerves, lips,
and other sites where potential injury might occur. They are filled with granules of acidic proteoglycans
and histamine. Acidic proteoglycans are released when there is a high affinity of antibody ‘IgE’
receptors are active, and histamine leads to vasodilation, thereby increasing blood flow to injured sites,
thus allowing more white blood cells to enter the injured tissue. ← Mast cells also release ‘cytokines’
which lead leukocytes to the site of infection. In short, Mast cells lead to inflammation and are often
involved in allergic reactions.
- The mast cell is a type of granulocyte, as it contains the granules histamine and acidic
proteoglycans.
Myeloblasts: precursor of several white non-specific blood cells - play a role in the Innate Immunity.
NOTE that white blood cells = Leukocytes!
1. Basophils: (<1%), control responses to parasites
- They are found in and outside blood vessels.
- Release histamine and other chemicals for inflammation and allergic reactions. Look at
Mast cell for the workings of histamine.
- Type of granulocyte, as it contains the granules histamine.
2. Neutrophil: (50-70%), phagocytosis/digestion and killing of pathogens
, 2
- They are found in the bloodstream but can move to the surrounding tissues, where they
oftenly accumulate in the pus of wounds and have a 24h lifespan. As it arrives within 2
hours, it is the first defence against bacterial infections.
- There are two types: Band neutrophils (newly developed when in sickness) and
Segmented neutrophils (remain, even during health).
- They are active in the phagocytosis of bacteria (non-specific towards species), and whilst
their lysosomal storage is limited, their 24h lifespan causes the neutrophils to die while
killing the pathogens (--> hence, found in pus).
- Type of granulocyte, as it contains the granules azurophil (lysosomal morphology),
lactoferrin, and lysozyme.
3. Eosinophil: (1-4%), kill parasites (pathogens) through phagocytosis with granules, and
present pathogens coated with antibodies
- They are found in and outside blood vessels, for example in the GI tract where they are
involved in food allergies.
- Type of granulocyte, as it contains the granules cytokines that enzymatically break down
the cell walls of pathogens, although this can also affect the host's own cells.
4. Monocyte & Macrophage: (12%) facilitate health and repair as they present antigens and
promote phagocytosis.
- When monocytes leave the bloodstream, they are called macrophages, and tend to come
into action after 12h.
- It phagocytose pathogens, debris, and dead cells. It also presents pieces of killed
pathogens to ‘T-lymphocytes’ that start to create antigens.
- The biggest white blood cell.
- They are also the precursor for Dendritic cells (Antigen presenting cells (APCs))
- Type of phagocyte
Common lymphoid progenitor cells:
The common lymphoid progenitor cell is a precursor of ‘Lymphocytes’, which are white blood cells
(leukocytes) that tend to be more highly concentrated in the lymphatic system (lymph nodes and
vessels) rather than the blood like other circulating cells, and are characterized microscopically by their
darkly-staining nuclei. The common lymphoid progenitor cell knows a couple of subtypes:
Natural Killer cells: they are leukocytes that kill/phagocytose virally infected-, tumour-, and stressed
cells. They act independently from MHC proteins, which act as a recognizer for foreign cells, hence
why they apoptose/phagocytose both infected and uninfected/sick host cells. It is also known as the
Large Granular Lymphocyte.
Small lymphocyte: (20-40%) precursor of several white specific blood cells - play a role in the Adaptive
Immunity. They are small cells with a relatively large nucleus, and only a small amount of cytoplasm
and poorly developed organelles. They have receptor molecules on their surface to which they bind to
antigen receptors of pathogens. Once bound to an antigen, they multiply into identical cells, and
release granules. They are non-functional as mature lymphocytes in the bloodstream but can be
activated by antigens in ‘Secondary Lymphoid Organs’, such as the spleen and lymph nodes. There are
two subtypes with a specific antigen:
1. B lymphocytes:
- They are produced in the bone marrow tissue
- Plays a role in the humoral response → a.k.a. responds to antibody production
OUTSIDE THE CELL
- B Lymphocytes produce antibodies which can bind onto pathogens.
, 3
- They can be subdivided into the multi-pathogen reactive antibody producing B1 cells
and the mono-reactive antibodies of B2 cells.
- B lymphocytes are also the precursor of Plasma cells: these produce antibodies for
defence against an infection.
2. T Lymphocytes:
- They are produced and mature in the Thymus
- Plays a role in the cellular response → a.k.a. responds to cytotoxic T helper cells and
the release of cytokines in response to antigens INSIDE THE CELL
- T Lymphocytes can be subdivided into (both have T-Cell-Receptors):
a. T-helper cells: produce cytokines, which thereby indirectly kills pathogens.
They also express CD4, which bind to MHC II molecules of pathogens
b. T-cytolytic cells: release granules filled with cytotoxic substances when in
contact with foreign cells.
Other important cells
Antigen-presenting cells (APC) are cells that capture microbes and other antigens, and display the
antigens to lymphocytes. This causes (1) the production of antibodies, and (2) stimulates the
differentiation and proliferation of lymphocytes. There are different types of APCs:
● Dendritic cells: respond to microbes by producing cytokines (phagocytic capabilities) that
recruit leukocytes, and initiate adaptive immune responses by presenting parts/antigens to
the T lymphocytes.
○ AND PLAYS AN IMPORTANT BRIDGE BETWEEN THE INNATE AND ADAPTIVE
IMMUNITY.
● Follicular Dendritic Cells (FDC): find, bind, and display protein antigen to T and B lymphocytes.
These FDCs are only found around the spleen and lymph nodes.
● Also macrophages and B lymphocytes can present antigens to T lymphocytes.
Transmigration of leukocytes from the bloodstream
to the site of infection
(step 1) Mast cells and basophils (which are already located outside a blood vessel) release histamine
in reaction to cytokines. These cytokines induce vasodilation, and more blood goes to the site of
damage. This results in warm and red skin, which is characteristic for inflammation.
(step 2) The vasodilation causes gaps in the endothelial cells, which causes plasma to leak out the
blood vessel, into the connective tissue. This results in swelling or edema, puts pressure on nerve
endings, and results in pain.
(step 3) At these sites of infection, macrophages and dendritic cells that have encountered microbes
produce cytokines and chemokines that activate the endothelial cells near venules to produce:
, 4
● Selectins (specifically P-
selectins): mediate weak
tethering (binding) and rolling
of blood neutrophils on the
endothelium
● Ligands for integrins
(specifically ICAM and VCAM):
mediate firm adhesion of
neutrophils
● Chemokines (specifically
CXCL8): activate neutrophils
and stimulate their migration
through the endothelium to
the site of infection.
The purpose of rolling and slow rolling is to bring the leukocyte into contact with the P-selectins of the
endothelial cell so that the leukocyte can be further activated by chemokines and other
proinflammatory agents presented on the surface of the endothelial cells. The chemokine CXCL8
receptor and the integrin LFA-1 of leukocytes bind to the chemokine CXCL8 and the ligands VCAM-1
(vascular adhesion molecule 1) and ICAM. This strong binding allows leukocytes to arrest/firmly bind
on the endothelial surface.
(step 4) Diapedesis is the process whereby the leukocytes squeezes in ameboid fashion across the
endothelial cells, with the help of Pcam1, and at this point, there is no return in the inflammatory
response. The other steps, like rolling and adhesion, are reversible
(step 5) When leaving the bloodstream, neutrophils genetically change to improve
phagocytosis/killing, and more of chemokine CXCL8 is released to recruit more neutrophils
(step 6) The inflammatory cells secrete factors for healing: (1) phagocytes clear debris, (2) angiogenic
factors restore blood flow, and (3) fibroblasts are attracted and produce collagen. Inflammation
causes 1) attraction of immune cells and chemical mediators to the site. 2) producing a physical
barrier to slow down the rate of infection. 3) promoting tissue repair once the infection is under
control.
Cytokines are soluble protein secreted by the cells of innate and adaptive immunity and therefore
mediate many of the functions of these cells. Based on their cellular sources:
● monokines (mononuclear phagocytes)
● lymphokines (lymphocytes)
● interleukins (leukocytes) (IL-2, IL-2, etc)
● chemokines
Wound healing
Hemostasis is the process to keep blood inside a damaged blood vessel
Blood vessels are located in the dermis of the skin and when you are speaking of bleeding, the rupture
of the epidermis and the dermis has resulted in a damaged blood vessel.
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