M103 T2 L5 Flashcards
What three cell types can a Common lymphoid progenitor cell differentiate into?
B lymphocytes, T lymphocytes
NK cells
What are the products of the myeloid progenitor cell? What does each produce? (BE.MEG)
basophil - basophils erythroid - erythrocytes megakaryocyte - platelets eosinophil - eosinophils granulocyte - neutrophils & monocytes
What are the four WBCs? (MEN.B)
monocytes
eosinophils
neutrophils
basophils
What WBCs are found in the tissue rather than in the blood?
mast cells, macrophages
fibroblasts
What is the function of tissue cells?
to secrete cytokines
Which lymphocytes are responsible for adaptive immunity?
B & T lymphocytes
Which myeloid cells are phagocytic? (NEMM)
neutrophils, eosinophils
macrophages, monocytes
Which cells are auxillary type cells?
basophils, mast cells
platelets (not strictly cells but still included)
Which cells are granululocyte type cells?
(BEN)
basophils
eosinophils
neutrophils
Why aren’t mast cells a granululocyte type cell?
bc this term is reserved for granulocytic cells that are present in the blood rather than in the tissue
What features do basophil cells have?
Lobed nuclei and heavily granulated cytoplasm
What percentage of lymphocytes are NK cells?
5%
What are the functions of basophils?
circulate in the blood and are recruited to sites of allergic reactions or ectoparasite infection
release pharmacologically active substances from their cytoplasmic granules
What do basophils do?
Express FCER1
can bind to allergen-specific IgE bound to the cell surface of basophils
this activates the basophil
causes degranulation of effector mediators - the granules are released to the outside of the cell to exert their biochemical effects
What are the features of eosinophil cells?
bilobed nuclei
granulated cytoplasm
What features do neutrophils have?
Multilobed nucleus
are very short lived so they are constantly being replenished
What is the function of neutrophils?
they are the first responders to infection
they are phagocytic and express enzyme myeloperoxidase and reactive oxygen species (are very toxic to pathogens)
What is the shape of a nucleus in a monocyte?
Kidney-shaped
What is the function of monocytes?
Blood-bourne phagocytes
Precursors to macrophages
Where are macrophages located?
in tissues
How do monocytes differ to macrophages?
macs are found in the tissue not in the blood or spleen
macs are 5-10 times larger than mons
macs contain many more organelles compared to mons
macs lifespan is much longer than that of mons
both are phagocytic
What features do cytokines have?
made up of small proteins or glycoproteins
have a low molecular weight (< 30 kDa)
secreted primarily by WBCs
What are the functions of cytokines?
messenger molecules of the immune system
help regulate immune effector cell development
paracrine signalling (act locally)
What are the functions of chemokines?
attract leucocytes
recruit monocytes and neutrophils to the site of infection
What are the four symptoms of inflammation? (HR, PS)
heat, redness, pain and swelling
What is the purpose of inflammation?
recruitment - to bring cells and molecules involved in host defence and repair to the site of infection / injury
What are three key components of the inflammatory response?
Blood vessels
Phagocytic leucocytes
Plasma proteins
What are the steps of the inflammatory response?
Blood vessels dilate, become more permeable
Circulating leucocytes migrate into tissue
Leucocytes are activated by the pathogen or by damaged tissue (injury)
Activated leucocytes destroy microbes and unwanted material
What is the time-frame like for acute inflammation?
it’s the initial, rapid response that happens in response to injury or infection
it develops very quickly, within minutes
doesn’t last very long - hours / days
Which cells predominantly mediate acute and chronic inflammation?
acute - neutrophils
chronic - mononuclear cells
What is the time-frame like for chronic inflammation?
Lasts weeks – months
When does acute inflammation clear up?
it resolves once the stimulus is removed - once the infection is cleared / once the injury has been repaired
How can chronic inflammation eventually lead to tissue destruction?
the body attempts to heal
instead of replacing damaged cells with cells from that tissue, it undergoes a fibrotic healing process and then tissue function is lost
Are acute and chronic inflammation linked?
old theory - acute would lead to chronic if it did not resolve in a long period of time
new theory - chronic is not necessarily preceded by acute
How are adhesion molecules useful in immunity?
plays a critical role in initiating and sustaining an effective immune response against foreign pathogens
What are the two types of contact between leukocytes and the endothelium?
Initial contact
Tighter adhesion
What substances is initial contact mediated by and how?
P-selectin and E-selectin molecules on the endothelium
they are recognised by oligosaccharides (sulfated sialyl-Lewis X) on leucocytes
What are the adhesion molecules involved in the tighter adhesion process and how do they work?
intercellular adhesion molecules on the endothelium
they are recognised and bound to integrins on leucocytes
What stimulates adhering molecules together and how does it work?
by MCP-1 to cross the endothelium and lodge in the intima
Why is activated endothelium a requirement for inflammation?
healthy, unactivated endothelium does not express P or E-selectin molecules, ICAMs or MCP-1
only when injured and activated are they expressed, so otherwise, initial contact and tighter adhesion can’t happen
What is the function of platelets in inflammation?
they recruit and inflame monocytes
How do activated monocytes drive inflammation?
secreates cytokines
can differentiate into macrophage
binds very well to the endothelial cell
What are the three main types of PRRs?
Macrophage mannose receptors
Scavenger receptors
TLRs
How are pathogens opsonized?
the antigen is coated with antibody to enhance phagocytosis - so that it can see it / recognise the antigen better
What three areas of pathogenesis does atherosclerosis involve? (DIE)
Dysregulation of lipid metabolism
Inflammation (mediated by monocytes/macrophages)
Endothelial cell dysfunction
What are the staged effects of lipid deposits and cytokine release in artery walls?
lipid deposits result in the production of chemokines and cytokines
these recruit monocytes
enter the artery wall and develop into macrophages
turn into foam cells
inflammatory response IN the artery wall
can lead to further damage of the endothelium and further deposition of lipids
potential positive feedback loop
What are the staged effects of lipid deposits and collagen exposure in artery walls?
can lead to the potential exposure of collagen
any exposure of collagen can potentially activate platelets and cause coagulation
What are NK cells otherwise known as?
large granular lymphocytes
What are MCP-1 proteins otherwise known as?
CCL-2 proteins
What does MCP-1 stand for?
Monocyte chemotactic protein-1
What does HHT stand for?
Hereditary haemorrhagic telangiectasia
What gender do the haemophilia diseases affect?
males as the condition is x linked
What is the life span of neutrophils?
8 hr- 4 days
Where are neutrophils located?
they are found in the blood (make up 60% of circulating leucocytes)
What substances are expressed by neutrophils?
myeloperoxidase and ROS
What are two examples of plasma proteins?
complement, antibodies
What is the role of P-selectin?
a cell adhesion molecule
helps with the initial recruitment of leukocytes and the recruitment & aggregation of platelets to the site of injury during inflammation
What is P-selectin produced by?
activated platelets and endothelial cells
Where is E-selectin expressed?
cytokines on inflamed endothelium
What is the difference between P & E-selectin?
P-selectin is expressed on endothelial cells first, followed by E-selectin later
What is the largest type of leukocyte?
monocytes
What is another term for WBC?
lymphocytes
What are the two tissue cells?
macrophages and mast cells
What are mononuclear phagocytes otherwise known as?
macrophages
What is unique about mobile phagocytic cells?
they can migrate from the blood into the tissues - AAR the majority are located in the tissues
What receptor do basophils and eosinophils express?
FCER1 on activation only
What does the FCER1 receptor on basophils and eosinophils bind to?
allergen-specific IgE
What parasitic areas of the body are targeted by the toxins in basophil granules?
GI, respiratory and genito-urinary tracts
What cell type levels increase during bacterial infections?
neutrophils (monocytes in chronic infection)
What cell type levels increase during viral infections?
lymphocytes (sometimes monocytes)
What cell type levels increase during fungal infections?
monocytes
What cell type levels increase during allergies?
basophils (eosinophils in chronic phase) and mast cell activation
Are basophils phagocytic cells?
no
Where are monocytes located?
there is a reservoir of monocytes in the spleen
they migrate into tissues about one day after release from the bone marrow
What are platelets mediated by?
by the endothelium and blood monocytes (recruit and activate them)
What is the lifespan of macrophages?
months to years
