What are ubiquitous long-lived cells that produce the interstitial ground substance (extracellular matrix) of supporting tissue throughout the body?
What is the main fiber of extracellular matrix (comprising an estimated 25% of the total protein in the body)?
What are the key cellular players in the process of tissue repair?
In addition to creating extracellular matrix, fibroblasts can differentiate into what?
specialized connective tissue cells (osteocytes, chondrocytes, adipocytes), but not epithelial cells
Describe how fibroblasts produce scar tissue (how is it made/functional capacity)
The fibrous tissue they produce to replace dead tissue is a scar.
Scar tissue is generally strong and good at holding things together
scars lack the specialized functional capacity of the tissue that it replaces.
Scars are generally smaller than the tissue they replace
T/F Wounds contract during the process of healing.
What are the effector cells of wound contraction?
T/F Scars lack the specialized function of tissues they replace and are smaller than the tissues they replace.
in a site of repair, what are large, metabolically active cells?
What are the general shapes of fibroblasts?
generally spindle shaped,
elongated, with tapering ends,
usually sharply pointed,
sometimes resembling a swallow tail
can be stellate (star shaped)
Describe the nuclei and cytoplasm characteristics of fibroblasts
nuclei are large, with prominent nucleoli.
cytoplasm tends to be basophilic because it has lots of RNA
Fibroblasts are recruited to and activated at sites of repair by what hormones? What secretes them?
transforming growth factor-beta (better known as TGF-beta),
fibroblast growth factor-2 (FGF-2)
platelet-derived growth factor (PDGF)
secreted by inflammatory cells, especially macrophages.
What are inactive fibroblasts? Why are they important?
retired fibroblasts are stable cells
always in reserve and capable to be called up to serve in active duty of repair
What are polymorphonuclear leukocytes (“polys”, “PMNs”, “segs”) are first responder phagocytes?
What are the predominant type of white blood cells in the innate immune system response to infection?
What are the predominant white blood cell type in acute inflammation?
Acute inflammation is essentially neutrophilic inflammation
In addition to responding to infection, polymorphonuclear leukocytes respond to what?
Partly because they respond to necrosis, neutrophils can be part of what?
T/F neutrophils have acute-on-chronic inflammation or chronic suppurative (pus-producing) inflammation.
How long do neutrophils live at the site of inflammation?
What are the majority of leukocytes measured in the blood?
Corticosteroids cause what wrt to neutrophils?
demargination of neutrophils
increase the number of neutrophils measured [up to double]
(make you think a patient has infection if you don’t know they are on steroids).
Increased number of (segmented) neutrophils in the blood is called what?
T/F neutrophils are granulocytes
How can you tell the difference between neutrophils and other granulocytes?
Neutrophils have neutral granules (neither red nor blue), hence the name.
other granules that are red or blue in routinely stained tissue sections or peripheral blood smears
What are moderate sized cells with a moderate amount of cytoplasm?
Describe the shape/size of neutrophils
moderate sized cells with a moderate amount of cytoplasm.
variably shaped nuclei, segmented into 2 to 5 lobes connected by thin filaments
Neutrophils with nuclei segmented into 6 or more lobes are hypersegmented.
Hypersegmented neutrophils are associated with what?
megaloblastic anemia due to vitamin B12 or folate deficiency
What are immature (adolescent) neutrophils, normally <5% of blood leukocytes?
Bands are a much higher percentage of the neutrophilic granulocytes where?
in the bone marrow
T/F Bands are not quite fully mature, but they are capable of phagocytosis.
When can bands be counted?
When the absolute neutrophil count of infection-fighting cells in the bloodstream is calculated
When a person has a severe infection, the bone marrow releases what into the blood? What is this referred to?
bands into the blood in increasing numbers
Really severe infection can cause the bone marrow to release even less mature cells than bands, even though they are ineffective phagocytes. What is this referred to?
increased numbers of immature leukocytes in the blood is referred to as a left shift
T/F Corticosteroids cause left shift or bandemia
False, they do not cause a left shift or bandemia
An abnormally increased percent of neutrophils can be indicative of infection, even when the total number of leukocytes is normal. What is this called?
neutrophilia w/o leukocytosis
The earliest bone marrow precursor cells of granulocytes in general and neutrophils in particular have what type of nuclei?
How does this change during maturity?
the nuclei of these precursor cells become flattened on one side and have an indentation
Describe how bands are formed
As they mature, nuclei of these precursor cells become flattened on one side.
flattening becomes an indentation.
indentation becomes deeper and deeper until the portions of the nucleus on either side of it are partially segmented.
it is a band (imagine the indentation having become a full circumference constricting band, hence the name).
Bands are approximately the same size as fully mature segmented neutrophils. Why is this a problem?
automated (machine-generated) counts of the types of leukocytes in a blood sample are based on the sizes of the cells
only way to know the proportion of bands is a labor-intensive counting by a trained human with a microscope (a “manual differential” white blood cell count
Why are band counts not very reliable?
hard to tell whether a neutrophil has a band nucleus that is folded over on itself
showing two distinct lobes lying on top of one another, which would make it a segmented neutrophil
band counts are not very reliable.
What are first responder phagocytes crucial in the rapid innate immune system response to acute infection?
What are phagocytes derived from blood monocytes?
Describe how long macrophages live in various tissues
live only a day in the blood
live months to years if they get recruited to become tissue macrophages
Monocytes and macrophages are part of the mononuclear phagocyte system. Name the other cells associated with the correct tissue
Kupffer cells in the liver,
sinus histiocytes in lymph nodes and spleen,
microglial cells in the central nervous system
alveolar macrophages in the lungs
What are the dominant players in chronic inflammation? When do they arrive to the site of damage?
macrophages arrive after neutrophils
Other than consuming bacteria and fungi, what other roles do macrophages play? What type of macrophages are these?
activated by microbes or interferon-gamma secrete IL-1, IL-12, IL-23 and chemokines,
summon and direct other inflammatory cells.
classical M1 activated macrophages
Macrophages activated by IL-13 and IL-14 are of what type? What is their role?
activated M2 macrophages
secrete transforming growth factor-beta and other growth factors that stimulate tissue repair and fibrosis
Which type of macrophages are pro-inflammatory vs anti-inflammatory?
M1 => pro-inflammatory
M2 => anti-inflammatory
Describe the shape of macrophages along with its nuclei
oval nuclei that can be flattened or indented on one side
abundant cytoplasm with small subtle granules and vacuoles
How would you recognize a monocyte in peripheral blood?
smears is blue-gray or “sky blue”
T/F Macrophages in tissue have variably colored cytoplasm depending on what they have eaten
Macrophages at the site of a recent hemorrhage have what color cytoplasm? why? At this point, what are they called?
Macrophages at the site of a recent myocardial infarction contain what? Why?
lipofuscin (wear and tear pigment) released from the dead myocytes in addition to hemosiderin
Macrophages in a pneumonia after about the third day and in arterial atheromas have bubbly cytoplasm cleared of lipid debris by tissue processing and are called what?
T/F Macrophages are the dominant players in the multi-cell-type drama of chronic inflammation.
What are the fundamental cellular players in the adaptive immune system?
Which cells carry out cell mediated immunity?
What cells carry out humeral immunity?
Of the lymphocytes in the bloodstream, Give the avg levels
60-70% are T cells
10-20% are B cells
What helps B cells make antibodies and help macrophages destroy phagocytosed microbes?
CD4 T cells
What cells are involved in directly killing virus-infected cells and malignant tumor cells?
CD8 T cells
What is The importance of the CD4+ helper T lymphocytes in the adaptive immune system?
What are also the fundamental cellular players in most autoimmune diseases?
Predominantly lymphocytic inflammation can be due to what?
nfection or an autoimmune disease
A few acute conditions such as aseptic meningitis feature what type of inflammation?
lymphocytic rather than neutrophilic inflammation
cerebrospinal fluid in a classic case contains what?
xclusively mononuclear cells, predominantly lymphocytes
but no neutrophils
Describe the shape/size of lymphocytes of nuclei and cytoplasm
small round dense nuclei
B lymphocytes and T lymphocytes look the same until when?
become abnormal or the B cells begin differentiating into plasma cells
What are derived from activated B cells and produce large amounts of single-specificity antibody in adaptive humoral immune responses?
What are terminally differentiated supersubspecialized immunoglobulin factories?
T/F Plasma cells are not normally present in peripheral blood
What type of cells have nuclear chromatin clumped around the periphery, sometimes in a “clockface” configuration? What else do these cells have?
prominent perinuclear Golgi apparatus
What are granulocytic leukocytes characteristically found in the inflammation around parasitic infestations and in allergic reactions, especially asthma?
What type of cells participate most in immune reactions that are mediated by IgE type immunoglobulin?
eosinophil granules contain what? What is the result?
major basic protein
resulting in a highly charged cationic substance toxic to parasites but also to host cells
What is the characteristic of eosinophil granules?
T/F Eosinophil nuclei frequently have only 1 lobe.
false, Eosinophil nuclei frequently have only two lobes.
Peripheral blood eosinophilia should prompt a search for what?
an allergen or a parasite.
What are sparsely distributed bone-marrow-derived sentinel cells around blood vessels, nerves and skin?
What type of inflammation do they participate in?
both acute and chronic inflammation
What has prominent cytoplasmic granules loaded with histamine?
Mast cells have chemotactic factors for what?
neutrophils and eosinophils,
platelet-activating factor and
cytokines such as tumor necrosis factor-alpha and IL-4.
Mast cells and basophils have surface receptors for what?
What happens when mast cells and basophils are stimulated by IgE bound to an antigen?
they degranulate and release their cornucopia of chemicals
What causes vasodilatation and endothelial cell contraction (creating gaps for fluid to extravasate from the blood)? What is the result in this?
Histamine (and leukotrienes)
mediating the vascular changes of inflammation
Multinucleated giant cells in a site of chronic inflammation generally represent what?
a syncytium of macrophages
There are multiple morphological types, but the two most common are what of the multinucleated giant cell?
the foreign body type
What forms when a single macrophage finds itself unable to engulf and phagocytose a large particle and it coalesces with additional macrophages in an effort to ingest the particle?
Foreign body type giant cells
What are associated with immune granulomas?
Langhans type giant cells
What is an aggregate of activated macrophages working together?
What is a distinctive form of chronic inflammation associated with autoimmune and infectious diseases?
What is a response to persistent material too large or undigestible for clearance, including talc and some types of suture?
foreign body granuloma
What forms when persistent antigen induces a cell-mediated immune reaction in, for instance, tuberculosis or sarcoidosis?
immune type granuloma
Cells that are not macrophage syncytia occur in multiple types of malignant tumors and in normal placentas are what?
Multinucleated giant cells
Describe the nuclei of the different multinucleated giant cell
Foreign body type giant cells=> haphazardly arranged nuclei.
Langhans type giant cells=> nuclei arranged peripherally in a horseshoe (semicircle).
Describe macrophages that form Langhans type giant cells
cytoplasm is smoother and more eosinophilic than typical macrophages and
referred to as epithelioid.
Whenever two or more activated macrophages gather together in the name of chronic inflammation, what is it called?
What are the chronic inflammation players?
Multinucleated giant cells