Flashcards in 2. Inflammation, Inflammatory Disorders, and Wound Healing Deck (85):
What activates TLRs?
What is the TLR4 co-receptor on macrophages that recognizes LPS (gram negative bacteria)?
What is the role of prostaglandins (E2, D2, and I2)?
vasodilation and increased vascular permeability
What is the more specialized role of PGE2?
mediates Fever and Pain
What is the role of LTC4, LTD4, and LTE4?
Vasoconstriction, bronchospasm, increased vascular permeability
What are the 4 mediators of neutrophil migration?
In what 3 ways are mast cells activated?
-Complement C3a or C5a
-Crosslinking of cell-surface IgE by Ag
What are the actions of histamine?
Increase vascular permeability (at post capillary venules)
What allows for delayed and prolonged response to histamine?
What can Hageman factor (Factor XII) lead to?
DIC (gram negative sepsis)
What are the roles of bradykinin?
Increased vascular permeability
What causes the rubor and calor of inflammation?
What causes the tumor of inflammation?
increased vascular permeability and tissue damage
What causes the fever of inflammation?
Macrophages release IL-1 and TNF which increase COX activity from the hypothalamus and increase PGE2 to raise the temperature set point
What molecules lead to "rolling" of neutrophils?
From where are P-selectins released and what is the stimulus?
histamine causes release of P-selectin from Weibel Palade bodies
What induces the release of E-selectins?
TNF and IL-1
To what do selectins bind on leukocytes?
sialyl Lewis X
What molecules lead to adhesion of the leukocytes?
ICAM and VCAM (upregulated by TNF and IL-1)
What is the cause of Leukocyte adhesion deficiency?
AR defect of integrins (CD18 subunit)
18 yo LADs have no INTEGRity
Into what type of vessels do leukocytes transmigrate across?
What is the underlying problem in Chediak-Higashi Syndrome?
protein trafficking defect due to decreased microtubule system (so no phagolysosomes can be formed)
In the O2 dependent killing pathway, what defect will NOT show blue NBT dye?
Chronic granulomatous disease
What is the underlying cause of chronic granulomatous disease?
AR or XL NADPH oxidase defect
What type of bacterial infection is seen in chronic granulomatous disease?
Catalase Positive bacteria
List the most high yield catalase positive bacteria.
In the O2 dependent killing pathway, what defect will show blue NBT dye?
MPO deficiency (because there is a normal NADPH oxidase)
What is the presentation of a patient with NADPH oxidase deficiency?
Candida infections (but mostly asymptomatic)
What happens to neutrophils post inflammation?
they undergo apoptosis
How do macrophages destroy phagocytosed bacteria?
enzymes (ex. lysozyme) in secondary granules that use O2 dependent killing
List the two anti-inflammatory cytokines released from macrophages during resolution and healing.
What cytokine released by macrophages recruits additional neutrophils for "continued acute inflammation"?
What type of T cell recognizes MHC class I?
What type of T cell recognized MCH class II?
What is the secondary activation signal for CD4+ T cells?
B7 on APC binds to CD28 on the T cell
What is secreted by Th1 cells?
What is secreted by Th2 cells?
What is the secondary activation signal for CD8+ T cells?
IL-2 from CD4+ Th1 cells
How do CD8+ T cells kill cells?
Perforin makes pores, granzyme enters, activation of caspase, apoptosis
Express FasL which binds to Fas on target cells
B cells present antigen to what kind of T cell?
CD4+ T cells
What is the second activation signal that B cells give to their CD4+ T cells?
CD40 on B cell binds to CD40L on T cell
What is the defining characteristic of granulomatous inflammation?
What are the other two features of granulomas that are commonly seen (other than epithelioid histiocytes)?
giant cells and rim of lymphocytes
List the top 5 causes of noncaseating granulomas.
-Cat-scratch disease (stellate shaped)
What do you immediately do when you see a caseating granuloma?
AFB for Tb
GMS for fungal infections
(differentiate between the two causes)
What is the first step a macrophage does to form a granuloma?
present antigen via MHC class II to CD4+ helper cell
What does a macrophage do after presenting antigen via MHC Class II to CD4+ helper cell?
secretes IL-12 to induce the CD4+ to differentiate into Th1
What do Th1 cells secrete to convert macrophages into epithelioid histiocytes?
What is the developmental defect in DiGeorge syndrome?
failure of the 3d and 4th pharyngeal pouches to develop
What is the chromosome mutation in DiGeorge?
What is one of the underlying causes of SCID?
Adenosine deaminase (ADA) deficiency
What is ADA?
necessary enzyme for deaminaion of adenosine and deoxyadenosine for excretion as waste products (if these are not excreted, they build up and are toxic to lymphocytes)
What is mutated in XLA?
Bruton tyrosine kinase
What are the 3 infections that occur due to lack of B cells?
bacterial (can't opsonize)
Enterovirus (low mucosal IgA)
Giardia lamblia (low IgA in GI)
People with CVID are at increased risk for what 2 conditions?
In what condiiton is IgA deficiency commonly seen?
What is the cause of Hyper IgM?
Mutated CD40L or CD40 receptor so helper T cells cannot get the secondary activation signal from B cells and no class switching occurs
With what type of deficiency are Neisseria infections most common?
What is the most common renal disease seen in SLE?
diffuse proliferative glomerulonephritis
What is the characteristic auto-antibody seen in drug-induced SLE?
What 3 drugs cause drug-induced lupus?
How do you definitely diagnose Sjogren's syndrome?
Biopsy of salivary glands shows lymphocytic sialadenitis
What are the two types of scleroderma?
Which type of scleroderma is associated with CREST?
What is CREST?
Calcinosis (and anti-Centromere Ab)
Telangiectasias on skin
Which type of scleroderma has a better prognosis?
Which type of antibodies are seen in diffuse scleroderma?
anti-DNA topoisomerase II
What antibodies are seen in Mixed CT disease?
antibodies against U1 ribonucleoprotein and ANA
What is the marker of hematopoietic stem cells?
Which type of tissue cannot repair and must scar?
permanent tissues (ex. myocardium, skeletal muscle, neurons)
What goes on with collagen in healing?
Type III collagen is replaced by ype I collagen
Type I collagen is seen in what tissues?
Type II collagen is seen in what tissues?
Type III collagen is seen in what tissues?
granulation tissue, embryos
Type IV collagen is seen in what tissues?
Name the epithelial and fibroblast growth factor.
Name the fibroblast growth factor that also inhibits inflammation.
Name the growth factor for endothelium, smooth muscle and fibroblasts.
List the growth factor used for angiogenesis and mediation of skeletal development.
List the growth factor used for angiogenesis only.
How does a wound come together with secondary intention?
myofibroblasts contract the wound
Why is Vitamin C needed for wound healing?
Procollagen needs Vit C for hydroxylation before it can be cross-linked
Why is copper needed for wound healing?
needed by lysyl oxidase for collagen crosslinking
Why is zinc needed for wound healing?
collagenase cofactor to remove type III collagen