Inflammation/Wound Healing Flashcards
Which cells of the immune system has cells with TLRs? Adaptive?
innate = macrophages and dendritic
adaptive = lymphocytes
What activates TLRs?
PAMPs
What is the CD molecule of macrophages?
CD14
What molecule does CD14 recognize?
LPS
TLR activation activates which txn factor?
NF-KB
What class of molecules does cycloxygenase produce?
prostaglandins
What class of molecules does 5-lipoxygenase produce?
leukotrienes
What are the three main prostaglandins produced from cycloxygenase? What two effects do these prostaglandins mediate?
PGE2/PGI2/PGD2
vasodilation and increased vascular permeability
What prostaglandin mediates fever and pain?
PGE2
Which leukotriene attracts neutrophils?
LTB4
What three effects are mediated by C4, D4 and E4?
vasoconstriction
bronchospasm
increased vascular permeability
Which two complement proteins can activate mast cells?
C3a and C5a
Which immunoglobulin can crosslink to activate mast cells?
IgE
Do mast cells release leukotrienes or prostaglandins?
leukotrienes
In the classical complement pathway, which two proteins activate C1?
IgG and IgM
Which ligand on bacteria can a complement protein bind? Which complement protein?
mannose
mannose-binding lectin
What protein do the classical and alternative complement activation pathways meet at?
C3 Convertase
Which proteins are contained within the MAC? Which C5?
C5-C9
C5b
Which complement protein is a chemoattractant for neutrophils?
C5a
Which complement protein is an opsonin?
C3b
What is another name for Factor Twelve? What activates this factor?
Hageman Factor
collagen
Which complement protein activates the Kinin system?
Factor twelve
What is another name for redness?
rubor
What is another name for warmth?
calor
Which molecule produces endothelial cell contraction?
histamine
What are the two mediators of pain?
bradykinin and PGE2
Which molecule from bacteria mediates fever?
LPS
Pyrogens from bacteria cause WHAT CELL to release which two mediators to produce fever?
macrophages
TNF and IL1
Which cells of the hypothalamus contain cycloxygenase? Which prostaglandin activates them?
Perivascular
PGE2
Which molecule mediates the release of P-selectin from WP bodies?
histamine
Which two proteins mediate the increase in E-selectin?
TNF and IL-1
Which protein do selectins BIND on inflammatory cells? What cell type is this protein found?
sialyl Lewis X
leukocytes
What cells express ICAM and VCAM?
endothelium
Which two cytokines upregulate ICAM and VCAM?
TNF and IL1
Which cells express integrins?
Leukocytes
Which two cytokines upregulate integrins?
C5a and LTB4
What general class of protein is deficient Leukocyte Adhesion Deficiency? Leukocyte adhesion deficiency would possess a lack of what CD molecule?
INTEGRINS
CD18
Which interleukin is responsible for macrophage mediated recruitment of neutrophils?
IL-8
Which complement protein is responsible for neutrophil attraction?
C5a
Which leukotriene is responsible for neutrophil attraction?
LTB4
What are the two main opsonins?
IgG and C3b
What is defective during Chediak-Higashi syndrome? Involving what protein?
protein trafficking deficiency
microtubules
The formation of what intracellular organelle is impaired during Chediak-Higashi Syndrome?
phagolysosome
Would Chediak-Higashi Syndrome result in neutropenia or neutrophilia?
neutropenia
What would be seen inside the leukocytes during Chediak-Higashi Syndrome? From which organelle?
fusion of giant granules
Golgi
What hematological defect is present duringChediak-Higashi Syndrome? Why?
defective platelet function
abnormal dense granules in platelets
What would be obvious during Chediak-Higashi Syndrome on physical exam? Why?
albinism
melanocytes cant disperse melanin
Other than albinism, what is the 2nd most common presenting symptom of Chediak Higashi syndrome?
peripheral neuropathy of DISTAL limbs
Which free radical is created by NADPH Oxidase?
superoxide
What rxn is catalyzed by Superoxide Dismutase?
superoxide to H2O2
What rxn is catalyzed by Myeloperoxidase?
H2O2 to HOCl
What enzyme is often absent during Chronic Granulomatous Disease?
NADPH Oxidase
Organisms possessing what enzyme are often the culprits for infection during Chronic Granulomatous Disease?
catalase
What is the mnemonic to remember the catalase positive organisms?
PLACESS
What is the P of PLACESS? Specific species?
pseudomonas
species = cepacia
What is the L of PLACESS?
Listeria
What is the A of PLACESS?
Aspergillus
What is the C of PLACESS?
Candida
What is the E of PLACESS?
E. coli
What are the S’s of PLACESS?
Serratia
Staph
What stain is used to screen for CGD?
Nitroblue tetrazolium
What is the anti-inflammatory interleukin?
IL-10
What is the anti-inflammatory cytokine?
TGF-β
Which two immune cells are indicative of chronic inflammation?
lymphocytes and plasma cells
What two proteins compose the TCR Complex?
TCR and CD3
Regarding T-cell activation, what protein is on the APC? What protein is on the CD4 cells?
CD4 = CD28
APC = B7
Would IFN-γ be indicative of a TH1 or TH2 response?
TH1
What are the two functions of IFN-γ?
activates macrophages
IgM to IgG switching
Which three interleukins does TH2 secrete?
IL4
IL5
IL13
What is the function of IL4?
isotype switch to IgE
What are the two functions of IL5?
recruit eosinophils
isotype switching to IgA
What is the function of IL13?
functions similar to IL4
What is the function of IL2?
2nd activation signal to CD8 T-cells
Which two immunoglobulins do naive B-cells express?
IgM and IgD
What metal is known to cause granulomatous inflammation?
Beryllium
Which infection can cause granulomatous inflammation?
Cat Scratch Fever
What two types of infections produce a caseating granuloma?
TB and fungal infections
What is the function of IL12?
induces CD4 cells to differentiate into TH1 subtype
What two metabolites build up in lymphocytes during SCID?
adenosine and deoxyadenosine
At what age would X-linked agammaglobulinemia present? Why?
6 months
mothers Ab’s are protective until this point
What three infections often present during X-linked Agammaglobulinemia?
recurrent infections
enterovirus
Giardia
Which has a necrotic core, caseating or non-caseating?
caseating
What two diseases is a patient with Common Variable Immunodeficiency at risk for developing?
Autoimmune
Lymphoma
What two proteins are defective during Hyper IgM Syndrome? What is the result of this?
CD40 and/or CD40L
B-cells cant undergo isotype switching
What is the triad of Wiskott Aldrich Syndrome?
thrombocytopenia
eczema
ecurrent infections
What is the major cause of death in patients with Wiskott-Aldrich Syndrome?
bleeding
C5-C9 defects predispose an individual to develop infections with what bug?
Neisseria
Hereditary Angioedema is caused by a defect in what protein? Why are the findings produced?
C1
C1 is constanly activating complement and activating
HMWK cleavage leading to bradykinin induced angioedema
AIRE mutations produce what sydrome? What is lost during this process?
Autoimmune Polyendocrine Syndrome
central tolerance
Autoimmune Lymphoproliferative Syndrome is due to mutations in what protein?
Fas apoptosis pathway
CD25 Polymorphisms are associated with what two diseases?
Diabetes Mellitus
Multiple Sclerosis
FOXP3 mutations lead to what disease?
IPEX
Which complement proteins are normally deficient in lupus? What is the function of these complement proteins?
early complement
clear antigen/antibody complexes
Which three early complement proteins are often deficient during SLE? What does this complex function as?
C1q, C2 and C4
C3 Convertase
Does lupus present with lymphadenopathy?
yes
What vascular abnormality can lupus cause?
Raynaud
What is the most severe form of SLE induced renal injury/
Diffuse Proliferatvie Glomerulonephritis
What type of endocarditis does SLE produce? Which valve? Which side?
Libmann Sacks
mitral
both sides
What are the two highly specific antibodies for lupus ?
anti-dsDNA
anti-smith
What are three important anti-phospholipid antibodies produced during lupus?
anti-cardiolipin
anti-β2 glycoprotein I
Lupus anti-coagulant
Anti-cardiolipin can give a false positive when screening for what disease?
Syphillis
What condition is anti-coagulant antibody associated with?
Hypercoaguable with elevated aPTT
Drug induced lupus will have auto-antibodies produced against what antigen?
Histone
What three drugs clasically produce lupus?
Procainamide
Isoniazid
Hydralazine
What should pateints with lupus avoid?
direct sunlight
What two glands are destroyed during Sjogrens Syndrome? What TYPE of hypersensitivity rxn?
lacrimal and salivary
type IV
What other disease is Sjogrens Syndrome likely to present with?
rheumatoid arthritis
Which three auto-antibodies does Sjogrens Syndrome often present with?
anti-SSA/Ro
anti-SSB/La
Rheumatoid Factor
What is the antigen for anti-SSA and anti-SSB?
ribonucleoprotein
Pregnant women with anti-SSA are at risk for delivering babies with what two conditions?
neonatal heart block
congenital lupus
What biopsy on the body can aid in the diagnosis of Sjogrens Syndrome? Where?
Lymphocytic Sialadenitis
LIP
What type of Lymphoma can Sjorens Syndrome produce? How does this present?
Marginal Zone Lymphoma
unilateral enlargement of the parotid
Which two organs undergo sclerosis during Systemic Sclerosis?
skin and visceral organs
Which autoantibodies present during CREST syndrome? Diffuse or limited?
anti-centromere antibodies
Limited
Where does Limited Type systemic sclerosis present?
hands and face
What four organs does Diffuse Type systemic sclerosis present?
Vessels
GI tract
lung
kidneys
How does Diffuse Type systemic sclerosis present in the GI tract?
esophagitis
How does Diffuse Type systemic sclerosis present in the Lungs?
interstitial fibrosis
pulmonary HTN
How does Diffuse Type systemic sclerosis present in the Vessels?
Reynaud
Which auto-antibody is often found during diffuse Systemic Sclerosis? What is the antigen for this AB?
anti-scl-70
DNA topoisomerase I
Which two autoantibodies are present during Mixed Connective Tissue Disorder?
ANA
anti-U1 ribonucleoprotein
What is the stem cell of the lung?
Type II pneumocytes
What structure are the stem cells of the GI tract contained?
mucosal crypts
What type of collagen is contained within fibroblasts?
Type III
What type of collagen is removed by collagenase? What is the cofactor for Collagenase?
Type III
zinc
What are the two growth factors for angiogenesis?
FGF and VEGF
What enzyme is copper a cofactor for?
Lysyl Oxidase
What does lysyl oxidase connect?
lysine and hydroxylysine
What type of collagen does collagenase replace type III collagen with?
Type I
What type of collagen is found in keloids?
Type III
Which cell count can increase during an acute MI?
Neutrophils
What type of molecule is CD14?
TLR
What molecule does CD14 recognize?
LPS
Leukotrienes cause which cells contract to increase vascular permeability?
pericytes
What is the four ways to activate mast cells?
Tissue trauma
C3a
C5a
cross-linked IgE by antigens
What is the immediate response of mast cell activation?
release of preformed histamine
What is the maintenance response of mast cell activation?
synthesis of leukotrienes
What is the function of mast cells releasing leukotrienes?
potentiating acute inflammation
What is another name for swelling?
tumor
What is another name for warmth?
calor
What structure mediates swelling?
post-capillary venules
By what mechanism do PGE2 and bradykinin produce pain?
sensitize nerve endings
Where does vasodilation occur?
postcapillary venule
What would be the first finding to arise due to Leukocyte Adhesion Deficiency?
delayed sepration of the umbilical cord
Would Leukocyte Adhesion Deficiency have an increased or decreased level of circulating Neutrophils? Why?
increased
inability of neutrophils to ‘hang’ and be marginated in the lungs
What are the three chemoattractant molecules for neutrophils?
LTB4, IL8, C5a
MPO deficiency puts a patient at an increased risk for developing infections cause by what organism?
Candida
How do neutrophils clear from a tissue after an infection? Forming what?
apoptosis
pus
Do macrophages rely more on oxygen dependent or oxygen independent killing? Via what enzyme?
oxygen independent
lysozyme
What is the primary mechanism by which macrophages kill pathogens?
enzymes
What interleukin is used to macrophages to recruit more neutrohils to a site of inflammation?
IL8
Which MHC molecule is located on platelets?
MHC one
Do CD4 or CD8 cells express FasL?
CD8
What is the first mechanism by which B-cells become activated? What is the result of this?
antigen binds IgM or IgD on B-cells
turns B-cell into plasma cell
What is the second mechanism by which B-cells become activated?
CD40 of B-cell binds CD40L on helper T-cell
What is the key defining feature of a granuloma?
epithelioid histiocytes
What two types of cells would an Epithelioid Histiocyte be surrounded by?
Giant cells
plasma cells
A stellate shaped granuloma is indicative of what disease?
Cat Scratch Fever
Would a TH1 or TH2 response generate a granuloma?
TH1
What is the main cytokine that drives the formation of Epithelioid Histiocytes?
IFN-gamma
What is the specific genetic mutation of DiGeorge Syndrome?
22q11 microdeletion
What two major presentations would a patient with DiGeorge Syndrome present with ?
recurrent infections
hypocalcemia
What is the 2nd mechanism by which a SCID may develop, other than Adenosine Deaminase?
MHC Two dysfunction
What cellular maturation defect is present in X-linked Agammaglobulinemia?
B-cells cant mature into plasma cells
What enzyme is defective in X-linked Agammaglobulinemia?
Brutons Tyrosine Kinase
What infections are a patient with Common Variable Immunodeficiency susceptible to?
bacterial
enterovirus
Giardia
Which cytokines would not be produced during Hyper IgM Syndrome? What type of infections? Where?
IgA/IgG/IgE
pyogenic
mucosal sites
Where on the body would a patient with Hyper IgM Syndrome most likely get an infection?
Mucosal sites
What is the most often site of edema during C1 Inhibitor Deficiency?
periorbital
What three condtions present in a apatient with Autoimmune Polyendocrine Syndrome?
Hypoparathyroidism
Adrenal Failure
recurrent Candida infections
What CD molecule is the Fas receptor?
CD95
Fas (CD95) apoptosis pathway mutations result in what syndrome?
Autoimmune Lymphoproliferative Syndrome
What are the three molecules of Tregs?
CD4+
CD25+
FOXP3+
How do Tregs suppess autoimmunity?
block T-cell activation
What special regulatory protein do Tregs express?
CTLA-4
What is the function of CTLA4? What can this lead to?
bind/inhibit B7
anergy
Which two anti-inflammatory cytokines can Tregs secrete?
TGF-β
IL-10
Which CD molecule is the IL2 Receptor?
CD25
FOXP3 mutations are associated with what syndrome? What does this syndrome stand for?
IPEX syndrome
Immune Dysregulation
Polyendocrinopathy
Enteropathy
X-linked
According to Sattar, what is the reason women more often present with autoimmune disease?
estrogen reduce apoptosis of self-reactive Bcells
Regarding Early Complement, what is the function of C3B?
act as opsonin to clear Ag/Ab complex
What is the most common early complement protein whose deficiency can lead to lupus?
C2
What type of hypersensitivity rxn would blood component problems be during Lupus?
Type Two
Which anti-body can be used as a prognostic antibody and to follow the disease activity of lupus?
anti-dsDNA
What are the two most common causes of death in lupus patients?
renal failure or infection
What are the three most typical presentations for Sjogrens Syndrome?
Dry eyes
dry mouth
recurrent dental caries
An immune reaction against what type of tissue is believed to initiate Systemic Sclerosis?
mesenchyme
Which two cell types are believed to be involved in the pathogenesis of Systemic Sclerosis? Which vasoconstrictor?
mesenchyme and endothelial
endothelin
What cell type can become activated during systemic sclerosis? What two cytokines are released?
Platelets
TGF-β and PDGF
Which part of CREST is the first to appear in a patient with systemic sclerosis?
Reynaud
In what layer of the epidermis are the stem cells located?
Stratum basale
Name two stable tissues?
liver
PCT
What type of collagen is seen in granulation tissue?
Type III
TGF-α is an important growth factor for what two cell types?
epithelial and fibroblasts
TGF-β is an important growth factor for what two cell types?
fibroblasts
PDGF is an important growth factor for what three tissues?
endothelial
smooth muscle
fibroblasts
What is dehiscence?
rupture of a wound
Interactions between what two proteins cause leukocytes to adhere to endothelium?
Integrins and CAMs
What is CD18?
Integrin β2
What type of hypersensitivity reaction is Sjogrens?
Type 4
Which three inflammatory mediators mediate arteriolar smooth muscle contraction?
bradykinin
prostaglandins
histamine
Which 3rd and 4th structure is absent during DiGeorge?
pharyngeal pouch
Which two viruses present during X-linked Agammaglobulinemia?
polio and coxsackie
What other autoimmune disease is most likely to present during Sjogrens?
Rheumatoid
What other autoimmune disease is Rheumatoid Factor present even though Rheumatoid Arthritis may not be present?
Sjogrens
What gland is involved with Sjogrens Syndrome transformring into a lymphoma?
Parotid
Where is LPS located on gram-negative proteins?
outer membrane
What is the relationship between Hagemann Factor and gram-negative bacteria?
DIC
What two proteins are contained in Weibel-Palade bodies?
P-selectin
vWF
Which species of Pseudomonas is mentioned as catalase positive?
cepacia
What type of cell forms a rim around a granuloma?
lymphocytes
Selective IgA Deficiency patients are at particular risk for what type of pathogen infection?
viral
What disease is particularly common in patients with IgA Deficiency?
Celiac
Which CD molecule mediates peripheral tolerance?
CD95
Which interleukin can limit MHC Two expression?
IL-10
What is the trigger for lupus?
UV damage
Can lupus cause pancytopenia? What type of hypersensitivity rxn?
yes
type two
Are CNS and renal involvement common on rare in drug induced lupus?
rare
Within how long do neutrophils undergo apoptosis with a lack of inflammatory signal?
24 hours
Mixed Connective Tissue has characteristics of which three diseases?
Lupus
systemic sclerosis
polymyositis
At what structure do prostaglandins mediate vasodilation?
arterioles
At what structure do prostaglandins mediate increased vascular permeability?
post-capillary venule
Which activates the Alternative Complement pathway?
bacterial products
Which cells express selectins?
endothelial
Why would Chediak-Higashi produce a defect in primary hemostasis?
defective dense granules in platelets
What is the mode of inheritance of Chediak Higashi?
autosomal recessive
Which stain to differentiate a TB in a TB vs. fungal caseating granuloma?
TB = AFP
Which stain to differentiate a Fungal in a TB vs. fungal caseating granuloma?
fungal = GMS
Which two specific types of Bcells are arrested in their growth during X-Linked Agammaglobulinemia?
pre-B
pro-B
Patients with X-Linked Agammaglobulinemia will get what three type of infections?
Bacteria
Enterovirus (polio and coxsackie)
Giardia
Patients with Common Variable Immunodeficiency will get what three type of infections?
Bacteria
Enterovirus (polio and coxsackie)
Giardia
Is CD40 or CD40L on Tcells?
CD40L
Is CD40 or CD40L on Bcells?
CD40
Where in the thymus does negative selection occur?
medulla
Where in the thymus does positive selection occur?
cortex
What kind of protein is AIRE? What is the function of AIRE?
transcription factor
transcribe self antigens
Which syndrome ensues if Fas Ligand is absent?
Autoimmune lymphoproliferative syndrome
Other than HLAB27, what gene is implicated in many autoimmune disorders?
PTPN22
Can lupus cause pancytopenia?
yes
Does PT or PTT get falsely elevated during lupus?
PTT
Which two organs are not affected by drug induced lupus?
CNS and renal
What does lupus do to CV System?
accelerated atherosclerosis
SSA and SSB are associated with what type of manifestation?
extraglandular
Which sjogren antibody can cross the placenta?
SSA
What is the most common cause of death in Diffuse Type Scleroderma?
pulmonary
What is the function of lysyl oxidase?
cross-link lysine and hydroxy-lysine
What type of collagen in a keloid?
type three
