Pathoma Chapter 2 Inflammation
Terms in this set (56)
What is the co-receptor with TLR4 that recognizes LPS?
The overall function of prostaglandins is __. Which prostaglandin mediates pain and fever?
Vasodilation and increasing vascular permeability
Which leukotriene attracts neutrophils?
C3a and C5a both have this action __. C5a also does this
Both activate mast cells; C5a attracts neutrophils
Mediators that attract neutrophils (4)
What is the mechanism behind vascular permeability (mechanically)?
Pericytes contract to pull endothelial cells apart
Immediate vs. delayed response of mast cells
Immediate - release of histamine granules
Delayed - production of arachnidonic acid metabolites, particularly leukotrienes.
3 complement activation pathways
Classical - C1 binds IgG/IgM that is bound to antigen
Alternative - microbial products activate complement
MBL - MBL binds to mannose on bacteria
Factor XII (also known as __) activates these 3 systems
Coagulation and fibrinolytic systems
Kinin system (HMWK -->bradykinin)
Bradykinin mediates (3)
Pain in inflammation is mediated by
PGE2 and bradykinin
COX activity takes place in
Perivascular cells of the hypothalamus
Leukocyte rolling is mediated by __. Adhesion is mediated by __.
P-selectin is released from __, mediated by __.
E-selectin is induced by __ and __.
Weibel-Palade bodies; histamine
IL-1 and TNF
Selectins bind __ on leukocytes
CAMs bind __ on leukocytes
Integrins are upregulated on leukocytes by __ and __.
C5a and LTB4
Leukocyte adhesion deficiency is usually due to an autosomal recessive defect of __, specifically __. At birth it presents with __, and in blood you would see __.
Delayed separation of the umbilical cord (neutrophils help to break it down and detach it)
Increased circulating neutrophils (they can't stay in the marginated pool because of impaired adhesion)
Autosomal recessive protein trafficking defect
Can't "railroad" the phagosome to the lysosome
- Neutropenia because you can't pull the two cells apart during division
- Giant granules because you can't distribute the Golgi products and they fuse
- Defective hemostasis because of abnormal dense granules in platelets (same principle as above)
- Albinism - melanocytes distribute pigment to other cells
- Peripheral neuropathy - some nerves are really long
O2 is converted to superoxide by __
Superoxide --> H2O2 by __
H2O2 to HOCl (bleach) by __
Chronic granulomatous disease (CGD) vs. MPO deficiency
Nitroblue tetrazolium test results for each
CGD - defect of NADPH oxidase; NBT abnormal
Recurrent infection of catalase + organisms (p. cepacia)
MPO - defect of MPO; NBT normal
Usually asymptomatic, more Candida susceptibility
CD4+ cells use MHC __
CD8+ cells use MHC __
Co-receptor with TCR (T cell receptor)
T cell binding always needs a 2nd activation signal.
__ on APC binds __ on CD4+ T cell
__ on B cell binds __ on CD4+ T cell
B7; CD28 (28/7 = 4)
Cytokines released by Th1 CD4+
Cytokines released by Th2 CD4+
IL-4, IL-5, IL-10
Th1 secretes IL-2 and IFN-y, what are their functions?
IL-2 - T cell growth factor and CD8+ activator
IFN- y activates macrophages
Th2 secretes IL-4, IL-5, and IL-10, what are their functions?
IL-4 - B cell class switching to IgG and IgE
IL-5 - eosinophil chemotaxis and activation, maturation of B cells to plasma cells, class switching to IgA
IL-10 - inhibition of Th1 phenotype
What is the 2nd activation signal for CD8+ T cells?
IL-2 release from CD4+ Th1 cells
What is the key cell type of granulomas?
Epithelioid macrophages (histiocytes), surrounded by giant cells and a rim of lymphocytes
Difference between caseating and noncaseating granulomas? Which one is seen in Crohn's disease?
Caseating - exhibit central necrosis
What are some etiologies of noncaseating granulomas?
Cat scratch disease
Describe the inflammatory loop leading to granulomas
Macrophages present antigen to CD4+ T cells
The interaction leads macrophage to secrete IL-12, which differentiates T cell into Th1 type
The Th1 cells secrete IFN-y, which activates macrophages further
What cytokine differentiates CD4+ T cells into Th1 subtype?
What is the only primary immunodeficiency? What is the chromosomal abnormality
DiGeorge syndrome (absence of 3rd and 4th pharyngeal pouches)
Etiologies of SCID
Defects in cytokines
Deficiency of MHC class II
Why doesn't it present until 6 months of age?
Complete lack of Ig due to disordered B cell maturation (can't mature to plasma cells)
Mutated Bruton tyrosine kinase
Recurrent bacterial, enterovirus, and giardia infections
maternal antibodies are protective until then
Common variable immunodeficiency (CVID)
Low Ig due to B/T cell defects
Bacteral, enterovirus, and giardia infections
Increased risk for autoimmune disease and lymphoma
This disease is associated with IgA deficiency
Mutated CD40L on T cell, or CD40 on B cell
Can't receive the signal to class switch
Recurrent pyogenic infection, mucosal sites especially
Genetics and inheritance
Defective humoral and cell immunity
Thrombocytopenia, eczema, recurrent infection
WASP gene, X-linked
C1 inhibitor deficiency results in __.
Hereditary angioedema - periorbital and mucosal edema
(overaction of complement system)
What kind of renal damage is seen in SLE?
Diffuse proliferative GN
What is a classic cardiac finding in SLE?
Libmann-Sacks endocarditis - small, sterile vegetations on both sides of the mitral valve
This autoantibody is characteristic of drug induced SLE. Drugs that can precipitate this are (3)
Procainamide, Hydralazine, Isoniazid
This Ab will lead to a false-positive syphilis test in SLE
What is the PTT in an SLE pt with antiphospholipid Ab (30% of SLE pts)
Falsely elevated PTT
Hypercoagulable - Budd-Chiari, placental thrombosis leading to recurrent pregnancy loss, stroke
Sjogren syndrome is autoimmune destruction of __ and __.
It is a Type __ hypersensitivity
What is the Ab seen?
Salivary and lacrimal glands
IV (T-cell mediated)
ANA, antiribonucleoprotein Ab (Anti-SS-A/Ro and Anti-SS-B/La)
Normally in Sjogren's, you'll see bilateral enlargement of the parotids. If you see a new, unilateral growth, think
B cell (marginal) lymphoma
Autoimmune tissue damage with activation of fibroblasts and collagen deposition
Diffuse type scleroderma
Localized type scleroderma
ANA and anti-DNA topoisomerase I (Scl-70) Abs
Skin and early visceral involvement - dysphagia
Local skin and late visceral
Mixed connective tissue disease
U1 ribonucleoprotein Ab
Mixed SLE, sclerosis, and polymyositis features
What is the labile tissue of the lung?
Type II pneumocytes
Scar formation is the replacement of type __ collagen with type __ collagen. __ removes the first type. It requires __ as a cofactor.
Type III collagen is present in
Granulation tissue, embryonic tissue, uterus, keloids
Primary vs secondary intention in wound healing
Primary - wound edges brought together (i.e, surgery closure)
Secondary - defect is filled with granulation tissue and myofibroblasts contract the wound
Vit C, copper and zinc are necessary for wound healing. What are they each cofactors for?
Vit C - hydroxylation of proline and lysine residues for eventual cross-linking
Copper - lysyl oxidase, which cross links lysine and hydroxylysine
Zinc - collagenase - replaces Type III with Type I collagen