Pathoma Flashcards
Genetic disease associated with Apo-E allele mutation
Late set Alzhemiers
Disease caused by Amyloid precursor protein, presenilin 1 gene on chromosome 14, presenilin 2 gene on chromosome 1
Early onset Alzheimers
There is a killed (Salk) and live (Sabin) vaccine against the polio virus. Which one is better at prolonged synthesis and secretion of local mucosal IgA?
Live virus
What kind of test is used to compare the means of 2 groups of subjects?
Two-sample T-test
What does acetylcholinesterase in the amniotic fluid typically indicate?
Failed fusion (Neural tube defect) Note: Alpha-fetoprotein (AFP) in the amniotic fluid suggests the same thing. Lack of close of the neural tube allows for these things to leak out into the amniotic fluid.
TLR found on macrophages that recognizes the PAMP (lipopolysaccharide) on the outer membrane of gram negative bacteria.
CD-14
TLR activation results in upregulation of ______, a nuclear transcription factor that activates immune response genes leading to production of multiple immune mediators.
NF-kappaB
Enzyme that causes arachidonic acid release from the phospholipid cell membrane.
Phospholipase A2.
Remember, AA precursor of prostaglandins and thromboxanes (via cyclooxygenase COX) or leukotrienes (via 5-lipooxygenase).
What function do the prostaglandins PGI2, PGD2, and PGE2 have?
They all three mediate vasodilation and increased vascular permeability.
Note: PGE2 also causes fEver and pain.
What type of immune cells will you find toll-like receptors?
innate immune cells (macrophages and dendritic cells).
What type of leukotriene will attract and activate neutrophils?
LTB4
Note: C5a (complement), IL-8 and bacterial products also attract and activate neutrophils.
Which type of leukotrienes will contraction of smooth muscle (vasoconstriction and bronchospasm), as well as increased vascular permeability?
LTC4, LTD4, and LTE.
What type of cell is activated by one of these three methods:
- Tissue trauma
- Complement proteins C3a and C5a
- Cross linking the cell surface IgE by antigen
Mast cells-which are widely distributed throughout connective tissue.
Note: when they are activated, they release preformed histamine granules, which mediate vasodilation of the arterioles and increased vascular permeability.
Three ways to activate complement are:
Classical pathway
Alternative pathway
Mannose-binding lectin pathway
What is each ones of these about?
- Classical: C1 binds IgG or IgM that is bound to antigen.
* ***Mneumonic: GM makes classic cars. - Alternative: microbial products directly activate complement.
- MBL: MBL binds to mannose on microorganisms, which activates complement.
All complement pathways result in production of C3 convertase (mediates C3–>C3a and C3b), which in turn produces C5 convertase (mediates C5–>C5a and C5b). C5b complexes with C6-C9 to form the membrane attack complex (MAC).
What do the following cause to happen:
- C3a and C5a
- C5a
- C3b
- Mac
- C3a & C5a: anaphylatoxins: trigger mast cell degranulation, resulting in histamine-mediated vasodilation and increased vascular permeability.
- C5a: Chemotaxis for neutrophils
- C3b: Opsonin for phagocytes
- MAC: Lyses microbes by creating a hole in the cell membrane.
Inactive proinflammatory protein produced in the liver which is activated upon exposure to subendothelial or tissue collagen, which in turn activates:
- Coagulation of fibrinolytic systems
- Complement
- Kinin System—>cleaves kininogen to bradykin, which mediates vasodilation and increased vascular permeability (similar to histamine), as well as pain
Hageman Factor (Factor XII)
What are the five cardinal signs of inflammation?
- Redness (rubor)
- Warmth (calor)
- Swelling (tumor)
- Pain (dolar)
- Fever
In inflammation, rubor and calor (redness and warmth) are due to vasodilation, which results in increased blood flow. What are the key mediators of this?
Histamine, Prostaglandins (PGI2, PGD3, and PGE2), and bradykinin.
Inflammation during swelling occurs due to leakage of fluid from POSTCAPILLARY venues into the interstitial space (exudate). What are are the key mediators?
- Leukotrienes: cause endothelial cell contraction.
2. Tissue damage: results in endothelial cell disruption
You will see pain (dolar) involved with inflammation. What mediates this pain?
Bradykinin and PGE2 sensitize sensory nerve endings.
Macrophages are responsible for fever during inflammation. This occurs when pyrogens (LPS from bacteria) cause macrophages to release ________ and _________, which increase COX activity in per vascular cells of the hypothalamus, resulting in PGE2, which raises the temp set point.
IL-1 and TNF
In acute inflammation, you will neutrophils will:
- Marginate (due to vasodilation)
- Roll
- Adhere
- Transmigrate and chemotax
- Phagocytose
What causes the rolling?
P-selectin (released from Weibel-Palade bodies–>from histamine)
E-sectin (induced by TNF and IL-1)
Remember TNF and IL-1 are released from macrophages and also cause fever.
In acute inflammation, you will neutrophils will:
- Marginate (due to vasodilation)
- Roll
- Adhere
- Transmigrate and chemotax
- Phagocytose
- What are the molecules that cause cellular adhesion?
- What molecules cause the upregulation of these adhesion molecules?
- ICAM and VCAM: on endothelium upregulated by TNF and IL-1.
- Integrin: on leukocytes upregulated by C5a and LTB
Interaction between the CAMs and Integrins result in firm adhesion of leukocytes to the vessel wall.
Autosomal recessive defect of integrins (CD18 subunit)
**Clinical features include delayed separation of umbilical cord, increased circulating neutrophils, and recurrent bacterial infections that lack pus formation.
LAD: Leukocyte adhesion deficiency