What is the most common cause of […] in HIV patients?
… encephalitis
… chronic meningitis
encephalitis: Toxoplasma gondii
chronic meningitis: cryptococcus neoformans
What kind of molecule is hydrogen peroxide?
An oxidant
Which mediators play a role on chemotaxis, leukocyte recruitment and activation?
TNF
IL 1
LTB4
C3a
C5a
What is the function of NF-kB (Nuclear factor kappa B) and what mechanism of action targets it.
When inhibited and inflammatory signal present -> IKK act & binds -> separates NF-kB from inhibitor -> nucleus -> transcription of inflammation associated genes
targeting mechanisms: Nuclear translocation inh., Proteasome inh., DNA-binding inh, IKK inh
What is a necessary factor for wound healing?
Oxgen -> cofactor for the enzyme "Proline Hydroxylase" which functions in collagen biosynthesis (Type I & III)
At a site of vascular injury, when & where do platelets bind to von Willebrand factor?
Primary hemostasis (vWF in subendothelium)
Which Ig Isotype most abundant in the human immune system?
IgA
Which Ig Isotype In Hypersensitivity Type 1?
IgE
What is the function of IgG?
protects fetus (crosses placenta)
protects ISP
blocks TNF in Rheumatoid arthritis patients
desensitises patient against allergens
How & where are IgG recognized & function?
receptor for IgG (Fc) heavy chain on Phagocytes-> promotes opsonization & phagocytosis
Which disorder is caused by a defect in the ability of neutrophils to kill microorganisms ?
Chronic granulomatous disease
What are the effector cells of type IV hypersensitivities?
T cells (CD4+ & CD8+)
What medication has an effect on cancer risk?
NSAID (Aspirin) use reduces risk of colorectal cancer development in multiple studies.
What disease associated with those symptoms:
Assoc. with HLA-B27
Anti-La & Anti-Ro Ab
Early complement component deficiency (C1q, C2, C4)
Ab against desmosomes
Demyelinizing plaques
Assoc. with HLA-B27 -> Anclosing spondylitis
Anti-La & Anti-Ro Ab -> Sjögren’s syndrome
Early complement component deficiency (C1q, C2, C4) -> SLE
Ab against desmosomes -> Pemphigus vulgaris
Demyelinizing plaques -> MS
Describe all Hypersensitivity Types + example
IgE -> Allergy, Anaphylaxis
Myastenia Gravis, Graves disease, newborn Hemolytic disease
immune complex mediated, vasculitis, fibrinoid & vessel wall necrosis -> Acute Serum sickness, Arthus reaction
delayed, Granuloma formation -> Tuberculin test
What microorganism is associated with development of Guillain-Barre Syndrome (GBS)?
Campylobacter jejuni
Trophoblast cells
What is microsatellite instability (MSI) and how may it occur?
MSI is a condition of genetic hypermutability (predisposition to mutation) due to f.e. Impaired Mismatch repair system (MMR)
What mutation/repair mechanism does the MLH1 gene play role in?
Missmatch repair system
Hereditary nonpolyposis colon cancer (HNPCC) also called what?
Lynch syndrome
Which genetic mechanisms play a role in Turner Syndrome phenotype?
Haploinsufficiency
Chromosomal missegregation
What are characteristics of EMT (epithelial to mesenchymal transition)?
Acquisition of a fibroblast-like cell
Aquisition of cell motility
colonoscopy polyps sigmoid colon tubular neoplastic glands above basement membrane, what pathological diagnosis?
Adenoma
What methods detect translocations at the DNA level?
Real Time PCR
FISH (Fluorescent in situ hybridization)
Southern blotting
What method detects translocations at protein level?
Western blotting
What method used for HER2 gene amplification & what case?
HER2 gene amplification can be detected most likely by fluorescence-in situ hybridization (FISH) in some forms of breast cancer
What are clinical features in mitochondrial diseases associated with accumulation of mtDNA mutations with age?
Alzheimer's disease
Cancer
Diabetes mellitus
Heart failure (NOT Secondary hypertension)
What characteristics of Crimean Congo Hemorrhagic Fever Virus (CCHFV)?
Nairovirus (Bunyaviridae)
segm. RNA
Hyalomma ticks & human-to-human
What is involved in the transformation of infected cells by by animal retroviruses, human oncoretroviruses, DNA tumor viruses?
Viral oncogenes & insertional mutagenesis -> transformation of infected cells by animal retroviruses
Transactivation of cellular genes -> by human oncoretroviruses
Tumor suppressor genes -> DNA tumor viruses
What are common opportunistic infections in untreated HIV patients?
Mycobacterium tuberculosis
Toxoplasma gondii
Cytomegalovirus (CMV)
Candida albicans
What are examples of human oncoretroviruses?
HTLV-I and II
What molecules are involved in the entry of HIV-1 to target cells?
CCR5
CXCR4
CD4
gp41
gp120
How are RAS pr activated & what result?
activated by GTP binding via guanine nucleotide exchange factors (GEFs)
can initiate PI3K/Akt and MAPK signaling pathways -> cell growth, proliferation and migration.
Coagulative necrosis
An accumulation of hydrogen peroxide in a cellular compartment can be converted to dangerous radical forms in the presence of which metal?
Iron
What does Niemann–Pick disease (lysosomal storage disorder) cause & how?
sphingolipidoses (accum. of excessive amount of lipids in spleen, liver etc.)
Defects in the enzyme breaking down the substance
What vitamins/enzymes can protect against free radical damage?
Vitamin C & E & Beta-carotene -> terminate chain propagation
Glutathione peroxidase -> removes hydrogen peroxide from the cell, converting it to water
Superoxide dismutase -> uses it as a substrate
What are the main outcomes of activation in all complement pathways?
Assist of phagocytosis by opsonization
Activation of Inflammation
Target cell cytolysis by Membrane Attack Complex (MAC)
What are the chronic inflammatory cells?
Lymphocytes
Macrophages
Plasmocytes
Eosinophils
Mast cells
What are acute inflammatory cells?
Neutrophils
What deficiency has negative effects on wound healing?
zinc
(Delayed epithelization, Decreased collagen synthesis, Impaired overall wound strength')
What enzymes are expressed during wound healing?
MMP-1 (Collagenase 1) -> Effects on keratinocyte migration, reepitelization
MMP-2 (Gelatinase A) -> Effects on keratinocyte migration, anti-inflammation
MMP-3 (Stromelysin 1) -> Effect on cell migration
What structure isformed of epitheloid histiocytes, multinucleated giant cells, lymphocytes and fibroblasts?
Granuloma
When does granulation tissue begins to appear in human wounds?
4-5 days after injury in the proliferative phase
What is a systemic thromboembolism?
an emboli traveling within the arterial circulation
arose from intracardiac mural thrombi
What is a paradoxical embolism?
caused by the embolus which gained access to the systemic circulation through an interatrial or interventricular defect.
What is colloidal osmotic pressure of plasma?
pressure resulting from the pumping action of the heart is the force that tries to pull the fluid into the vein.
What is hydrostatic pressure?
the force that tries to push the fluid out of the vein
Is postmortem thrombi attached to the underlying wall or not
not attached to the underlying wall.
Decsribe venous thrombi
typically contain more red cells and fewer platelets which is also called as red thrombus and the thrombi often takes the shape of the vein.
Describe arterial thrombi
gray-white and friable, typically consists of a meshwork of platelets, fibrin, red cells and degenerating leukocytes, usually superimposed on an atherosclerotic plaque.
What substance induces apoptosis in hypovolemic shock?
Cytochrome c
What is the function of NNRTIs?
block the nucleic acid synthesis of the human immunodeficiency virus (HIV)
What NSAIDs is used via parenteral administration to induce closure of the atrial opening in premature infants with patent ductus arteriosis?
Ibuprofen
What irreversibly inhibits the aggregation of platelets necessary for blood clot formation?
Aspirin/Acetylsalicylic acid
What is the function of protease inhibitors?
The protease inhibitors inhibit the late protein synthesis and processing of the human immunodeficiency virus.
In contrast to COX-1, what is the preferential expression site of COX-2 targeted by coxibs?
activated macrophages
Glucocorticoids can cause what in laboratory results?
Glucocorticoids tend to cause hypernatremia, hypocalcemia and hypercholesterolemia sometimes hypokalemia
When are steroids contraindicated?
systemic fungal and local herpes infections
Progressive multifocal leukencephalopathy
Graft vs. host disease due to which hypersensitivity?
Type IV hypersensitivity (delayed type)
What characterizes Kossmann syndrome in infants
Phagocyte deficiency
Define tolerance
immunological uneesponsiveness to self-Antigens
What cytokine produced in Type I hypersensitivity & by what?
IL4 by Th cells
9:00-10:00
What is the most common cause of aneuplodies?
Nondisjunction
Same genetic mutation different phenotype, why?
Locus & Allelic heterogeneity
Modifier gene effect
Xanthelesma
What are characteristics of reactive oxygen species (ROS)?
short half-life
damage biomolecules, cells, tissues
highly reactive
generate new radicals by chain reaction
What is maple syrup disease?
inborn error of metabolism
defective branched chain keto acid dehydrogenase complex
urine build up of branched chain keto acids
What kind of muttion in alpha talassemia?
Loss of function
What are regulatory mechanisms in inflammation associated gene expression?
infl induced epigenetic regulation
continuous exposure to cytokines
CpG islands mediated transcriptional control
Granuloma formed in what kind of inflammation?
chronic inflammation
Mast cells (histamine)
What kind of inflammation in burns, severe burns, mucous inf.
burns -> serous inflammation
deep burns -> fibrinous infl.
severe burns + tissue necrosis -> ulceration
mucous membrane inf. -> Catarrhal inflammation
What growth factors in wound healing
What are systemic factors involved in wound healing?
Metabolic diseases (DM)
Immunosuppressants
Trauma
Smoking
Age
Nutrition
(Not hypoxia)
What starts every shock state?
Lack of oxygen
What is the order of events in wound healing?
Hemostasis
Inflammatory
Proliferative
Remodeling
What happens in glycogen storage disease Type VII (Tarui disease)
defective phosphofructokinase -> causes exercise intolerance, fatigue and myoglobinuria.
HIV what genes & what encodes
Polymerase gene encodes reverse transcriptase, integrase, protease
Gag gene encodes p24 (capsid) & p17 (matrix)
What kind of virus is HIV
env diplod RNA
What are the results of a RAS loss of fct mutation?
Increased G-protein cascade activation
Decreased or lost GTPase activity
Decreased GAP activity
Increased cell cycle progression
Which mechanisms control response of mature lymphocytes that recognize self antigens during peripheral tolerance?
Non-responsive status (anergy) through inhibitory co-receptors.
Supression through regulatory T cells
Deletion by apoptosis
What is the function of
PGE1
PGI2
PGE2
PGF2α
PGE1 -> vasodilation
PGI2 -> vasodilation
PGE2 -> erythema, edema, pain
PGF2α -> uterine contraction & vasodilation
What drug most likely caused severe broncospasm in 40-y.o. woman who was brought to the emergency department because of her serious breathing difficulty? She had taken a drug for a headache two hours earlier as she had been suffering from sinusitis and nasal polyps for 6 months.
What is used in the treatment of respiratory syncytial virus (RSV)–induced severe lower respiratory infections in hospitalized children?
Ribavirin
Describe arboviruses
All RNA enveloped except Reovirus
C1q
C6
C1q -> induces apoptosis via AgAb complex
C3b -> phagocyte & opsonization
C5a -> induces inflammatory response & recruit phagocytes
C6 -> MAC member (disrupts membrane integrity ofinfectious non-self cells)
What is the mediator of late phase response in biphasic reactions of anaphylaxis?
Cytokines prod by cellular infiltrates
Anergy specific to…
Peripheral tolerance
What immunodeficiencies most likely predisposes a young child to both bacterial and viral infections?
SCiD (Severe combined immunodeficiency)
Where red/white infarct
Red infarct: testis, lung small intestine
White infarct: brain, heart, kidney
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