Lecture Exam 1 Flashcards
contains DNA/RNA
cell nucleus
ribosomes on outer surface synthesize proteins
endoplasmic reticulum
- production of steroid hormones
- synthesize glycogen
smooth endoplasmic reticulum
packages proteins and lipids in vesicles
golgi bodies
produces cell energy (ATP) via respiration
mitochondria
myeloid cell that targets bacteria and fungi
neutrophil
myeloid cell that targets parasites and allergic inflammatory response
eosinophils
myeloid cell that releases histamine for inflammatory responses
basophil
myeloid cell that migrates from vasculature to tissue and differentiates in macrophages
monocyte
lymphoid cell that binds tumors and virus-infected cells without antigen stimulation and kills them by granule insertion
natural killer cell
lymphoid cell that directly kills infected cells by injecting proteins
-produces proteins that regulate immune system to kill pathogens and can distinguish between self and non-self
T lymphocytes
lymphoid cell that recognizes surface antigens on bacteria and viruses to produce antibodies to activate the immune system and destroy pathogens
B lymphocyte
B lymphocyte that differentiates into a plasma cell with help from T-cells. Ab it produces is similar to receptor on B lymphocyte. Abs released to bind to antigen to cause its destruction.
Plasma cells
intracellular stores of calcium
mitochondria and endoplasmic reticulum
increases in intracellular calcium triggers what enzymatic pathways that can be injurious to the cell?
ATPase = no ATP, no energy
phospholipase and protease = cell membrane damage
endonuclease = nuclear chromatin damage
anoxia
no oxygen delivery
asphyxia
no oxygen delivery due to an interruption of breathing
what are examples of reversible cell injury
- decreased respiration and loss of ATP
- glycogenolysis and glycogen depletion
- reduction in intracellular pH (lactic acid)
- failure of membrane transport systems (cellular edema - H2O accumulation due to increase in intracellular Na+)
- detachment of ribosomes and decreased protein synthesis
irreversible cell injury
- massive influx of calcium
- membrane damage (phospholipases, ROS)
- intracellular release of lysosomal enzymes (RNAases, DNAases, proteases)
coagulative necrosis
- preservation of cell outlines and tissue structure
- prototype - myocardial infarction
liquefactive necrosis
- insult leading to an influx of neutrophils releasing catalytic enzymes
- loss of cell outlines and tissue structure
- ex: bacterial abscess, brain
early changes in coagulative necrosis
- hypereosinophilia (more red “red means dead”)
- cytoplasmic vacuolization
- nuclear changes: 1) pyknosis (shrunken and hyperchromatic)
2) karyorrhexis (fragmented)
3) disappearance
granuloma is different from granulation tissue
granulation tissue: new tissue that forms as part of the healing of an injury
granuloma: chronic area of inflammation
saponification
pancreatic enzymes break down fat tissue around the pancreas, which then complexes with cations and essentially forms soap
inducers of apoptosis (programmed cell death)
- cytochrome C is released from mitochondria > induces caspases that break down protein and DNA
- engagement of death receptors on cell (TNF) which is a ligand that directly activates caspases
regulatory protein of apoptosis that inhibits the release of cytochrome C from mitochondria?
bcl-2 in cytoplasm
only in dividing cells, usually cells under hormonal control - increase in cell number
hyperplasia
alzheimers diseases is an example of ________
brain atrophy
differentiation of one cell type by another, often replacing a whole tissue
metaplasia
earliest step in atherosclerosis development
abnormal accumulation of cholesterol in macrophages on the inner lining of arterial walls
major leukocytes for inflammatory response
monocytes (macrophages), neutrophils, antigen-specific lymphocytes
hallmark of inflammation
infiltration of tissue with any of the classes of leukocytes
- neutrophils: acute inflammation
- lymphocytes and monocytes: chronic inflammation
sequence of events in acute inflammation
1) increased blood flow to area
2) extravasation and deposition of fluid and plasma proteins
3) emigration of neutrophils from microcirculation and their accumulation at the site of injury
- secreted by mast cells (and basophils), present in most tissues
- causes vasodilation and increased permeability
- results in fluid leak
- prominent role in allergic response, causing edema
histamine
regulator of vascular permeability similar to histamine, present in circulating platelets
(extra: acts as neurotransmitter in CNS)
serotonin
C3a and C5a protein function
vasodilation and permeability
complement protein that is a powerful chemotactic agent for neutrophils
C5a
prostaglandins and leukotriene function
mediators of acute inflammation
- prostaglandins inhibited by aspirin (an anti-inflammatory)
- leukotrienes involved in immune response
characteristics of chronic inflammation
- infiltration by monocytes and lymphocytes
- 24 hours for maximum infiltration, persists for weeks
- functions: phagocytosis, secrete cytokines, kill virus-infected cells, etc
- often due to immune response
all leukocyte traffic requires adhesion between:
- leukocytes and surface of opposing cells
- leukocytes and extracellular matrix proteins
- mediated by cell surface adhesion molecules
- requires cytokines (chemotactic) as initial step
______ on neutrophils and monocytes bind to _____ on endothelial cells
Mac-1 on neutrophils and monocytes bind to ICAM-1 on endothelial cells
(integrins that help leukocytes exit the bloodstream to find the area of inflammation)
integrin presented by lymphocytes in order to bind to ICAM-1 on endothelial cells
LFA-1 is the integrin shown on lymphocytes
Mac-1 is shown on neutrophils and monocytes
selectin function
mediates adhesion to ligands shown on endothelial cells at sites of inflammation
key features of selectin-mediated adhesion
- rapid on-rate
- low bind affinity, too weak to stop cells in shear of flowing blood (hence the rolling)
major regulatory molecule of angiogenesis
VEGF
Vascular Endothelial Growth Factor
major stimulatory molecule of fibrogenesis
TGF-beta
Transforming Growth Factor-beta
characteristics of neoplasms
clonal - derived from a single cell
proliferative - they grow
HER2 is overexpressed in what cancers? How is it activated?
HER2 is an oncoprotein that is overexpressed in breast and gastric cancers.
Activated by amplification
genetics of gametes (sperm or ovum) that can be passed down (also non-tumor cells)
germline
refers to the genetic composition of cells other than gametes, cannot be passed to offspring
somatic
condition that occurs in families - can be genetic or lifestyle-related
familial
present at birth (may or may not be genetic)
congenital
- chromosomal germline disease
- most common genetic cause of developmental delay
- sporadic (meiotic nondisjunction in ovum in 95% of cases - low risk of recurrence)
trisomy 21 - down syndrome
describe marfan syndrome
- mendelian autosomal dominant disorder
- if heterozygous, can result in haploinsufficiency, dominant negative effect, and gain-of-function
-mutation in fibrillin gene (FBN1) that then decreases structure of connective tissue and allows TGF-beta to destroy ECM
advantages of next generation sequencing
- highly multiplexed sequencing
- higher analytical sensitivity
- markedly decreased cost per base sequenced
autosomal dominant mendelian disorders
if the trait is carried in heterzygous fashion, the disease may manifest
haploinsufficiency
dominant negative effect
gain of function
If one parent is affected, 50% chance of offspring will be affected
the amount of wild-type protein is insufficient to perform normal function
haploinsufficiency
mutant protein is nonfunctional and interferes with the function of the wild-type protein
dominant negative effect
mutation introduces new function of the altered protein or increases wild type function with deleterious sequelae
gain-of-function
Liver function tests
Transaminases - AST and ALT
Biliary enzymes - Alk Phos, GGT
-not true tests of liver function - liver enzymes that are released when it is damaged
chronic hepatitis B histology
- ground glass hepatocytes
- sanded nuclei hepatocytes
- portal inflammation
chronic hepatitis C histology
- macrovesicular steatosis (fat droplets)
- portal lymphoid aggregates
- bile duct injury/damage
gallstone risk factors
fair: white population
fat: BMI >30
female
fertile: one or more children
forty: age > 40
conditions for pathologic autoimmunity
- presence of autoimmune rxn
- evidence that it is not due to tissue damage
- absence of another cause of disease
breakdown in self-tolerance
pathologic autoimmunity
classic example of type 2 cytotoxic reaction
blood transfusion reaction
Goodpasture’s disease
aka Anti-GBM antibody disease
-patients make an ab to alpha-3 chain of type 4 collagen
-collagen is present in the lung
Patients have glomerulonephritis and pulmonary hemorrhage
what are the type 2 cytotoxic diseases
- pemphigus vulgaris
- bullous pemphigoid
- dermatitis herpetiformis
- anti-GBM/Goodpasture’s
what are the non-cytotoxic reactions?
1) thyrotoxicosis (Grave’s)
2) myasthenia gravis
clinical features of grave’s disease (type 2 non-cytotoxic rxn)
increased thyroid hormone (T3, T4) secretion > hypermetabolic state:
heat intolerance, weight loss, hyperreflexia, protruding eyes
clinical features of myasthenia gravis (type 2 non-cytotoxic rxn)
skeletal muscle acetyl choline receptors are blocked or bound by ab.
This causes blocking of neuronal impulse transmission across neuron-muscular junction = muscle weakness
clinical features of systemic immune complex diseases (type 3)
- fever
- urticaria (itchy, swollen skin)
- arthralgias (joint pain)
- proteinuria and hematuria (glomerular injury)
- lymphadenopathy
describe type 3 immune complex rxn
- abs (IgG, M or A) form against foreign or self antigens in circulation or localized in tissue
- complement system is activated > PMNs, swelling, tissue destruction, positive feedback loop
examples of Type IV T-cell mediated rxns
effector cells: t-cell-activated macrophages
ex: TB skin test rxn, TB, fungal infections
Type IV delayed hypersensitivity time course:
local erythema and induration occurs after 8-12 hours
-rxn peaks after 2-7 days and slowly subsides
type IV granulomatous hypersensitivity time course
requires weeks to months to develop and may resolve slowly or persist indefinitely (ex: TB granuloma)
autoantibodies in SLE (systemic lupus erythematosus)
ANA - present in 95% lupus pts, diagnostic criterion.
Anti-native DNA and anti-Sm: specific for SLE
granulomatosis with polyangiitis
- type II
- aka ANCA-associated vasculitis
- anyone can get it
- mostly white
- median age 41
- Wegener’s triad:
1) necrotizing granulomatous vasculitis
2) focal segmental glomerular nephritis
3) necrotizing vasculitis of median and small vessels - open lung biopsy gold standard for diagnosis
test for granulomatosis with polyangiitis
ANCA- antineutrophil cytoplasmic antibody test
-90% is c-(cytoplasmic)ANCA
example of mendelian autosomal recessive disease
cystic fibrosis
-blocked airway, pancreatic duct, bile canaliculi, decreased Cl reabsorption in sweat ducts
Testing: next gen sequencing
fragile X syndrome
- X-linked genetic disorder
- aka trinucleotide repeat disorder
- 2nd most common genetic cause of developmental delay (1st is trisomy 21)
