Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
462 Cards in this Set
- Front
- Back
|
A.A are broken down into what? |
Urea |
|
|
What is BUN? |
Blood urea nitrogen Found on basic metabolic panel (BMP) Shows how well kidneys are working. |
|
|
Nucleotides are broken down into what? |
Uric acid |
|
|
When is uric acid elevated? |
In people with gout |
|
|
The sugar molecule in the cell membrane acts as what? |
A receptor (for immune recognition) |
|
|
What is the rough ER continuous with? |
Nuclear membrane |
|
|
What does the rough ER do? |
Make proteins (enzymes, antibodies, etc.), some hormones, mucus |
|
|
What does the smooth ER do? |
Makes lipids and steroid hormones, controls calcium mobilization |
|
|
What does the golgi apparatus do? |
Modifies, packages, and stores things |
|
|
Proinsulin is modified into what by the golgi? Where is it stored? |
Insulin In granule |
|
|
What is autophagy? |
Cleanup in the cell Cell digests things inside itself |
|
|
What is a primary lysosome? |
Inactive lysosome |
|
|
What is a secondary lysosome? |
Lysosome that has bound with something inside cell and is digesting it |
|
|
What is heterophagy? |
Digestion of exogenous things (things from outside the cell) |
|
|
What cells have a lot of mitochondria? What cells do not have a lot? |
A lot- Muscle cells Not a lot- Skin cells |
|
|
What is the cytoskeleton? |
Controls cell shape and movement of cells |
|
|
What are examples of microfilaments? |
actin and myosin |
|
|
Why are microtubules important? |
Important in mitosis/meiosis, transport (move vesicles) Ex. Neurotransmitters moving in neuron |
|
|
How does colchesine work? |
Binds to the subunit of microtubule (tubulin) > Inhibits migration of neutrophils (active in gout) > Prevents exacerbation of inflammation from gout |
|
|
What is diffusion? |
High to low gradient Affected by size, temperature, etc. |
|
|
What is osmosis? |
Diffusion of water across semi-permeable membrane Water follows salt |
|
|
What is facilitated diffusion? |
Diffusion that requires a carrier molecule |
|
|
What is active transport? |
Low to high gradient or high to low gradient movement across a membrane that requires energy (ATP) |
|
|
What is an example of active transport? |
The sodium potassium pump |
|
|
What is the sodium potassium pump important for? |
Nervous system and heart |
|
|
What is the voltage of every cell? |
1/10th of a volt |
|
|
What are the three types of ion gates? |
Voltage gated (becomes more positive) Ligand gated Mechanically gated (vibration, stretching, pressure, etc.) |
|
|
How are larger molecules transported into the cell? |
Pinocytosis, endocytosis (including receptor recycling), and phagocytosis |
|
|
How do things get turned on in the cell? |
2nd messenger pathways |
|
|
How does the cAMP pathway work? |
Ligand binds to receptor > Activates G protein > Activates effector (adenylate cyclase) > Activates cAMP (2nd messenger) > Activates protein kinase > triggers cell response |
|
|
What ligands can activate the cAMP 2nd messenger pathway? |
catecholamines, ACTH, FSH, LH, Glucagon, PTH, TSH, Calcitonin |
|
|
What form of energy is needed to activate a G protein? |
GTP |
|
|
How does the IP3 pathway work? |
Ligand binds to receptor > Activates G protein > Activates effector (phospholipase) > Cleaves PIP2 into DAG and IP3 (2nd messengers) > IP3 goes to smooth ER and causes calcium (2nd messenger) to be released > Calcium activates other things and triggers a cell response |
|
|
What ligands can activate the the IP3 pathway? |
catecholamines, TRH, ADH, LHRH, oxytocin |
|
|
What does endocrine mean? |
Cell acts on distant target cells Long distance Slow acting |
|
|
What does paracrine mean? |
Cell acts on nearby cell Short distance Short acting (Ex. neuron-neurotransmitters) |
|
|
What does autocrine mean? |
Cell acts on itself (Ex. T cells create cytokines such as IL-2 which act on themselves) |
|
|
Where is genetic information stored? |
Chromosomes |
|
|
How many chromosomes do humans have? Autosomes? Sex chromosomes? |
23 pairs 22 pairs 1 pair |
|
|
What is a karyotype? |
Visual representation of chromosomes arranged in order of size, used in diagnosis of chromosome disorders |
|
|
What is genotype? |
The actual genetic information carried by the individual (all cells except the gametes have the same genotype) |
|
|
Are all genes expressed in all cells? |
No, this could result in cancer |
|
|
What is phenotype? |
Expression of genes Appearance of the individual's characteristics |
|
|
When was the Human Genome Project launched? |
1990 |
|
|
What is HAP MAP? |
A database developed to include genetic variations within the human genome |
|
|
What is pharmacogenomics? |
Tailoring of disease treatments for a particular patient based on their genetic information |
|
|
How many genes have been discovered that cause disease? |
Over 1800 |
|
|
How many genetic tests are there for human diseases? |
2000 |
|
|
How many biotech-based products are there in clinical trials? |
350 |
|
|
Do we understand the genetics of heart disease? |
No |
|
|
How many bases and paste pairs does the human genome contain? |
6 billion bases and 3 billion base pairs |
|
|
How much of the human genome encodes proteins? |
Less than 2% |
|
|
How many human genes encode protein? What is this similar to? |
20-25k the mustard plan |
|
|
Two individuals share how much of their DNA? |
99.5% |
|
|
What are SNPs? |
Single-nucleotide polymorphisms (single-nucleotide substitutions of one base for another), two or more versions of a sequence must each be present in at least 1% of the population Doesn't necessarily mean disease, but can Two types- Linked and causative |
|
|
What are linked SNPs? |
SNPs outside gene No effect on protein production or function |
|
|
What are causative SNPs? |
SNP in gene Non-coding SNP- In regulatory sequence, changes amount of protein produced Coding SNP- In coding region, changes amino acid sequence |
|
|
What are copy number variations (CNVs)? |
Repeat sequences within DNA Can cause diseases, Ex. Cancer Can have protective effects, Ex. Against HIV (repeats increase expression of cheekiness which recruit immune cells to fight HIV) |
|
|
What does micro RNA do? |
Inhibits gene expression on post translational level (silences genes) |
|
|
What happens in Huntington disease? |
Huntington chorea 1 normal gene and 1 abnormal Abnormal proteins build up in brain and cause symptoms |
|
|
How could micro RNA help treat Huntington disease? What is an issue with this treatment? |
Micro RNA could silence the abnormal gene in Huntington disease There is difficulty getting Micro RNA to the brain |
|
|
What cells don't have a nucleus? What cells have more than one nucleus? |
RBC Skeletal muscle (needs lots of protein) |
|
|
What happens during DNA transcription? |
DNA unzips to transcribe (mRNA) |
|
|
What happens during translation? |
Protein is made |
|
|
How many amino acids are there? How many codons are there? What does this create? |
20 64 Redundancy in the genetic code |
|
|
Why care about mutations in noncoding sequences? |
A mutation in a splicing site can prevent exon formation (prevents proper gene expression/protein) Can't chop out intron (trash of the code) |
|
|
What is an example of a point mutation? |
Sickle cell |
|
|
What is the benefit of having sickle cell? |
Prevents against malaria |
|
|
What is an example of a trinucleotide repeat mutation? |
Huntington disease |
|
|
Mutations can cause issues with proteins such as what? |
Structural (Collagen) Protein hormones (insulin/glucagon) Contractile proteins (actin/myosin) Antibodies Transport (Hemoglobin) Enzymes (PKU) Tumor suppressors (P53) |
|
|
What are congenital disorders? |
Disorders present at birth Include inherited or developmental disorders |
|
|
What can cause inherited disorders? |
Single-gene expression (one gene affected) Chromosomal defect Polygenic expression (multiple genes) |
|
|
What are single gene disorders? |
Trait controlled by one set of alleles Transmitted to subsequent generations |
|
|
What can cause Chromosomal anomalies? |
Usually caused by an error in meiosis such as nondisjunction (chromosomes don't separate properly during division) or translocation (rearrangement of parts between non-homologous chromosomes) |
|
|
What are teratogenic agents? |
Agents that cause damage during embryonic or fetal development Ex. Thalidomide |
|
|
What are multifactorial disorders? |
Many factors are involved Large number of disorders are of this type Often have pattern of familial inheritance Environmental component |
|
|
What are some causes of other congenital or developmental disorders? |
Premature birth Difficult labor and delivery Ex. Cerebral palsy |
|
|
What are single-gene disorders? |
Classified by inheritance patterns ( recessive, dominant, X-linked recessive) Single gene controls a specific function (Ex. color blindness) May have systemic effects (Ex. CF, Tay-Sachs, phenylketonuria (PKU)) |
|
|
What are autosomal recessive disorders? |
Both parents must pass on the allele for the disorder Male and female children affected equally Homozygous recessive child has the disorder Heterozygous child has no clinical signs of the disease and is a carrier |
|
|
What are some examples of autosomal recessive disorders? |
CF, PKU, Tay-Sachs |
|
|
What are autosomal dominant disorders? |
Inheritance of one allele causes the disorder (only one parent needs to carry the allele) No carriers Some conditions become evident later in life. This is called delayed lethal genotype (Ex. Huntington disease) |
|
|
What are some examples of autosomal dominant disorders? |
Adult polycystic kidney disease Huntington's Disease Familial hypercholesterolemia Marfan's syndrome |
|
|
What is a recessive X-linked disorder? |
Allele is carried on the X chromosome but not the Y chromosome Manifested in heterozygous males lacking the matching unaffected gene on the Y chromosome Heterozygous females are carriers Homozygous recessive females may be affected Inheritance may appear to skip generations Ex. Duchenne muscular dystrophy, classic hemophilia |
|
|
What is a dominant X-linked disorder? |
Heterozygous males and females affected Reduced penetrance in females Ex. Fragile X syndrome (Most common genetic cause of cognitive deficits, effects are variable and related to the extent of the mutation of the allele) |
|
|
What is a CBC? |
Complete blood count (includes platelet count, hemoglobin, and WBC |
|
|
What is a CBC with diff? |
Complete blood count with differential (immune cells) |
|
|
What is a BMP? |
Basic metabolic panel (checks kidney function) |
|
|
What is a CMP? |
Complete metabolic panel (checks kidney and liver function) |
|
|
What is Gaucher disease? |
Most common lysosomal storage disease Buildup of lipids in lysosomes Autosomal recessive Mutation in gene encoding enzyme glucocerebrosidase (defective) Defect in mononuclear cells (macrophages) Jewish population Adults affected Can live a long life Causes splenomegaly and possibly hepatomegaly Bone involvement Pancytopenia Thrombocytopenia Osteopenia |
|
|
What bone deformities can Gaucher disease cause? |
Lytic lesions (bone is weak) Erlenmeyer flask deformity Fracture May require hip replacement from avascular necrosis |
|
|
What is an Erlenmeyer flask deformity? |
Caused by cortical hard bone thinning Can cause fracture |
|
|
Where are blood cells born? |
In the bone marrow |
|
|
How does the bone marrow appear normally? |
Well organized |
|
|
What do fibroblasts do in the bone marrow? |
Secrete collagen (organize structure of the bone marrow) |
|
|
What do stream cells do in the bone marrow? |
Secrete growth factors that help other cells grow |
|
|
How does the bone marrow appear in Gaucher disease? |
Fuzzy appearing Gaucher cells are visible |
|
|
What are Gaucher cells? |
Enlarged macrophage that appears as crumpled tissue in the cytoplasm |
|
|
Why are platelets low in Gaucher disease? |
Bone marrow is taken over by the Gaucher cells (causes bone pain) |
|
|
How does the spleen appear in Gaucher disease? |
Finely granular and enlarged |
|
|
What causes the enlarged spleen of Gaucher disease? |
Macrophages are affected in the spleen Platelets are sequestered in the spleen because of angry macrophages |
|
|
What causes low hemoglobin in Gaucher disease? |
Macrophages become active in the spleen and eat RBC |
|
|
How do are lysosome enzymes made? |
Made in the rough ER Packaged in the golgi Tagged with mannose-6-phosphate in the golgi Bind with mannose-6-phospate receptor which acts as the address for mannose-6-phosphate to go to the lysosome |
|
|
What happens in the lysosome (in the macrophage) in Gaucher disease? |
There is a defect in the gene encoding the lysosome enzyme glucocerebrosidase This creates a lysosomal enzyme deficiency Normal lysosomal degradation does not occur Lipids buildup in the lysosome and cause the macrophage to enlarge |
|
|
What is the treatment for Gaucher disease? |
Recombinant enzymes (give back defective enzymes) Recombinant enzymes are expensive Bone marrow transplant is not done often (risky-high mortality) |
|
|
What causes Tay-Sachs disease? |
Defective hexosaminidase A (results in deficiency of hexosaminidase A) Accumulation of GM2 gangliosides (lipids in cell membrane) in heart, liver, spleen |
|
|
Where is the Tay-Sachs mutation located? |
Alpha-subunit locus on chromosome 15 |
|
|
What are the symptoms of Tay-Sachs? |
Begin at 6 months of age Motor and mental deterioration Blindness 1-2 years vegetative state Death 2-3 years Nervous system and retinal symptoms are most prominent Prone to seizures Accumulate mucus in the lungs (predisposes to infection) |
|
|
What happens to the vacuole in Tay-Sachs? |
The vacuole balloons because hexosaminidase A is defective (lysosome can't chew up stuff) |
|
|
How does a neuron look up close in a patient with Tay-Sachs? |
Like an onion (whorled) The onion appearance is from the lysosome |
|
|
What happens to neurons when gangliosides accumulate? |
Neuron becomes unhappy and dies Microglial (macrophage in brain) cells in the brain become angry which can cause inflammation and swelling in the brain |
|
|
Where are rods and cones located? |
In the macula |
|
|
What type of vision is the macula responsible for? |
Central vision |
|
|
What type of vision is the fovea responsible for? |
Sharp vision |
|
|
What happens in the eye in Tay-Sachs? |
Ganglions (like neurons) are a collection of cell bodies in the macula In Tay-Sachs the ganglions become full of lipids This causes a milky halo (build up of lipids) in the macula and a cherry-red spot in the fovea |
|
|
What is the treatment for Tay-Sachs? |
No cure Symptom relief |
|
|
What is cystic fibrosis? |
1 in 2500 live births Most common lethal genetic disease that affects caucasian populations Carrier frequency 1 in 20 Caucasians Autosomal recessive |
|
|
What are the symptoms of cystic fibrosis? |
From mild to severe Normal Azoospermia Sinusitis, absent vas deferens Mild lung disease, polyposis (nose polyps predispose to sinusitis), pancreatic insufficiency Bronchiectasis, pancreatic insufficiency, male infertility Meconium ileus, pancreatic insufficiency, mild lung disease Bronichiectasis, pancreatic insufficiency, male infertility, hepatic cirrhosis (classical cystic fibrosis) |
|
|
What causes cystic fibrosis? |
Mutation on chromosome 7 Abnormal cystic fibrosis transmembrane conductance regulator |
|
|
What is meconium? |
First bowel movement |
|
|
What is meconium ileus? |
Meconium stuck in the ileum |
|
|
What can meconium ileus cause? |
Obstruction Distention in the small intestine caused by the obstruction |
|
|
What is ill atresia? |
Narrowing of the ileum Happens in utero from a lack of blood flow Lack of blood flow causes part of the intestine to die |
|
|
What causes the bowel obstruction in the cystic fibrosis infant? |
Mucus plugs in GI tract (common in people with CF; contributes to meconium ileus) Ileal atresia |
|
|
What causes edema in the CF infant? |
Low albumin (protein that affects pressure in vessels; causes fluid to leak from vessel into interstitial space) |
|
|
What causes the foul smelling/floating bowel movements in the CF infant? |
Fatty bowel movements (steatorrhea) from not absorbing fat |
|
|
Why is the liver enlarged in the CF infant? |
Fatty liver |
|
|
What are band forms? What causes them? |
Immature neutrophils (non-functional) Bacterial infection that the body cannot keep up with The bone marrow pumps out neutrophils whether they are mature or not in an effort to keep up with the infection |
|
|
What organisms are people with CF prone to? |
Psuedomonas aeruginosa Staphylococcus aureus Hemophylis influenzae |
|
|
What can sometimes be found in the airways of people with CF? |
pus |
|
|
How do the bronchi appear in patients with CF? |
Dilated Thickened walls |
|
|
What does a scarred and thickened airway refer to? |
Fibrosis |
|
|
What happens in bronchiectasis? |
Widening of airways Obstruction of airways (from mucus) Chronic inflammation |
|
|
What does chronic mucus in airways predispose CF patients to? |
Infection |
|
|
What type of cells do bronchi have? Bronchioles? |
Bronchi- epithelial cells (strong) Bronchioles- Pseudostratified cells (weaker) |
|
|
What do the bronchi of a patient with early CF look like? |
Respiratory epithelium intact Mucus in the bronchi Inflammatory cells |
|
|
What do the bronchi of a patient with late CF look like? |
Fibrosis visible Mucus in bronchi Inflammatory cells Epithelial cells not intact Dilated and flabby |
|
|
What happens in the pancreas of a CF patient? |
Pancreas affected Causes cysts and fibrosis Can cause chronic pancreatitis Dilated ducts in pancreas (filled with mucus which blocks the duct) |
|
|
What causes steatorrhea in CF patients? |
Acini cells (exocrine) in pancreas secrete digestive enzymes Mucus in the pancreatic ducts block digestive enzymes Digestive enzymes not available to break down fat |
|
|
What cells in the pancreas produce insulin? Are they intact in CF patients? |
Islet cells Yes CF patients do not generally have diabetes, though, it is possible if they have chronic pancreatitis |
|
|
What does the cystic fibrosis transmembrane conductance regulator (CFTR) do? |
Maintains the balance of chloride |
|
|
How does the cystic fibrosis transmembrane conductance regulator (CFTR) work in a normal person? |
Agonist binds to receptor > Rise in cAMP > activates protein kinase > puts phosphate on the R woman of CFTR > allows CL to be excreted |
|
|
What happens to CFTR in a patient with CF? |
Abnormal CFTR is produced Sits in cytoplasm and is eventually degraded |
|
|
What does the CFTR do in the sweat duct of a normal person? |
CFTR allows Cl in the cell CFTR regulates the epithelial Na channel (ENaC) which allows sodium to come into the cell |
|
|
What happens in the sweat duct of a person with CF? |
CFTR is abnormal Can't bring Cl into the cell Non-functioning ENaC (sodium can't come in) which makes skin salty |
|
|
What does the CFTR do in the airway/gut of a normal person? |
CFTR allows Cl to be excreted from the cell CFTR allows a little Na to come into the cell via the ENaC (water follows salt) |
|
|
What happens in the airway/gut of a person with CF? |
CTFR is abnormal Cl can't exit the cell No regulation on ENaC makes it extra active (more Na enters the cell along with water) Mucus becomes dehydrated and is extra thick and sticky |
|
|
Why are CF patients prone to chronic colonization of Pseudomonas aeruginosa? |
Thickened mucus creates a hypoxic environment which Pseudomonas thrives in Pseudomonas creates an alginate (capsule/biofilm that protects it from antibodies and antibiotics) Many CF patients die from pseudomonas |
|
|
What is Marfan syndrome? |
1 in 5000 Autosomal dominant; can be sporadic Disorder of connective tissue Mutation in FBN1 gene (codes fibrillin-1) |
|
|
What is fibrillin? |
Fibrillin serves like a bridge (foundation of extracellular matrix) ECM provides nourishment and structure to the cell Fibrillin forms a network of microfibrils Elastin provides tensile strength Microfibrils surround elastin Lack of fibrillin causes lack of tensile strength (predisposes to aneurysms) |
|
|
What are symptoms of Marfan syndrome? |
Eye lens dislocation (causes ectopia lentis) Myopia Pectus carinatum/excavatum Vertebral deformity Long arms Joint hyper mobility Aneurysms (aortic) Mitral valve prolapse |
|
|
Why might some people with Marfan syndrome have Mitral valve prolapse? |
Chordae tendinae in heart become weakened and elongate |
|
|
What things might MVP be associated with? |
mid systolic click palpatations |
|
|
If MVP is severe enough, what may occur? |
Mitral regurgitation |
|
|
How can mitral regurgitation from severe MVP cause heart failure? |
Heart senses there is not enough oxygen (can cause finger clubbing) Heart try to compensate by increasing cardiac output and beating harder The heart gets tired which leads to heart failure |
|
|
Why can't people with Marfan syndrome participate in sports? |
Risk of ruptured aneurysm |
|
|
What does a lack of fibrillin cause? |
Weakening of the aortic wall which predisposes to aortic aneurysm |
|
|
What is Turner Syndrome? |
Complete or partial monosomy X of the X chromosome Most common sex chromosome abnormality in females 1 in 2000 live born females |
|
|
What are symptoms of Turner syndrome? |
Small stature Webbed neck Widely spaced nipples and poor breast development Amenorrhea in 1/3 of patients Accelerated loss of ovaries before puberty (basically menopausal by puberty) Multiple nevi Lymphedema of hands and feet (lymphatic abnormalities) Wide carrying angle of arms Coarctation of aorta and bicuspid aortic valve (rather than tricuspid) Antibodies against thyroid gland Horseshoe kidney Short 4th metacarpal |
|
|
What can the bicuspid aortic valve in Turner syndrome cause? |
Stenotic valves Causes LVH which leads to heart failure |
|
|
What does the horseshoe kidney of Turner syndrome cause? |
Kidneys fuse together Normal renal function Prone to UTIs |
|
|
What is Klinefelter syndrome? |
Male hypogonadism Male infertility 2 or more X chromosomes and 1 or more Y chromosomes 1 in 660 males Difficult to diagnose before puberty Mean IQ is lower |
|
|
What are symptoms of Klinefelter syndrome? |
Tall stature Lack of facial hair Gynecomastia Wide hips Decreased pubic hair Testicular atrophy Long arms and legs |
|
|
What is a possible cause of Klinefelter syndrome? |
Advanced maternal age |
|
|
What are some diseases that people with Klinefelter syndrome are predisposed to? |
Mitral valve prolapse Diabetes Breast Cancer Systemic Lupus (SLE) |
|
|
What is pathogenesis? |
The sequence of events in the response of cells or tissues to the etiologic agent (trauma, bacteria, etc.), from the initial stimulus to the ultimate expression of the disease |
|
|
How do we adapt to stress? |
If the stress is not removed, this can lead to cellular injury If stress is removed, the cell can adapt |
|
|
Are hypertrophy, hyperplasia, atrophy, and metaplasia reversible or irreversible? |
Reversible |
|
|
What is hypertrophy? |
Increase in cell size (from gene activation, protein synthesis, and production of more organelles) Ex. LVH- High bp increases peripheral vascular resistance, heart beats harder against pressure, heart undergoes hypertrophy |
|
|
What is hyperplasia? |
Increase in cell number Requires stem cells (heart, brain, and bones do not have stem cells) Hyperplasia can predispose to cancer (endometrial hyperplasia), but not necessarily (BPH) |
|
|
What is atrophy? |
Cells dying or becoming smaller Ex. Not using muscle Ex. Pregnancy (uterus atrophies and becomes smaller after birth) |
|
|
What is metaplasia? |
Changing cell types Not necessarily good Ex. Barret's esophagus- Reflux causes change of cell types in esophagus from irritation (protective mechanism), can be precancerous Ex. Smoking- Affects cells that have cilia expression, changes cell type (no longer have cells that express cilia), cilia is required for moving things up and out, lack of cilia predisposes to infection Ex. Vitamin A deficiency- Cells in conjunctiva in eye change from columnar goblet cell type to squamous epithelia, causes dry eyes, can damage eyes and eventually lead to blindness |
|
|
What are results of cellular injury? |
Decrease of ATP Mitochondrial damage Entry of calcium Increase in ROS Membrane damage (irreversible injury) Protein misfolding, DNA damage |
|
|
What does a decrease in ATP cause? |
Multiple downstream effects |
|
|
What does mitochondrial damage cause? |
Leakage of pro-aptotic proteins Ex. Cytochrome C leakage can cause apoptosis |
|
|
What can entry of calcium cause? |
Increase in mitochondrial permeability Activation of multiple cellular enzymes |
|
|
What can increased ROS cause? |
Damage to lipids, proteins, and DNA |
|
|
What can membrane damage cause? |
Plasma membrane- Loss of cellular components Lysosomal membrane- Enzymatic digestion of cellular components |
|
|
What can protein misfolding and DNA damage cause? |
Activation of pro-apoptotic proteins |
|
|
What happens in the cell as a result of ischemia? |
Decrease in oxygen > Decrease in oxidative phosphorylation (in mitochondria) > Decrease in ATP |
|
|
What are three things that can happen in the cell as a result of decreased ATP? |
Sodium and Calcium pumps start to fail Increase in anaerobic glycolysis Detachment of ribosomes |
|
|
What happens when the sodium and calcium pumps start to fail? |
Influx of calcium, water, and sodium Efflux of K ER swelling, cellular swelling, loss of microvilli blebs Cellular swelling is the hallmark of reversible cellular injury |
|
|
What happens in the cell when there is and increase in anaerobic glycolysis? |
Decrease in glycogen Increase in lactic acid > decrease in pH > clumping of nuclear chromatin (causes non-functional DNA) |
|
|
What happens in the cell when there is detachment of ribosomes from the rough ER? |
Decrease in protein synthesis > Lipid deposition Lipoproteins carry cholesterol (HDL removes cholesterol and LDL deposits cholesterol) Lack of protein causes lipids to accumulate in the cell |
|
|
What can lipid deposition in the liver cause? |
Fatty liver |
|
|
Is myocardial ischemia reversible? Infarct? |
Myocardial ischemia is reversible, but infarct is not Infarct is dead heart tissue |
|
|
What initially happens when Calcium enters the cell (uncontrolled-when it's not supposed to)? |
Mitochondria and smooth ER vomit their calcium into the cytoplasm (bad) |
|
|
What does the increased calcium in the cytoplasm cause to happen? |
Activation of cellular enzymes (phospholipase, protease, endonuclease, ATPase) Increased mitochondrial permeability (causes decrease in ATP) |
|
|
What happens when phospholipase is activated in the cell? |
Decrease in phospholipids > membrane damage |
|
|
What happens when protease is activated in the cell? |
Disruption of membrane and cytoskeletal proteins > Membrane damage Disruption of cytoskeleton proteins can prevent immune cells from getting to the site of infection |
|
|
What happens when endonuclease is activated in the cell? |
Nuclear damage |
|
|
What happens when ATPase is activated in the cell? |
Decrease in ATP |
|
|
What is a ROS? |
Reactive oxygen species (free radicals) Unpaired electron (highly reactive and unstable) Can damage the cell membrane |
|
|
What is the most damaging ROS? |
Hydroxyl (OH-) |
|
|
What happens when there is an increase in ROS in the cell? |
Free radicals set off chain reaction > erosion of cell membrane |
|
|
In membrane damage, what is chocolate mary? |
Chocolate mary is on the outside of the cell |
|
|
What can cause membrane damage in the cell? |
Increase in ROS Decrease in O2 Increase in cytosolic Ca |
|
|
How does an increase in ROS cause membrane damage? |
Causes lipid peroxidation (free radicals go to membrane and steal electrons and mess up the integrity of the membrane) Lipid peroxidation causes phospholipid loss > Membrane damage |
|
|
How does a decrease in O2 cause membrane damage? |
Causes decrease in ATP > Decrease in phospholipid synthesis > Phospholipid loss> Membrane damage |
|
|
How does an increase of cytosolic Ca cause membrane damage |
2 ways- Phospholipase activation and Protease activation Phospholipase activation > Increase in phospholipid degradation > Phospholipid loss and lipid breakdown products cause membrane damage Protease activation > cytoskeletal damage > membrane damage |
|
|
What happens when a cell undergoes necrosis from irreversible injury? |
Cell swells causing myelin figures (pieces of membrane rolled up indicating the membrane is falling apart) and membrane blebs If there is progressive injury there is a breakdown of the plasma membrane, organelles, and nuclease The cell leaks its contents Enzymes leak into the plasma and can be found on lab tests (Ex. Troponin, a cardiac enzyme, shows up on labs after an MI) Inflammation occurs |
|
|
What happens when a cell undergoes apoptosis (controlled cell death) from irreversible injury? |
Condensation of chromatin and membrane blebs The cell fragments and apoptotic bodies (cell fragments) are present Phagocytes eat the apoptotic cells and fragments No inflammation |
|
|
What is autophagy? |
Cell eats its own contents Autophagic vacuole forms and fuses with lysosome (autophagolysosome) Autophagolysosome digests products Ex. Anorexia- An anorexic patient's cells eat themselves which causes cell death |
|
|
What is the clinical relevance of apoptosis? |
Thalidomide At 5 weeks gestation the hands look like paddles Apoptosis starts to occur vertically to form fingers Thalidomide interferes with apoptosis Patients are born with paddle-like hands |
|
|
What category drug is thalidomide? |
Category X (affects the fetus) |
|
|
How do we get rid of damaged or necrotic tissues and foreign invaders? |
Inflammation and innate immunity Inflammation brings cells to the site Inflammation does not always mean infection |
|
|
What are the cardinal signs of inflammation? |
Redness Swelling Heat Pain Loss of function |
|
|
What are some causes of acute inflammation? |
Infections Tissue necrosis Foreign body Immune reactions |
|
|
What is the innate immune system |
Nonspecific immune system Ex. Macrophages, dendritic cells, and mast cells |
|
|
What are macrophages? |
Eat things and present antigens to T cells |
|
|
What are dendritic cells? |
Antigen presenting cells More efficient than macrophages |
|
|
What are mast cells? |
Release histamine in response to things like allergens |
|
|
What are the three phases of acute inflammation? |
Vascular phase Cellular phase Leukocyte activation and phagocytosis |
|
|
How long does acute inflammation typically last? |
Minutes to hours |
|
|
What occurs normally in the arteriole/capillary/venule? |
Some fluid leaks out in the arteriole, but is reabsorbed by the venule or lymphatics Occasional resident lymphocyte or macrophage |
|
|
What occurs in the arteriole/capillary/venule during inflammation? |
Increased blood flow (dilation of arteriole and venule) > heat and redness Increased vascular permeability in post capillary venule > leakage of plasma proteins > swelling and edema Neutrophil emigration |
|
|
What is hydrostatic pressure? |
Occurs at the beginning of the arteriole Pressure is greater inside the arteriole which causes some fluid to leak out |
|
|
What is colloid osmotic pressure? |
Occurs at the end of the capillary bed Fluid is reabsorbed (albumin draws the fluid back in) |
|
|
What is transudate? |
Fluid leaks outside the vessel where is shouldn't be |
|
|
What causes transudate? |
Increased hydrostatic pressure (causes venous flow obstruction which is seen in congestive heart failure) Decreased colloid osmotic pressure (causes decreased protein synthesis which is seen in liver disease, and increased protein loss which is seen in kidney disease) In liver disease albumin can't be made (can't bring the fluid back in) In kidney disease albumin leaks out into the urine (can't bring the fluid back in) |
|
|
What is exudate? |
Fluid and proteins leak out of the vessel (Inflammatory) |
|
|
What causes exudate? |
Fluid and protein leakage from the vessel Vasodilation and stasis of the vessel Increased interendothelial spaces Inflammatory Ex. Cancer and autoimmune diseases |
|
|
How do you treat transudate? Exudate? |
Transudate- Pull the fluid off Exudate- Treat the underlying cause |
|
|
Where does increased vascular permeability occur? |
At the post capillary venule |
|
|
What does a normal vessel look like? |
No gaps between endothelial cells WBC do not leak out |
|
|
How does retraction of the endothelial cells occur? |
Induced by histamine (short acting and released from mast cells) and other mediators (kinins, serotonin, NO) Mediators cause retraction at the post capillary venule (causes gaps) Fluids and proteins leak out |
|
|
Other than causing retraction of the endothelial cells, what do the other mediators (kinins, serotonin, NO) do? |
Bradykinin kinds to receptor and causes pain Bradykinin, histamine and serotonin cause vasodilation |
|
|
What happens when there is endothelial injury? |
Caused by burns, some microbial toxins Rapid; may be long-lived (hours to days) Endothelial cells necrose and cause bigger gaps that WBC can leak out of Initiates nasty inflammatory response |
|
|
What do lymphatics do? |
Remove fluid from the interstitial area Filter the blood |
|
|
What are lymph nodes and what occurs in them? |
Network of immune cells Presentation of immune cells in lymph nodes |
|
|
What can cause lymph vessels to become inflamed? |
Growing infection Lymph vessel cells proliferate to compensate for increased fluid coming entering during acute inflammation/infection |
|
|
What are the first cells to the site of inflammation? |
Neutrophils/PMNs |
|
|
How do PMNs leave the vessel? |
Macrophages in tissue sense something is wrong in the tissue, get pissed off and release chemical mediators (cytokines TNF and IL-1 which stay localized) > Cytokines upregulate P and E selectin which serve as speed bumps to slow down the neutrophils/PMNs > A sugar molecule on the Neutrophils/PMNs binds to the selectins and begin to slow down > Integrin is present on neutrophils/PMNs; usually it is in the closed conformational (low affinity) state which will not bind to receptors (ICAM-1); As the neutrophils/PMNs start to slow down the integrin will change to the high affinity state > Integrin on neutrophils/PMNs will bind to ICAM-1 which stops the neutrophil > CD31 receptor then helps the neutrophil/PMN squeeze through the vessel into the extracellular matrix |
|
|
How do the Neutrophils/PMNs know where to go after they leave the vessel? |
They follow chemokines like IL-8 |
|
|
TNF and IL-1 released by macrophages upregulate selectins and what else? |
ICAM-1 |
|
|
What do chemokines do? |
Bring the cells to the site and also help change the affinity of integrins |
|
|
After initiation of an inflammatory response, when does edema occur? |
Within 24 hours |
|
|
After initiation of an inflammatory response, when do neutrophils/PMNs come to the site? Monocytes/Macrophages? |
Neutrophils/PMNs- 1-2 days (first cells in acute inflammation) Monocytes/Macrophages- 2-3 days monocytes/macrophages come from the blood (macrophages already in the tissue call for back up) |
|
|
What do Neutrophils/PMNs do at the site of inflammation? |
Eat whatever is at site and then die within 24-48 hrs Don't want neutrophils/PMNs to be long lived because when they eat stuff they release chemokines and cytokines (long lived chemokines and cytokines could cause a massive immune response which is bad) |
|
|
What is the life cycle of a macrophage? |
Born in bone marrow (monoblast) > Move to blood (Monocyte) > Move to tissue (macrophage) > Activated macrophage |
|
|
What are the two types of macrophages? |
Classically activated (M1) Alternatively activated (M2) |
|
|
What determines what type of macrophage a monocyte will become? |
A monocyte turns into either a M1 or M2 macrophage based on how it is tickled |
|
|
What is a Toll like receptor (TLR) |
Receptors on monocytes/macrophages |
|
|
What does a monocyte need to be tickled by to turn into a M1? To turn into a M2? |
M1- Microbes, TLR-ligans, IFN-y M2- IL-13, IL-4 |
|
|
What do M1 macrophages do? |
Elicit inflammation Release ROS, NO, and lysosomal enzymes > microbicidal actions (phagocytosis and killing of many bacteria and fungi) Release IL-1and chemokines > pathologic inflammation |
|
|
When can pathologic inflammation occur? |
In autoimmune disorders |
|
|
What do M2 Macrophages do? |
Release TGF-B and IL-10 > Anti-inflammatory effects TGF-B > Wound repair and fibrosis |
|
|
How do chemokine receptors work? |
Receptor located on the Neutrophil/PMN cell surface Chemokine binds > Causes cytoskeletal changes (necessary for chemotaxis) and signal transduction > Increased integrin avidity (adhesion to endothelium) and Chemotaxis (migration into tissues) |
|
|
How do CD14 receptors, TLR, and cytokine receptors work? |
Receptors located on the Neutrophil/PMN cell surface CD14 Receptors recognize LPS (lipopolysaccharhides on gram negative bacteria) TLR recognize little bits of bacteria and viruses Cytokine Receptors recognize cytokines Recognition > Production of mediators ( arachidonic acid metabolites, cytokines) and production of ROS and lysosomal enzymes Mediators amplify the inflammatory reaction ROS and lysosomal enzymes kill microbes |
|
|
How do phagocytic receptors work? |
Neutrophil/PMN eats something > Phagocytosis of microbe into phagosome and production of ROS and and lysosomal enzymes > Killing of microbes |
|
|
What is required to kill microbes by phagocytosis? |
Oxygen (used to make ROS which kill microbe) |
|
|
What happens in the arachidonic acid pathway? |
Immune cells recognize something foreign in the body > phospholipases activated > release of arachidonic acid from cell membrane > 2 pathways (COX and 5-Lipoxygenase)
COX leads to several pathways including PGE2 which causes pain and fever; other pathways cause vasodilation In the 5-lipoxygenase pathway, leukotriene B4 brings Neutrophils/PMNs to the site Activating the 5-Lipoxygenase pathway causes bronchospasm and increased vascular permeability (associated with asthma) |
|
|
What inhibits phospholipases? COX? |
Phospholipases- Steroids COX- COX-1 and COX-2 inhibitors |
|
|
What are the side effects of COX-1 inhibitors |
Serious GI side effects which can lead to ulcerations Inhibiting COX-1 can cause increased production of COX-2 which can lead to increased risk of cardiovascular incidents |
|
|
When can decreased blood flow from COX inhibitors be good? |
For pain relief during menses |
|
|
When can decreased blood flow from COX inhibitors be bad? |
In patients with high BP (poor perfusion) Kidneys get mad because they're not getting enough blood flow COX inhibitors decrease the blood flow even further |
|
|
When is the 5-lipoxygenase pathway mainly activated? |
In asthma |
|
|
How does singulair affect the 5-lipoxygenase pathway? |
Block Leukotriene B4 which blocks chemotaxis of Neutrophils/PMNs |
|
|
How is histamine stored? What does it do? |
Stored in preformed granules (allows quick release) Vasodilation (redness) and endothelial retraction (swelling) |
|
|
What are complement proteins? |
Cause inflammation Make microbes more tasty Made in the liver Found in the blood |
|
|
What happens to complement protein C3? |
Enzymes cleave it into C3a and C3b |
|
|
What does C3b do? |
Binds to microbe and makes it more tasty for Neutrophils/PMNs and macrophages |
|
|
What does C3a do? |
Recruits leukocytes (Neutrophils/PMNs) and causes more inflammation |
|
|
What happens to complement protein C5? |
Enzymes cleave it into C5a and C5b |
|
|
What does C5a do? |
Recruits leukocytes (Neutrophils/PMNs) and causes more inflammation |
|
|
What does C5b do? |
Lands on the microbe and recruits other complement proteins (C6, C7, C8, C9) > forms MAC complex (pore on bacteria that causes lysis) |
|
|
How does the alternative complement pathway work? |
C3b coats the microbe and makes it more tasty |
|
|
How does the Classical complement pathway work? |
Antibodies and C3b bind to microbe making it more tasty |
|
|
What does NO cause? |
Vasodilation? |
|
|
What is the NO clinical correlation? |
Nitroglycerin works in a dose dependent manner (taking more = greater effects) and causes arteriole and venous dilation When someone with angina takes nitroglycerin they get dilation of arteries and veins (in a dose dependent manner) Dilation of the venous system causes blood to pool > Blood entering the heart is less (preload is less) > Heart doesn't have to work as hard (gives heart a break) Arteriole dilation > decreased peripheral vascular resistance > Heart doesn't have to work as hard |
|
|
What is the acute inflammatory response that occurs when you pull a hangnail? |
Quick, short vasoconstriction > vasodilation > redness and heat > endothelial retraction > fluid and proteins leak out > swelling > neutrophils/PMNs slow down, stop, and leave the vessel to go to the site of trauma |
|
|
What happens if during acute inflammation there is pus formation (abscess)? |
Healing by fibrosis (scarring) |
|
|
What is the ECM? |
Extracellular matrix Secreted locally and assembles into network of spaces surrounding tissue cells |
|
|
What are the three components of the ECM, and what do they do? |
Fibrous structural proteins (fibrillar collagens and elastin) Water hydrated gels (proteoglycans and hyaluronan) provide resilience and lubrication Adhesive glycoproteins (fibronectin and laminin) The three components connect the matrix elements to each other and to the cells |
|
|
What are the two forms that the ECM exists in? |
Basement membrane- surrounds epithelial, endothelial, and smooth muscle cells Interstitial matrix- presents in spaces between cells and connective tissue |
|
|
What is the purpose of the ECM? |
Provides support to cells and the body Provides turgor to soft tissue and rigidity to bone Involved in the regulation of growth, movement, and the differentiation of cells surrounding it Provides storage and presentation of regulatory molecules that control the repair process (when the tissue is injured) Provides the framework for cell migration Maintains cell polarity |
|
|
What are some of the cells in the ECM, and what do they do? |
Fibroblasts, macrophages, etc.
Produce growth factors, cytokines, and chemokines that are important for regeneration and repair |
|
|
What is collagen? |
The most common animal protein Without collagen we would look like a blob |
|
|
What is the importance of vitamin C? |
Vitamin C is necessary for wound healing (it is needed to make collagen) |
|
|
What is elastin? |
Proteins of the collagen family that provide tensile strength Gives tissues the ability to expand and recoil (compliance) |
|
|
What is the structure of elastin like? |
Elastin fibers consist of central elastin surrounded by a network of microfibrils The microfibrils that surround the core consist of fibrilin The microfibrils serve as part of the scaffolding for deposition of elastin and the assembly of elastin fibers |
|
|
What is regeneration? |
The replacement of damaged tissue with native tissue |
|
|
What is regeneration dependent on? |
The regenerative capacity of the tissue |
|
|
What are the 3 types of tissue based on regenerative capacity? |
Labile- Possess stem cells that continually cycle to regenerate tissue (Ex. Small and large bowel, skin basal cells, bone marrow) Stable- Comprised of cells that are quiescent (still in G0 phase); quiescent cells can be tickled to reenter the cell cycle to regenerate tissue when necessary (Ex. Liver) Permanent- Lack significant regenerative potential (Ex. Cardiac tissue, skeletal tissue, neurons) |
|
|
What is repair? |
The replacement of damaged tissue with a fibrous scar (regenerative stem cells are lost) (Ex. Deep skin cut or myocardial infarction) |
|
|
What occurs in the first 24 hours in the healing of a thin wound? |
Inflammation |
|
|
What happens from days 3 to 7 in the healing of a thin wound? |
Building of new tissue to fill the wound space The fibroblasts secrete collagen and other things necessary for wound healing Fibroblasts produce a family of growth factors that induce angiogenesis (new blood vessel growth) Formation of granulation tissue (serves as the foundation for scar tissue development) Granulation tisse is fragile and bleeds easily (because of newly forming capillaries) Epithelial cells migrate and proliferate at the edge of the wound (contributes to wound healing) |
|
|
What happens weeks into the healing of a thin wound? |
Maturation and remodeling This depends on the extent of the wound |
|
|
What is the purpose of sutures after surgery? |
Carefully sutured wounds immediately after surgery have about 70% of the strength of normal skin Sutures provide strength in the wound and allows people to move freely after surgery without fear of wound separation |
|
|
What is healing by primary intention? |
Wound edges are brought together Minimal scar formation Occurs in thin wounds |
|
|
What is healing by second intention? |
Wound edges not brought together Granulation tissue fills the defect Scarring Occurs in wide wounds |
|
|
What is the purpose of myofibroblasts in wound healing? |
Contract the wound and form scar |
|
|
What is scar formation? |
Deposition of collagen and ECM Fibroproliferative response that "patches" rather than restores the tissue |
|
|
What occurs in the process of scar formation? |
Inflammation Angiogenesis Migration and proliferation of fibroblasts Scar formation Connective tissue remodeling |
|
|
What is the role of the macrophage in tissue repair? |
Debridement Removal of injured tissue and debris Antimicrobial activity Chemotaxis and proliferation of fibroblasts and keratinocytes Angiogenesis Deposition and remodeling of ECM |
|
|
What are factors that affect wound healing |
Malnutrition Blood flow and O2 delivery Impaired inflammatory responses Infection |
|
|
How does malnutrition affect wound healing? |
Protein deficiency > Prolonged inflammatory phase of healing > impairs fibroblast's ability to proliferate and regenerate ECM > Impairs body's ability to repair itself Carbohydrates needed as energy source for WBC; without sugar, cells can't do the processes required to get rid of infection Fat needed for cell membranes Vitamin A supports epithelial cells, capillary formation, collagen synthesis B vitamins are important cofactors for wound healing Vitamin K is needed for clot formation |
|
|
How does blood flow and O2 delivery affect wound healing? |
O2 is needed for collagen synthesis and angiogenesis Wounds in ischemic tissue are much more likely to become infected (PMNs and macrophages need O2 to kill bacteria) |
|
|
If a tissue injury occurs and the stimulus is removed (acute injury), what are the two ways that the body can heal itself? |
Regeneration (Restitution of normal structure) (Ex. Liver regeneration, superficial skin wounds, resorption of exudate in lobar pneumonia) Repair (Scar formation) (Ex. Deep excisional wounds, myocardium infarction) |
|
|
If a tissue injury occurs and the stimulus is not removed (persistent tissue damage), how does the body heal itself? |
Fibrosis (Tissue scar) (Ex. Chronic inflammatory diseases such as cirrhosis, chronic pancreatitis, and pulmonary fibrosis) |
|
|
What are common entry points for pathogens into the body? |
Skin, GI, and respiratory tract (all lined with epithelial cells) |
|
|
What is the purpose of epithelial cells? |
Epithelial cells serve as barriers (can produce natural antibiotics which block the entry of microbes) This is the first line of defense |
|
|
What are the two components of the immune system? |
Innate and adaptive |
|
|
What does the adaptive immune system consist of? |
B and T cells |
|
|
Is acute inflammation part of the innate or adaptive immune response? |
Innate It is not specific and does not generate memory |
|
|
What are some components of innate immunity? |
Neutrophils Receptors involved in early recognition Complement NK cells |
|
|
What cells are the first responders in acute inflammation? |
Neutrophils |
|
|
What are the receptors on the macrophage that are involved in early recognition of an antigen? |
CD14
TLR Cytokine (IFN-y) |
|
|
What does tickling of these receptors cause to happen
|
Killing of microbes Inflammation, enhanced adaptive immunity Tissue remodeling Enhanced antigen presentation |
|
|
What does the role of the CD14 receptor? |
Recognizes LPS on gram negative organisms > Activates the macrophage/neutrophil |
|
|
What is the role of the TLR?
|
Can activate the macrophage/neutrophil
|
|
|
What are cytokines, and what do they do? |
Tiny, short lived proteins secreted by other immune cells (released in response to bacteria/virus Help activate the appropriate immune response |
|
|
Activation of macrophage receptors can cause release of Phagocyte oxidase, what does this do? |
Makes the macrophage angry Leads to killing of microbes |
|
|
What are NK cells? |
Innate immune cells (not specific) Kill cells infected with virus/bacteria |
|
|
How do NK cells kill infected cells? |
NK cells notice down regulation of MHC I receptor (indicates infection with virus/bacteria) and kills the cell by apoptosis (takes away the ability of the virus to replicate |
|
|
What happens in the innate immune response is overwhelmed? |
The adaptive immune response comes in |
|
|
What is complement? |
Group of 25 + proteins made in the liver Are pro-proteins (must be cleaved to become activated) Cleavage creates a domino effect which amplifies the immune response Complement or complement fragments facilitate phagocytosis Human cells have regulatory proteins that do not allow complement or complement fragments to bind |
|
|
If complement proteins are made in the liver, what might happen to a patient with liver disease? |
May not make enough complement which leads to immunodeficiency |
|
|
In regards to complement, what might happen in a septic patient? |
A septic patient may have complement activation on human cells |
|
|
How does complement activation work? |
IgG or IgM antibody binds to bacteria > C1 proteins bind > C1 becomes activated and cleaves C4 and C2 > forms C4b2a (also called C3 converts) > cleaves C3 into C3a and C3b > C3a will go and cause inflammation at the site and C3b will be activated and cleave C5 into C5a and C5b >C5a initiates inflammation and C5b starts the MAC attack |
|
|
Other than causing inflammation, what else do C3a and C5a do? |
Recruit phagocytes/neutrophils to take care of the infection |
|
|
Other than cleaving C5, what else can C3b do? |
Make bacteria and viruses more tasty (opsonization) by coating them |
|
|
What happens when a patient has a deficiency in C3? |
Increased susceptibility to infections Usually fatal early in life |
|
|
If there is too much C3a and C5a, what can this contribute to? |
Anaphylactic shock |
|
|
What do C5b-C9 do? |
Initiate the MAC attack |
|
|
How does the MAC attack complex form? |
C5b binds to C6 and C7 > C5b,6,7 complexes bind to the membrane via C7 > C8 binds to the complex and inserts into the cell membrane (C8 is the anchor) > C9 molecules bind to the complex and polymerize >10-16 molecules of C9 bind to form a pore in the membrane> Pore formation causes electrolyte imbalances which kill bacteria |
|
|
Are TLR part of the innate or adaptive immune response? |
Innate response |
|
|
What does activation of TLR cause? |
Activation of transcription factors Transcription factors go to the nucleus and act as genes (Mainly for cytokines which shape the immune response) Triggers production of cytokines |
|
|
What are some things that TLR can recognize? |
Bacterial parasites, Gram + bacteria and fungi, Gram - bacteria, flagellated bacteria, viral RNA, Bacterial DNA |
|
|
Which parts of the cell are TLR expressed on in immune cells like macrophages? |
On the outside of the cell and on the inside on a lysosomal compartment The TLR on the lysosomal compartment recognize viruses/bacteria that come into the cell |
|
|
What is the humoral immune system? |
Part of the adaptive immune response Mediated by antibodies made by B cells Antibodies can activate complement, make organisms more tasty, and keep organisms from entering the cell Main defense against microbes with capsules |
|
|
How are antibody responses to different antigens classified? |
T cell dependent or independent (antibodies can be activated in a T cell dependent way or a T cell independent way) |
|
|
Where do B cells like to live? |
The spleen and lymph nodes |
|
|
How do B cells recognize antigen? |
Through the BCR B cells can recognize antigen in its native form (huge chunk of bacteria/virus) unlike T cells which require antigen to be degraded and presented on the surface of an antigen-presenting cell in the context of MHC The antigen recognition molecule (BCR) of the B cell is the membrane Ig (antibody on surface of B cell) |
|
|
What does antigen binding to the BCR initiate? |
A cascade of signals in the cell |
|
|
What do BCRs and TCRs have in common? |
Are integral membrane proteins Are present in thousands of identical copies exposed at the cell Are made before the cell ever encounters an antigen Are encoded by genes assembled by the recombination of segments of DNA. This is how antigen receptor diversity is generated Have a unique binding site |
|
|
What happens in the T cell dependent B cell response? |
B cell eats an antigen and chops it up > B cells expresses piece of antigen in MHC II molecule (Shows the CD4/TH cell what is has) > Interaction between T cell and B cell provides signal for B cell to activate and make antibodies (activated B cell is called a plasma cell) Another explanation: B cell recognizes antigen > B cell presents antigen to TH cell and is stimulated> Stimulation by T cell activates B cell and causes clonal expansion > B cell can differentiate into IgM plasma cells, IgG, IgG subtypes, or IgA plasma cells (isotope switching), High affinity IgG plasma cells (Affinity maturation- B cell is tickled for a long time and antibodies mature and become good at binding bacteria/viruses), or memory cells |
|
|
What is the first antibody to be secreted? |
IgM |
|
|
What cytokines are released by the T cell to signal the B cell to mature and make a certain type of antibody? |
Cytokines Il-2, 4, 5 |
|
|
How do B cells provide costimulation for T cells? |
B cells provide costimulation (B7 expression) for T cells (CD28) |
|
|
What type of antibody response occurs after the first infection? |
Primary antibody response Starts with naive B cells Creates memory cells |
|
|
What type of antibody response occurs after a repeat infection? |
Secondary antibody response Starts with memory cells Much faster than primary response |
|
|
What do memory B cells secrete? |
The antibody that they have been programmed to secrete |
|
|
Compare the primary and secondary Ab responses |
Primary response- 5 -10 day lag after immunization, smaller peak response, IgM > IgG, lower antibody affinity Secondary Response- 1-3 day lag after immunization, larger peak response, increase in IgG and isotope switching occurs, higher antibody affinity |
|
|
What are antibodies? |
Part of the adaptive immune response Also called immunoglobulins (Ig) Consists of 2 light chains and 2 heavy chains Fab portion of the Ig is the antigen binding part Fc portion is recognized by things like macrophages (tasty) |
|
|
What is the constant region of the antibody? |
Made of both heavy and light chains Can be rearranged to for different isotypes (Monomers- IgD, IgG, IgE; Dimer-IgA; Pentamer- IgM) Fc functions- Binds to specific Fc receptors on immune cells and can initiate the classical complement cascade |
|
|
Which types of antibodies can activate complement? |
IgG and IgM |
|
|
What can antibodies do? |
Neutralization- Prevent virus and bacterial adherence to cell surface receptors Opsonization- Facilitate phagocytosis (tasty) Complement activation |
|
|
What is agglutination? |
Binding of antibody to toxins in the circulation and in tissues Antibody-antigen complexes (clumping) are formed and phagocytosed Antibodies can immobilize and agglutinate infectious agents by binding to surface antigens Agglutination serves as the basis for some basic lab tests |
|
|
What is opsonization |
A process in which bacteria, virus-infected cells, and others are tagged for destruction (made more tasty) The Fab portion of the antibodies binds to an antigen on the surface of the cell or organism The Fc portion binds to receptors on phagocytic cells (macrophages, neutrophils) The Fc receptor signals the phagocyte to engulf and destroy the organism or cell |
|
|
What occurs during complement fixation? |
The Fc fragments of IgM and IgG are effective activators of the classical pathway of complement fixation Complement activation leads to formation of the MAC The MAC inserts into cell membranes and destroys the osmotic integrity of target cell membranes (sodium and water enter and the cell pops/dies) |
|
|
What are the functions of the Fc? |
Fc is recognized by Fc receptors on cell Fc can trigger classical complement pathway Fc serves as the basis for many lab tests |
|
|
How diverse are antibodies? |
Limitless specific variable regions Only a limited number of constant regions |
|
|
What are the properties of IgA? |
Found in mucous, saliva, tears, and breast milk Protects against pathogens |
|
|
What are the properties of IgD? |
Part of the B cell receptor Activates basophils and mast cells |
|
|
What are the properties of IgE? |
Protects against parasitic worms Responsible for allergic reactions |
|
|
What are the properties of IgG? |
Secreted by plasma cells in the blood Able to cross the placenta into the fetus |
|
|
What are the properties of IgM? |
May be attached to the surface of a B cell or secreted into the blood Responsible for early stages of immunity |
|
|
What are more properties of IgM? |
Membrane bound Ig on the plasma membrane of B cells or a pentameric molecule secreted by plasma cells mIgm does not polymerize sIgM can travel through the blood sIgM has 10 antigen binding sites IgM antibodies appear early in the course of an infection Do not pass across the human placenta (it is a big molecule) Binds to antigens on the surface of bacteria like a spider Efficient activator of complement Efficient at agglutination First isotope produced in response to infection |
|
|
How many IgM molecules does C1 bind to? IgG? |
IgM- 1 IgG- 2 or more |
|
|
What are more properties of IgD? |
Co-expressed with IgM on the surface of the majority of mature B cells before antigenic stimulation and functions as a transmembrane antigen receptor (so an antigen naive cell) Enhances mucosal immunity (binds microbial virulence factors as well as pathogenic respiratory bacteria and viruses) Very small amount of IgD is secreted |
|
|
What are more properties of IgG? |
Most abundant antibody class in the blood Four subclasses of IgG Monomeric Very high affinity for antigen Unlike IgM, IgG can leave the blood and enter tissues Only class of antibody that can pass the placental barrier Subclass of IgG produced is dependent on the cytokines present Good at activating complement Most effective Ig for opsonization using Fc receptors on phagocytes Important for neutralizing toxins from bacterial infections |
|
|
Which IgG subtypes are important for opsonization of microbes? |
IgG 1, 2, 3 |
|
|
Which IgG subclass is the most efficiently transported across the placenta? The least? |
Most- IgG1 Least- IgG2 |
|
|
When during the pregnancy are most of the antibodies acquired by the fetus? |
3rd trimester |
|
|
What are more properties of IgE? |
Particularly effective at mucosal surfaces (such as when you ingest a peanut and have a peanut allergy) Serum concentration normally very low Most IgE bound to Fc receptors on mast cells and basophils Responsible for Type I hypersensitivity reactions (allergic and anaphylactic) Increases greatly in response to parasitic infection Also involved in inflammatory responses through its role in mast cell degranulation |
|
|
What is mast cell degranulation? |
Allergen binds to Fc receptor specific for IgE > Degranulation and release of granule contents (histamine and other substances that mediate allergic reactions) |
|
|
What are more properties of IgA? |
Monomeric form in the serum and Dimer in mucosa Most common and most active at mucosal surfaces |
|
|
Which Ig function in agglutination of bacteria and viruses? |
IgM |
|
|
Which Ig function in opsonization of bacteria? |
IgG |
|
|
Which Ig function in neutralization of bacterial toxins? |
IgG |
|
|
Which Ig function in complement activation? |
IgM and IgG |
|
|
Which Ig function in protection of mucosal surfaces? |
IgA |
|
|
Which Ig function in mast cell degranulation and parasitic expulsion? |
IgE |
|
|
How are B memory cells formed, and what is their function? |
Antigen stimulation and T cell-derived cytokines together induce maturation of naive B cells into plasma cells Some of the B cells that recognize the antigen differentiate into B memory cells B cell memory allows the secondary response to be much faster than the primary response The secondary response is also much greater, more sensitive, and usually comprised of IgG |
|
|
How long does it take to become immunized? What does immunization make? |
10 days Memory B cells that are ready to go when exposed to virus |
|
|
What is isotope switching? |
The plasma cell will produce antibodies of different isotopes such as IgG or IgE Only switches once Antigen specificity remains the same (recognizes the same part of the antigen) |
|
|
What is affinity maturation? |
The gradual increase in the affinity of antibodies synthesized by a B cell clone |
|
|
Where are blood cells born? |
In the red marrow |
|
|
How does the red marrow biopsy appear? |
Red marrow is well organized |
|
|
What occurs in hematopoiesis? |
Multi potential stem cell > exposed to certain growth factors > turns into different cell types in the bone marrow Common myeloid progenitor cell > Basophils, neutrophils, eosinophils, monocytes Common lymphoid progenitor cell > Nk cells, B cells, T cells |
|
|
Where do B cells like to live? |
In the spleen in lymph nodes |
|
|
Where do T cells go to be trained? |
Thymus |
|
|
What is the thoracic duct? |
The largest lymph vessel in the body |
|
|
When is the thymus biggest? What does a shrinking thymus make people prone to? |
Biggest in childhood and shrinks over time Elderly people have a small thymus and are prone to infections |
|
|
What type of cells in the thymus educate T cells? |
Epithelial cells |
|
|
Is there any foreign antigen in the thymus? |
No, there is only self antigen |
|
|
How does the T cell education process in the thymus work? |
Pro-T cell (double negative CD4 and CD8) goes into thymus and becomes a pre-T cell (has an immature T cell receptor) In the thymus the pre-T cells becomes a double positive immature T cell (expresses both CD4 and CD8) The immature T cell interacts with epithelial cells in the thymus Epithelial cell/APC presents a peptide (located in MHC class I or II) to T cell Weak recognition of MHC class II > T cell becomes a mature CD4 T cell (helper T cells) Weak recognition of MHC class I > T cell becomes mature CD8 T cell (cytotoxic T cell) No recognition or strong recognition > Apoptosis |
|
|
What are MHC molecules? |
Receptors that are expressed on all antigen presenting cells (macrophages, B cells, and dendritic cells) All nucleated cells express MHC class I |
|
|
What percent of T cells live? |
5% |
|
|
Where do T cells live after leaving the thymus? |
The lymph nodes and the spleen |
|
|
What is the role of the lymph nodes? |
Filter antigen B cells and T cells are exposed to foreign antigens in the lymph nodes |
|
|
What is the role of the spleen? |
Filters the blood |
|
|
What is a High endothelial venule (HEV)? |
Capillary vessel in which naive T cells circulate throughout the body |
|
|
Where in the lymph node do B cells live? T cells? |
B cells- Germinal center T cells- T cell zones |
|
|
Why do B cells and T cells need to be close together in the lymph node? |
Because T cells can activate B cells which then spit out antibodies |
|
|
How does the antigen enter the lymph node? |
Comes in from tissue through the afferent lymphatic vessel |
|
|
How does an APC present to a T cell? |
Epithelium takes up viruses > virus goes to ECM > Dendritic cells live in the ECM and pick up antigen, bring it into cells, chews it up, and presents it on MHC molecule > migrates to lymph node > Finds T cell |
|
|
How common is an interaction between a T cell and an APC? |
Very rare (very specific) |
|
|
When does the T cell become activated? |
After recognizing peptide in MHC molecule |
|
|
What is the function of APC? |
Uptake and processing of antigen Expression of the antigen on the cell surface in the context of MHC class II |
|
|
What are the two pathways of antigen processing and presentation? |
Exogenous and Endogenous |
|
|
What occurs in the exogenous pathway? |
Eating the cookie Bring the bacteria (cookie) into the cell > break apart cookie > present a piece of the broken cookie on MHC class II > Recognition by CD4 T cell |
|
|
What occurs in the endogenous pathway? |
Making cookie Virus enters the cell and starts replicating (ingredients used to make cookie) > Tiny piece (chocolate chip) will be presented on MHC class I > Recognition by CD8 T cell |
|
|
What is the CD3 complex? |
Closely associated with TCR Transduces activation signals to the cell following antigen interaction with the TCR All T cells express CD3 |
|
|
What is the role of CD4 and CD8? |
Stabilize the interaction to help activate the T cell |
|
|
How many TCR must you engage to get T cell activation? |
100+ T cells have many TCR and they are all the same |
|
|
What 2 signals must you have for T cell activation? |
Signal 1- TCR engaged with MHC molecule Signal 2- Co-stimulatory signal from CD28/B7 If both signals are not present then the T cell will be non-functional |
|
|
Does a memory T cell need both signals? |
No, a memory T cell only needs signal 1 (engaging MHC molecule) |
|
|
If a T cell in the lymph node interacts with APC and CTLA4 (on T cell) interacts with B cell (on APC), then what will happen? Why is this important? |
The T cell will be down regulated (Tells the T cell not to activate) This interaction is important in certain thyroid diseases |
|
|
How does T cell activation occur? |
Naive T cell and APC interact > T cell becomes activated > Mainly CD4 cells produce IL-2 (binds to IL-2 receptor on T cell and causes it to proliferate/clonally expand) > Become either either Effector T cell (CD4 or CD8) or memory T cell (CD4 or CD8) |
|
|
What can CD4 Effector T cells do? |
Activation of macrophages, B cells, other cells |
|
|
What can CD8 Effector T cells do? |
Killing of infected cells Macrophage activation |
|
|
What can activated CD4 T cells differentiate into? |
TH1 cells (promote more inflammation) TH2 (mediate allergic reactions and provide defense against helminths-big worms) TH17 (important in gut immunity, help with inflammation in the gut to get rid of things like fungi or parasitic infections |
|
|
What do TH1 cells do? |
Produce IFN-y > Activates macrophage and also inhibits TH2 response Produce IL2 which is very important in activating and clonal expanding T cells (without IL2, T cells cannot clonal expand) TH1is important for viral infections |
|
|
What do TH2 cells do? |
Produce Il-10 (inhibits TH1 response) and IL-4 and IL-5 which activates mast cells, eosinophils, and B cells (produce IgE which is associated with allergic responses and helps get rid of parasitic infections) |
|
|
What occurs in a TH1 response? |
Naive T cell is activated and becomes TH1 cell The T cell either stays in the lymph nose and activates a B cell with IFN-y (causes it to produce IgG antibodies) OR In the T cell goes to the tissue it can produce IFN-y which activates macrophages and helps the macrophage to kill organisms better |
|
|
What occurs in a TH2 response? |
APC interacts with CD4 T cell > Cytokines expressed in the local environment (such as IL-4) cause the naive T cell to become a TH2 cell TH2 cells in the lymph nodes interact with B cells which then produce antibodies (IgG4 or IgE depending on the B cell) IgE will kill tape worms by mast cell degranulation (histamine kills tapeworms) TH2 cells can also cause intestinal mucous secretion and peristalsis (important for getting rid of tape worm) TH2 cells can also activate eosinophils which are important in allergic reactions and getting rid of the tape worm TH2 cells also activate macrophage (for fibrosis and tissue repair) |
|
|
What occurs in a TH17 response? |
TH17 cells are prominent in the mucosa (mouth and GI) Promote inflammation and a neutrophil response Can also cause tissues to release antimicrobial peptides (like antibiotics-can kill bacteria) Increase barrier (make integrity of the epithelial cells stronger which prevents things from invading) |
|
|
What diseases do TH1 play a role in? TH2? TH17? |
TH1- Autoimmune diseases, tissue damage associated with chronic infections TH2- Allergic diseases TH17- Autoimmune and inflammatory diseases |
|
|
What do cytotoxic T cells target? |
Tumor cells Viral transformed cells Transplanted tissue Other antigens (fungal, parasitic) |
|
|
What is cross presentation? |
If APC eats whole virus/ piece of the virus and the virus is not replicating inside the APC then the APC can do cross presentation (presents piece of cookie/chocolate chip to MHC class I to CD8 T cells) Dendritic cells do cross presentation Dendritic cells eat virus and normal go through MHC class II The Dendritic cell has a way of eating viruses and presenting to MHC class I instead of class II |
|
|
What are two ways that CD T cells can kill virally infected cells? |
Fas Ligand Fas- CD8 T cell interacts with target cell infected with virus; slow process of inducing death (like dunking head in toilet many times before dying) Perforin is shot into infected cell and kills cell Apoptosis occurs in both types |
|
|
How would you summarize T cell activation in a flu virus? |
APCs eat virus and become activated > Goes to nearest lymph node (T cell area) > finds CD4 T cell and interacts with it through MHC II and CD28/B7 > APCs secrete cytokines (like IL-12) which causes the T cell to become a TH1 cell (more inflammatory cell) At the same time: APCs interact with CD8 T cell through MHC class I (2 signals) > CD8 T cell becomes activated Then: Activated T cells look for MHC class I expression on cell surfaces (look for peptides-little pieces of flu virus) > CD8 T cell will kill cell expressing flu virus Also: CD4 T cells interact with macrophages and activate them (cause them to kill flu better) |
|
|
Do SLE patients always have skin lesions? |
No |
|
|
What is pleural friction rub? |
Inflammation of pleural membranes |
|
|
If the costophrenic angle is not visible on x-ray, what is this indicative of? |
Pleural effusion
|
|
|
Is pleural effusion from SLE exudative or transudative? |
Exudative |
|
|
What may low hemoglobin indicate? |
Anemia of chronic disease |
|
|
What does protein in the urine indicate? |
Renal problems |
|
|
What do red-cell casts in the urine indicate? |
Renal problems |
|
|
Why do SLE patients have a false positive VDRL test? |
SLE patients make antibodies against cardiolipin (expressed in cell membranes) Do an anti-treponemal antibody test to determine if patient actually has syphilis A false positive indicates autoimmune disease |
|
|
Why would Bun and creatinine be elevated? |
Kidneys upset |
|
|
Why would the SLE patient have hypoalbuminemia? |
The patient is peeing albumin out (4+ protein) |
|
|
Why would the SLE patient have hypergammaglobulinemia? |
The patient is producing lots of antibodies |
|
|
What is a blood cell (WBC or RBC) cast? |
Blood cells stick together Reflects active disease in kidneys |
|
|
What test is sensitive for SLE? |
ANA |
|
|
What tests are specific for SLE? |
dsDNA antibody and Anti-Smith antibody |
|
|
Why are the complement levels low in the SLE patient? |
Complement is getting used up In SLE patients antigen antibody complexes form and become so big and they get stuck in the kidneys > leads to complement protein activation |
|
|
What happens to the glomerulus in SLE? |
Antigen-Antibody complexes form in the glomerulus (deposition) > complement binds and initiates inflammation > basement membrane of glomerulus is destroyed > protein and RBC leak out into urinary space |
|
|
What is the theory of the malaria rash of SLE? |
UV light damages DNA > kills cells by apoptosis or necrosis > Cells release auto antigens (self antigens) > Antibodies go to site of antigen and are directed against self > APC tries to eat antigen antibody complexes (clumping) > APC activates and secretes cytokines 2 Theories about what happens next: 1. APC tickles T cell receptor at site (self reactive T cell) > Strong inflammatory response > Malar rash 2. APC goes to lymph node and interacts with self reactive T cell |
|
|
How does the kidney look in chronic SLE? |
Lumpy/granular |
|
|
What is the role of the glomerulus? |
Filters the blood |
|
|
What is the structure of the glomerulus like? |
Mesangial cells build the matrix which provides nourishment for the glomerulus basement membrane Capillaries in the glomerulus have tiny holes (fenestrae) which allow filtration, but don't let things like protein out The basement membrane has a negative charge Proteins like albumin have a negative charge In severe SLE, the basement membrane is destroyed (negative charge lost) so proteins leak out into the urine |
|
|
How does a SLE glomerulus biopsy look different than a normal biopsy? |
Abnormal glomerulus is hyper cellular The mesangial cells proliferate because of the stuck antigen-antibody complexes in SLE Endothelial cells in the capillary also proliferate Because of complement activation, many neutrophils are also found Proliferation leads to destruction of the basement membrane |
|
|
What are wire loops? |
Seen on SLE glomerulus biopsy From endothelial cells in capillary that are proliferating and deposition of antigen-antibody complexes |
|
|
What happens in the glomerulus from too much inflammation that can be seen on biopsy? |
Necrosis from too much inflammation Nucleus breaks down which leads to even more inflammation |
|
|
What are hylenized loops that can be seen on a glomerulus biopsy in a patient with SLE? |
Homogenous/glassy appearance Caused by proliferating mesangial cells which secrete more things into the matrix (proteins and collagen) |
|
|
Why is immunofluorescence used to look at the kidney? |
Immunofluorescence sumps fluorescence on the kidney tissue which helps to determine specific disease states (what type of disease is occurring in the kidney)
In SLE, and immunofluorescent kidney looks very lumpy/bumpy |
|
|
What causes the lumpy/bumpy appearance of the kidney in SLE? |
Antigen-antibody complexes get stuck in the subendothelial of the glomerulus |
|
|
What type of hypersensitivity reaction occurs in SLE? |
Type III |
|
|
What can happen to the lungs of a person with chronic SLE? |
The serous membrane of the lungs becomes opaque Interstitial fibrosis causes trouble with breathing |
|
|
What can happen to the heart of a person with chronic SLE? |
Libman sacs endocarditis can form on the heart valves (primarily mitral valve) Libman sacs look like warts Formed on both sides of the valve Sterile endocarditis (not caused by bacterial infection) |
|
|
What is SLE? |
A chronic, multisystem inflammatory autoimmune disease of unknown origin Characterized by the presence of autoantibodies that lead to immune complex deposition, inflammation, and permanent organ damage Prognosis of patients with SLE has improved over the past 4 decades, morbidity and mortality are of concern Many SLE patients die from kidney disease |
|
|
What goes wrong with the immune system of someone with SLE? |
Production of antibodies directed against the cell nuclei Failure of IC clearing with subsequent IC deposition Failure of B-cell apoptosis (B cells do not die after recognizing self in the bone marrow) Failure of induction of tolerance |
|
|
What occurs in the tissue of an SLE patient? |
Antigen-Antibody complexes form and stick together > Bind to endothelial cells > complement binds > Inflammatory reaction occurs and neutrophils come to the site > Damage to the cell causes platelet aggregation > Inflammation of the vessel (vasculitis) |
|
|
What is one theory about where the antibodies come from in SLE? |
Some individuals have genes which predispose them to lupus > Self reactive T cells or B cells escape from being deleted An external trigger causes apoptosis/necrosis of cells > apoptotic bodies form > apoptotic bodies are not cleared quickly Self reactive antibodies bind to the apoptotic bodies > B cells and dendritic cells engulf the antigen-antibody complexes >Antigen-antibody complexes bind to TLR inside the B cells and Dendritic cells > The dendritic cells secretes type 1 interferons which stimulate the B cell to release more self reactive IgG antibodies If this occurs in the tissue or the lymph node is unknown (This theory refers to what happens at the tissue) |
|
|
What is another theory about where the antibodies come from? |
Apoptotic bodies travel in the lymphatics to local lymph node where self reactive B cells and T cells are > B cell binds to the apoptotic body and presents it to the T cell via MHC class II > B cell starts to produce self reactive IgG antibodies which can circulate through the blood > antibodies bind to self antigen and form complexes > complement activation occurs |
|
|
What is tolerance? |
Not initiating an immune response against self |
|
|
What is autoimmunity caused by? |
A break down of tolerance |
|
|
What is central tolerance? |
Occurs in the thymus or bone marrow In the thymus, T cells binding too tightly or not binding at all leads to apoptosis However, this is not always the case. Sometimes these T cells become regulatory T cells (do not die) Regulatory T cells are CD4 T cells that express hight levels of IL-2 receptor In the bone marrow, B cells that recognize self antigen with either die by apoptosis or will change its BCR (rearrange so that it doesn't recognize self antigen) |
|
|
What is Peripheral tolerance? |
Occurs outside of tissues/bone marrow There are protective mechanisms which protect the body from escaped self reactive T cells: If a T cell binds to a MHC molecule and does not have signal 2 then the cell undergoes anergy (goes to sleep) Regulatory T cells that leave the thymus look for self reactive T cells and suppress them |
|
|
How do regulatory T cells work? |
If a regulatory T cell interacts with an APC first, it can cause the APC to down regulate MHC class II and its coreceptor If the APC has these things down regulated, then it will not interact with the self reactive T cell T regulatory cells have a lot of IL-2 expressed on the surface IL-2 is needed for T cells to grow Regulatory T cells can deprive self reactive T cells of IL-2 (they cannot clonal expand |
