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364 Cards in this Set

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Lecture 27: Endocrine 6
Thyroid Basics and Hyperthyroidism
What primary hormone is increased or decreased in the following diseases?
- Cushing syndrome
-Conn syndrome
-Addison disease
Cushing-- increased Cortisol

Conn-- increased aldosterone

Addison disease-- decreased aldosterone, decreased cortisol
What is the drug of choice for anaphylactic shock? Cardiogenic shock? Septic shock?
Anaphylactic shock: Epinephrine

Cardiogenic shock: Dobutamine (Stimulates β2 receptors)

Septic shock: Norepinephrine (Stimulates α1 WITHOUT β2 Thus, clamps down the vessels)
What cancers are associated with RET gene mutation?
MEN 2A

MEN 2B

Medullary papillary thyroid carcinoma
Graves’ Disease (very high yield): What does in cause, what are the lab features, and what 2 drugs are used to treat it?
•Causes Hyperthyroidism

Clinically will see in a patient:
- Increased T3 and T4
- Decreased TSH
- Increased resin radioactive T3 uptake (specific for Graves’ Disease)
- Increased radioactive iodine scan

Drugs: methmazole, thyropropioluracil
A 35-year-old woman presents with diffuse goiter and hyperthyroidism. What are the most likely relative values of TSH and thyroid hormones?
Graves’ Disease

Decreased TSH

Increased thyroid hormone (free T3 or T4)
What is the most common location for ectopic thyroid tissue?
Tongue
How would pregnancy affect serum thyroid hormone levels?
Increased thyroid binding globulin (TBG)

Increased total T4 and total T3

Normal free T4 and T3
What two medications can be given to inhibit synthesis of thyroid hormone in patients with hyperthyroidism?
Methimazole

Propylthiouracil
Which of the 2 previous drugs blocks the peripheral conversion of T4 to T3?
Propylthiouracil (PTU)
Lecture 28: Endocrine 7
Hypothyroidism and Thyroid Cancer
In the dark, both pupils are dilated. (see image) In the light, the control pupil is miotic while the pupil given drug X remains mydriatic. What is drug X?
Sympathetic agonist: Epinephrine

Anticholinergenic: Atropine
What are some of the clinical uses for somatostatin?
Pituitary excesses:
-Acromegaly
-TSH-secreting tumor
-ACTH-secreting tumor

GI endocrine excess
-Carcinoid syndrome
-Zollinger-Ellison syndrome
-VIPoma
-Glucagonoma
-Insulinoma

Diarrhea

Reduce splanchnic blood circulation
-Cirrhosis with bleeding esophageal varices
-Bleeding peptic ulcers
What is the name given to a thyroid hormone-secreting teratoma?
Struma ovarii
What type of carcinoma like to secrete calcitonin *****
High Yield
Medullary carcinoma

Proliferation of parafollicular (C) cells

Associated with MEN2A & 2B

-These like to secrete calcitonin *** HIGH YIELD ***
During a thyroidectomy the parathyroid glands and recurrent laryngeal nerve can get damaged. What will this result in?

***HIGH YIELD***
Parathyroid glands- Will affect calcium (Ca+2) levels

Recurrent laryngeal nerve (Branch of the Vagus nerve), Innervates the thyroid and vocal cords. Damage will cause ------>Hoarseness
What is the mechanism of action of propylthiouracil? What other drug works like PTU? What are their side effects?
Acts by blocking the addition of iodine to tyrosine groups on the thyroglobulin (blocks thyroid peroxidase)

Also inhibits the peripheral conversion of T4 to T3 in the tissue

Methimazole: only blocks synthesis of thyroid hormone in the gland, does NOT affect peripheral conversion

Side effects
-Rash
-Agranulocytosis
-Aplastic anemia
Rapid- Fire Fact: Most common thyroid cancer
Papillary
Rapid- Fire Fact: Cold intolerance
Hypothyroidism
Rapid- Fire Fact: Enlarged thyroid cells with ground- glass nuclei
Orphan- Annie eye nuclei of Papillary cancer of the thyroid
Lecture 29: Immunology I
Immunology Basics
What are the differences between oligodendroglia and Schwann cells?
•Oligodendroglia
-Found in the CNS
-Each cell myelinates multiple axons

•Schwann cells
-Found in the PNS
-Each cell myelinates ONLY ONE axon (remember that peripheral axons are very long, so each axon has multiple Schwann cells myelinate it)
Describe the sensory innervation of the tongue.
•Anterior 2/3rd of the tongue
-Taste – CN VII
-Sensation – CN V3

•Posterior 1/3rd of the tongue
-Taste and sensation – CN IX and CN X
What is the location of the B cells in a lymph node?
***High Yield***
Follicle
What is the location of T cells in a lymph node?
*** High Yield***
Paracortex
Where can B cells and T cells be found in the lymph nodes?
•B cells – follicle of the cortex
•T cells – paracortex
Which MHC are found in T helper cells? Which MHC are found in cytotoxic T cells?
•Helper T cells – MHC 2
•Cytotoxic T cells – MHC 1
Lecture 30: Immunology 2
Antigen Presentation
A 48-year-old woman has been suffering with progressive lethargy and extreme sensitivity to cold temperatures. What is the most likely diagnosis?
•Hypothyroidism: most common cause – Hashimoto thyroiditis
What is the most common salivary gland tumor?
•Pleomorphic adenoma
What are the different sinuses that can become infected and cause sinusitis?
•Maxillary sinuses
•Frontal sinuses
•Ethmoidal air cells
•Sphenoidal sinuses
What characteristic finding would you see on electron microscopy of a dendritic cell with Langerhans cell histiocytosis?
•Birbeck granules (appearance of tennis rackets)
What molecules are expressed on the surface of antigen presenting dendritic cells?
•MHC I

•MHC II

•B7 co-stimulatory signal (CD 80 or CD 86)

•CD40

•CD80

•CD86
What are 3 cell types that are known for presenting antigens to T cells?
•B cells

•Dendritic cells

•Macrophages
Lecture 31: Immunology 3
T cells
What are the various clinical uses for the following sympathomimetics?
-Dopamine
-Clonidine
-Amphetamine
-Terbutaline
-Epinephrine
•Dopamine
-Shock

•Clonidine
-HTN
-HTN urgency
-Renal disease

•Amphetamine
-ADHA
-Weight loss
-Daytime sleepiness
-Narcolepsy
-Major depressive disorder (especially while waiting for and anti-depressant to kick in)

•Terbutaline
-Asthma
-Tocolysis

•Epinephrine
-Anaphylactic shock
Where can you find nicotinic acetylcholine receptors in the body?
•Neuromuscular junction
•Autonomic ganglion
What structures are derived from the branchial pouches?
•1st branchial pouch
oMastoid air cells
oMiddle ear cavity
oEustachian tubes

•2nd branchial pouch
o Lining of the palatine tonsil

•3rd branchial pouch
oThymus
oInferior parpthyroids

•4th branchial pouch
oSuperior parathyroids
Important cytokines: IL-2, IFN-y, IL-10, IL-4 and IL-5
•IL-2
o T cell stimulator
o Target of drugs in inflammatory diseases

•Interferon gamma (IFN-y)
o Stimulates macrophages

•IL-10
o Inhibits T cells and macrophages

•IL-4 and IL-5
o B cell stimulators
Corticomedullary junction (KNOW)
Where Positive and Negative selection takes place
Negative= apoptosis
What brachial pouch is the thymus derived from?
Derived from epithelium of 3rd brachial pouch

Outer layer= cortex (contains immature T cells)

Middle= medulla(contains mature T cells)

T cells mature as they move from the cortex to the medulla selection
Which cytokines are produced by Th1 cells? Which cytokines are produced by Th2 cells?
•Th1 cells
IL-2: Stimulates cytotoxic T cells (CD8 cells)
IFN-y: Stimulates macrophages

•Th2 cells
IL-4 & IL-5: stimulates B cells and Antibody production
IL10: Inhibits Th1
Which cytokines inhibit Th1 cells? Which inhibit Th2 cells?
•Inhibit Th1 cells: IL-10

•Inhibit Th2 cells: IFN-y
How do cytotoxic T cells kill virus-infected cells and Neoplastic cells?
Induce apoptosis by releasing cytotoxic granules (perforin and granzyme)

Apoptosis can be mediated by the Fas-FAS ligand interaction
Lecture 32: Immunology 4
Monocytes and macrophages
What are the common side effects of β-blockers?
Bradycardia

AV block

Decrease myocardial contractility (May trigger CHF)

Bronchoconstriction (non-selective β-blockers)

Increase blood glucose slightly

Mask sympathetic symptoms of hypoglycemia
What is the medication of choice for the treatment of atrial fibrillation due to hyperthyroidism?
Drugs for Heart rate control in A-fib:
-Nondihydropyridine CCB (diltiazem)

-β-blocker (propranolol)
Will decrease HR
Block some of the adrenergic symptoms of hyperthyroidism
Some B-blockers can decrease T3 slightly

Treat the hyperthyroidism
•Methimazole
•Radioactive iodine
What is the precursor molecule of ACTH synthesis?
Pro-opiomelanocortin (POMC)
Encapsulated bacteria
“Even Some Killers Have Pretty Nice Capsules”

•Escherichia coli

•Streptococcus pneumonia**

•Klebsiella pneumonia

•Haemophilus influenza**

•Pseudomonas aeruginosa

•Neisseria meningitides**

•Cryptococcus neoformans

Pts without a spleen need to get a vaccine for the organisms we have vaccines against (denoted by **)
Which cytokine more than any other should be known as the macrophage-activating cytokine?
IFN-y


* IL-10 interferes with macrophage activity
What are the acute phase cytokines that are produced by macrophages?
TNF-y

IL-1

IL-6
What is the function of macrophages in the spleen?
Removal of encapsulated bacteria

Removal of dysfunctional cells (especially RBCs)
What name is given to RBCs partially digested by splenic macrophages?
Degmacytes (bite cells)
Lecture 33: Biochem 1
RNA
What gene complex gives rise to a protein that initiates VDJ recombination in B and T cell development?
Recombination activating gene complexes (RAG)

RAG-1 and RAG-2
What are the different types of collagen, and where can they be found in the body?
“Strong, slippery, bloody, BM”

Type 1 (strong)
-Tendon
-Bone
-Dentin
-Skin
-Fascia
-Cornea

Type II (slippery)
-Cartilage
-Vitreous body

Type III (bloody)
-Blood vessels
-Granulation tissue
-Uterus
-Fetal tissue

Type IV (BM)
-Basement membrane (lamina)
What medication inhibits the cellular sodium ATPase? What is its clinical application?
Digitoxin (digitalis): Cardiac glycoside

Clinical application
-CHF: Positive inotropic (increases contractility)
-Atrial fibrillation (decrease AV node conduction and control HR)
Stop codon mRNA —KNOW!!!
“U Go Away, U Are Away, U Are Gone”

UGA

UAA

UAG
Regulation of Transcription ***High Yield***
Operon

Transcription Factors

Common structural motifs

Operator region

Response elements: Enhancer region and Repressor region
What does the Operon consist of?
Structural genes that are transcribed + promoter region (coding region) + all regulatory regions
What are transcription Factors and where do they bind?
Proteins that must bind to the promoter region

Promoter regions:
-25 Hogness/Pribnow/TATA box
-75 CAAT box ( in eukaryotes)
What are the different structures that allow transcription factors and other proteins to interact with DNA?
Helix-loop-helix: allows the transcription factor/ protein in incorporate into the major groove of DNA

Helix-turn- helix

Zinc finger

Leucine zipper
What does the operator region do?
Binds repressor (stops transcription), or inducer (starts transcription), located between the promoter region and start site
What do Response elements (Enhancer region and Repressor region) determine?
The rate of transcription

Response elements increase or decrease the rate of transcription when bound by protein factors

Location may be close to, far from, or within the promoter region
Where is rRNA synthesized?
Synthesized in the nucleolus
Where are mRNA and tRNA synthesized?
Synthesized in the nucleoplasm
How are introns spliced out of eukaryotes?
Spliceosomes

Introns stay in the nucleus when they are cut out of the RNA sequence
What amino acid frequently has more coding sequences in the mRNA than are represented in the peptide that is created from that mRNA?
Methionine

There is more methionine (AUG) in the mRNA than there will be in the protein
What is the difference between an intron and an exon?
Introns-- noncoding segments of DNA which stay in the nucleus

Exons-- coding sequences for specific protein products that leave the nucleus
How is transcription of the lac operon regulated?
Lac Operon is regulated by 2 main things

CAP: facilitates RNA polymerase binding and promotes β-galactosidase production
-Must have CAP in order to transcribe the gene but CAP is inhibited by excess glucose levels

Lac repressor: inhibits/blocks transcription
-Inhibits β-galactosidase production
-When lactose is present, the lac repressor can’t bind to the operator site

Lac operon is only “switched on” when glucose is absent and lactose is present
What environmental conditions must be met in order for the lac operon to allow expression of β-galactosidase in lactose-fermenting bacteria?
Glucose must be absent and excess lactose must be present
Lecture 34: Biochem 2
Protein
What are the mRNA stop codons?
UAG
UAA
UGA
What substance inhibits RNA polymerase II in eukaryotes causing liver damage?
α-Amanitin-- found in lethal mushrooms
Which amino acids are modified by the Golgi apperatus? ***HIGH YIELD***
Serine
Threonine
Asparagine
Where does aminoacyl tRNA synthetase work?
3’ end (hydroxy end)

Where the AA is charged onto the tRNA molecule so that it can generate the polypeptide
Translocation requires:
KNOW
Elongation Factor G – prokaryotes

Elongation Factor -2 – eukaryotes
What enzyme matches amino acids to tRNA?
Aminoacyl-tRNA synthetase
What antibiotics are inhibitors of prokaryotic protein synthesis at the 50s ribosome?
“Buy AT 30, CCELL’S at 50”

Chloramphenicol

Clindamycin

Erythromycin (macrolides)

Lincomycin

Linezolid

Streptogramins


Aminoglycosides

Tetracyclines
What antibiotics are inhibitors of prokaryotic protein synthesis at the 30s ribosomal subunit?
Aminoglycosides

Tetracyclines
Lecture 35: Immunology 5
B cells and Antibodies
What medications are known for having anticholinergic side effects?
•Typical neuroleptics
-Thioridazine
-Chlorpromazine

•1st generation antihistamines
•Tricyclic antidepressants
•Amantadine
Describe the usefulness of the dexamethasone suppression test.
Determining the different causes of Cushing syndrome

Normal individual
-Low dose –--> cortisol decreased

Ectopic ACTH-producing tumor
-Low dose and High dose –---> cortisol remains high

ACTH-producing pituitary tumor
-Low dose –----> cortisol remains high
-High dose –----> cortisol decreased

Cortisol-producing adrenal tumor
-Low dose and High dose –---> cortisol increased/ remains high
What enzyme of the adrenal steroid synthesis pathway is inhibited by ketoconazole?
Desmolase
B cell surface markers
KNOW
CD19

CD20

CD21

IgM

IgD
Characteristics of antibody structure

Just read
Variable part of L and H chains recognizes antigens

Fc portion of IgM and IgG fixes complement

Heavy chain contributes to Fc and Fab fractions

Light chain contributes only to Fab fraction
Fab
Antigen- binding fragment

Determines idiotype: unique antige-binding pocket; only 1 antigenic specificity expressed per B cell
Fc
Constant

Carboxy Terminal

Complement binding at CH2 (IgG + IgM only)

Carbohydrate side chains

Determines isotype (IgM, IgD, etc.)
Antibody diversity is generated by:
Random "recombination" of VJ (light chain) or V(D) J (heavy- chain) genes

Random combination of heavy chains with light chains

Somatic hypermutation (following antigen stimulation)

Addition of nucleotides to DNA during recombination by terminal deoxynucleotidyl transferase
Immunoglobulin Structure

Just read
Immunoglobulins are glycoproteins consisting of 2 identical heavy (H) chains and 2 identical light (L) chains linked by disulfide bonds in a Y shape

Variable regions exist on both the L and H chains

The H chain is composed of Fc and Fab fragment.

The L chain is composed of Fab fragment only.

The Fab is the antigen-binding fragment.

The Fc fragment is constant and, in the case of immunoglobulin (Ig) M and IgG, it is complement binding. It also contains a carboxy terminal and carbohydrate side chains.
What are 3 antibody functions?
Opsonization-- in which the antibody promotes phagocytosis

Neutralization-- in which the antibody prevents bacterial adherence to cells and membranes

Complement activation-- in which antibody activates complement, enhancing opsonization and lysis
Allotype, Isotype, Idiotype
Allotypes: are Ig epitopes that are different among the members of the same species. It is secondary to polymorphisms in the constant portion of the H chain or L chain. When trying to find appropriate transplant donors, allotypes are matched.

Isotype-- an Ig epitope that is common to a single class of immunoglobulins. For example, IgG, IgM, and IgA are different isotypes of Ig. It is determined by the constant region of the H chain

Idiotype-- an Ig epitope that is specific for a given antigen. It is determined by the antigen- binding site contributed by the variable and hypervariable regions
Associated with allergies because it is bound by mast cells and basophils and causes them to degranulate and release their histamine
IgE
Comprises 70-75% of the total immunoglobulin pool
IgG
Present in large quantities on the membrane of many B cells
IgD

IgM
Crosses the placenta and , additionally, confers immunity to neonates in the first few months of life
IgG
Can occur as a dimer
IgA
Largely confined to the intravascular pool and is the predominant early antibody frequently seen in the immune response to infectious organisms with complex antigens
IgM
Distributed evenly between the intravascular and extravascular pools
IgG
The predominant immunoglobulin in mucoserous secretions such as saliva, colostrums, milk, tracheobronchial secretions, and genitourinary secretions
IgA
Can be a pentamer
IgM
Which cellular organelles are particularly important to plasma cell function?
•Plasma cell function
-Rough endoplasmic reticulum
-Golgi apparatus
What initiates recombination of V(D)J sequences?
Recombination activating gene complex (RAG 1 and RAG 2)
Lecture 36: Immunology 6
Immunization and Autoantibodies
Name of monocytes in Blood, alveoli, intestines
Macrophages
Name of monocytes in connective tissue
Histocytes
Name of monoctyes in the Liver
Kupffer cells
Name of monocytes in Kidney
Mesangial cells
Name of monocytes in the Brain
Microglia
Name of monocytes in the bone
Osteoclasts
Which types of proteins are responsible for fostering the progression through the cell cycle?
Cyclins
Cyclin-dependent kinases
What structural motifs allow for proteins to bind DNA?
Helix-Loop-Helix
Helix-Turn-Helix
Zinc Finger Motif
Leucine Zipper Protein
What are the autoantibodies in Lupus and CREST Scleroderma?

****
•ANA
-Screening test for Lupus (important to know)
-Non-specific (seen in other diseases)

•Anti-centromere
-Seen with CREST scleroderma
Which viral vaccines are potentially dangerous to patients with an egg allergy?
Egg-based: Flu, Yellow fever
What autoimmune disease is associated with anti-dsDNA antibodies?
SLE (renal disease)
What stain is used to identify amyloid microscopically, and how is its appearance described?
•Congo red stain -- apple green birefringence under polarized light
Lecture 37: Immunology 7
Granulocytes, Cytokines, and Immunosuppressants
What hematologic changes would you expect to see in a patient without a functional spleen?
Target cells
Thrombocytosis
Howell-Jolly bodies in RBCs
What are the different RNA polymerases in eukaryotes?
RNA polymerase I – makes rRNA

RNA polymerase II – makes mRNA

RNA polymerase III – makes tRNA
In what order is there an abnormal breakdown of elastin?
α1-antitrypsin deficiency

*Excessive breakdown of elastin in the lung ---> emphysema
DDx for Eosinophilia
“DNAAACP”

Drugs

Neoplasm

Atopic disease
-Allergy
-Asthma
-Eczema

Addison disease
-Primary adrenal insufficiency

AIN (Acute interstitial nephritis)

Collagen vascular disease
-Systemic lupus
-Chrug-Strauss vasculitis

Parasites
-Ascaris (Loeffler eosinophilic pneumonitis)
What are the actions of IL-1 through IL-5?
“Hot T-Bone stEAk”

IL-1 – Fever (“hot”)

IL-2 – T cells

IL-3 – Bone marrow

IL-4 – IgE and IgG production

IL-5 – IgA production, and eosinophils
Neutrophil's Chemotactic Agents

KNOW
IL-8

C5A

Leukotrine B4
Cyclosporine MOA & SE
MOA: binds cyclophilins; the complex blocks the differentiation and activation of T cells by inhibiting calcineurin, thus preventing of IL-2 and its receptor

Use: Prevent organ rejection & in autoimmune disorders

SE: NEPHROTOXICITY
Tacrolimus (FK506) (Protopic) MOA & SE
MOA: binds to FK-binding protein, inhibiting calcineurin and secretion of IL-2 and other cytokines

Use: Potent immunosuppressive used in organ transplant recipients

SE: Nephrotoxicity

Side effects: Nephrotoxicity and Neurotoxicity
Pimecrolimus (Elidel)
Given topically for excema
Not used systemically
Azathioprine
MOA: antimetabolic precursor of 6-mercaptopurine that interferes with the metabolism and synthesis of nucleic acids; toxic to proliferating lymphocytes

Use: kidney transplant, autoimmune disorders (including glomerulonephritis and hemolytic anemia)

Toxicity: bone marrow suppression, active metabolite mercaptopurine is metabolized by xanthine oxidase; thus toxic effects may be increased by allopurinal
Muromonab
MOA: monoclonal antibody that binds to CD3 on the surface of T cells, blocks cellular interaction with CD3 protein responsible for T-cell signal transduction

Use: Immunosuppression after kidney transplantation

SE: Cytokine Release syndrome, hypersensitivity reaction
Daclizumab
High affinity for IL-2 on T cells (CD25)
Mycophenolate
Inhibits inosinephosphate dehydrogenase which is needed for the production of Guanine

Uses: transplants and lupus neuritis
Aflixamab, adenlinonab, etanercept
Anti- TNF alpha agents

Chromes diseases, RA, Psoriatic arthritis, Ankylosing spondylitis, Inflammatory bowel disease, Reactive arthritis (Reiter Syndrome)
Absixamab

Important to know
Glycoprotein 2B3A inhibitor on platelet (inhibit platelet activity)

Used in CVD
Trastuzumab (Herceptin)
Useful for treating breast cancer expressing HER-2
Rituximb
CD20 antagonist
Treatment of B cell non-Hodgkin lymphoma
Umbilizimab
Anti- IgE

Used: type 1 hypersensitivity, severe asthma
Cytokines that promote B cell growth and differentiation
IL-4

IL-5
Cytokines that are produced by Th1 cells
IL-2

Interferon-y
Cytokines that are produced by Th2 cells
IL-4

IL-5

IL-10
Cytokines involved in growth and activation of eosinophils
IL-5
Cytokines secreted by helper T cells and activates macrophages
Interferon-y
Cytokine that inhibits macrophage activation
IL-10
Pyrogenes secreted by monocytes and macrophages
IL-1

IL-6

TNF- a
Inhibits production of Th1 cells
IL-10
Inhibits production of Th2 cells
Interferon- y
Cytokines that mediate inflammation
IL-1

IL-6

TNF- a
Enhances synthesis of IgE and IgG
IL-4
Enhances synthesis of IgA
IL-5
Released by virus-infected cells
Interferon- a

Interferon- B
Supports growth and differentiation of bone marrow stem cells
IL-3
Supports T cell proliferation, differentiation, and activation
IL-2
Precursor of 6-mercaptopurine
Azathioprine
Antibody that binds to CD3 on T cells
Muromonab
Antibody that binds IL-2 receptor on activated T cells
Daclizumab
Inhibits inosine monophosphage (IMP) dehydrogenase
Mycophenolate mofetil
Inhibits calcineurin resulting in the loss of IL-2 production and blockage of T cell differentiation and activation
Cyclosporine
Binds FK-binding protein (FKBP) leading to loss of IL-2 production
Tacrolimus
Binds FKBPI2 leading to inhibition of mTOR and T cell proliferation
Sirolimus
Used for lupus nephritis
Cyclosporine

Azathioprine

Mycophenolate mofetil
Metabolized by xanthine oxidase, therefore increasing allopurinol toxicity
Azathioprine

6-Mercaptopurine
What malignancy is associated with mycophenolate mofetil?
Lymphoma
Why is mycophenolate mofetil not used in pregnancy?
Congenital malformation of the ear and face

1st trimesters miscarriage

Teratogenic
Lecture 38: Immunology 8
Complement and Hypersensitivity
What enzyme is responsible for tRNA charging? What enzyme catalyzes peptide bond formation?
tRNA charging -- Aminoacyl-tRNA synthetase

Catalyzes peptide bond formation -- Peptidyltransferase
Which cytokines are secreted by the two different types of helper T cells?
Th1 makes: IL-2 & IFN-y

Th2 makes:
-IL-4
-IL-5
-IL-10
-IL-13
What substances are utilized by natural killer cells to induce apoptosis in other cells?
Granzymes

Perforin
Hypersensitivity ***HIGH YIELD – 4 star/5 star topic***

What are the characteristics of Type I hypersensitivity?
Free antigen cross-linking IgE of pre-sensitized mast cell and basophils

Wheal and flare

Allergy, asthma, anaphylaxis, excema, Hay fever, hives
What are the characteristics of Type II Hypersensitivity?
Antibodies against self

Complement mediated damage, macrophages, NK cells

Starts with antiself antibody

Diagnosis: Test= Coon’s test

Examples:
Hemolytic anemia
Pernicious anemia
ITP
Erthyroblastosis fatalsis transfusion reaction
Rheumatic fever
Goodpasture syndrome
Pemphigus vulgaris
Grave’s disease
Myathenia Gravis
What are the characteristics of Hypersensitivity III?
Antibodies against soluble antigens deposited in tissues

Excess antibody- antigen complexes saturate the tissues


Activates complement & neutrophils

Examples:
Serum sickness
Arthrous reaction
Systemic lupus
RN
Polyarthritis nodous
Post streptococcous glomerularnephritis
Characteristics of Hypersensitivity Type IV?
T cell-mediated, delayed hypersensitivity

Examples:
Posion ivy
PPD skin test
Type I diabetes
MS
Guillia- Barre
Hashimoto’s thyroiditis
Graft vs. Host disease
Contact dermatitis
Type IV hypersensitivity-- Contact Dermatitis *****
•Poison ivy
•Poison oak
•Nickel allergy
-Seen in places on the body where you would commonly be exposed to nickel (watch area, belt buckle, buckle of sandals, jewelry)—I have this so, I’ll know if you ever buy me cheap jewelry muwahahaha… look at that--------- it’s sparklely!!!)
A patient suffers from recurrent Neisseria infections. What complement proteins are deficient?
Any of the Membrane Attack Complex (MAC) complement proteins C5, C6, C7, C8, C9
What complement is responsible for neutrophil chemotaxis?
Complement C5a
Lecture 39: Immunology 9
Immunodeficiencies
Which type of collagen is abnormal in Alport syndrome?
Type IV collagen
Which type of collagen is abnormal in Ehlers-Danlos syndrome?
Type III collagen
What are the mRNA stop codons?
UGA
UAA
UAG
Thymic aplasia (DiGeorge) *****
3rd and 4th pouches fail to develop
-No thymus = no T cells
-No parathyroids = Low Ca2+ & tetany

Congenital defects in heart/great vessels

Recurrent viral, fungal,protozoal infections

90% have a chrom 22q11 deletion (detect with FISH)
Chromosome 22q11 Deletions *****
Associated with DiGeorge syndrome


Associated with heart and great vessel malformations

“CATCH 22”
Severe Combined Immunodeficiency (SCID) *****
Defect in early stem cell differentiation

Can be cause by at least 7 different gene defects-- KNOW: ADENOSINE DEAMINASE DEFICIENCY

Last defense is cytotoxic NK cells

Presentation triad:
1) Severe recurrent infections
-Chronic mucocutaneous Candidiasis
-Fatal or recurrent RSV, VZV, HSV, HSV, measels, flu, parainfluenza
-PCP pneumonia

2) Chronic diarrhea

3) Failure to thrive

No thymic shadow on newborn CXR
Wiskott-Aldrich Syndrome *****
“WAITER”

Wiskott

Aldrich

Immunodeficiency

Thrombocytopenia and purpura

Eczema

Recurrent pyogenic infections
-No IgM v. capsular polysaccharides of bacteria
-Low IgM, high IgA
- X-linked

Truncal eczema – associated with Wiskott-Aldrich
Chronic Granulomatous Disease (CGD) ***HIGH YIELD***
Lack of NADPH oxidase activity ----> impotent

Susceptible to organisms with catalase (S. aureus, E. coli, Klebsiella spp., Aspergillus spp., Candida spp.)

Dx: (-) nitroblue tetrazolium (NBT) dye
- No yellow to blue-black oxidation (because phagocytes do not engulf the dye)

Prophylactic TMP-SMX

IFN-y also helpful
Bruton Agammaglobunlinemia *****
X-linked (Boys)

B cell deficiency-- defective tyrosine kinase-- low levels of all immunoglobulins

Recurrent bacterial infections after 6 mos
IgA deficiency *****
Most common

Most appear healthy

Sinus and lung infections

1/600 European decent

Associated with atophy, asthma

Possible anaphylaxis to blood transfusions and blood products
Chronic mucocutaneous Candidiasis *****
T cell dysfunction v. C. albicans

Rx: ketoconazole
Hyper- IgM syndrome (3 types) High IgM & Low Ig *****
X-linked: no CD ligand

AR: no CD40

NEMO deficiency

Can't switch to other Ig isotypes
What are the X-linked immunodeficiencies?
Wiskott- Aldrich

Bruton's Agammaglobinemia

Chronic granulomatous disease (can be inherited in other ways)

Hyper-IgM syndrome
Ataxia- Telangiectasia *****
IgA deficiency

Cerebellar ataxia, and poor smooth pursuit of moving target with eyes

Telangiectasias of face >5yo

Increased cancer risk: lymphoma and acute leukemias

Radiation sensitivity (try to avoid x-rays)

+/- Increased AFP in children > 8mos

Average age of death: 25 yo
Chediak- Higashi Syndrome*****
Defective LYST gene (lysosomal transport)

Defective phagocyte lysosome ----> giant cytoplasmic granules in PMNs are diagnostic

Presentation triad (KNOW)
1. Partial albinism

2. Recurrent respiratory tract and skin infections

3. Neurologic disorders
Job syndrome (Hyperimmunoglobulin E syndrome) *****
Deficient IFNy -- PMNs fail to respond to chemotactic stimuli (C5a, LTB4)

High levels of IgE and eosinophils

Presentation triad:
1. Eczema

2. Recurrent cold S. aureus abscesses (think biblical Job with boils)

3. Coarse facial features: broad nose, prominent forehead ("frontal bossing"), deep set eyes, and "doughy" skin

Also common to have retained primary teeth resulting in 2 rows of teeth
Leukocyte Adhesion Deficiency Syndrome *****
Abnormal integrins ---> inability of phagocytes to exit circulation

Phagocytes can not integrate into tissues

Delayed separation of umbilicus
What would you expect to see in a patient with Wiskott-Aldrich syndrome?
“WAITER”

Wiskott

Aldrich

Immunodeficiency

Thrombocytopenia and purpura

Eczema

Recurrent pyogenic infections

Deficiency of IgM antibodies, and elevated IgA antibodies
What is the cause of chronic granulomatous disease? What infections are these individuals susceptible to?
Caused by absence of NADPH oxidase

Phagocytes can’t generate oxygen-free radicals

Susceptible to infections by:
Staph aureus
E. coli
Klebsiella
Aspergillus
Candida

All have CATALASE
A young child presents with tetany from hypocalcemia, and candidiasis resulting from immunosuppression. What cell type is deficient in this patient?
DiGeorge Syndrome:

T cell deficiency

Thymic aplasia

Parathyroid dysfunction  hypocalcemia
Rapid fire fact: Most common infections seen in chronic granulomatous disease
Staph aureus

E. coli

Klebsiella

Aspergillus

Candida
Rapid fire fact: Eczema, recurrent URI, high serum IgE
Hyperimmunoglobulin E syndrome – (Job syndrome)
Rapid fire fact: Large lysosmal vesicles in phagocytes
Chediak-Higashi disease
Thyroid development 4 stars****

Where does the Thyroid diverticulum come from?
Thyroid diverticulum arises from the floor of the primitive pharynx and descends into the neck
What connects the thyroid diverticulum to the tongue?
Thyroglossal duct

Which normally disappears, but may persist as pyramidal lobe of thyroid

Foramen cecum is the normal remnant of the thyroglossal duct
What is the most common site of ectopic thyroid tissue?
Tongue
How does a thyroglossal duct cyst present?
As an anterior midline neck mass that moves with swallowing
How does a persistent cervical sinus present?
Causes a branchial cleft cyst in the lateral neck
What would you suspect to be the cause of hyperthyroidism in a patient presenting with the symptoms of hyperthyroidism in addition to each of the following findings?

Findings: Extremely tender thyroid gland
Subacute (de Quervain's) thyroiditis

*This is a transient hyperthyroidism
FInding: pretibial myxedema
Grave's disease
Finding: Pride in recent weight loss, medical professional
Thyroid hormone abuse
Finding: Palpation of multiple thyroid nodules
Toxic multinodular goiter
Finding: Palpation of a single thyroid nodule
Toxic thyroid adenoma
Finding: Recent study using IV contrast (iodine)
Jod-Basedown phenomenon
Finding: eye changes-- proptosis, edema, injection
Grave's disease
History of thyroidectomy or radioablation of thyroid
Too much exogenous thyroid hormone
What type of thyroid cancer matches each of the following statements?

- Most common type of thyroid cancer (70-75%)
Papillary carcinoma
-Second most common type of thyroid cancer (10%)
Follicular carcinoma
-Activation of receptor tyrosine kinase
Papillary carcinoma

Medullary carcinoma
-Hashimoto thyroiditis is a risk factor
B-cell lymphoma
- Cancer arising from parafollicular C cells
Medullary Carcinoma
- Commonly associated with either a RAS mutation or a PAX8- PPRP gamma I rearrangement (lower yield)
Follicular carcinoma
-Commonly associated with rearrangements in RET oncogene or NTRKI
Papillary carcinoma
- Most common mutation in the BRAF gene (serine/ threonine kinase)
Papillary carcinoma
Lymph drainage 4 stars ****

Where does the upper limb/ lateral breast drain to?
Axillary nodes
Where does the lymph from the stomach drain to?
Celiac nodes
Where does the lymph from the duodenum and jejunum drain to?
Superior mesenteric nodes
Where does the lymph from the sigmoid colon drain to?
Colic nodes and then to ----> Inferior mesenteric nodes
Where does the lymph from the Rectum drain to?
Internal iliac nodes
Where does the lymph from the anal canal above the pectinate line drain to?
Internal iliac nodes
Where does the lymph from the testes drain to?
Para-arotic nodes
Where does the lymph from the scrotum drain to?
Superficial Inguinal nodes
Where dose the lymph from the thigh drain to?
Superficial inguinal nodes
Where does the lymph from the lateral side of the dorsum of the foot drain to?
Popliteal lymph nodes
What drains into the right lymphatic duct?
Right arm and Right half the head

Obstruction of the right lymphatic duct will cause NON-pitting edema in these regions
Where does the thoracic duct enter back into the circulation?
Junction of the Left Subclavian Trunk & Left Internal Jugular Vein
All T cells have CD____
3
Cytotoxic T cells= CD___
8
Helper T cells= CD___
4
What do Th1 cells activate?
Macrophages and cytotoxic T cells
What doe Th2 cells activate?
Plasma cells to make antibodies
A potentiate stimulator of T cells is?
IL-2
What Human leukocyte antigen molecules code for
MHC 1?
HLA-A

HLA-B

HLA-C
What HLA molecules code for MHC 2?
HLA- DR

HLA- DQ

HLA- DP

Dr. going into DQ to get a Dr Pepper
What condition is associated with HLA-A3?
Hemochromatosis
What condition is associated with HLA-B27?
"PAIR"

Psoriatic arthritis

Ankylosing spondylitis

Inflammatory bowel disease

Reiter' Syndrome

Also called the Seronegative arthropathies because they don't have an elevation in Rheumatoid factor
What condition is associated with HLA- DR3 and HLA- DR4?
Diabetes Mellitus Type I
What are the different types of Dendritic cells?
Langerhans-- from immature epithelial tissue in epidermal layers of skin (CALT)

Interstital-- from immature non-epithelial, interstitial tissue; in all interstitial spaces of virtually all organs except the brain
What are follicular dendritic cells?
Do not arise from bone marrow like the dendritic cells

Do not express class II MHC---> do not present antigen to Th cells

Exclusively reside in lymph node

Important in the maturation and diversification of B cells
What is the clinical use of Dopamine?
Tx: Shock
Clinical use of Clonidine?
HTN

HTN urgency

Renal Disease
Clinical use of Amphetamine?
ADHA

Weight loss

Daytime sleepiness

Narcolepsy

Major Depressive Disorder
Clinical Use of Terbutaline?
Asthma

Tocolysis (suppress premature labor)
Clinical use of Epinephrine?
Anaphylactic shock
What structures are derived from the 1st brachial pouch?
Mastoid air cells

Middle ear cavity

Eustachian tubes
What structures are derived from the 2nd brachial pouch?
Lining of the palatine tonsil
What structures are derived from the 3rd branchial pouch?
Thymus

Inferior parathyroids
What structures are derived from the 4th branchial pouch?
Superior parathryroids
Tho ---> Th1 through which cytokine?
IL-12
Tho ---> Th2 through which cytokine?
IL-4
What is the 2 step process for T helper cell activation?
1. T cell receptor + CD4 complex with MHC II + antigen

2. CD 28 on the Th cell recognizes B7 on the APC

*B7= costimulatory signal (aka CD80 or CD87)
What is the 2 step process for Cytotoxic T cell activation?
1. TCR + CD8 complex with MHC I + viral protein

2. CD28 recognizes B7
What are the 4 main steps in B cell activation?
1. Endocytosis of antigen by B cell

2. Antigen is presented to a Th cell by using the MHC 2 found on APCs

3. Use of co-stimulatory signal of CD40 receptor on B cells and CD40 ligand on Th cell

4. Steps 1-3 -----> Th2 cell to generate IL-4, IL-5, IL- 6
By which surface markers are NK cells identified?
CD 16

CD 56
What interleukins enhance NK cell activity?
IL- 12

IL-2

INF - B

INF -a
Do NK cells secrete IFN- y?
Yes
What cells are CD16 found on?
NK cells

Macrophages

Monocytes

Neutrophils

*Binds to the constant region of antibodies as well
How does CD 16 recognize and kill immunglobulin coated cells?
Antibody Dependent Cell Mediated Cytotoxicity

(ADCC)
Describe the maturation and migration of monocytes?
Leave bone marrow for blood -----> circulate 8 hours to mature -----> migrate into tissue to become macrophages
What are monocytes in the blood, alveoli, and intestines called?
Macrophages
What are monocytes in the connective tissue called?
Histiocytes
What are monocytes in the liver called?
Kupffer cells
What are monocytes in the kidney called?
Mesangial cells
What are monocytes in the bone called?
Osteoclasts
What are monocytes in the brain called?
Microglia
What surface markers does macrophages have?
CD40

CD16-- binds to constant region of immunoglobulins

CD14-- binds lipopolysaccharide or endotoxin of Gram (-) bacteria
What type of cytokines do macrophages secrete?
Acute phase cytokines:

IL-1

IL-6

TNF - a
What are the actions of IFN- y secreted from Th1 cells and NK cells?
Stimulates macrophages

Stimulates NK cells to kill virally infected cells
What are actions of INF- a and INF- B produced from virally infected cells?
Place neighboring cells in an anti-viral state by:

-Inhibiting cellular protein synthesis thus blocking replication

-Encouraging the activation of ribonuclease that degrades viral RNA

- Can also induce the lytic activity of NK cells
What other cytokines (besides IL-1, IL-6, & TNF- a) mediate inflammation?
C Reactive Protein (CRP)

Complement

Coagulation factors

Ferritin

* These are made in hepatocytes
Where are T-cells found in the spleen?
PALS ---- Periarterial Lymphatic Sheath of the spleen
Where are B - cells found in the spleen?
Follicles of the white pulp
What are common findings in Post Splenectomy patients?
Increased Howell- Jolly Bodies

Increased Target cells

Increased Thrombocytosis
With increased splenomegaly you will tend to have ________
Thrombocytopenia because the spleen sequesters platelets
What does Th2 cells secrete that stimulate B cells?
IL-4

IL-5
When B cells encounter antigens what do they produce?
Plasma cells

Memory B cells
As you age what happens to your number of memory B cells?
Memory B cells Decrease

* This is why vaccine effectiveness decreases and people need boosters
What organelle are plasma cells rich in?
Rough ER
Plasmacytoma is also know as
Multiple Myeloma
Do Multiple myelomas secrete polyclonal antibodies or monoclonal antibodies?
Monoclonal antibodies

* Will see a monoclonal antibody spike and a shift in the lamba: kappa ratio
What histological feature is characteristic of MM?
Russell bodies--- immunoglobulin acculumations within plasma cells
What are the surface proteins of Helper T cells?
CD4

CD3

TCR

CD28

CD40
What are the surface proteins of cytotoxic T cells?
CD3

CD8

TCR
What are the surface proteins of Macrophages?
CD14

CD 40

CD 16

MHC II

B7
What are the surface proteins of NK cells?
CD 16

CD 56
What surface protein do all self cells have except RBCs?
MHC i
Where are disulfide bonds in an antibody?
1. Connecting the 2 heavy chains

2. Connecting light chain to heavy chain

3. Within the light chains and heavy chains they know
What are the different heavy chains types?
Mu--- IgM

Delta--- IgD

Gamma--- IgG

Epsilon--- IgE
What are the 2 different types of light chains?
Lamba

Kappa
What is the normal Kappa: Lamba ratio in humans?
2: 1
V (D) J recombination highlights

Just read
Rearrangements of the DNA segment named variable (V), diversity (D), and joining ( J )

The recombination process begins with breaks in the dsDNA at Recombination Signal Sequences (RSS) that flank the V, D, J coding regions

V (D) J recombination is initiated by the recombination activating gene complex (RAG 1 and RAG 2) which recognize the RSS

Mutations in either of the RAG genes in mice causes an inability to initiate V (D) J rearrangements and an arrest in B & T cell development
Where does the rearrangement process begin?
Recombination signal sequences
What initiates the recombination process?
Recombination activating gene complexes (RAG 1 & RAG 2) by recognizing the RSSs
Key characteristics of IgG
Most abundant type in blood

Delayed immune response (not involved in acute infection)

Fixes complement

Crosses placenta

Opsonizes Bacteria

Neutralizes bacterial toxins and viruses

Half- life is 21 days
Key characteristics of Ig A
Secreted by MALT

Circulation (monomer)

Secreted (dimer)

Can cross through the epithelial cells to get into the gut lumen--- transcytosis

Found in:
Secretions
Tears
Saliva
Mucus secretion
Breast milk
Key characteristics of IgM
Primary immune response (associated with acute infections)

Does NOT cross placenta

Surface of B cells (monomer)

Circulation (pentamer)
IgD is one what cell surface?
Immature B cells
What are the key characteristics of IgE?
Binds to:
Mast cells
Basophils
Eosinophils

Mediates:
Type I hypersensitivity
Parasitic worm infections (by activating eosinophils)
What are some examples of live attenuated virus vaccine?
Smallpox

Yellow fever

Chickenpox (Varicella/ VZV)

Sabin's polio virus (oral polio)

MMR

Influenza (intranasal)

"Live! One night only! See Small Yellow Chickens get vaccinated with Sabin's and MMR! It's INcrediable
* Live attenuated vaccines induce humoral and cell-mediated immunity
What are some examples of inactivated (killed) virus vaccine?
Rabies

Influenza (intramuscular/ injected)

Salk Polio (injected)

Hepatitis A

"SalK= Killed"
"RIP Always"

*Also Cholera

* Killed vaccines only indue humoral immunity
Yellow fever, Influenza, and a small amount of MMR are
________ based vaccines
Egg- based

* Pts allergic to eggs need to have a scratch test done before getting these vaccines
What component must killed virus vaccines have?
Thymus- dependent antigen
What is the difference between Thymus- dependent and Thymus- independent antigen?
Thymus- independent: lacks a polypeptide component and therefore cannot be presented to T cells on their MHC
- Example: lipopolysaccharide the endotoxin of Gram neg. bacteria
- Will NOT result in memory immune system

Thymus- dependent: have a peptide component that will induce MHC and will rest in making a memory immune system
What disorders are associated with antinuclear antibodies (ANA)?
Systemic Lupus (SLE)

Nonspecific
What disorder is associated with Anti-dsDNA?
Lupus RENAL disease
What disorder is associated with Anti- smith?
SLE
What disorder is associated with antihistone?
Drug- induced lupus
What disorder is associated with Rheumatoid factor and
anti- CCP?
Rheumatoid arthritis
What disorder is associated with Anticentromere?
Scleroderma (CREST syndrome)
What disorder is associated with Anti- Scl- 70 (anti-DNA topoisomeraseI)?
Scleroderma (diffuse)
What disorder is associated with antimitochondrial?
Primary biliary cirrhosis
What disorder is associated with IgA antiendomysial, IgA anti-tissue transglutaminase?
Celiac disease
What disorder is assoc. with anti-basement membrane?
Goodpasture's syndrome
What disorder is assoc. with anti-desmolgein?
Pemphigus Vulgaris
What disorder is assoc. with antimicrosomal and antithyroglobulin?
Hashimoto's thyroiditis
Anti-Jo-1

Anti- SRP

Anti- Mi-2
Polymyositis

Dermatomyositis
Anti- SSA (anti- Ro) & Anti- SSB (anti- La)
Sjorgen's syndrome
Anti- U1 RNP (ribonucleoprotein)
Mixed connective tissue disease
Anti- smooth muscle
Autoimmune hepatitis
Anti- glutamate decarboxylase
TYpe 1 diabetes mellitus
c-ANCA (PR3- ANCA)
Granulomatosis with polyangitis (Wegener's)
p- ANCA (MPO- ANCA)
Microscopic polyangiitis

Churg- Strauss syndrome
Immunologic amyloidosis:

Protein?

Fibril?
Protein: Ig Light Chains

Fibril: AL (primary)

Can occur as a plasma cell disorder or associated with multiple myeloma
Secondary amyloidosis:

Protein?

Fibril?
Protein: Serum Amyloid A

Fibril: Amyloid A

Seen in chronic diseases like RA, IBD, spondyloarthropathy, chronic infections
Senile amyloidosis:

Protein?

Fibril?
Protein: Transthyretin

Fibril: ATTR
Type 2 amyloidosis:

Protein?

Fibril?
Protein: Amylin

Fibril: AIAPP
Medullary thyroid CA amyloidosis:

Protein?

Fibril?
Protein: Calcitonin

Fibril: A-CAL
Alzheimer's amyloidosis:
Protein: B- amyloid

Fibril: APP
Dialysis associated amyloidosis:
Protein: B2- microglobin

Fibril: AB2M
What Hypersensitivity is responsible for each of the following clinical problems?

Poststreptococcal glomerulonephritis
Type III
Asthma is a ____ HS reaction
Type I
Rheumatic Fever is a ________ HS reaction
Type II
TB skin test is a _________ HS reaction
Type IV
Allergies, anaphylaxis, and hay fever is a ___________ HS reaction
Type I
Polyarteritis Nodosa is a _______ HS reaction
Type III
Serum sickness is a ____________ HS reaction
Type III
ABO blood type incompatibility is a ________ HS reaction
Type II
Poison ivy is a __________ HS reaction
Type IV
Eczema is a _____________ HS reaction
Type I
Contact dermatitis is a ________ HS reaction
Type IV
Goodpasture syndrome is a ______________ HS reaction
Type II
What are the key characteristics of Bruton Agammaglobulinemia?
X-linked

B- cell deficiency---> defective Tyrosine Kinase gene---> Low levels of all immunoglobulins

Recurrent bacterial infections after 6mos
What are the key characteristics of IgA deficiency?
Most common Ig deficiency

Most appear healthy

Sinus and lung infections

1/600 European descent

Associated with atopy, asthma

Possible anaphylaxis to blood transfusions and blood products
What is the start codon that codes for methionine?
AUG
What are the requirements for transcription to start?
Transcription factors binding to the promoter region

Inducers binding to the operator region
What prevents transcription?
Repressor binding to an operator region
What increases or decreases the rate of transcription?
Response elements binding to an enhancer or repressor region
What is the result of a promoter region mutation?
Commonly results in a substantial decrease in the amount of mRNA that is transcribed
What is B- galactosidase?
Breaks down the dimer molecule of lactose into glucose and galactose

It is necessary for a prokaryote to be a lactate fermenter
What are the 3 eukaryotic polymerases?
I- rRNA

II- mRNA

III- tRNA
What can polymerase II be inhibited by?
a- amantin a mushroom toxin that can cause hepatotoxicity and possibly liver failure
What drug inhibits prokaryotic RNA polymerase?
Rifampin
What are the R's of Rifampin?
rRNA polymerase

Revs up cytochrome P450 (induces)

Red secretions (like red urine)
What are the 2 mechanisms which terminate prokaryotic RNA transcription?
Rho factor--- RNA dependent ATPase removes a polymerase from the template

Rho independent mechanism
Describe the mechanism of Rho independent termination
GC rich DNA---->

GC same strand binding forms stem- loop in RNA (hairpin)---->

Causes a pause in RNA polymerase--->

Subsequent weak RNA bonds (uracil rich region)---->

Separation of RNA polymerase
What is RNA called after it has been transcribed, but before it has left the nucleus?
hnRNA (heterogenous nuclear RNA)
What processes must occur to the hnRNA for it to leave the nucleus and become mRNA?
Capping of the 5' end via S- adenosyl- methionine (SAM)

Polyadenylation on the 3' end (AAUAAA)

Splicing of the introns via spliceosomes
What is the structure of tRNA?
Cloverleaf
What are the ribosomal subunits of prokaryotes?
30S + 50S= 70S
What are the ribosomal subunits of eukaryotes?
40S + 60S= 80S
What occurs during post-translation modification?
N-terminal or C- terminal can be trimmed off

Polypeptide can be covalently modified by: phosphorylation, glycosylation, hydroxylation