Week 4 Flashcards
Where in the body does VDJ occur?
Bone marrow
Where is the first place T and B cells will go once they enter the lymph node?
Pericortical region
Name two Antimicrobial peptides present in blood or tissue that can kill certain bacteria (by disrupting membrane integrity).
Defensins and Cathelicidin
True/False: Defensins and Cathelicidins are most effective together than they are alone.
True
An Acute Phase Protein includes another type of protein within its class that responds to pro-inflammatory cytokines, and acts as an Opsonin. What is the protein?
C reactive protein (CRP)
C reactive protein is elevated in ALL but:
1) Infection
2) Cancer
3) Oral contraceptive patients
4) Healthy individual
Elevated CRP exists in all BUT a healthy individual.
Yes, even in pregnant women does it exist.
Dendritic cells can link the ____ and ____ immune response.
Innate and adaptive
True/False: Large number Macrophages are present prior to infection.
False! They will get recruited 1-2 days after infection.
Macrophages contribute to adaptive immunity by activating _______.
T- cell antigen presentation
Does the Phagosome do the “killing” in the process of Phagocytosis?
No, It is further down the line when it fuses and makes Phagolysosome.
True/False: Natural Killer cells can kill bacteria or other microbes directly.
False! Only responsible for virus-infected cells.
Would the expression of MHC I on a cell be an inhibitory receptor ligand or an activating receptor ligand to the Natural Killer cell?
It would be an inhibitory receptor ligand. Saying, “Wait, you’re killing you own!”
Are PRRs part of the innate or adaptive immune system?
Innate
In Ultrasound imaging, the dark areas seen there would be termed: ______
Anechoic
When contrast is added to CT, what shows up most strongly?
Vessels and viscera appear brighter
Would a stroke show up light or dark on a brain CT?
Chronic hemorrhage (e.g. stoke) would show up dark.
Satellite regions: stretches of DNA ____ that don’t code for anything.
repeats
What is the directionality of DNA?
5’ to 3’ (the way it is synthesized)
In order to read DNA, you need access through the _____ groove.
Major
RNA includes ___ instead of ____ (bases)
Uracil instead of Thymine
True/False: Only 5% of the average gene is exons!
True
Promoter region of a gene is ~____ upstream.
25-30
DNA Recombination leads to ______ changes in genetic info.
Permanent
Name the Chemical/Protein Mediators of Inflammation:
1) ____ 2)____ 3) _____ 4) _____
1) Histamine
2) Kinins
3) Cytokines
4) Proteins present in serum that are activated following infection (like complement)
What are the most common Interleukins associated with Cytokines?
IL-6 and IL-1
Within the inflammation mediators, list the types of Cytokines. 1) ___ 2) ___ 3) ____ 4) ____
1) Interleukins
2) Tumor necrosis factor (TNF-alpha)
3) Interferons (anti-viral)
4) Chemokines
C3a and C5a can serve as ______ within the Complement system when tissues are damaged/infected.
Anaphylatoxins
The enzyme _____ is ONLY found in B cells, and allows the B cell to make cuts in the DNA, furthermore allowing class switching.
AID (Activation-Induced Deaminase)
Where in the body does Somatic Hyermutation occur? (2 places)
1) Germinal center of lymph node
2) Spleen
What happens if there is no function in AID?
Hyper IgM Immunodeficiency
People will have a hard time making other antibodies other than IgM. (see Goodnotes Somatic Hypermutation)
What are the two proteins involved in Mismatch Repair?
1) MSH2 and 2) MSH6
Does Somatic Hypermutation only occur in B cells?
Yes
The ____ in any given cell is just a subset of all possible gene products, (not all genes are expressed in every cell)
Proteome
______: act for good of the patient.
Beneficence
_____: do not harm patient.
Nonmaleficence
Uniparental Disomy occurs in ______ of Meiosis __?
Anaphase in Meiosis II
How do the following components of the innate immune system identify pathogens?
1) Phagocytes
2) Complement (3 answers)
3) Natural Killer cells (2 answers)
1) PRRs that recognize PAMPs on microbes.
2) a. IgM b. Microbial membrane c. Mannose-binding lecithin
3) Recognize (e.g. viruses) with inhibitory receptors (NKG2d) and activating receptors (NKG2a and KIR)
Describe the “Four topics” approach to clinical case analysis.
1) Medical Indications (Beneficence and nonmaleficence)
2) Patient preferences (Autonomy)
3) Quality of Life (Beneficence, nonmaleficence, and Autonomy)
4) Contextual features (Justice and Fairness)
_______: rightfulness determined by usefulness to those affected. Maximize the net good to the most people.
Utilitarian
_____: general universal moral laws; act is either right or wrong.
Deontology
______: based on consequences, “The end justifies the means.”
Consequentialism
_____: Enzymes that catalyze the same chemical reaction but differ in their physical and kinetic properties (e.g. tissue location, sequence)
Isozymes
Disease and cell/tissue damage cause release of intracellular enzymes. What kind of enzymes will we see in liver damage?
ALT (alanine aminotransferase)
What enzyme is associated with myocardial muscle and can determine myocardial infarction damage?
Creatinine Kinase (CK)
The transition state is when the substrates are at the _____.
Highest level of reaction
Lock and Key Model vs. Induced Fit Model in terms of enzyme binding. Explain the differences.
L&K: Absolute substrate specificity.
IF: Substrate must fit close enough, but there is flexibility in binding by the enzyme at the active site.
An example of an Induced Fit Model involves Glucose, what is the name of the enzyme?
Hexokinase
Glucose ——–> Glucose-6-phosphate by Hexokinase
Chymotrypsin, pancreatic protease uses ____ and _____ catalysis.
Acid-base and Covalent catalysis
Amino acids involved in Chymotrypsin’s cleaving cycle mechanism are:
1) Asp 102
2) His57
3) Ser195 (one that turns into Alkoxide ion)
1st step of mechanism of Chymotrypsin: _____
Histidine acts as base to abstract proton from Serine next to it.
An example of a suicide enzyme and also has a part in Direct Repair: ______
Methylguanine Methyltransferase (MGMT)
When thinking on Cofactors, 1) what are the two types? and 2) List an example of a cofactor and an enzyme it helps.
2 types: 1) Coenzymes and Metal cofactors
2) Cofactors: Nicotinamide Adenin Dinucleotide (Lactate Dehydrogenase), Biotin (Pyruvate carboxylase), and Mg2+(Hexokinase).
What is a type of enzyme that acts similarly to a “substrate”?
A cofactor
Prosthetic groups function as ______.
Co-enzymes
Give an example or two of a coenzyme.
1) Biotin in pyruvate carboxylase (PC)
2) Heme in Hemoglobin (non-enzyme)
In the TCR, which of the receptor chains has ITAM (Immune receptor activation motif)?
Gamma, delta, epsilon x2, and zeta x2.
NOT alpha and beta chains
Activated T cell binds to IL-2 that it makes, making it an _____ stimulation.
Autocrine
Stages of Change Model:
1) ______: no intent to change, problem NOT acknowledged.
2) _____: no intent to change, problem IS acknowledged.
3) Prepration: ________
4) Action: _____________
5) _______: work to prevent relapse.
1) Pre-contemplation
2) Contemplation
3) Intent to change
4) Modifies behavior or environment
5) Maintenance
Doctor-patient relationship has been replaced by _________ relationship.
Team-patient
The role of generation of energy done in the mitochondria is called: ________.
Oxidative phosphorylation
What happens if there is a misfolded protein within the RER? What happens if there’s an excess of misfolded proteins?
If just one or few misfolds: the cell will just degrade it/get rid of it.
If excess misfolds: then Unfolded protein response is initiated.
Define Unfolded protein response
When there is excessive misfolding of proteins in the RER, placing RER under stress further triggering cell to either try to re-fold the proteins or degrade them. The cell can stop making the protein, committing apoptosis.
Peroxisomes: Degrade ____ and ____ compounds. They are the PRIMARY organelle for __________.
fatty acids and toxic compounds
Primary organelle for: fatty acid Beta-oxidation.
Peroxisomes: also take part in the synthesis of ______, a phospholipid in the myelin sheath.
Plasmalogen
Term that describes actin being added to the positive end of microfilament while being removed from the negative end.
Treadmilling
When thinking of what the cytoskeleton does well, and looking deeper into the microfilaments of the cytoskeleton, what drugs would effect microfilaments?
Cytochalasin: blocks microfilaments elongation (binds + end)
Phalloidin: Inhibits dissociation of actin into monomers. (binds - end)
What is a drug that can block Mitosis from happening all the way, because it binds to tubulin (inhibiting polymerization)?
Colchicine and Colcemid
What drug stabilizes microtubules but blocks cell division from happening? Often used in breast and ovarian cancer.
Taxol
What is the Extracellular matrix made up of?
Tough, fibrous proteins (collagen)
Matrix adhesion proteins
Basal laminae (thin sheet-like ECM, on which epithelial cells sit.
What type of junction plays a part in epithelial mesenchymal transition (differentiation and morphogenesis)?
Adherens junctions
In the replication fork, what is the purpose for the clamp?
Clamp ensures processivity, keeps DNA polymerase bound.
What enzyme remove RNA primers on Okazaki fragments (lagging strand)?
RNase H
How do dNTPs (Deoxyribonucleoside triphosphate) interact with DNA Polymerases?
DNA polymerases use dNTPs to extend a DNA primer hybridized to a complementary DNA template.
What are some drugs that can inhibit Topoisomerase?
Antibiotics: ciprofloxacin
Anti-cancer drug: etoposide (for Topo II)
What is the overall fidelity of genomic integrity?
~1 error in 1*10^10 bases
What is the Plasma membrane defect of some of the RBCs in sickle cell diseases?
Phosphatylserine is exposed on outer leaflet “Eat me” signal.
What would occur adding cytochalasin to a tread milling actin filament?
Filament would become shorter due to reduced addition at the + end.
What is the mechanism of the cisplatin drug used in chemotherapy?
Cross-linking agent that will structurally alter DNA by causing bends.
HNPCC (Lynch Syndrome) is supposed to be corrected by what repair mechanism? (although it is defective here)
Mismatch Repair
Describe the mechanism of Chloramphenicol (antibiotic).
It inhibits protein chain elongation by peptidyltransferase.
What is the degeneracy of genetic code?
Each amino acid may be coded by multiple codons.
What is a toxin that is metabolized by P450, and causes indirect structural damage to DNA?
Aflatoxin = fungal toxin
Mismatch repair: recognizes mutations on ______ DNA strands. Hint: think of post-replication/recombination repair.
Newly synthesized DNA strands.
Not by damage like in BER.
In NER for Xeroderma Pigmentosum, what is the mechanism of Pol nu?
Incorporates AA opposite cyclobutane thymine dimer to continue replication.
True/False: you have loss of DNA in Homologous Recombination.
False, there is no loss of DNA.
What is the essential protein used in Homologous Recombination?
Rad51
In Apoptosis, what is the molecule that forms the Apoptosome?
Apaf-1
How can you detect apoptosis in the lab?
You will see DNA Fragmentation on agarose gel electrophoresis or TUNEL.
What is the process where cells remove/recycle components to get back to homeostasis, and can come from a reversible cell injury, and do not need caspases?
Autophagy
Can other T cell antigens (ex: lipids and carbohydrates lead to memory B cells?
No, it must be peptide antigens that can be seen.
In Primary immune response, what antibody should be produced more in regard to starting memory B cell response?
IgG should be, due to its high affinity
Where in the body is IL-7 generated (multiple)?
Bone marrow, thymus, keratinocytes, Dendritic cells, Hepatocytes, and epithelial cells.
Where in the body is IL-7 NOT generated?
In other lymphocytes.
What are the two versions of CD45, the cell surface ligand that helps with identifying T cells?
1) CD45RA
2) CD45RO
If Central memory T cells are activated by their antigen again, what happens?
It will proliferate again and produce new effector T cells.
True/False: Effector Memory T cells remain in lymphoid tissues until activated.
False, central memory T cells do.
What can cytokines do to immune cells?
Activation, Proliferation, and Differentiation.
How can cytokines signal other cells?
By autocrine, paracrine, and endocrine (but only a little) signaling.
True/False: Cytotoxic T cells are good at making IL-2.
False, they need it made from CD4+ T helper cells by paracrine signaling.
What else will IL-1beta and TNF-alpha do besides endocrine signaling?
Recruit other immune cells to enhance inflammatory response.
True/False: IFN-gamma is a type I Interferon.
False, it is a type II interferon.
What can the Colony Stimulating Factor, GM-CSF stimulate to produce?
Granulocytes and macrophages
TGF-beta is an inhibitory factor that will also help _____ become Regulatory cells to slow down _______.
CD4+ Helper T cells become regulatory cells to slow down inflammatory response.
Cytokines can be one of three things (3 functions):
1) Pro-inflammtory
2) Anti-inflammatory
3) Growth factors
What can the pro-inflammatory response do?
Enhance the innate and adaptive immune response, using IFN-alpha and IFN-beta.
By Neutrophils, Macrophages, and Fibroblasts, what does IL-8 do?
Recruits phagocytes!
Name the 5 classes of Cytokines.
1) Interleukins
2) Tumor Necrosis Factors
3) Interferons (IFNs)
4) Transforming Growth Factors (TGFs)
5) Colony Stimulating Factors (CSFs)
The main response types of Cytokines:
1) _______
2) _______
3) Parasite/____
4) ______
5) Growth and ______
6) ______ agents
1) Acute Inflammatory
2) Pro-inflammatory
3) Parasite/Allergy
4) Regulatory
5) Growth and differentiation
6) Chemotactic agents
CD8+ T cells use adhesion molecules like ____ on their surface to bind to molecules like ICAM which is found on the surface of most cells.
LFA-1
Increase IL-2 production triggers _______ in T cells.
Clonal expansion
Both natural killer cells and CD8+ T cells kill target cell by releasing granules which contain ______ and ______.
Perforin and Granzymes
Natural killer cells are also able to kill using a method known as _______ which depends on their CD16 proteins that can bind to IgG antibodies.
Antibody dependent cell-mediated cytotoxicity (ADCC)
During cross-presentation, costimulation is when a ligand called CD28 on the surface of a T cell binds to a ligand called ____ on the antigen presenting cell.
B7 (CD80)
CD16 on Natural Killer cells recognize which Ig protein attached to dead T cell? Furthermore, what cytokine is produced to activate macrophages?
IgG
IFN-gamma