Kasman Flashcards
What mediates innate immunity?
Epithelial barriers, phagocytic cells, natural killer cells and serum protein called complement
What is a major difference between the pathogens that cell mediated vs humoral immunity defends against?
Cell mediated defends against intracellular while humoral defends against extracellular and they are both types of adaptive immunity.
What mediates adaptive immunity?
T and lymphocytes and their products
What is an immunogen? a hapten? An epitope?
An antigen that can induce an immune response. A hapten is an antigen that cannot induce an immune response. An epitoe is a specific part of the antigen that is recognized.
What are MHC proteins?
Cell surface molecules that present the peptide antigens to T cells
Granulocytes belong to what part of the immune system?
Innate
What are the 3 APCs?
Dendritic cells- present antigens to naive T cells
Macrophages- present antigens to mature T cells
B cells- present to CD4 cells to stimulate the immune response
How do dendritic cells direct the adaptive response?
Present to either MHC 1 (intra) orMHC II (extra)
What is the significance of codominant expression and polymorphic genes in terms of disease fighting ability?
increases the no. of mhc molecules that can present t T cells. polymorphic genes ensure tht diff individuals ar able to respond to diff microbes
Role of Tap 1 in class 1 pathway?
transports peptides into ER to bind to MHC1
What are the two complement inhibitors?Mode of action?
DAF- acts on convertase and CD59 aborts MAC formation
Role of C3a, C5a and C3b?
C3a degranulates mast cells, C5a recruits neutrophils and C3b releases opsonins which increase phagocytosis.
How is a M1 macrophage formed? What does it secrete?
By IFN-gamma and PAMPS> SecreteTNF, IL-1,IL-6 and IL-12
How is a M2 macrophage formed? What does it secrete?
By IL-4, IL-13. Secrete TGF-beta, IL=10 and litlle IL-12
Cell surface mediators of signal 2 are called?
Co stimulatory molecules
What are the two polyclonal activators of T cells?
PHA and Con A..they bind to carbohydrates and elicit activation without the presence of an antigen
Suprantigens crosslink MHC on APC attached to T cell complexes and elicit responses in the absence of a specific antigen
LFA-1?
Important adhesion molecule in cell mediated immunity
Th1? Transcription factor?
A T helper cell, secrets IFN-gamma. Activates killing of phagocytised microbes, induces increased opsonization.
Tbet
Th2? Transcription factor?
Release eosinophils, release IL-4 to anatgonize Th1, non opsonizing. IL-5 induces eosinophils
GATA-3
Th 17? Transcription factor?
Immune respne,recruits neutrophils. ROR gamma T
The PAMP, LPS, which is on the outside of GN bacteria is recognized by what PRR?
CD14
What 4 mediators recruit neutrophils?
IL-8, C5a, LTB4 and bacterial products
Three ways by which mast cells are activated?
Tissue trauma
Complement proteins- C3a, C5a
IgE
Histamines mode of action?
Vasodilation of arterioles and increased permeablity of post capillary venules
Mast cell mechanism?
Early- release of histamines
Late- production of archidonic acid particularly leukotrienes
Key mediators of vasodilation?
Histamine, PGs and bradykinin
Which 2 cells express CCR7?
Naive T cells and dendritic cells
What is the source of proteins for the class i pathway vs the class II pathway?
Class II- endosomal and lysomal proteins while class I- cytosolic proteins
Proliferation of immature lymphocytes is driven by?
IL-7
How are diverse receptors created?
Somatic recombination- that is enzymes catalyze the deletion of DNA to bring different coding sequences together.
Where are the V,D and J cassetes found?
D found in heavy chains and beta of TCR
V and J are found in light chains and alpha of TCR
Combinatorial diversity vs junctional diversity?
Combinatorial diversity- random joining of segments
Junctional diversity- Ligases add nucleotides to the sites. Endonucleases cleave nucleotides and the Tdt enzyme adds them randomly. It provides most of the repertoire
Role of RAG in generating diverse antigen receptors?
They activate VDJ recombinase in Pre T and B cells
Each B cell expresses one heavy chain and one light chain. How?
Allelic exclusion
Which cytokines mediates clonal expansion of T cells?
IL-2. More CD8 and not as much CD4 because CD4 act via cytokines while CD 8 act directly on cells
Describe the class II pathway?
Antigen is phagocytysed by the APC. In the ER, MHC II and CLIP assemble. The vesicle fuses with the endosome and HLADM removes CLIP and peptides compete for the binding site.
Describe the class i pathway.
Ubiquitin degrades the protien which is transported to the ER by Tap. MHCII won’t bind those peptides because the invariant chain is present.
How do naive T cells know where to migrate to?
Lselectin, LFA and CCR7
How do mature T cells know where to go?
E and P ligand, LFA and CRCX3
How do TH1 cells activate macrophages?
By CD40 L and IFN gamma
What cyotkines are expressed on Th17?
!L-17 and IL-22
How does the Epstein barr virus inbit CMI?
By secreting IL-10. This downregulates CMI.
Inhibition of CMI?
Prevent phagosome formation by preventing fusion with lysosomes and escaping the phagsome.
Preventing antigen presentation by MHC1
Herpes- inhibits tap
Epstein barr- inhibts proteases
Cytomegalovirus removes MHC1 from the ER
In the immunological synapse, what molecules are passed from the T cells to target cells?
Granzymes and perforins
How is epinephrine administered?
Pharmacologic effects on heart and vasculature?
Not effective orally- better subcutaneously, iv, intramuscular, inhalation
Heart- increases contractility, conduction, heart rate and relaxation
Vasculature- vasodilation (b-2) at a low dose and vasoconstriction (a-1) at a high dose.
Pharm effects of epinephrine on bronchial smooth muscle, epinephrine, mast cells and renin?
Bronchial smooth muscle- relaxation
Metabolic effects- increase blood glucose and fatty acids, decreases insulin seceretion through alpha 2(DOMINANT)
increase insulin secretion through beta 2 (MINOR)
increases potassium uptake by skeletal muscles
Mast cells-inhibits them
Renin- stimulates its release
Main therapuetic effects of epinephrine?
anaphylactic shock (alpha and beta)- causes vasocnstriction to get b back up and bronchial relaxation
to prolong anesthetics (alpha receptors) via vasoconstriction
reduces production of aqueous humor through PG production]
Cardiac arrest (alpha nd beta)
bronchial asthma
cardiac stimulant
local hemostasis (aplha)
Adverse reactions of epinephrine?
Hypokalemia- leads to cardac arrythmias
Non selective beta blockers enhance alpha 1 mediated vasoconstriction.
Interaction with diabetes- increase in blood glucose may require more insulin
increase blood glu and fatty acids—> metabolic acidosis
anxiety, fear, headaches
tachycardia, hypertension,MI
How is norepi administered? Therapeutic effects? Adverse reactions?
Norepi administered intravenously, Its used in shock- excessive vasoconstriction.
Adverse reactions- phlebitis, tissue sloughing off, arythmias, increased oxygen demand
Which drug is used to treat polymorphic long QT sndrome?
Isoproterenol…
How is albuterol (b-2) admistered? Therpeutic uses? Side effects?
Administerd- subcutaeoulsy, orally, inhale it, intravenously
Use- bronchial asthma
SE- cardiac stimulation, tremors.
How is dobutamine administered?
Orally, used in CHF to increase CO.
Good why? doesn’t change heart rate and bp much
CAUTION: a-fi due to increase in AV conduction
Tell me about dopamine
B-1»>a-1
Administered intravenously
cardiac stimulant, renal and mesenteric vasodilator
USE:
Shock- cardiogenic and septic
severe CHF (esp w/ oliguria)
Which drug is used as a nasal decongesant?
Phenylephrine (alpha 1 agonist)
CAUTION- careful use in hypertensive patients, rebound hyperemia, urinary reduction
Also used in vasoconstriction and opthamology (mydriasis)
Clonidine?
Alpha 2 agonist. Its an antihypertensive drug. In vascular smooth muscle- it causes a rise in bp
used in treating withdrawl symptoms
What is a major difference between the diff types of B cells?
B-1 and marginal respond to non-protein antigens
What are the costimulatory molecules in humoral immunity that amplify the signal?
C3d through the CR2 receptor and activation of Toll like receptors
What is the signal to switch and what determines what thngs switch to in humoral immunity?
CD40- CD40L - signal to switch and cytokines signals what to switch to
What is the molecular mechanism of affinity maturation?
somatic hypermutation
requires CD40/Cd40L and AID
How do you make haptens immunogenic?
By attaching them to a carrier protein. The hapten carrier effect allwos us to make antibodies agains discontinuous epitopes ..B cells internalize the hapten while T cells recognize the protein carrier
Inhibitor of the classical pathway? How?
C1 INH inhibits classical pathway by preventing C1s and C1r interactions
How does Factor I, H and C4BP inhibit the classical pathway?
Factor I cleaves C3b—> iC3b, Factor H is a cofactor
Factor H also causes dissociation of C3bBb
C4BP catalyzes dissociation of C4bC2b complex
How does CD59 regulate the complement pathway?DAF, CR1?
It blocks C9 so prevents formation of MAC. NB! It doesn’t prevent C3a and C5a release
DAF and CR1 catalyze dissociation of C3 convertase
IgG transport vs IgA transport?
IgG is transported into the placenta via FcRN receptors.
IgA dimerizes using J protein. Ploy Ig receptor (on the basal surface of epithelial cells)is then used for its transport
Three main ways microbes can evade humoral immunity?
Antigenic variation
Inhibit complement activation
Slime capsules
How does salmonella get a competitive advantage over host cells?
By converting the thiosulfate to tetrathionate.Tetrahionate is then used as an electron acceptor so that salmonella will be able to respire in anerobic conditions.able to use waste products for food eg. ethanlamine and propanediol. Tetrathionate also inhibits coliforms.
NB! Rem tetrathionate respiration is only useful when inflammation is present
What are the 6 secretory pathways in G- bacteria?
Type 1- proteins are exported directly across the membrane
Type 2- General secretory pathway
Type 3- Molecular syring
Type 4-use syringe but this time, you’re able to transport DNA
Type 5- Similar to 2 but protein goes across OM and CM
Type 6- wo HcP and VgrG are secreted
What is required for the molecular syringe to work?
ATP hydrolyis
How does E. coli become pathogenic?
It makes receptors, injects them into host cells. Bacteria then bind to these receptors
What is Psuedomonas aureginosa MOA?
First ExoT inhibits wound healing
Exo U and S block inflmation block IL-1 beta and IL-18
When inflmmation occurs, Exo U amplifies the iflammatory response.
Exo S, T, U and Y impair phagocytes and make the lungs prone to infection
Unique identifier of pathogenicity islands?
Higher G+C content compared to the rest of the genome..They are usually flanked by DR. They are usually transferred by horizontal transfer mechanisms. They encode antibiotic resistance, metabolic capability, symbiosis and pathogenesis
They are usually mobile
1) Yersinia psuedotubercolosis can move from one tRNA site to another
2) some are mobilized by phages (staph A and V. cholerae
What are the 4 stages of transcription?
1) Template recognition
2) Initiation
3) elongation
4) termination
Negative control?
Mediated by repressors. They prevent transcription translation. Most promoters are controlled via negative control.
What is negative control gene expression in terms of the lac operon system?
Negative control–No lactose, Repressor binds to the operator, RNAP can’t bind to structural genes , operon is off. However this negative control can be DEPRESSED. When lactose is pressent, allolactose can bind to the receptor, altering it’s shape . RNAP can now bind and make stuctural proteins Lac Z,Y and A
What is positive control in the lac operon system?
Positive control requires an activatng signal. The repressor needs to be inactivated! With lactose present and low glucose, cAMP levels are high which bind to the CAP protein. This opens up the promoter to RNAP.
Also with both glucose and lactose present, you’ll get a SMALL amount of transcription. Glucose is the preferred energy source
What is phase variation?
Normally bacteria make H-2 flagellin and a H-1 repressor. With phase variation however, only H-1 is made.
What are the two types of termination?
Factor independent
use RNAP and DNA alone
Factor Dependent
needs an additional protein component
For factor independent- spotthe site because it is flanked by inverted repeats followed by a string of A’s. A hairpin falls and once you get to the A-U region, there is destabilization, RNAp falls off terminating transcription
2 component signaling..purpose? MoA?
It’s used by bacteria to detect a wide range of environments and to adapt accordingly.
Types of exotoxins?
A-B exotoxins catalyze he ADP ribosylation ofeEF2- therefore it is a RNA translation inhibitor. - the exotoxin of pseudomonas and diptheria behave in this manner
membrane pore forming..they form pores in te membranesto let the cytplasmic contents out. eg- hemolysins
The exotoxins of clostridium perfringes?
Release of hydrolytic enzymes- collagenases, hyaluronidasesand proteases. The result is gas gangrene
