Glossary of MIP: Random Compilation (Block A)
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- What are the differences between First tail and second tail of the IgMs?
- First tail:
Hydrophobic and membrane spanning
No Sulf-hydryl group
Contains an SH group
IgM translocated into ER lumen
- What is the orders of the isotype in relation to gene location?
- IgM/IgD, IgG, IgA, and IgE
- Describe the characteristics of B1 cells?
- Mostly IgM
Don't have memory
Produce T-cell independent reactions (Can't class switch so stuck in IgM mode)
Limited somatic hypermutation
Responds to CARBOHYDRATE antigen and may respond to protein antigen
- Describe the characteristics of B2 cells
- Have memory
Respond principally to protein antigens
T-cell dependent reactions
High levels of somatic hypermutation
- At what age is T-cell repertoire mainly determined?
- 10-12 yo
- In which order is the T-cell chains made?
- Beta first
Failure of Beta goes to gamma delta
Success of Beta goes to alpha
- Characterize the gamma delta T cells
- minor population of T cells
Concentrated in the skin
Functionally and topographically sub-specialized forms of Tcells
Neonates and infants make a transient population that survive at most 1-2wks after birth
- What is a double positive cell in reference to T cells?
- CD3, CD4, and CD8 expression awaiting to undergo positive and negative seleciton
- What do the different sections of thymus primarily contain (cortex and medulla)
Rich in epithelial cells and thymocytes
Close to where cells are secreted in to circulation
Rich in macrophages and dendritic cells
- What is the predominant T-cell type?
- What percentage of T-cells from the bone marrow make it through positive thymic education?
- How long might a Naive T-cell circulate for in hopes of finding their corresponding antigen?
- What steps would occur when a Naive T-cell enters a lymph node from a high endothelial venule?
- If T0cell does not encounter its antigen, it leaves the secondary lymphoid tissue via the efferent lymph.
If a T-cell does encounter its antigen it is "trapped" and activated by AgPCs and proliferates and differentiates into a multitude of effector cells. It leaves through the efferent lymph to go to the site of infection
- What are the molecular processes that occur for crossing of naive T and B cells from high endothelial venules into lymph nodes?
- Step 1: L-selectin on naive T0cells binds to vascular addressins GlyCAM-1 and CD34 on high endothelial venules. Vascular addressin MAdCAM-1 is expressed by capillaries in mucosal tissue
Step 2: Chemokines on the endothelial surface activate integrin LFA-1 (on the surface of all T-cells, which binds to the Ig superfamilies ICAM-1 and ICAM-2 on the vascular endothelial surface
Step 3: Diapedesis occurs as T-cells squeeze through the endothelium via PCAM receptors and finally into the secondary lymphoid tissue
- What are the steps in T-cell screening within a Lymph node?
- Step 1: both T0cells and AgPCs express LFA-1 (integrin). LFA-1 on T-cells binds to Ig superfamily ICAM-1 and ICAM-2 on AgPCs with low affinity. LFA-1 on AgPCs bind to Ig superfamily ICAM-3 on T-cells
Step 2: Ig superfamily CD2 on T-cells binds to LFA-3 on AgPCs
- What co-stimulatory molecule on professional AgPCs distinguishes them and binds to T-cells and what do they bind to?
- B7 binds to CD28 on the T-cell
- What happens after the T-cell becomes activated by B7:CD28 interaction?
- B7 is then bound to CTLA-4
- What is the purpose of CTLA-4?
- It functions as a down regulator so that over proliferation of the T-cells don't occur
- What are the three "Professional" antigen presenting cells?
- Dendritic Cells
- Describe what happens to Dendritic cells from peripheral tissues to the lymph nodes?
- Immature dendritic cells in tissue take up antigen and migrate to lymph nodes
Become mature (interdigitating reticular cells) and no longer take up antigent.
Express high levels of MHCII and costimulatory and adhesion molecules
Produce high levels of cytokines and chemokines
They present obth Viral Ag on MHC I and extracellular pathogens on MHC II
- Describe what a Macrophage does in relation to T-cell stimulation?
- It is a phagocytic cell that presents peptides on MHC II to CD4 T cells.
Expresses co-stimulatory molecule upon degradation of intracellular pathogen
Also present to CD8 via MHC-I when infected
- Describe what a B-cell does in relation to T-cell stimulation?
- B-cells use their surface receptors to internalize specific antigen by receptor-mediated endocytosis delivering it to the surface through MHC II
- What cytokine is important to dividing T-cells?
- IL-2 causes both proliferation and differation
Naive T-cells express the low affinity receptor for IL-2
Upon actiavtion IL-2 and the high affinity receptors are induced
When IL-2 binds the T-cell is triggered to divide
IL-2 has both an autocrine and paracrine effects
- What happenes to T-cells once they become effectors?
- They increase expression of CD2 and LFA-1 but decrease expression of L-selectin in exchange for VLA-4 which allows them to bind adhesion molecules on endothelial cells of blood vessels at infected and inflamed sites
They no longer require a second signal
- What cytokines do CD4 TH1 and TH2 cells produce?
- CD4 TH1: IFN Gamma and TNF Alpha
CD4 TH2: IL-3, IL-4, IL-5, and IL-10
- How many times do neutrophils and CD8 cells release their cytotoxins?
- Neutrophils: 1x
CD8: over and Over
- What do Cytotoxic T-lymphocytes secrete as a cytotoxin and what does it do?
- Interferon Gamma
It inhibits the replicatoin of viruses in infected cells, increase MHC I expression and helps to activate nearby macrophages
- What do Fas molecules and Fas ligands do?
- Fas molecules on the target call and Fas ligand on the EFFECTOR T-cells can induce apoptosis
- What two signals are needed to stimulate a macrophage?
T-cell CD40 ligand interaction with macrophage CD40
- What is the difference between CD8 cytotoxins and CD4 TH1 cytokins?
- CD8s are premade
CD4TH1s are made during response
- What are the primary selectin and integrin bindings between a T-cell and an APC during stimulaiton?
LFA-1 binding to ICAM-1 and ICAM-2
C2 binding to LFA-3
ICAM-3 to LFA-1
- On a B-cell what is the name for the motif that gets phosphorylated in connection to binding of antigen by the antibody?
- ITAMS or ITIMS (immunoreceptor tyrosine activation motifs and immunoreceptor tyrosine inhibitory motifs)
- What does ITAMS and ITIMS do?
- When multiple crosslinking on a B cell occurs they are phosphorylated. If doubly phosphorylated they will activate two Syk proteins (tyrosine kinases) that autophosphorylate each other to eventually enact some nuclear change.
- How many proteins make up the B-cell co-receptor, what are they, and what do they do?
CD19, CR2 (CD21), and CD81
CR2 binds to C3d (complement protein on the pathogen membrane
CD19 brings the tail of CD19 in close proximity to the Lyn tyrosine kinase
Phosphorylation of Cd19 tail enhanses a nuclear signal for proliferation and differentiation
- How many thymus independent antigens are there, what are they, and what do they do?
TI-1 and TI-2
TI-1: cell walls and capsules of bacterial pathogens
Ex. Peptidoglycan (Binds TLR2 on the B-cell membrane)
Ex. LPS binds LPS binding protein which binds CD14 on B-cell membrane
Formation of IgM only
TI-2: Include pathogens with highly repetitive polysaccharide or protein epitopes
Ex. flagella of bacteria due to repetitive nature
However, can also form IgG not just IgM
- Which B-cell is the only one that recognizes TI-2 antigens and when do they begin to develop?
- B-1 cells
Develop around 5 years of age
- What three processes for B-cells require T-cell help?
- Somatic hypermutation
- On a follicular dendritic cell's surface what captures antibodies and what captures complement to be presented?
- FcR captures antibodies bound to antigen
CR3 receptor captures antigen bound to complement
- What are the stimulatory isotype switching cytokines in a TH2 cell?
- IL-4, IL-5, IL-10, and TGF beta for IgM, IgG2, IgG4, IgA, and IgE
- What are the stimulatory isotype switching cytokines in a TH1 cell?
- IL-12 and IFN-gamma for IgG1
- What is the name of receptor that is used to secrete IgM and IgA across barriers in the lung ang gut?
- Poly-Ig receptor (unidirectional transport unlike FcRn)
- Once secreted following transcytosis what is the poly-Ig called and what is the poly-Ig bound to IgA called?
- The Poly-Ig is called secretory component
The antibody is now referred to as secretory IgA
- What receptor can transport IgG across the membrane?
- FcRn - pH dependent binding(Fc gamma receptor - multidirectional transport unlike Poly-Ig receptor)
- What process is described by antibody dependent cellular cytotoxicity?
- ADCC is a process by which antibody-coated cells are killed by NK cells (NK's have a low affinity Fc-gamma [CD16] which requires that antibodies be crosslinked)
- What is the most common immune protein deficiency in humans?
- Partial lack of C4 (Lack of C4A can lead to SLE)
- What is the purpose of C1INH?
- Binds C1r and C1s and prevents them from binding to C1q
- What is the purpose of C4BP?
- Binds to C4b causeing the release of C2b and the recruitment of factor I which degrades C4b
- What is the purpose of Factor H?
- Directly attacks C3b forming a region in the C3b suscptible to factor I degradation
- What is the purpose of DAF?
- Inhibits C3 convertase formation. Causes release of Bb.
- What is the purpose of Membrane Co-factor protein (MCP)?
- It is also to release Bb from the C3 convertase but also it makes C3b susceptible to Factor I
- What does Properdin (factor P) do?
- Binds to and stabilizes the C3bBb so that degradation cannot occur
- What does CD59 do?
- Prevents Mac Attack
- name the antibacterial peptides that protect the skin, gut, and lungs and how do they work?
- Alpha defensins - neutrophil granules in the form of cryptdins made by paneth cells of hte cmall intestines
Beta Defensins - secretino by epithelial cells of the epidermis, respiratory tract, and GI tract
Defensins kill pathogens by disrupting their membranes. Require lower ionic concentrations of sweat, tears, or lumen of gut
- What are the macrophage receptors and what do they bind with?
- Fc - receptors for IgG
CR1 (complement receptor) - C3b
CR3 and CR4 - bind iC3b, cleavage product of C3b
CD14 - binds LPS-LBP
Mannose Receptor - binds lectins (CHO molecules)
Scavenger receptor binds molecules with sialic acid (S. pyrogenes and S. Aureus)
Glucan receptors - Bind sugars not present on human cells
TLR- various bindings
- What do TLR's bind to?
- Pathogen-Associated Molecular patterns (PAMPS)
Includes: DNA, LPS, Peptidoglycan, flagellin, mannin, etc.
- What does TLR-3, TLR-4, TLR-5, and TLR-9 bind to?
- TLR-3: Double stranded RNA (Virus)
TLR-4: LPS (Gram Neg)
TLR-5: Flagellin (Gram Neg - Only TLR that binds directly to a microbial product)
TLR-9: DNA CpG motifs (Bacteria - Only intracellular receptor that sense microbial genomic DNA)
- Describe the MyD88 dependent pathway of TLR activation (Fast)
- MD2 ligand binds TLR-4
TLR-4 sensitizes LPS and allows LPS to bind with CD14
CD14 allows MyD88-mediated cascade
MyD88 is an intracellular adaptor molecule that activates IRAK (IL-1 receptor associated kinase 4) and TRAF6 (TNF-receptor associated kinase 6) Cascade started by MyD88 causes the degradation of the inhibitory Molecule IkappaB that allows NFKappaB to enter the nucleus and being transcription of Inflammatory cytokines
- Describe the MyD independent pathway of TLR activation (Slow)
- TLR3 affects NFkappaB and causes slow cytokine making
- What do IL-1 Beta and TNF-alpha?
- Local effects - both increase the permeability of the vascular endthelium and allow IgG complement, neutrophils, and other WBC to enter the tissue
Il-1Beta induces fever and cause an increase in production of IL-6
TNF-alpha induces fever and is the main cytokine responsible for causing septic shock
- What does IL-6 do?
- TH2 cytokine
Local Effects: Increase lymphocyte activation and increases plasma cell antibody production
Systemic effects: it causes fever and induces acute phase protein production by hepatocytes
- What does IL-8 or CXCL8 do?
- Binds CXCR1 and CXCR2
Local effects: acts as a chemotactic facto rand recruits neutrophils, basophils, and T-cells to the site of infeciton
- What does IL-12 do?
- TH1 cytokine
Local Effects: Activates NK cells and induces the differentiation of CD4 cells into TH1 cells
- What are the acute phase proteins and what is their net effect?
- C0reactive protein and Mannose-binding protein
They increase the supply of the recognition molecules of innate immunity and activate compliment
- What does C-reactive protein do?
- Binds to the microbial surface and then associates with C1q initiating the classical complement pathway
- What does Mannose-Binding Lectin (MBL)?
- In the lectin pathway of complement activation, MBL binds mannose on the surface of yeast and bacteria. Cleaves C4 and C3 to form the classical C3 convertase
- What PMN has a special receptor to specifically recognize N-formylmethionine?
- What are 3 things that IFN alpha and beta do in the face of a cytoplasmic infection?
- Induces resistance to viral replication in all cells
Increase MHC class I expresssion and antigen presentation in all cells, thus making virus-infected cells more visible to CTLs
Activate NK cells to kill virus infected cells
- What is the mechanism for release of IFNs?
- IRF3 (IFN Response Factor 3) detects viral assualt and induce translocation to the nucleus with NFkappaB and AP-1 to promote transcirption of IFN-beta
- What are two ways that IFN-beta functions?
- Paracrine: IFN-beta stimulates local uninfected neighboring cells to also undergo an interferon response and thus preparing that cell for a possible viral infection
Autocrine: IFN-Beta also binds a receptor on itself that stimulates IRF7 (IFN Response Factor 7).
- What do CTLs secrete as a feedback loop to stop NK cell actions?
- What would happen if a cell were infected by a vrus and the MHC-I was down regulated to bypass the T-cell adaptive immunity?
- NK cells notice the decrease in MHC Class I and kill it
- What is the meaning of Autologous and Allogenic?
- Autologous: Cells derived from the same individual
Allogenic: same species, genetically different
- What are T-cells that express an NK cell receptor called?
- NKG2D (they are not NK cells)
They also carry a gamma-delta receptor
- Infected epithelial cells express what two proteins and what do theose proetins resemble?
- They express MIC-A and MIC-B. They are like MHC I-like.
- What is the Th1/Th2 paradigm for stimulation of TH1?
- Dendritic cells release IL-12 causing NK cells to release IFN-gamma which prevents gorowth/activation of Naive CD4 cells into TH2 cells and facilitates the differentiation of naive CD4 cells into TH1 cells
- What is the Th1/Th2 paradigm for facilitating Th2?
- Inflammatory condition - IL-4 produced and lack of IL-12 and IFN-gamma favor TH2 differentiation. TH2 secrete IL-10 which prevents TH1 response by inhibiting DC and macrophage antigen processing and presentation
TGF-beta inhibits the growth/activation of TH1 cells
- What type of CD45 do Naive and memory T cells express?
- Naive: CD45RA
- What promotes survival of memory cytotoxic T-cells and memory B-cells?
- What inhibits memory T cells?
- Describe Antigenic drift
- A point mutation which causes significant differences in the viral surface antigens and in particular hemaggglutinin
- Describe Antigenic shift
- A third party host that can obtain virus from 2 different sources provides an environment where their genetic segments can recombine in such a way that they produce hemagglutinin that is significantly different from the original and against which previous antibodies are ineffective
- Describe Antigenic variation
- An infectious organism can produce a variable surface protein that can be selected for when the primary representation has had an immunity built up to it, thereby continuously reinfecting the host
- Describe Latency in reference to infections
- Virus resides and waits till the right time to infect
- What is inhibit humoral immunity?
- Surface of virus0infected cells have an Fc Gamma receptor oreiented so that the antibodies face out instea dof binding. Or the infectious agent encodes their own complement receptor
- What is inhibition of the onset of inflammation
- Virally encoded soluble cytokines block proinflammatory cytokines
Inhibits adhesion molecules
Secretes little TLRs that mimic TLRs
- What is an example of inducing of immunosuppression for viral escape from immune protection
- Viruses that produce IL-10 to deactivate TH1 instead of activating it.
- Describe SCIDs
- Many possible causes
Complete absence of T-cells and/or B-cells
Patient susceptible to almost all organisms
- Describe what would happen in an MHC-I deficiency?
- CTLs are not present
- Describe what would happen in an MHC-II deficiency?
- Absence of CD4 T-cells
- Describe what happens in an X-Linked hyper IgM syndrome
- Because you don't have the ability to isotype switch, you only have an increase in IgM
Individuals are very susceptible to extracellular organisms
- Describe what would happen in if someone had a selective deficiency in IgA?
- No IgA synthesis
Very susceptible to respiratory infections
Upper respiratory system IgA predominates
Down in the lung, IgG is more prevalent so less likely to get an infection there
- What happens in X-Linked agammaglobulinemia
- B cells do not progress beyond the pre-B cell stage
Important protein kinase on the X-chromosome missing. THerefore, missing a Tyrosine kinase for B-cells to mature
- What would happen with a deficiency in C5-C9?
- Susceptibitlity to infections by Neisseria
- What would happen from a deficiency in DAF, CD59?
- Not protected from attack by the alternative complement pathway
Autoimmune like conditions invluding paroxysmal nocturnal hemoglobinuria (acidosis during sleep is thought to cause hemolysis due to enhancement of complement pathway)
- Describe the components of the quintessential HIV?
- Nucleocapsid - protects RNA
Protease - breaks up the polyprotein encoded by the genome
Integrase - allows the cDNA to be incorporated into host's genome
gp160 - envelope glycoproteins necessary to infect gp120 and gp41
- What are the 9 essential proteins of HIV-1?
- gag(Group specific antigen) - proteins form the nuclear protein and stabilize RNA
pol (polymerase) - reverse transcriptase, protease break up polyprotein, integrase enzyme which integrates viral genome to host
env (envelope) - transmembrane glycoproteins (gp120 binds CD4 and CCR5, GP41 required for virus fusion)
nef (Negative-regulation factor) - Pulls CD3 and MHC class I off the membrane (maybe not true anymore)
- What is Human Beta Defensin 3?
- Antagonist of the HIV-1 coreceptor CXCR4
when stressed the CXCR4 coreceptor is pulled off the membrane. This may protect the cell.
- What are the stages of HIV/
- Infection with large drop in T cell numbers
Seroconversion - phase of infection when antibodies agains thte infecting agent are first detected (T-cell levels rise)
Protease inhibitors prolong the depletion (asymptomatic phase)
Level of T-cells becomse too low and opportunistic infections
- What does haart stand for?
- Highly active anti-retroviral therapy
- In what clinical context would a defect in immune function present itself as most significant?
- What deficiency is the most common primary immunodificiency?
- Antibody deficiency
- What type of symptoms would suggest an underlying immune problem?
- Single episode of osteomyelitis, septic arthritis, or meningitis
Two episodes of sepsis or pneumonia
several episodes of sinusitis, bronchitis, or pneumonia
- What are the 10 warning signs of PID from Jeffrey Modell Foundation)?
- Eight or more new ear infections (otitis media) within 1 year
Two or more serious sinus infections w/in 1 yr
Two or more months on antibiotics with little effect
Two or more pneumonias within one year
Failure of an infant to gain weight or grwo normally
Recurrent deep skin or organ abscesses
Persistent thrush somehwere after age 1
Need for IV antibio to clear infections
Two or more deep seated infections
Family history of PID
- What is stage 1 of testing if PID is suspected?
- H and P with height and weight
Lab tests: CBC and differential with quantitative Ig profile
- What is stage 2 of testing if PID is suspected
- Ab response
response to vaccination
Ig subclass analysis
- What is Stage 3 of PID testing?
- candida and tetanus skin test
lymphocyte surface markers
mononuclear lymphocyte proliferation study
Neutrophil oxidative burst study
- What is Stage 4 of PID testing?
- Complement screen for CH50, C3, and C4
NK cytotoxic studies
studies of Complement AH50
Neo antigen to test antibody production
cytokine receptor study
family genetic study
- What are specific CD markers for B cells?
- CD19, CD20, CD21
- What is the primary biological mechanism of clearance of solubilized immune complexes in humans?
- RBC will bind to complement and be filtered by the spleen
- Describe Contact hypersensitivity and identify the type of hypersensitivity reaction it is?
- Typically occuring in individuals who are sensitive to metals. Prototype hapten is poison ivy. Pentadecacatechol acts as a hapten which mediates a CD4 response and elicits and allergic reaction. Second exposure can call in basophils and other cells leading to a permeability change
Type IV hypersensitivity
- Describe granulomatous response and identify the type of hypersensitivity reaction it is
- Exposure to antigen is chronic and the antigen is not eliminated by the cell-mediated response, the chronic exposure can give rise to a granulomatous response
Type IV hypersensitivity
- What does the AIRE gene do?
- Allows ectopic expression of non-thymus tissue-specific antigens in the thymus
Presence of tissue-specific proteins in the htymus means that peptides derived from these proteins can be bound by MHC class I and II molecules to form complexes that participate in negative selection of the T-cell repertoire
If AIRE gene is wiped out, only have thmuse antigens expressed, therefore, no negative selection fro other organs outside of the thymus
- What does C4 do?
- Involed with antigen clearance and opsonization.
Polymorphisms increase the susceptibility of SLE.
- What does CTLA-4 do?
- Turns off the immune response
Deficiency will cause an overimmune response
- What does Fas and FasL do?
- Causes apoptosis of autoreactive B-cells. Without it develop an autoimmune response due to longer lasting self reactive cells
- What does FoxP3 do?
- Associated with T-regulatory cells
Knowck out that gene, get a deficiency of regulatory T cells and you get this autoimmune polyendocrine disease called IPEX
- What happens during SLE autoimmune disease?
- Cells are infected by a virus and cause a surface expression of a second signal along with the expressions of MHC bound DNA and intranuclear antigens
- What is the process of plasmapherises in the treatement of autoimmune disease?
- Autoimmune processes are cellular or humoral
Remove large volume of blood
replace the red blood cells
Administer back some Intravenous Immunoglobulin (IVIg)
Adverse Effect: Downregulate the B cell responses via the Fc inhibitory receptors by adding the IVIg
- What is the process of Immunosupression in the treatment of autoimmune disease?
- Often done with steroids
Cyclosporin A is a drug that inhibits the production of cytokines like IL-2
Neutralize the T-cell responses by reducing cytokine communications
- Do bacterial capsules present well to the groove on top of the MHC?
- No because the groove is specific for peptides
- What kind of response to bacterial capsules do we get?
- IgM with no memory therefore T-independent
- How can you create antibodies to the polysaccharide?
- Conjugate it to a protein so that the protein sticks in the MHC pocket and the hapten sticks out to be recognized
No T-cell immunity generated
- What is the purpose of the various adjuvants?
- All adjuvants:
Create a greater immune response, act as an antigen depot, and allow a slow release of the antigen into circulation
Freund's incomplete: Oil-in water emulsion
Conjugate carrier gel made from alum
- What does Azothioprine do in reference to tissue transplants?
- It is a cytotoxic drug
Converted into a nucleotide derivative
Derivative is designed to hit nucleic acid metabolism
- What does cyclophosphamide do in reference to tissue transplantation?
- Functions as a cross-linking agent.
Have 2 active chlorine.
Cross-link between DNA strands so that the strands can't separate
- What does methotrexate do in reference to tissue transplantation?
- Works on vitamin pathways and nucleotide pathways to kill cells
- What are some signal transduction specific drugs in relation to tissue transplantation?
- Cyclosporin A, Rapamycin, and Tacrolimus
They act in the cytoplasm on some of the proetins that are involved in calcium metabolism
Prevent formation of IL-2
- What makes up Gram (+) bacteria outer layers?
- THICK peptidoglycan
Lipoteichoic acid and Teichoic acids interwoven into the peptidoglycan
- What makes up Gram(-) bacteria outer layers?
- Outer membrane (LPS: called O-antigens, Porins (AKA outer membrane proteins), Lipoproteins)
Cell wall (peptidoglycan layer [thinner in gram (-)])
- What type of motion and pili do bacteria typically use?
- Type IV pili
- In regards to flagella what is the H and K antigens?
- H is flagella
K is capsule
- What are two types of Plasmids that bacteria carry?
- R-Plasmids: carry genes encoding enzymes or proteins that conver antibiotic resistance
Virulence plasmids: carry genes encoding toxins or other virulence factors
- What is a mesosome?
- Invaginations of the cell membrane involved in chromosomal segregation and septation
Bacteria divide by binary transverse fission
- What is an endospore?
- Resting phase of bacteria
Formed when the environment is not very suitable for the bacteria such as lack of nutrients, water, etc.
- What are four phases of bacterial growth?
- Lag phase - adaptation to new surroundings
Log phase - bacteria exponential growth
Stationary phase - nutrients start becoming scarce and toxic metabolites begin to build up (death = growth)
Death or Decline Phase - toxic metabolites build up even further and the nutrients run out
- What is metabolic parsimony in reference to bacteria?
- Lack of nutrients force use of new nutrients. Very efficient in how they spend energy to prevent waste
- What is meant by countermeasures in reference to bacteria?
- Ex. Iron
Bacteria have developed siderofores which have a higher binding affinity for iron that the cells in our bodies.
- What is Passive diffusion?
- Nutrients move by virtue of a concentration gradient
- What are siderophores in relation to passive diffusion?
- Proteins on the outside of the cell with a higher affinity for iron. Bring nutrients into a cell whether there is a concentration gradient or not. Diffusion uses NO energy from the cell
- What is active transport in relation to a bacteria?
- Pumps that rely on energy to bring in sugars, most amino acids, organic acids, and many inorganic ions even against the concentration gradient
- What is group translocation in relation to a bacterial cell?
- Similar to active transport, but the nutrient is modified before being brought into the cell
- What are the three pathways of bacterial nutrient production?
- Emden-Myerhof-Parnas (EMP) pathway (AKA: glycolytic or anaerobic pathway)
Tricarboxylic acid cycle (TCA)
Pentose Phosphate Pathway
- What is the CNA plate specific for?
- Gram positive bacteria
- What does the MacConkey plate select for?
- Gram negative bacteria and lactose fementing bacteria
Color changes pink when the bacteria are able to ferment lactate because the pH is lowered
- What is the name of the first antibiotic (discovered by Gerhard Domagk)?
- Prontosil Rubrum: red azo dye that prevented mice from dying of streptococcal infection.
- What does prontosil do and how does it work?
- It blocks the synthesis of folic acid.
- What does Trimethoprim do?
- Blocks the enzyme dihydrofolate reductase fond in humans and bacteria but is 50,000X more potent for bacteria so that the bacteria are unable to make folic acid
- How do Aminoglycosides such as Streptomycin work?
- It binds to the 30S ribosomal subunit and kill the bacteria by blocking initiation of hte peptide chain
- How do Marcrolides such as Erythromycin work in reference to bacterias?
- Binds to the 50S subunit and prevent chain elongation, a reversible phenomenon. bacteriostatic
- How does Rifampin work and what does it work on?
- Rifampin blocks RNA polymerase and is an anti-TB drug
- What is the definition for Adhesins?
- Allow a microbe to bind to a variety of eukaryotic cells
Prevents the microbe from being removed by washing or flushing actions
eg. urinary tract infections
- What is the definition for Invasins?
- Allow the microbe to enter eukaryotic cells that are not professional phagocytes
Advantage for microbe to be intracellular
- What is the definition for Aggressins?
- Directly damage the host or actively promote the spread of a pathogen
ex. toxins and proteases
- What is the definition for Modulins?
- Modulate host cell activity with pathogenic consequences.
LPS modulates T cells and macrophages into expressing toxic levels of cytokines
- In regards to Extrachomosomal Genetic Elements, more specifically plasmids, what are Replicons?
- Plasmids that can replicate independently from chromosomes
- In regards to extrachromosomal genetic elements, more specifically plasmids, what are episomes?
- Plasmids that can integrate into the host bacterium's chromosome
Once integrated, can mediate chromosomal transfer from one cell to another
- What has the properties of being circular, doublestranded DNA elements, encode virulence determinants or resistance to antibiotics, and present as a single element or as multiple copies?
- What is quorum sensing?
- Quorum sensing is the ability of bacteria to communicate and coordinate behavior via signaling molecules.
- What is a quorum sensing molecule for gram-negative bacteria?
- Acyl homoserine lactones (AHL's)
Small diffusible signaling molecule
- What are the details of conjugation in bacteria?
- Transfer of genetic material (usually a plasmid) from one cell to another
Sex pilus is sued as a conduit for getnetic exchange
DNA is transferred as a single stranded molecule and becomes double stranded after transfer
Endonucleases do not affect the transfer of DNA
Integrated plasmid (episome) promotes transfer of genomic DNA, which integrates into recipient DNA
Usually occurs between related species
- What are the details of Transposition in bacteria
- Transposons inserts itself into chromosomes
Can cause frameshift mutations
can also carry drug resistance markers
Normally transferred via plasmids
- Of the simple transposons what do they consist of?
- Insertion sequences: inverted repeats that flank the transposase gene
Transposase gene: helps the DNA insert into the bacterial chromosome
- What are the composite transposons?
- Genes in addition to the transposase that are flanked by inverted repeats
Additional genes are usually for antibiotic resistance or virulence
- What are pathogenicity islands?
- genes encoding a large number of virulence factors that are flanked by transposon-like mobile elements
Mobile and can be transferred horizontally to other bacteria
Typically found in virulent organisms and not environmental isolates
- What are the four staphylococcus?
Saprophyticus - Often invovled in UTI
Lugdunensis - similar disease to S. aureus
- which is the only staph that is coagulase positive?
- S. aureus
- What test will differentiate between staph and strept?
Only Staphylococcus is Catalase positive
- What are the different methods of staph typing and description?
- Phage typing - different phage attach to different strains of staph
Multi locus enzyme electrophoresis (MLEE) - types different enzymes according to strain of staph
Pulse field gel electrophoresis - replaced MLEE, cut up chromosomal DNA and run on gel
Multi locus sequence typing
staph protein A typing - virulence factor with a lot of mutations
Ribotyping - rRNA types differ among strains
- What are the virulence factors of S. aureus?
- What are the S. aureus virulence adherance factors?
- Clumping factor: coagulase
Fibronectin binding protein: extracellular matrix is covered by fibronectin
- What are the methods of avoidance of immunity for staph aureus?
- Encapsulated in biofilm
Capsule to prevent phagocytosis
- What are two ways that S. aureus prevents opsonization?
- When no Ab bind: capsule prevents Ab binding to peptidoglycan, capsule coats the organism but appear to be labeled as self
Ab do bind: capsule is large neought that it blocks the receptors necessary for opsonization
- What are the three toxins of S. aureus?
- Exotoxins: destroy tissue, RBCs, WBCs causing inflammation
Superantigens: "suicide by staph" because toxin is released (include enterotoxins)
Teichoic acid: mechanisms similar to TLR system and cause phagocytes to release cytokines leading to WBC recruitment, inflammation, and tissue destruction
- Following infection or internalization of S. aureus what are the two options available?
- Parental form: produce alpha-toxina nd kill host
Small colony variant: hang out for up to years, then produce alpha-toxin and kill host
- General info on S. aureus
- Harder to culture and harder to kill (slow growing - typically Abs are designed to kill growing bacteria)
- What are the virulence factors for S. aureus?
- Clumping factor
Collagen binding protein
- What are two spreading factors of S. aureus which destroys the extracellular matrix?
- Hyaluronidase: strain which causes cellulitis
- What destroys host defense molecules in a staph aureus infection?
Protease V8 (destroys Ab, proteinaceous host defense molecules)
- What are the superantigens produced by S. aureus?
- Enterotoxins: Producs of lysogenic conversion
TSST-1: causes toxic shock syndrome (APC produce IL-1 and TNF --> fever; CD4 produce IL-2 and gamma IFN --> nausea, vomiting, diarrhea...)
Exfoliative toxin: considered a protease
Induces host cell to make metalloproteinases and turns on immune system which is the cause of disease
- What are the methods of quorum sensing for gram negatives vs. gram positives?
- Gram (-): sugars
Gram (+): peptides
- What are some things that Staph. Pyodermas cause?
- Folliculitis - infected hair follicles. Once pus is let out it heals
Furnucles - boil
Carbuncle - multiple skin lesions (boils) connected by sinuses in the connective tissue
Impetigo - crusting vesicle formation of the skin (serous, looks like honey and common in children)
Paronychina - infection fo the nail bed. Usually on the sides, sometimes underneath
Cellulitis - spreading connective tissue infections
Eye infections - stye, belpharitis, keratitis
- What are the big 3 location of staph infections?
- What organism causes the quintessential food poisoning from mayonaise sitting in a potato salad dish?
- Staph: releases a super antigen toxin that is toxic to gut and stomach nerves
Symptomes are clear within 24 hours with diarrhea and vomiting for 2-6 horus
No therapy necessary
- What are the associated factors of TSS?
- Progression from erythroderma to erythematous mucus membranes to desquamation (peeling off may start in the fingernails) to finally hair and nail loss accompanied by:
fever, pain, hypotension, confusion, headache, diarrhea
- Where does the exfoliative toxin production stem from?
- Chromosomal DNA or
Two toxins - one heat labile and one is heat stabile
- How long would you treat for a staph infection?
- 2 wks
up to 6 or more for prolonged infection
Remove devices if necessary
Look for pus and drain it
watch for resistance
- What is the most common staph?
- Epidermidis: it's all ove rthe normal flora of the skin
- What is one staph that is similar to aureus, and is highly virulent?
- Describe staph saprophyticus.
- Vaginal adherence by hemagglutin
Bacteria from stool spreads to urinary tract during sexual activity
S. saprophyticus adhere to the urinary tract and releases urease
Once the bacteria adheres using hemagglutin 1 in the urinary tract and travels up the bladder it utilizes hemagglutin 2 which combines with urease to cause an infection.
- What are some characteristics of Staph Vax?
- Staph Vaccination
Effective in dialysis patients
- What are four major pyogens?
- Gram positive: Staph and strept
Gram negatives: Neisseria and Haemophilus
- What four pyogens can cause meningitis?
- Gram Positive: Staph and Strept
Gram negatives: Neisseria and Haemophilus
- What can cause endocarditis?
- Staph, Strept, and Neisseria
- What can cause Otitis Media?
- staph, Strept, and Haemophilus
- What is the primary method of bacterial classification for Streptococci?
- Type of Hemolysis
- How is Strept classified immunologically?
- Through serogroups based on antigenic variation of the cell surface associated structures
Based on Carbohydrate (C-carbohydrate) or glycerol teichoic acid
- Which Strept serogroups contain C-carbohydrate (as a hint they are also beta hemolytic)
- C, A, B, G
- Which strept serogroups contain teichoic acid?
- N and D
- Which of the strept groups cause alpha-hemolysis (as a hint they do not contain C-carbohydrates or glycerol teichoic acid)?
- Strept. Viridans (strept. Pneumonia...)
- Grp. A strept the largest number of dieseas from all strept have 2 basic syndromes from skin infection (impetigo) and/or a pharyngeal infection. what are they?
- Acute (suppurative disease) -Pustules in throat, lesions in skin, organism may cause bacteremia and septicemia (ex. fasciitis), can be cultured and treated with antibiotics
Non-suppurative sequelae - ARF and PSGN, usually cannot be cultured, Ab therapy not effective
- What does the M-protein of GAS do?
- Mediates attachment to the epithelial cells via fibronectin, allows multiplication and toxin production of GAS
Confers type specificity - opsonin antibody epitopes
- What are the antiphagocytic properties of GAS and GGS' M-protein?
- Binds fibrinogen which masks C3b binding sites
Binds factor H of the alternate complement pathway that can inhibit both C3 convertase and C5 convertase
- What does lipotechoic acid (LTA) do for GAS?
- Facilitates attachment of strept to fibronectin by a 2 way process
Helps orient the M protein
Antigenic but does not confer immunity
- What does F-protein do for GAS?
- Binds fibronectin, facilitating attachment and subsequent colonization
- Three cell surface structures that facilitate attachment of strept to epithelial cells?
- M-protien (Only one that confers immunity)
- What does M-like protein do (Hint: analogous to Protein A of the Staph groups)?
- Binds Fc region of Ig to present outward so that it appears as self
Binds alpha-2 macroglobulin that can inhibit PMN proteases
- What does Plasminogen Binding Protein do for GAS?
- binds plasminogen that can bind activators such as tPA, urokinase, and streptokinase that convert plasminogen to plasmin a broad spectrum protease
Aids in the dissolution of host protein structures thus facilitating tissue spread in such diesease as necrotizing fasciitis, cellulitis and erysipelas
Plasmin is a potent activator of the alternate complement pathwy
- What does the hyaluronic acid capsule do for GAS?
- indistinguishable from ground substance hyaluronic acid so that encapsulated organisms tend not to be phagocytized
- What does 60kD Rheumatic Fever Associated Antigen (RFAA) do for GAS?
- implicated in generation of antibodies that cross react with cardiac tissue proteins that contribute to the pathogeneis of ARF in a manner similar to that for M-protein
- Is streptolysin O antigenic?
- If the source of the GAS infection is skin would the ASO titer be high and what other test can be performed?
- ASO titer will be low and performe a DNAse B test because it will not be blunted
- What are three streptococcal pyrogenic exotoxins?
- Superantigens SpeA, SpeB, and SpeC
- Which of the 3 strept pyrogenic exotoxins are encoded by phages?
- SpeA and SpeC
- What is SpeA from GAS implicated in?
- Scarlet fever, necrotizing fasciitis, and TSS
- Describe SpeB from GAS
- present in all GAS, some G and some C
Cysteine protease, responsible for massive tissue destruction and invasiveness
Highly virulent serotype M1
SpeB along with SpeA thought to be highly involved in the spread of necrotizing fasciitis
- What do DNAse A, B, C, and D do for strept Group A
- reduces viscosity of pus and spread infection from abscesses
- Streptokinase does what and comes from what?
- Comes from Strept Groups C, A, G, E
Complexes with host plasminogen to activate plasminogin to plasmin
- Group A strepts produce C5a for what purpose?
- Degrade C5a to reduce inflammation and phagocyte recruitment
- Group A strepts produce IgA Protease for what purpose?
- Splits secretory IgA (sIgA) to prevent opsonization of streptococcus
- Through the Jones Criteria when should one test for ARF or PSGN in the possible event of GAS?
- 2 Major or 1 Major/1 Minor
Majors: carditis, polyarthritis, chorea, erythema marginatum, subcutaneous nodules
Minors: preveious ARF, or rheumatic heart disease, arthalgia, fever, anomalous erythrocyte sed rate, C-reactive proteins, leukocytosis, or prolonged PR interval
- What is the order for GAS testing for ARF or PSGN?
- Jones criteria, ASO titer, and DNAse B
- Which Strept groups can cause Post-streptococcal Glomerulonephritis?
- Groups C, A, G
- What antibiotic is Group A strept susceptible to? It is used in determining if it is GAS.
- What are the 3 types of group B strept diseases that we learned?
- Early Neonatal (III - capsule)
Delayed Neonatal (III - capsule)
Adult Onset (II - capsule)
- GAS rarely enters the blood stream. So, if you do a Gram-stain (positive), Beta-hemolytic, catalase negative, chainforming coccus... what could it be?
- Group B strept
- In vertical transmission (also what is meant by this) to type III capsular neonatal GBS what are the associated symptoms?
Vertical transmission (Mother to child during birth)
- In Horozontal transmission (also what is meant by this)of type III capsular neonatal GBS what are the associated symptoms?
Horizontal Transmission means between caregivers and other infants; nosocomial)
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