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Unit 4: LGS > Week 3 > Flashcards

Week 3 Flashcards

1
Q

Structure of antibodies

A
  • looks like Y
  • consists of heavy chain and light chain
  • tops of heavy and light chain on N terminus is variable region
  • rest is constant region
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2
Q

Fragments of Ag

A
  • 2 Fab pieces (arms of Y)

- 1 Fc portion (stem of Y)

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3
Q

Importance of hinge in Ig

A

-flexible hinge allows for it to bind to many different arrangement of antigens with both arms

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4
Q

Ig isotypes

A
  • defined by differences in heavy chain C regions
  • differences in length of the heavy-chain C regions, the locations of the disulfide bonds linking the chains, presence of a hinge region (IgG, IgA, and IgD), differ in distribution of carbs on heavy chain
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5
Q

Membrane vs secreted forms of Ig isotypes

A
  • all membrane bound Ig are monomers
  • secreted Ig differs; IgD, IgE, and IgG are always monomers; IgA forms monomers and dimers; and IgM forms only pentamers
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6
Q

V domains

A
  • hypervariable region
  • 3 regions (loops) surrounded by 4 framework regions
  • loops are also called complementary determining regions
  • contribute to antigen specificity
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7
Q

Epitopes

  • what is it?
  • how many?
  • types?
A
  • specific parts of an antigen that binds antibody
  • antigens will contain multiple epitopes that vary in shape and physical properties
  • linear: continuous AA; discontinuous: AA from different parts of antigen that are brought together when chain folds
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8
Q

What affects affinity of Ig to antigen?

A

-can be altered by small differences in shape and chemical properties of binding site

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9
Q

Monoclonal antibodies

A

-identical antibodies made by a hybridoma

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10
Q

hybridoma

A
  • modern method for making antibodies
  • fusion of b-cell to tumor cell that will grow and produce antibodies indefinitely
  • the hybridoma that produces the antibody with the desired specificity is chosen
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11
Q

Flow cytometry

A

-used to analyze the cell populations in peripheral blood and detect perturbations caused by disease

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12
Q

monoclonal antibodies as treatment

  • first
  • new types
A
  • first used to help with kidney rejection, but used mouse antibodies and humans were forming antibodies against C region of mouse antibodies
  • chimeric (mouse V region and human C region); humanized (all human except for CDR loop); human (made in mice with huan Ig genes or using human hybridomas)
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13
Q

Formation of Ig

A
  • heavy-chain locus on chromosome 14,
  • 2 light-chain locus one on chromosome 2, and other on chromosome 22.
  • 3 gene segments at each locus, L (leading), V (variable), C (constant)
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14
Q

V region of light chain

A

-2 gene segments (variable and joining)

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15
Q

V region of heavy chain

A

-2 gene segments (variable, joining, diversity)

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16
Q

Diversity in binding site of Ag

A

-random gene segment recombination lead sto diversity

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17
Q

somatic recombination

A
  • random combination of portions of variable region allowing for diversity in the binding site of the antigen.
  • for light chain there is only one recombination-between V and J
  • for heavy chain there is 2 recombinations, one between J and D, the other between V and D
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18
Q

RSS role in recombination

A
  • Recombination signal sequences
  • sequences that flank 3’ end of V region (7), (9) and (7)both sides of D segment and 5’ end of J region (9)
  • function is to act as recognition sites for enzymes to know where to cut and rejoin the DNA as well as ensure that the DNA gets put back into correct order (V-D-J)
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19
Q

12/23 rule

A

-ensure correct order by having the heptamer only bind to the nonamer RSS

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20
Q

VDJ recombinase

A

-set of enzymes needed in order to recombine the 3 segments

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21
Q

RAG complex

A

-consists of RAG1, RAG2, and high-mobility group of proteins

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22
Q

how recombination occurs

A
  • RAG complex will bind to one of RSS sequences and will pull the other RSS towards it.
  • RAG cleaves the DNA on the heptamer side making a clean break
  • The RSS is then aligned and RAG complex holds in place while DNA repair enzymes rejoin the two ends (non-homologous end joining) forming a coding joint
  • The small amount of DNA cut out has its ends joined together forming a circle and is called a signaling joint and has no function
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23
Q

Recombination and extra bases

A
  • there are random nucleotides added in coding joints which creates more diversity
  • when DNA is cleaved by RAG complex it makes a single stranded end (DNA hairin)
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24
Q

Transcription of recombined genes

A
  • rearrangement of the V, D, and J segments brings a gene promoter and an enhancer into closer juxtaposition enabling the gene to be transcribed
  • separate exons encode the constant portion of the antibody which decides what kind of Ig it will be
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25
Q

IgD and IgM regulation by mRNA

  • why?
  • how to make each?
A

are co-expressed and so regulation of which Ig is actually made into protein is regulated by RNA.
- Transcription initiated at VH promoter extends through Cμ and Cδ genes
- Transcript then goes through cleavage, polyadenylation, and splicing
○ Making IgM: Cleavage and polyadenylation at the μ site and splicing between Cμ exons makes μ heavy chain
○ Making IgD: Cleavage and polyadenylation at the δ site different pattern of splicing that removes the Cμ exons making δ heavy chain

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26
Q

Allelic exclusion

A
  • developing B cells undergo Ig gene rearrangement so that only one heavy and light chain are expressed (cell will express only one of is two copies of a gene
  • results in B-cells with specificity to single antigen and allows them all to bind to that antigen the same
  • if Ig for specific antigen was made with multiple kinds of heavy and light chains then they would all bind to the antigen differently and some may not bind as well as others
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27
Q

Combinatorial diversity

A

-association of unique heavy and light chain to form a novel antigen binding site

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28
Q

Lack of allelic exclusion

A

results in B-cell receptors with low

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29
Q

Membrane bound Ig

A
  • In order for Ig to travel to the membrane it muct be bound to transmembrane proteins called Igα and Igβ
  • The complex of IgM, Igα, and Igβ forms the receptor for antigen on naive B cells
  • The Ig part of the complex is used to bind the antigen and the trans-membrane receptors are used to conduct the signal into the B cell and cause it to proliferate and mature into a plasma cell
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30
Q

Ig forms

A
  • Membrane bound: serves as B cell receptor for antigen
  • Antibody: secreted and soluble effector molecule
  • Difference lies in carboxy teminus heavy chain: membrane is hydrophobic and antibody is hydrophilic which is determined by differential splicing
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31
Q

Somatic hypermutations

A

-once B cell has been activated there is further diversification of the variable region of light and heavy chain with introduction of single-nucleotide substitutions randomly and at high rate through the use of AID

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32
Q

AID

A
  • activation induced deaminase
  • converts cytosine to uracil and since guanine on opposite strand of DNA cannot bind well it will try to fix through mismatch repair or base excision repair which allows for a daughter cell to have different antigen specificity than parental cell
  • also allows B cell to make cuts in DNA which can cause the cell to class switch from IgM to IgG-A-orE
  • if there are substitutions in the antigen binding site it can allow for increased affinity to the antigen which will then be preferentially selected to mature into antibody secreting plasma cells
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33
Q

Affinity maturation

A

antibodies of progressively higher affinity for the infecting pathogen are produced

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34
Q

Isotype switching

A
  • allows for the rearranged V-region coding sequence to be used with other heavy-chain C genes at switch regions
  • allows for antigen specificity to remain unchanged
  • dependent on AID effecting switch regions which then causes UNG to remove the uracil leaving a nucleotide lacking a complementary base, that nucleotide is then removed by APE1 which leaves a nick in the DNA and facilitates recombination by excising genes that will not be used into circular DNA fragments and bringing V region of the constant portion of the heavy chain closer to the end of the J region of the variable portion of heavy chain, which then leads to a new mRNA being transcribed
  • only occurs when B cell is proliferating and patterns are regulated by cytokines secreted by activated T-cells
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35
Q

IgD

A
  • concentrated in upper airway of bronchial tract; make Ab for commensal and pathogenic respiratory bacteria and
  • basophils will bind to IgD in absence of antigen and whne antigen comes along the IgD will signal basophils to eliminate the bacteria
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36
Q

IgG

A
  • most abundant Ig in blood and lymph
  • smaller and more flexible than IgM which gives more access to antigens in extracellular spaces
  • Fab portions can move separately of eachother to bind two separate antigens due to hinge joint
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37
Q

4 subclasses of IgG

A
  • differ in the constant region of the heavy chain and within the hinge
  • G1: most abundant and versatile of the four subclasses; intermediate in its flexibility, susceptibility to proteolysis, and capacity to activate complement
  • G2: second most abundant subclass; reduced flexibility, susceptibility to proteolysis, and the capacity to activate complement.
  • G3: best at activating complement; greater flexibility in binding to antigens and also makes the Fc more accessible for binding to C1; deficiency is associated with recurrent infection leading to chronic lung disease.
  • G4:least abundant; does not activate complement; can exchange one heavy and light chain for a different one from another Ig4 which allows for binding of 2 different antigens; anti-inflammatory because it can only neutralize a pathogen
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38
Q

IgA

A
  • two subclasses (IgA1 and IgA2)

- neutralizes very well, opsonizes, and activates complement system

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39
Q

IgM

A
  • Is a polymer of 5 of the monomers giving it 10 antibody binding sites
  • First class of antibody made in primary immune response
  • low affinity but makes multi-point attachment to the pathogen
  • constant region will initiate reactions with complement that can kill pathogen immediately
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40
Q

IgE

A

-sensitization of mast cells

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41
Q

Final stage of B cell maturation

A
  • occurs in secondary lymph tissue (lymph node)
  • use CCR7 (receptor) to follow and bind to CCL21 secreted by stromal cells in lymph node; also will follow CCL19 released by dendritic cells
  • will congregate in the primary lymphoid follicle by following CXCL13 from follicular dendritic cells
  • Interaction with FDC’s allows for B-cells to continue to mature
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42
Q

What happens if Bcell does not encounter its antigen in lymph node?

A
  • B cell detaches from the FDC and leaves the lymph node in the efferent lymph to continue its circulation as a naive mature B cell
  • if it meets its specific antigen it will respond by proliferating and undergoing differentiation into antibody-producing plasma cells
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43
Q

What happens to anergic B cells?

A

-can enter lymph nodes, but fail to reach a primary follicle and instead concentrate at the boundary between the follicle and the T-cell zone.

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44
Q

B cell activation

A

-the surface IgM molecules of a naive, mature B cell become physically cross-linked to each other by the multimeric antigen and are drawn together in a localized area of B-cell contact with the microbe. This clustering and aggregation of B-cell receptors sends signals from the receptor complex to the inside of the cell.

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45
Q

B cell co-receptor

A
  • comprised of three proteins that binds to complement
  • complement receptor 2: recognizes the iC3b and C3d derivatives of the C3b fragments deposited on a pathogen
  • CD19: signaling chain of the co-receptor
  • CD81: binds to CD19 and is essential for
    bringing it to the B-cell surface
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46
Q

Follicular dendritic cells provide long-lasting depositories of B cell antigen

A
  • differentiation of FDCs depends on cytokines of the TNF family made by lymphocytes, such as TNF-α and the lymphotoxins LT-α and LT-β,
  • extensive surface area of the dendrites that allows large quantities of antigens and even intact viral particles to be accumulated
  • FDCs lack phagocytic activity, which preserves the antigens intact
  • FDC’s contain CR2 and 1 which attach to C3d- and C3b-tagged antigens are and hold them at the surface of the FDC.
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47
Q

subcapsular sinus macrophage

A

have little phagocytic activity and have CR1 and CR2 for taking up antigens tagged with C3d or C3b and then holding them at the cell surface.

48
Q

medullary sinus macrophage

A

highly phagocytic and filters the lymph before it leaves the node by removing and destroying the remaining pathogens and their antigens.

49
Q

B cells and helper t cells

A
  • helper T cell delivers cytokines and signals to the B cell that induce the B cell to divide and differentiate
  • T-cell area by the chemokines CCL21 and CCL19, and then into a B-cell follicle by the chemokine CXCL13
  • If specific antigen is found, the B cell enters the B-cell area of the follicle to interact with TFH cells and complete its activation.
  • activation is started by expression of CD69 which prevents expression od the SIP receptor which allows for B cell to stay activated.
  • antigen activated B cells begin to endocytose and process the complexes of B-cell receptor with antigen and then present peptides from the degraded antigen on MHC class II molecules
  • expression of the chemokine receptor CCR7 is induced, which binds to CCL21 and CCL19 and draws the activated B cell to the boundary between the B- and T-cell areas where they meet up with newly activated Thelper cells
  • The T helper cells will then ind their specific antigen on MHCII of B cells, the T cell and the B cell form a conjugate pair
  • This interaction induces the T cell to express CD40 ligand, which then binds the B-cell’s CD40 .
  • B cell activates the transcription factor NFκB and increases the surface expression of the adhesion molecule ICAM-1, which engages integrin LFA-1 on the T cell strengthening the interaction between the 2 cells
  • This reorganizes the T-cells cytoskeleton and golgi facilitating the efficient and focused delivery of cytokines onto the B cell
50
Q

B cells that do NOT require helper t cells

A

CD5-expressing B-1 population of B cells, which do not undergo isotype switching and affinity maturation
-Naive B cells arriving from the blood attracted to

51
Q

T helper cells and isotype switching

A
  • T-cell cytokines induce isotype switching by stimulating transcription from the switch regions that lie 5ʹ to each heavy-chain C gene
  • requires CD40 on the B cell to be bound by CD40 ligand on the TFH cell
52
Q

Hyper IgM syndrome

A

do not contain CD40 ligand

53
Q

What happens after conjugate pair is formed?

A
  • move together out of the T-cell area in the cortex and into the medullary cords and begin to divide forming the primary focus of clonal expansion
  • gives rise to dividing B lymphoblasts secreting IgM antibody that leaves the nodes in the efferent lymph. Some B cells also differentiate into plasma cells through IL5 and 6 secreted by TfH cells
54
Q

Differentiation of B cell to plasma cells

A

-determined by a transcription factor called B-lymphocyte-induced maturation protein 1 (BLIMP-1), which stops transcription of the genes necessary for proliferation and increases expression of the immunoglobulin chains and factors involved in their synthesis

55
Q

difference between naive B cells and plasma cells

A
  • B cells have surface Ig, MHC class II, can grow, experience somatic hyper-mutation, and isotype switch
  • Plasma cells only have high rate of Ig secretion
56
Q

When did HIV start??

A

1986 in the Congo and Uganda and spread pretty fast.

57
Q

Incidence

A

number of new cases during some time period

58
Q

Prevalence

A

proportion of cases in the population at a given time rather than rate of occurrence of new cases

59
Q

in 2011 ages 25-34 yrs old has spike in number of dx of HIV, Why?

A

-more people were starting to get screened because there was more access to it

60
Q

HIV in 1988

A

proper case definition for HIV that was identified, so then we actually knew what HIV was

61
Q

Social environment where each person has one new sexual partner per year w/o taking precautions, after 6 yrs new person entering environment is exposed to

A

-sexual history of 15,625

62
Q

envelope glycoproteins of HIV

A
  • gp120 binds to host cell receptor
  • gp41 is for fusion and entry into the host cell
  • These two glycoproteins aid in the first two steps of HIV replication
63
Q

HIV and reverse transcriptase

A
  • carries its own because it does not have VPg (viral protein genome-linked) region which is a sequence that attaches specifically to ribosomes from our cells to get the process started
  • HIV RNA alone is not infectious and needs to bring its own reverse transcriptase in order to make a cDNA copy
64
Q

2 copies of HIV genome

A
  • o reverse transcriptase can bounce btwn the both of them to increase genetic variability
  • HIV just dumps the genetic material into the cytoplasm genetic material is going to be damaged a little. So the fact that there are 2 copies of the genome is beneficial, because if one copy has significant damages, it has a backup to say “no problem, I got you”
65
Q

p24

A
  • capsid antigen
  • virus gets to cell membrane, virus releases its stuff in the cell and p24 comes in and gets degraded by proteasomes inside the cell which is why one of the first things detected when you do HIV testing.
66
Q

HIV envelope

A
  • HIV has an envelope so it has to fuse with our cellular membrane to dump its genetic material whereas naked viruses attach to a cellular receptor and they’re escorted into the cell.
67
Q

Integrase

A
  • Enzyme that takes the provirus and inserts into host genome
  • Cell will always be infected
  • There is no mechanism of cutting it out
  • Host cell will notice viral insert and kill itself (Pyropoptosis)
68
Q

Specific genes in HIV

A
  • Gag: group specific antigen: core and capsid proteins
  • Pol: polymerase: reverse transcriptase, protease, integrase
  • Env: envelope
  • Nef: decrease cell surface of CD4; facilitates T-cell activation, progression to AID
69
Q

How did we get HIV

A
  • Chimpanzee: SIV - not to virulence of HIV; Viruses will become tame so that they do not kill host and continue living
    ○ How?Hunting for meat and there was transfer of blood
70
Q

Genetic drift

A

slow process, natural evolution

71
Q

Genetic shift

A

complete change of genes

72
Q

Binding of HIV to Cell

A
  • GP120 from the virus binds cell expressing CD4 or CCR5 (t cell, macrophage, etc)
73
Q

CCR5 mutation

A

causes immunity to HIV

74
Q

Binding after 7–10 yrs of having infection

A

The virsuses GP120 mutates and will switch from binding binds CCR5 to binding CD4 and CXCR4 which in only on T cells

75
Q

Uncoding HIV

A
  • Binding: to CD4 or CCR5 on t-cells and macrophages
  • Uncoating: going to uncoat from envelope and capsid so genetic material can be dumped into the cell
  • Reverse transcriptase: makes CDNA (single stranded)
  • Integration: endonuclease is going to splice DNA and add viral CDNA into genome making a provirus
  • Transcription: DNA to RNA to Protein
  • Assembly: Making all parts of the virus and putting it together to infect other cells
  • Budding: Leaving the cell- making more GP21 and stuff that are just waiting so that virus can leave
76
Q

Role of CD4 T cells

A
  • growth and control of innate immune responses
  • Activation of epithelial cells, neutrophils, macrophages: which will control bacteria and fungi
  • Growth and control of B cells
  • Growth of NK, CD4 and CD8 Tcells: which will control viruses, intracellular bacteria, tumors, and HIV progression
77
Q

What is AIDS?

A
  • syndrome of HIV

- criteria: CD4 less than 200 cells per micoliter OR Viral load 75,000 copies per mL

78
Q

Clinical presentation of HIV

A
  • flu- or mono-like symptoms with lymphadenopathy: do a mono spot test, HIV test, and a list of STDs that you have to test for if pt is HIV+
79
Q

Does HIV kill the patient?

A

no, it just lower immune system and then opportunistic infections will kill them

80
Q

NRTIs

A

Competitively inhibit nucleotide binding to reverse transcriptase and terminate the DNA chain. All need to be phosphorylated to be active.

81
Q

NNRTIs

A

Bind to reverse transcriptase at site different from NRTIs. Do not require phosphorylation to be active or compete with nucleotides

82
Q

PIs

A

Assembly of virions depends on HIV-1 protease (pol gene), which cleaves the polypeptide products of HIV mRNA into their functional parts. Thus, protease inhibitors prevent maturation of new viruses.

83
Q

Binding and Fusion Inhibitors

A

Prevent HIV from being able to bind and fuse to the cell membrane of CD4 or macrophage

84
Q

Integrase Inhibitors

A

Inhibits HIV genome integration into host cell chromosome by reversibly inhibiting HIV integrase

85
Q

Fuzeon

A

drug that is inserted to inhibit that pullover effect and inhibits fusion on cellular membrane

86
Q

AZT

A
  • nucleoside analog
  • As the genome is being made, you know that you have to have a polymerase that is bringing in these tRNAs. And what happens is, if you give so much of AZT, their #s compete with thymidine, and they start being incorporated instead of T. Viral polymerase goes to read, and it’s a stuttering effect b/c it doesn’t recognize AZT. After a couple of stutters, it gives up and it’s no longer able to do it’s job.
87
Q

Can AZT effect human cells?

-side effects

A
  • Human polymerase can fix the error and move on while viral polymerase cannot. Our enzyme has proofreading abilities, viral polymerase does not.
  • overload system with AZT, our enzyme is still prone to errors so you can’t remove all of them, and AZT can become toxic to cells.
88
Q

Prevention of HIV

A
  • Condoms

- PrEP

89
Q

Brands of PrEP

A

-Truvada (emtricitabine and tenofovir): both NRTIs

90
Q

Risk percentage with PrEP

A
  • reduces sexually acquired risk by 90% if taken daily

- reduces risk by 70% in people who inject drugs

91
Q

HIV treatment targets for 2020

A
  • Will diagnose 90% of HIV+ patients
  • Will place 90% of people diagnosed on ART
  • Will have 90% of people placed on ART with undetectable viral load
92
Q

HIV spread and viral load

A

Studies have shown that even if you’re HIV +, if you’re in 90% suppression with HIV viral load, you can have sexual intercourse and the infectivity rate reduces by 99%.

93
Q

Difference between PrEP, PEP, and nPEP

A
  • PrEP is pre-exposure prophylaxis.
  • PEP is post-exposure prophylaxis (to be taken within 72 hours after high-risk exposure.
  • nPEP is non-occupational post-exposure prophylaxis.
94
Q

How long does PrEP need to be taken? and how long does it have to be taken before it starts to be effective?

A
  • daily
  • PrEP reaches maximum protection from HIV for receptive anal sex at about 7 days of daily use. For receptive vaginal sex and injection drug use, PrEP reaches maximum protection at about 20 days of daily use
95
Q

Tests to order in homeless patient from detroit with CNS involvement

A
  • CT-because of the history of the intercranial bleed or pressure being elevated.
  • CSF sample to run a histoplasmosis antigen test which was negative in this case.
  • Brain biopsy to rule out or confirm Blastomyces. You would find yeast to confirm blastomyces
  • India ink to rule out Cryptococcosis
  • Any time you have a homeless person, run an HIV and TB test.
96
Q

Central nervous system blastomycosis treatment

A

Amphotericin B

97
Q

Amphotericin B

  • what is given with it? why?
  • normal CNS penetration?
  • what limits use?
  • difference in new formulation?
  • what is 2nd line treatment
A
  • Amphotericin B and Flucytosine are given together to allow better penetration to the CNS If there is CNS involvement.
  • Normally only 1-2% of Amphotericin B penetrates the CNS so it is used for CNS fungal infection but used intrathecally so it can get into the CNS.
  • What limits use is its toxicities which include hepatotoxicity, infusion toxicity which is experienced in all patients, and drug induced renal impairment which is also experienced by most patients.
  • The new Amphotericin B formulation is the liposomal Amphotericin B which reduces non specific binding to human cell membranes. This reduction in the ability of the drug to bind to human cell membranes leads to a reduction in the toxicities observed.
  • This is the first line of treatment and the second line is Azoles which have less toxicity , they are new and along with corticosteroids are given for this case.
98
Q

Systemic fungi that can affect humans

A

Histoplasma capsulatum, Blastomyces dermatitidis, and Coccidioides immitis

99
Q

difference between a mold and yeast

  • cellular wise?
  • reproduction
  • parasitic
  • invasive
A
  • Mold( Saprobic form) is multicellular( branchy and filamentous) and yeast(parasitic form) is unicellular
  • Yeast divide by asexual reproduction( budding) and mold uses sexual reproduction.
  • Yeast on the right is the parasitic version and it is form that is being passed on or transmitted and the form that gets caught up in the lungs and the mold is the one you will find in nature.
  • When you do tissue biopsy you might see the hyphae forms that’s the more invasive forms the ones in the right are the ones in the air.
  • Mold is not infectious but it can be invasive
100
Q

distribution of fungi in the United States

  • C. Immitis/gatti
  • Histoplasmosis
  • Blastomyces
A
  • s important because different fungi are found in different regions and Board exam cases are presented as such
  • C. Immitis is seen mostly across the Southwest United States. C. immitis and C. gattii are both found in southwest and only difference between them is whether you are in California or right outside of California. They cant be distinguished by tests other than by RT-PCR but you are still going to treat the same.
  • Histoplasmosis is SE, from Texas to florida and all the way up to Iowa, Michigan, and West Virginia
  • Blastomyces has overlap with histoplasmosis and seen in east side of US from Minnesota down to lousiana and across to North and South virginia
101
Q

Treatment for C. Immitis/gatti, Histoplasmosis, and Blastomyces

A

• First line is Amphotericin B because it has very broad spectrum and very high efficacy then you transition to an azole again because it is less toxic.
-Best azole o=is Itraconazole because of dimorphism in fungi

102
Q

C. Immitis biopsy

A

shows a spherules with endospores inside

103
Q

Blastomyces biopsy

A
  • circular and clumps together. It is found east of the Mississippi river and found in Africa, middle east as well. So on patient history you need to ask where the patient has recently travelled to.
  • may or may not see the hypha form but you will see the mold form when grown on agar and looks more hair-like, and filamentous. You cannot grow the parasitic ones on agar and only look like that in our bodies.
104
Q

Toe fungus as an example of mold and yeast

A

When you itch from toe fungus it is in the hypha form( mold form) that is when it has become invasive but once it gets treated it goes back to the spore form ( yeast form) where you stop itching. That is, it becomes dormant.

105
Q

Histoplasma

  • how to confirm
  • treatment
A
  • Serum Test

- Ampho B and then Azole

106
Q

Why are Azoles less Toxic than Amphoteric B

A

-It is because they have a greater affinity for the fungal cytochrome p450 than human ones

107
Q

effect of taking an Azole with another hepatically cleared drug

A

• It increase the amount of that drug and the effect of pro-drug and also the toxicities

108
Q

main difference between the agents in the azoles class

A

Some of them have high water solubility and can penetrate the CNS( Fluconazole and Voriconazole)and the rest don’t

109
Q

Aspergillus

-treatment

A
  • pulmonary- use Itraconazole plus a corticosteroid,

- CNS involvement: amphotericin B plus a corticosteroid

110
Q

Amphotericin B is hydrophobic but we give it when the fungus affects the CNS. Why?

A

inflammation increases the spaces between the tight junctions in the endothelia cells of the blood brain barrier and allows the drug to gain access. So it is only under inflammatory conditions of the meninges can Amphotericin B gain access into the CNS get into the CSF and have an effect.

111
Q

Aspergillus biopsy

A

mold is looked at under a microscope for a differential, the hyphae seen in this fungi here will be acute or less than 45 degrees branched. It is called a closed hyphae branching which is smaller than other fungi ; has a head type of region which is distinct and on top of that is the spores that will be released into the environment

112
Q

Pneumocystis

A

• Pneumocystis used to be classified as a protozoa because it looks like a protozoa and acts like a protozoa but its rRNA looks like a fungus that is why now its classified as a fungi. It was thought to come from rats that were living close to the homeless people and so was called Pneumocystis carinii but rats do carry Pneumocystis carinii which is also a thing but the Pneumocystis Jirovecii is for humans

113
Q

Treatment for Pneumocystis

A
  • TMP/SMX- We are able to use this medication even though it is not an antifungal because this is not a typical fungal and it also makes use of folate in its DNA synthesis and it has a cell wall-like structure. But mostly because it acts like a protozoa.
  • Another treatment will be clindamycin
114
Q

C. Neoformans

A
  • The capsule(cyst with halo) of Neoformans is anti-phagocytic and illicit the strongest immune response
  • It is also used for diagnosing purposing using the India staining.
  • It exist as yeast and can be picked up In bat droppings, Pidgeon droppings in caves. It is seen everywhere but only becomes a problem when you are immunocompromised.
  • It is the most common cause of fungal meningitis.
115
Q

Where drugs attack

A
  • Amphotericin B and nystatin attack proteins in fungal wall
  • Azole prevents lanosterol from being converted into ergosterol
  • Terbinafine prevents squalene from bein turned into squalene expoxide which will eventually prevent production of ergosterol
  • echinocandins prevents beta-gulcan synthase which effects the cell membrane
  • Flucytosine targets the fungal DNA/RNA synthesis
116
Q

Are integrase and reverse transcriptase virulent factors of HIV

A
  • No they are not.
  • Virulence factor is anything that the pathogen has that will evoke an immune response from the host.
  • So the virulence factors for HIV are p24, gp 120, gp41.

Unit 4: LGS (7 decks)

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