Function of Cytotoxic T lymphocyte simplified

“Cytotoxic T cells use enzymes as their weapons. Stab, punch holes & hypnotize the cell to die.. They are rightly called the killer T cell.” What is the function of the Tc lymphocyte?
To defend against pathogens that live in the cytoplasm (mostly viruses) & certain tumor cells.

How does the Tc cell recognize a normal cell with a hidden enemy inside?
T cell receptors bind to an antigen fragment & a self molecule.
(MHC class I is the self molecule. It collects peptides derived from proteins synthesized in the cytosol. Any viral protein made by the cell is also displayed and helps in recognition.)

What activates the T cell?
IL-2 produced by Helper T cell.
Is there an other way to activate the Tc cell?
Yes! Through potent antigen presenting cells.
It happens in case of certain viral infections only.

How does it kill the target cell?
Tc cells come in close contact with the target cell, and release preformed cytoxins from their granules.
(It’s like coming close & stabbing someone).
Cytotoxins are released tightly focused at the site of contact without killing any uninfected cells nearby.
(They are very lethal so they have to be very precise in killing.)
Perforins deliver granzymes
(Perforins are like an injection for delivering medicine).
Granzymes induce apoptosis.
(They convince the cell that it is infected & it must die).
Granulysins creates holes in the target cell. It causes osmotic damage to the cell.
(Something like stabbing & letting them bleed to death).

It can also induce apoptosis through Fas-Fas ligand interaction.
But it is not used for killing infected cells, it is used for disposing unwanted lymphocytes.
(That’s why I haven’t included it in the diagram.)

That’s all!

I’ll be doing the detailed mechanisms a bit later. This is just a very short summary.
Hope you are having an amazing month so far!


A human lymphocyte (pink pseudo-color) scans the surface of a dendritic cell (blue pseudo-color). The image was obtained using a field emission scanning electron microscope. Scale bar = 1µm.

Dendritic cells trigger an adaptive immune response by activating two major classes of T lymphocytes—cytotoxic T cells that can kill infected host cells, and helper T cells that direct the activities of other immune cells. Cytotoxic T cells recognize class I MHC receptors loaded with antigen, whereas helper T cells recognize class II MHC-peptide. Dendritic cells constitutively express high levels of both class I and class II MCH molecules, making them the most potent activators of T cells, capable of stimulating even ‘naive’ T cells that have never encountered antigen.

By Olivier Schwartz and the Electron Microscopy Core Facility, Institut Pasteur

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Oral Ulcers - Secondary to Chemotherapy

In this article, we give a brief description about a type of oral ulcers that occur related to chemotherapy.

Table of Contents

Anticancer Cytotoxic

Ulcers 2nd to Chemotherapy

Ulcer on the Tongue due to Chemotherapy[/caption]


the ulcers by be due to direct or indirect effect of Chemotherapy.

  • Direct: It interferes with replication and growth of the oral epithelium.
  • Indirect: Depressed bone marrow formationLeukopenialiability for bacterial, viral and fungal infectionOral ulcer.

Mucositis, A side effect of Chemotherapy[/caption]

Clinical Picture

  • Ulcers are large, deep, and irregular.
  • Necrotic and foal odor.
  • Not surrounded by inflammatory halo.


  • Heals within two weeks after stopping Chemotherapy.




Under the Microscope #6 (by CambridgeUniversity)

Dude. Our body is so cool!  Crazy cytotoxic T cells ftw! (except in transplants..damn you rejection!)

Wogonin was cytotoxic to HPV 16 cervical cancer cells SiHa and CaSki but not to HPV negative cells.

PMID:  Cell Biol Toxicol. 2013 Aug ;29(4):259-72. Epub 2013 Aug 18. PMID: 23955116 Abstract Title:  Wogonin induces apoptosis by suppressing E6 and E7 expressions and activating intrinsic signaling pathways in HPV-16 cervical cancer cells. Abstract:  Wogonin is a flavonoid compound extracted from Scutellaria baicalensis and is well known as a benzodiazepine receptor ligand with anxiolytic effects. Many recent studies have demonstrated that wogonin modulates angiogenesis, proliferation, invasion, and tumor progress in various cancer tissues. We further explored the mechanism of action of wogonin on cervical cancer cells that contain or lack human papillomavirus (HPV) DNA. Wogonin was cytotoxic to HPV 16 (+) cervical cancer cells, SiHa and CaSki, but not to HPV-negative cells. We demonstrated that wogonin induced apoptosis by suppressing the expressions of the E6 and E7 viral oncogenes in HPV-infected cervical cancer CaSki and SiHa cells. The modulation of p53 and protein retinoblastoma (pRb) were also triggered by the suppression of E6 and E7 expressions. However, p53 was not altered in HPV-negative cervical cancer C33A cells. Moreover, wogonin modulated the mitochondrial membrane potential and the expression of pro- and anti-apoptotic factors such as Bax and Bcl-2. Wogonin also provoked the cleavage of caspase-3, caspase-9, and poly ADP ribose polymerase. After transfection of siRNAs to target E6 and E7, additional restoration of p53 and pRb was not induced, but processing of caspases and PARP was increased compared with wogonin treatment alone. Together, our findings demonstrated that wogonin effectively promotes apoptosis by downregulating E6 and E7 expressions and promoting intrinsic apoptosis in human cervical cancer cells.

Read the full paper at:

DOI: 10.4236/ajps.2014.519302

Kartini Ahmad, Siow-Ping Tan, Mohd Aspollah Sukari, Abdul Manaf Ali, Mohd Azlan Nafiah

Department of Chemistry, Faculty Science and Mathematics, University Sultan Idris, Tanjong Malim, Malaysia.
Department of Chemistry, Faculty Science and Mathematics, University Sultan Idris, Tanjong Malim, Malaysia.
Department of Chemistry, Faculty Science, University Putra Malaysia, Serdang, Malaysia.
School of Biotechnology, Faculty of Agriculture, Biotechnology & Food Science, University Sultan Zainal Abidin, Kuala Terengganu, Malaysia.
Department of Chemistry, Faculty Science and Mathematics, University Sultan Idris, Tanjong Malim, Malaysia.

Murraya koenigii (L.) (Rutaceae) is an indigenous medicinally important herb of Indian origin and now is widely distributed throughout southern Asia. The stem bark, leaves and roots of Malayan Murraya koenigii were selected for phytochemical investigation. Eight carbazole alkaloids was isolated and identified using spectroscopic methods including NMR, IR, UV, MS spectra data. Crude extract and isolated compounds from the roots of this plant were screened for cytotoxic activity and antitumor promoting activity. All crude extracts of the roots including the isolated compounds, mahanimbine, mahanine and murrayafoline-A exhibited significant cytotoxic activity against CEM-SS cell line with IC50 3mg/mL. Girinimbine inhibited EBV-activation in the antitumor promoting assay. gjreww140916

Carbazole, Rutaceae, Murraya koenigii, NMR, Cytotoxic

This study was performed to investigate cytogenetic effects of NSAID flurbiprofen which was used as active ingredient in some analgesic, antipyretic and anti-inflammatory drugs.

What gives carboplatin its selectivity for cancer cells?

Carboplatin is a close relative of the well-known platinum-based anticancer drug cisplatin, formed by replacing the chloride leaving groups of cisplatin with the 1,1-cyclobutanedicarboxylato ligand and thereby increasing leaving group stability. High chloride concentration in blood plasma ensures this hydrolysis reaction is held off until the drug enters a cell, where it generates a potent electrophile able to react with protein sulfhydryl groups, or the π-bonded nitrogen in the imidazole ring of DNA purine bases.

Mole-for-mole, carboplatin is some 45 times less cytotoxic than cisplatin, but the mechanism of action is generally comparable. Cytotoxicity is an antineoplastic agents’ modus operandi, but carboplatin is actually no less effective than cisplatin from this gain in selectivity. Granted, it must be given at around 20-fold higher doses, but this is tolerated given the lower toxicity.

Alkylating agents bind DNA to attach alkyl groups to guanine bases, generating lesions that prove difficult to repair. Platinum-based cancer therapeutics are commonly misclassified in the literature as alkylating, but as visible in their structure they have no alkyl group, and are said to be ‘alkylating-like’ (i.e. in their effects), producing intrastrand (as well as interstrand) crosslinks and platinum diammine adducts.

The two 'ends’ of the molecule that swap their leaving group for water ('aquation’) are reactive with purine bases in DNA (predominantly guanine). The intrastrand portion of these adducts kink the DNA helix ~30-40° dependent on position, and cause purines to become destacked. Cisplatin is notably more likely to induce the severely distoring [1,2-] adducts on adjacent bases vs. carboplatin’s tendency to [1,3-] and [1,4] adducts.

These changes in DNA conformation subsequently activate DNA damage repair and signal transduction pathways, stall cells in G2 phase of the cell cycle, and block the action of DNA polymerase. The 'aim’ of repair processes is to rescue cells from this limbo, yet when unsuccessful will culminate in programmed cell death or apoptosis. A 2007 review of ’the resurgence of Pt-based cancer chemotherapy’ noted the remnant ambiguity to this chain of events.

There is continued debate as to which of the various platinum–DNA adducts might be the more biologically significant. These adducts cause distortions in DNA, including unwinding and bending, and are recognized by several cellular proteins; some of which are involved in DNA-repair pathways (discussed further below). The final cellular outcome is generally apoptotic cell death, although the pathway(s) from platinum–DNA binding to apoptosis remains incompletely elucidated.

Last year, a review in Clinical Cancer Research gathered evidence for the role of immune system potentiation in platin drug activity.

High mobility group (HMG) domain-containing proteins are non-histone chromosomal polypeptides involved in chromatin remodelling, recombination, replication and transcription. Some HMG proteins (e.g. HMGB1) bind cis/carboplatin-based DNA adducts, towards their repair by nucleotide excision pathways. Further damage recognition proteins include the Fas/FasL complex, ATR, Chk2, c-Abl, and p73.

It is long established that intact p53 function (such as found in the germ cells of testicular cancer) renders tumours more susceptible to selective activity of alkylating agents (that is, there is a signficant contribution from p53-dependent apoptotic induction pathways). 50-70% of cancers do in fact retain unmutated p53, hence platinum-based drugs’ common use as a first treatment (often in combination with other cancer type-agnostic anticancer agents). It’s been proposed that the interaction of HMGB1 with p53 may be one link between DNA repair and p53 signalling.

Though some chemotherapies do aim to simply damage hyperproliferative cells, cytotoxicity does not correlate with platin drugs’ inhibition of DNA synthesis ‒ which as I understand it means it’s not their higher growth rate that leads cisplatin to preferentially target cancer cells. These drugs exploit another general weak point seen in tumours: checkpoint defects. Chk2, mentioned above as one of the sensors of platinated DNA adducts, is a checkpoint kinase.

In my interpretation of the literature, the drugs’ selectivity therefore comes from cancer cells’ greater degree of constitutive, 'starting’ DNA damage compared to healthy, non-tumour cells, and their hampered repair pathways. There is also widespread discussion of resistance, one mode of which is for cancer cells to increase their tolerance for DNA damage (countering genotoxicity), suggesting again that it is the distinction in cell homoeostasis quality that gives the treatment greater cytotoxicity in tumours.

Recommended (long) read: Cell cycle dependence of cisplatin- and carboplatin-induced DNA damage responses in human cells lacking or expressing DNA polymerase η, thesis by Sangamitra Villalan, Centre for Chromosome Biology, National University of Ireland, Galway (now at the Wolfson Gene Therapy unit, UCL)

Thimerosal, a mercury-containing preservative, is one of the most widely used preservatives and found in a variety of biological products. Concerns over its possible toxicity have reemerged recently due to its use in vaccines. Thimerosal has also been reported to be markedly cytotoxic to neural tissue. However, little is known regarding thimerosal-induced toxicity in muscle tissue. Therefore, we investigated the cytotoxic effect of thimerosal and its possible mechanisms on mouse C2C12 myoblast cells…


Body’s ‘serial killers’ captured on film destroying cancer cells in 3D

A dramatic video has captured the behaviour of cytotoxic T cells – the body’s ‘serial killers’ – as they hunt down and eliminate cancer cells before moving on to their next target. - See more at:

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This study demonstrates the efficacy of EGCG in reversing the progression of crescentic glomerulonephritis in mice by targeting multiple signaling and inflammatory pathways.

PMID:  PLoS One. 2015 ;10(3):e0119543. Epub 2015 Mar 18. PMID: 25785827 Abstract Title:  Green tea polyphenol (-)-epigallocatechin-3-gallate restores Nrf2 activity and ameliorates crescentic glomerulonephritis. Abstract:  Crescentic glomerulonephritis (GN) is the most severe form of GN and is associated with significant morbidity and mortality despite aggressive immunotherapy with steroids, cytotoxic drugs, and plasmapheresis. We examined the therapeutic efficacy of the green tea polyphenol (-)-epigallocatechin-3-gallate (EGCG, 50 mg/kg BW/day x3 weeks), a potent anti-inflammatory and anti-oxidant agent, on experimental crescentic GN induced in 129/svJ mice by administration of rabbit anti-mouse glomerular basement membrane sera. Routine histology and key molecules involved in inflammatory and redox signaling were studied. EGCG treatment significantly reduced mortality, decreased proteinuria and serum creatinine, and markedly improved renal histology when compared with vehicle-treated mice. The improvements in renal function and histology were accompanied by the restoration of Nrf2 signaling (which was impaired in vehicle-treated mice) as shown by increased nuclear translocation of Nrf2 and cytoplasmic glutamate cysteine ligase catalytic subunit, glutamate cysteine ligase modifier subunit, and glutathione peroxidase. EGCG-treated mice also showed reduction in p-Akt, p-JNK, p-ERK1/2 and p-P38 as well as restoration of PPARγ and SIRT1 levels. Lower dose of EGCG (25 mg/kg BW/day x2 weeks) treatment also significantly decreased proteinuria and serum creatinine, and markedly improved renal histology when compared with vehicle-treated mice. Thus, our data illustrate the efficacy of EGCG in reversing the progression of crescentic GN in mice by targeting multiple signaling and inflammatory pathways as well as countering oxidative stress.

On A New Day--


Life is a gateway drug.
Open up those channels
Let it all rush in.
Swirls of serotonin and dopamine clogging those reuptake inhibitors.

180 flip and the world is starting to feel right side up again.

Your memories don’t belong here anymore.
Neither of us deserves that.

Hallelujah. Rest in Peace.

Clarity swooshing in like a random windstorm
to clear out the dusty cobwebs in my heart’s hidden nooks and crannies.

Hello again, old friend!
I see him.
For the first time it seems.
Really see– to peer into instead of through.
And I do believe I like what is there.

You were cytotoxic.
Poison to my very cells.
Just your presence alone
was enough to prove lethal.
I was always told
but it’s one thing to hear
and another thing to have lived.
I’m so thankful to have lived– even if that is a cut & sewn existence.

I will be okay.
It’s actually in sight now–
a finish line to signify a start.

Once again, I urge
hold steadfast.

We were never good for one another.
This way we can both begin to find something better.
More apt.
I wouldn’t change a thing because now I’m here..
Standing with new perspective and outlook.

I may not know who I am but I do know whoever this is now
quite well.
And she’s pretty straight in my book.
Maybe tomorrow that’ll change– who knows?
Who honestly cares?
Who says Mister Right Now can’t also be Mister Right?

It feels good to be on the sailboat looking back at how small the shore is.
To see how far you’ve paddled.
And to be coasting into the sunrise as another day is upon you.
Those warm rays of supernova hitting you
making you feel like your atoms are really vibrating.
It’s alive!

One day I’ll find the words.
Lest they find me sooner.
I’ll just enjoy the ride until then.
No pressure, right?
Jesus. Fuck it, fuck it, fuck it!
He knows. He’s psychic.

This is going to be an interesting run.


Interleukin-12 (IL-12) is a heterodimeric cytokine produced mostly by phagocytic cells in response to bacteria, bacterial products, and intracellular parasites, and to some degree by B lymphocytes. IL-12 induces cytokine production, primarily of IFN-gamma, from NK and T cells, acts as a growth factor for activated NK and T cells, enhances the cytotoxic activity of NK cells, and favors cytotoxic T lymphocyte generation.


Killer T Cell: The Cancer Assassin

How does a Killer T Cell Kill its target?

Our new film captures the behaviour of cytotoxic T cells – the body’s ‘serial killers’ – as they hunt down and eliminate cancer cells before moving on to their next target.

Nitric Oxide and Cancer: Pathogenesis and Therapy free ebook ,

Nitric Oxide and Cancer: Pathogenesis and Therapy

<p>Advances in Nitric Oxide and Cancer is a volume that&nbsp;serves to give the latest research on nitric oxide (NO) and cancer. More specifically, the volume reviews&nbsp;significant&nbsp;advances in the application of NO-mediated drugs. The volume explores nitric oxide&nbsp;and its relationship to cancer spanning from its roles in the pathogenesis, prognosis, gene and protein modifications, regulation of resistance to cytotoxics, and therapeutic applications. With chapters written by leading experts, the volume addresses the burgeoning interest in a rapidly advancing&nbsp;field and provides a valuable resource to&nbsp;scientists who have initiated research as well as clinical investigations in their laboratories on the various roles of NO and cancer.</p> <h2>Editorial Reviews</h2> <h3>From the Back Cover</h3> <p><em>Nitric Oxide and Cancer: Pathogenesis and Therapy</em>&nbsp;provides the latest research and applications of nitric oxide (NO) in cancer written by experts in the field. The volume reviews significant advances in the biochemical and molecular biology of NO-mediated effects in cancer. Additionally, it explores NO and its relationship to cancer, delineating its roles in the pathogenesis, prognosis, gene and protein modifications, regulation of resistance to cytotoxic drugs and immunotherapies, and potential therapeutic applications.&nbsp;<em>Nitric Oxide and Cancer</em>&nbsp;addresses the burgeoning interest in a rapidly advancing field, and serves as both a valuable resource for scientists, clinicians, students, and health professionals and a reference for teaching and educational purposes.</p> <h3>About the Author</h3> <p>Dr. Benjamin Bonavida is a professor at UCLA&#39;s David Geffen School of Medicine for the Department of Microbiology, Immunology, &amp; Molecular Genetics. His other appointments include being a member of the Department of Defense Congressionally Directed Medical Research Program, Member of the National Cancer Institute&#39;s SPORE Program, member of the International Scientific Advisory Board of the Israel Cancer Research Foundation, to name a few. He&#39;s currently a scientific reviewer for several journals and a member of editorial boards including Journal of Clinical Immunology, International Journal of Oncology, and Cancer Biotherapy &amp; Radiopharmaceuticals.</p> <ul style=“list-style-type:none”> <li><strong>Hardcover:</strong>&nbsp;308 pages</li> <li><strong>Publisher:</strong>&nbsp;Springer; 2015 edition (June 14, 2015)</li> <li><strong>Language:</strong>&nbsp;English</li> <li><strong>ISBN-10:</strong>&nbsp;3319136100</li> <li><strong>ISBN-13:</strong>&nbsp;978-3319136103</li> </ul>

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