A human dendritic cell (blue) interacting with and activating a lymphocyte (pink).

Image by Olivier Schwartz and the Electron Microscopy Core Facility, Institut Pasteur.

THIS WEEK’S QUESTION!

Every Sunday, a question will be asked about one of the images from the past week. Be the first to answer correctly, and your blog will be promoted on Monday’s image post and Biocanvas’s main site!

Neurogenesis, the birth of new neurons, occurs throughout adulthood in two locations of the brain. One of these locations is in the hippocampus, which is responsible for processing memories and aiding in learning. If neurogenesis occurs throughout life in this area, then one would expect the hippocampus to increase continuously in size. This, however, is not the case.

How does the hippocampus remain relatively the same size while still having active sites of new cell genesis?

Answer: Present cells die at an equal rate to the generation of new cells, resulting in a net gain of approximately no new cells.

Scientists Report First Cure of HIV In A Child, Say It’s A Game-Changer

Scientists believe a little girl born with HIV has been cured of the infection.

She’s the first child and only the second person in the world known to have been cured since the virus touched off a global pandemic nearly 32 years ago.

Doctors aren’t releasing the child’s name, but we know she was born in Mississippi and is now 2 ½ years old – and healthy. Scientists presented details of the case on Sunday at a scientific conference in Atlanta.

The case has big implications. While fewer than 130 such children are born each year in the U.S., an estimated 330,000 children around the world get infected with HIV at or around birth every year, most of them in sub-Saharan Africa.

Until now, such children have been considered permanently infected. Specialists thought they needed lifelong antiviral drugs to prevent HIV from destroying their immune system and killing them of AIDS.

The Mississippi child’s surprising cure came about from happenstance – and the quick thinking of a University of Mississippi pediatric infectious disease specialist named Hannah Gay.

Read more.

Microscopy image of HIV infecting an immune cell from the NIAID Flickr stream.

6

Trametes Versicolor: Turkey Tail Mushrooms Help Immune System Fight Cancer

A promising clinical study shows that the turkey tail mushroom (Trametes versicolor) improves the immune systems of breast cancer patients. The multiyear study, funded by the National Institutes of Health (NIH), tracked whether or not turkey tails could positively affect the immune system of patients rebound after they ended their radiation therapy.

Immunity — as measured by the number of lymphocyte cells and natural killer cell activity — usually declines dramatically after radiotherapy. Natural killer (NK) cells protect us from tumors and viruses. Researchers at the University of Minnesota Medical School and Bastyr University Research Institute hypothesized that breast cancer patients’ health can be improved after radiation treatment if NK cell counts increased quickly to attack remaining cancerous cells.

The study titled "Phase I Clinical Trial of Trametes versicolor in Women with Breast Cancer," recently published in the ISRN Oncology Journal, shows that turkey tail mushrooms can augment conventional therapies for treating breast cancer by increasing NK and CD8+T cell activity. This study suggests that turkey tail mushrooms are an effective adjunct to conventional chemotherapeutic medicines and radiation therapy. The authors concluded:

… research by our center continues to indicate that Trametes versicolor represents a novel immune therapy with significant applications in cancer treatment … The CD8+ T cell counts over the 9-week dose escalation study were enhanced in the 9 gm Tv dose cohort compared to both the 3 g or 6 g group. One-way ANOVA was used to analyze the overall difference between dosage groups over the treatment period (2-4-6 weeks). It showed the statistically significant increase in the CD8+ cytotoxic T cells for the 9 g group compared to both the 3 g and 6 g group (F(2, 6) = 42.04, P = 0.0003).

Due to its long history of therapeutic use, however, turkey tail prepared and packaged as an immune therapy drug is unlikely to be patentable, deterring big pharmas from conducting costly clinical studies. Typically, the longer the historical use of natural medicines for treating an ailment, the less likely derivatized drugs from these natural products will be patentable. To fill this research gap, the NIH established The National Center for Complementary and Alternative Medicine (www.nccam.nih.gov), which funded and oversaw this study. NIH’s interest is not surprising — more than 70 percent of new drugs are estimated to originate from natural sources.

Turkey tail mushrooms have been used to treat various maladies for hundreds of years in Asia, Europe, and by indigenous peoples in North America. Records of turkey tail brewed as medicinal tea date from the early 15th century, during the Ming Dynasty in China. Our ancestors certainly encountered them and most likely explored their uses long before written history. Since the late 1960s, researchers in Japan have focused on how turkey tail benefits human health and how extracts of turkey tail can boost the immune system.

What are turkey tail mushrooms?

This super-abundant colorful mushroom grows on dead trees, logs, branches, and stumps. Turkey tail mushrooms are called bracket fungi, meaning that they form thin, leather-like and leaf-like structures in concentric circles. Rather than gills underneath, as in shiitake mushrooms, their undersides have tiny pores, which emit spores, placing them in the polypore family. These mushrooms grow throughout the world, practically wherever trees can be found. In fact, turkey tails are some of most common mushrooms found on wood on the planet.

They are commonly called “turkey tail” because their various colors: brown, orange, maroon, blue and green — reminiscent of the plume of feathers in turkeys. In China, their common name is yun zhi. In Japan, this mushroom is known as kawaritake or “cloud mushrooms,” invoking an image of swirling clouds overhead. In many Asian cultures, turkey tails’ incurving cloud forms symbolize longevity and health, spiritual attunement and infinity.

What are the medicinal properties and how is it used?

Traditionally, our ancestors boiled mushrooms in water to make a soothing tea. Boiling served several purposes: killing contaminants, softening the flesh, and extracting the rich soluble polysaccharides. The mushrooms — called fruiting bodies by mycologists — are made of densely-compacted cobwebby cells called mycelium. With modern laboratory methods of cell tissue culture, the large-scale production of mycelium brought to light a whole new array of medicinal preparations. Nowadays, the commercial production of mycelium enables a cleaner and more digestible product than traditional mushroom preparations. Surprisingly, novel compounds are continually being discovered, which are not available using traditional preparations of the fruiting bodies, but are detectable within, and excreted from the rapidly growing mycelium.

The natural killer cells promoted by ingesting turkey tails also target virally-infected cells. Moreover, turkey tail mycelium excretes strong antiviral compounds, specifically active against Human papillomavirus (HPV), which causes cervical cancer, and hepatitis C virus (HEP-C), which causes liver cancer. Viruses that induce cancer are called “oncoviruses.” The virus-to-cancer connection is where medicinal mushrooms offer unique opportunities for medical research. The current thinking amongst many researchers is that turkey tails and other medicinal mushrooms lessen the odds of getting cancer by reducing causal co-factors such as oncoviruses.

Full Article

Watch on medicalstate.tumblr.com

Why You Are Still Alive - The Immune System Explained by Kurzgesagt.

Watch on scinerds.tumblr.com

How T Cells Work

Made With Paper

This is not a kidney, but a lymph node, where B cells differentiate into antibody-secreting plasma cells and memory cells which play a big role in our body’s humoral immune response. In the humoral immune response, B cells secrete antibodies which neutralise pathogens (esp. viruses) and prevent them from binding to host cells during a prolonged infection. 

7

Magnifying Human Disease

As our ability to peer into the very, very small increases, we’ve had the opportunity to see the normally invisible pathogens that have plagued humankind for centuries. Some shown here will only cause achey joints or a highly unpleasant 24 hours of food poisoning; others are much more sinister, and can cause haemorrhage, necrosis, permanent disfigurement and death.

Image, top: Scanning electron micrograph (SEM) image of Borellia burgdorferi, a spirochaete bacterium responsible for lyme disease in humans.

Second row, left: RNA is seen in yellow in the core of these polioviruses; its protein coat is seen in blue. Second row, right: Yersinia pestis, a rod-shaped Gram negative bacterium, is the causitive agent of the bubonic, pneumonic, and septicemic plagues, and was responsible for the deaths of over 1/3 of the European population at its height. It’s probably best known for causing necrosis - the violent, premature death of cells in living tissue.

Third row, left: Looking deceivingly like an oil painting, these smallpox viruses - variola major and variola minor - were some of the most infectious viruses on the planet before their eradication. The protein coat is coloured yellow, and DNA is seen in red. Third row, right: The ebola virus, seen through a coloured transmission electron micrograph. Ebola is a haemorrhagic fever, and has claimed up to a 90% fatality rate in certain epidemics.

Fourth row, left: While Escherichia coli is usually a harmless gut-dweller in humans, under certain conditions it can cause gastroenteritis, urinary tract infections, and food poisoning. Fourth row, right: A false-colour image of human papilloma viruses (HPV). Best known as the cause of genital warts, it also has a sinister side: Virtually all cervical cancers are caused by HPV infection.

Source, as well as other images, here.

2

HIV antibodies neutralize 88% of worldwide HIV types & 2/3 of subtype C

A unique change in the outer covering of the virus allowed for antibodies to attach and neutralize 88% if HIV types around the world. This is known as a broadly neutralizing antibody response and was due to the body pressuring the virus to change its surface coating to have a sugar (glycan) ‘tag’ in the 332 position which then allowed the immune systems antibodies to attack it.

According to Professor Salim Abdool Karim, president of the Medical Research Council, “Broadly neutralizing antibodies are considered to be the key to making an AIDS vaccine. This discovery provides new clues on how vaccines could be designed to elicit broadly neutralizing antibodies.”

Though, because the weak point at position 332 is only in ~70% of the subtype C viruses (the subtype most common in Africa), antibodies will need to be developed that can target more glycans on the virus.

Photo 1 is structure of HIV
Photo
 2 is of HIV budding from a cell 

Via nature.com in the article “Evolution of an HIV glycan-dependent broadly neutralizing antibody epitope through immune escape

3

TOP:  Anatomy of a Bacteriophage
MIDDLE:  A Bacteriophage Attacking a Bacterium
BOTTOM:  What a Phage Does to its Host

The cycle begins when the virus uses its tail fibers to attach itself to its victim. The details of what happens next vary, but the process is always the same: the phage’s genetic material, which is located in its head, enters the bacterium.

Here, we’ll use T4, a well-studied phage infecting the Escherica coli bacterium, as an example.

(1) T4 contracts its tail sheath which pushes a tube located within the tail through the membrane of the bacterial cell.

(2) The phage’s DNA is passed through the tube into the cell, where it takes control, brutally stops many of its vital functions and forces it to churn out new virus components – heads, tails, tail fibers – in production-line style.

(3). Finally, enzymes dissolve the wall of the bacterium from the inside and the newborn bacteriophages reach the exterior, ready to attack new victims.

(4)  But these viruses proceed very selectively as they do so. Most of them attack only a subgroup of a single bacterial species. Generally, they don’t touch animal or human cells, which is why they are harmless to human beings.

Read more

[ X - images and basic text]

Macrophage (red) engulfing tuberculosis bacteria (yellow), taken with ZEISS FE-SEM. Courtesy of Dr. Volker Brinkmann, Max Planck Institute for Infection Biology, Berlin/ Germany.

What you can see here is the body trying to cure itself.  The yellow cigar shaped objects are tuberculosis bacteria.  Around it is macrophage.  A macrophage is a phagocyte, and these are the cells that protect us by attempting to ingest and harmful foreign objects.  The name comes from the Greek phagein – to devour and the word cyte which denotes a cell in biology.

From Kuriositas.

Stop cleaning yourself! You’re damaging your immune system.

This is not a joke, but it is the point of the Hygiene Hypothesis, a theory that could explain why people of underdeveloped countries don’t suffer of allergic and autoimmune diseases, and why these ones are spreading in west countries.

Hygiene Hypothesis states that a lack of early childhood exposure to infectious agents, symbiotic microorganisms and parasites increases susceptibility of immune system. It is hypothesized that the TH1 polarized response is not induced early in life, leaving the body more susceptible to developing TH2 induced disease, responsible of hypersensitivity reactions.

So the immune system, without pathogenic stimuli, starts attacking harmless antigens - such as pollen or penicillin, causing allergies - or "self" antigens - self cells, causing autoimmunity.

(Read more about Hygiene Hypothesis. Picture showing red cells, white cells, platelets (coloured yellow/green) and fibrin (light brown), from http://www.cell.com/).

Leukocytes ~ macrophages, neutrophils, mast cells, natural killer cells, dendritic cells
- macrophages = phagocytose pathogen and then act as antigen presenting cell.
- neutrophils = Polymorphonuclear leukocytes = PMNs = phagocytose pathogen and destroys it.
- mast cells: release histamine during an allergic response, bring about inflammation.
- natural killer cells: kills infected/abnormal cells.
- dendritic cells: the best antigen presenting cells.

T-lymphocytes

- Matures in the Thymus.
- Cytotoxic T cells recognize antigen on infected cells, and signal for apoptosis.
- Helper T cells recognize antigen on antigen-presenting cells, and signal for activation of B cells, T cells, and macrophages.

B-lymphocytes, plasma cells

- Matures in Bone marrow.
- B cells form plasma cells and memory cells when exposed to antigen.
- Plasma cells = secrete Antibody.
- Memory cells = stick around in case the same Antigen attacks in the future.

 

Tissues

Spleen
- Provides a site for WBCs to reside and proliferate.
- Removes pathogens from blood.
- Removes old RBCs and platelets.

Thymus: T lymphocytes differentiate in the thymus.

Lymph nodes
- Provide a site for WBCs to reside and proliferate.
- Removes pathogens from lymph.
- Residing lymphocytes monitor lymph for foreign antigens, and initiate an immune response when exposed to foreign antigens.

 

Basic aspects of innate immunity and inflammatory response: INNATE immunity= first line of defense = kills anything that doesn’t look right = not specific to a particular pathogen / antigen

  • - Skin: natural flora, layer of keratin.
  • - Mucus membranes: traps pathogen in mucus, and cilia moves it out.
  • - Phagocytes: engulf pathogen.
  • - Natural killer cells: destroy infected cells.
  • - Antimicrobial proteins: tears (lyse bacteria), interferons (interfere with virus replication), complement (punches holes in cell/pathogen membrane).
  • ~Fever/inflammation: WBCs are more active at higher temperature, and inflammation recruits WBCs to site of infection by sending out chemical signals and making capillaries more permeable.

ADAPTIVE immunity = highly specific for a particular pathogen / antigen.
- Antigen presenting cells present foreign antigen on their surface.
- Antigen is recognized by T and B cells.
- Cytotoxic T cells kill infected cells.
- Helper T cells Activate Macrophages, T and B cells.
- B cells produce AntiBodies.
- AntiBodies bind to antigens and bring about: 
        ~~ Neutralization: pathogen can’t adhere to host cell
        ~~ Opsonization: makes it easier for phagocytosis
        ~~ Complement activation: kills infected cell by punching holes in cell membrane.
- Memory cells are made that are much more efficient (does NOT need T cell activation) in proliferating and making antibodies in case the same infection strikes in the future.
- Memory cells allow the body to mount a greater, and more sustained response against the same pathogen during secondary response.

Concept of Antigen and Antibody
- AntiBody = lock, Antigen = key. Each antibody is specific to the binding of an antigen.
- AntiBody is like a Y, the tips of the fork bind antigen.
- The tips of the fork are called hypervariable regions because they are unique to each antigen-specific antibody.
- The AntiBody consists of 2 light chains and 2 heavy chains linked together by disulfide bonds.

Mechanism of stimulation by antigen; antigen presentation
- pathogen enters antigen-presenting-cell (APC)
- pieces of the pathogen gets displayed at the surface of APCs.
- T cell receptors recognize the presented antigen, and activates various immune responses.

scenario 1: EXTRAcellular pathogen
1. Macrophage engulfs pathogen.
2. pieces of the pathogen becomes the antigen and gets presented at the macrophage’s cell surface.
3. Helper T cells recognize the presented antigen, and Activates Macrophages to destroy pathogen. Helper T cells also Activate B cells to produce antibodies against the pathogen.

scenario 2: INTRAcellular pathogen
1. pathogen invades host cell.
2. pieces of the pathogen gets presented on the host cell surface.
3. Cytotoxic T cells recognize the presented antigen, and signals the infected cell to self-destruct.

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