Posted in interesting, learn something new, Post, Posts, Science, Uncategorized

The Immune System

I’ve spent the last week or so learning about the immune system, something I find absolutely fascinating.

I thought I’d compile all the information to make a concise word document covering:

  • Barrier defence
  • Haemostasis
  • Inflammation
  • Innate immunity
  • Adaptive immunity
  • Cell-mediated defence
  • Humoural defence
  • Allergies
  • Autoimmune disorders

Here is a link to it as a word document: The Immune System

Sorry for the poor quality images, I have to convert my textboxes to JPEG files via paint… please let me know if there is a better way to do that!

 

First Responsesfds.jpg

Barrier Defence

Before a pathogen can even enter the body, it has to get past many external defences. This strategy aims to prevent pathogens from entering the body in the first place.

Skin – The biggest defence is the skin, which acts as a physical barrier – physically blocking entry. The skin is made of tough, keratinized dead cells which make penetration hard. Fatty secretions from the sebaceous glands also help to disrupt microbial membranes.

Saliva – Bacteria in the mouth can be flushed out and down to the stomach by saliva – which also contains antimicrobial agents like lysozyme and lactoferrin.

Mucous – The airways (pharynx, trachea etc) are lined with a thick, sticky mucous (secreted by goblet cells) which traps pathogens. The airways also have a lining of ciliated epithelium and the tiny hair-like cilia waft the mucous up to the back of the throat where it can be swallowed.

Urine – Urine helps flush out any pathogens in the genitourinary tract.

Stomach Acid – Finally, the stomach plays a big part. Parietal cells in the stomach lining produce hydrochloric acid which helps to kill many (but not all) of the microbes in digested food, saliva and swallowed mucous.

Haemostasis      

When you cut yourself, it breaches the physical barrier provided by the skin – meaning that pathogens have a way into the body. When the pathogen (e.g. bacteria) first enters the body, it remains unnoticed as it uses up the body’s resources in order to reproduce. Once a certain population is reached, the pathogens change their behaviour and start damaging the body by changing the environment around them.

However, the first thing your body does is try to stop you from losing too much blood through your damaged blood vessels. This is called Haemostasis. The blood vessels that have been damaged constrict to slow the flow of blood (so that you don’t lose too much) and the damaged epithelial tissue of the vessel wall now has collagen fibres exposed so that as blood flows over it, platelets react with the collagen and become sticky and glue-like. Fibrinogen from the blood is converted by thrombin (a clotting enzyme) into fibrin, which forms a mesh to trap platelets and red blood cells and reinforce the platelets that have already clotted. The strands of fibrin then pull the sides of the wall together so that the vessel can be repaired.

 

Inflammationh

The inflammatory response acts as a message to the rest of the body to prepare for defence.

When the skin is broken, the skin cells (especially Mast cells) release chemicals, such as histamine, that act as messengers to the rest of the immune system.

The first thing histamine does is cause vasodilation. The blood vessels around the damaged area dilate and stretch. This means that more blood can flow to that area, so the site of the wound becomes red (increased blood flow) and heated (blood is warm). As the vessels stretch, they get thinner and small gaps emerge between cells. This makes the vessels permeable to fluids, so plasma and cell fluid start to accumulate in the tissue space. This is what causes swelling. As the tissue swells, it presses on nerves, thus causing pain.

Therefore, the signs of inflammation are:

  • Redness
  • Heat
  • Pain
  • Swelling

This is actually a good sign that the body is preparing to repair itself.

As plasma flows through the permeable vessels, it brings proteins like fibrinogen and platelets. Just like with the blood vessel, this helps to form a clot and scab which can block the hole letting pathogens inside the body. The leaked fluid is then picked up by the lymphatic system and it is returned to the blood after filtration.

However, the important part of inflammation is that the histamine attracts lots of local phagocytes. When the skin is broken, it al The increased permeability of your blood vessels helps this by making it easier for the leukocytes to access the inflammation site.

 

Innate Immune System

The innate system is non-specific – it treats all foreign bodies equally and will respond to any threat in the same way, regardless of whether it has been encountered before. This makes it a very quick response, but most infections don’t get beyond this stage.

 

Neutrophils are the first to arrive, and they squeeze through the capillaries through a process called diapedesis before entering the tissue (this is possible due to their ability to signal the blood vessels to open up gaps between cells for them. They destroy the pathogens by phagocytosis, but they are very short-lived – they die as soon as they have destroyed the pathogen they targeted. The dead neutrophils then collect as pus. They are also the most abundant leukocyte, making up about 60% of all leukocytes in the body.

 

Macrophages (big eaters) don’t move around as much or as quickly as the neutrophils. They remain in organs in case of infection so they may be the first to respond. They act almost as bodyguards. These cells have much longer life spans and can eat up to 100 pathogens before dying. Macrophages can be free and able to move around tissues looking for pathogens, or fixed and attached to fibres in specific organs where they lie in wait for any passing pathogens. Quite a lot of macrophages are “resident” in a certain tissue and stick to this area (unlike the neutrophils which move around and flock to where they are needed).

Macrophages also help clear up dead cells and debris as well as anything with foreign antigens.

 

dThe final type of phagocyte is a Natural Killer Cell. These are still part of the innate system, and they are cytotoxic cells – this means they destroy human cells as well as pathogens. Body cells have surface receptors called the Major Histocompatibility Complex (or MHC), and these receptors provide information about the cell. Natural Killer Cells monitor these receptors, as an infected cell will avoid displaying (or stop producing) them to evade detection. Natural Killer Cells are activated when they detect reduced numbers of MHC receptors on a cell’s surface, and the NKC will then bind to the infected cell (be it a host to a virus, or a malignant cancer cell) and secrete cell membrane dissolving enzymes into it to enable its destruction.

 

 

Adaptive System

If this is not enough to defeat the pathogen, then the adaptive/specific immune system is activated.

This response is started off by antigen-presenting cells, which include dendritic cells and also macrophages (which display the antigens of pathogens they have ingested). The cells line all surfaces that come in contact with the environment. After exposure to a pathogen, the dendritic cell is activated. It engulfs the pathogen then displays short peptide chains from the pathogen it has just consumed on its MHC II receptors. It then migrates to the lymph nodes. Here, it presents the antigens to T and B lymphocytes – depending on the required response.

Macrophages are also capable of antigen presenting.

 

APCs present the microbial antigen first to a helper T-Cell – this has to be a specific type of T-Cell that can recognise it. Information about the pathogens location and properties are communicated through chemicals called interleukins (signalling molecules produced by leukocytes) – specifically interleukin 1. The helper T Cells then travel around the body releasing other interleukins to alert the rest of the immune system and activate other cells. They also serve as confirmation during the initiation of lymphocyte – without which the lymphocyte will remain dormant. They help to organise and coordinate the whole response.

It is important to have Helper T Cells acting like messengers as there are only a few lymphocytes of each specificity (lymphocytes specialise to only recognise one type of antigen). Rapid circulation helps to increase the chance of them encountering pathogens, but they still need Helper T Cells to confirm the threat and initiate replication (this is done via lymphokines).

The KT Cells then migrate to the site of the infection via the blood and lymphatic vessels. They are directed by tissue recognition and the information they have on location as well as by the effects of inflammation and cell damage (e.g. increased tissue permeability).

 

 

Cell Mediated                r

This response targets pathogens that infect cells.

If the pathogen is a virus or parasite (or even some bacteria) then it is likely that cells will be infected. This is dealt with by Killer T Cells. Once a KTC has encountered a corresponding antigen, it will wait for confirming signals from an HT cell before becoming activated. It then undergoes clonal expansion – a process whereby the matching cell divides into many clones that can then specialise themselves. Effector cells exit the lymph nodes and locate the pathogen that the original KT cell was imprinted with (all clones will have the location/pathogen information presented to the initial KTC by the HT cell).

Memory cells are also formed, and these stay in the lymph nodes in order to quickly recognise the pathogen and provide a rapid response if it ever infects the body again.wThe KT cells created all have a receptor for the specific antigen representing the pathogen. They then monitor body cells in the infected tissue for this antigen (which will be presented by an infected cell’s MHC receptor). When the KTC recognises the antigen, this means the cell is infected, and the KTC will then proceed to destroy it by releasing granzymes (cytotoxic molecules). These penetrate and pierce the cell membrane to induce cell death – this is known as apoptosis. The important part of this process is that it degrades the contents of the cell (thus killing the cell and the pathogens inside) without releasing the infecting components to limit their spread.

 

Humoural (or antibody mediated)         e

Cells are not always infected by pathogens. The humoral response, therefore, targets extracellular pathogens – ones that are in infecting tissue fluids or the blood. These are often bacteria.

tThe lymphatic system filters the body’s fluids, so if they are infected, the responsible pathogen will eventually be conveyed to the lymph nodes (or to the spleen via the blood). Most of the clones will differentiate into effector (or plasma) B cells. These then locate the infection and produce antibodies that match the parent cells specificity. The antibodies bind tightly to the antigens on the invading pathogen’s surface and disable/immobiliseu it – making it easier to destroy. They also flag the pathogen as a threat and attract other immune cells (phagocytes), as well as activating the complement system, so that the pathogen can be destroyed.

Antibodies cannot kill the pathogen themselves.

As with the cell-mediated system, some B Cells differentiate into memory cells. Again, this means that in the case of a future infection, the pathogen will be quickly recognised and large amounts of the right antibody will be produced quickly.

 

Allergies (hypersensitivity) 

For a person with hypersensitivity, when the body is first exposed to an allergen (such as pollen), the white blood cells respond by producing antibodies. These antibodies then bind to mast cells, which means that if the allergen enters the body again, they will bind to the antigens on the mast cells and activate them. The mast cells have stores of chemicals in coarse granules within the cytoplasm. If an allergen links two or more antibodies on the mast cells surface together, then degranulation will be triggered, and the granules will release chemicals like histamine and interleukins.y

This process also occurs if a mast cell is damaged by a pathogen – which is what triggers inflammation during an actual infection.

Histamine then binds to the receptors on nearby cells and causes an allergic response:

Vasodilatation – blood vessels dilate allowing leading to increased blood flow (to help white blood cells travel to the site quickly) and increased blood vessel permeability (which in turn causes fluid to collect in the area causing swelling or hives).

Nasal Symptoms – dilated vessels contribute to congestion (blocked nose) and histamine also causes goblet cells to hyper-secrete mucus (a runny nose).

Neurotransmitter – histamine can act as a neurotransmitter, and when they bind to receptors on nociceptors (pain sensing neurones), they produce an itching sensation.

Tear Production – increases tear production to cause watery eyes.

Smooth Muscle Contraction – this is responsible for breathing difficulties and shortness of breath as the airways tighten.

Antihistamines are antagonistic drugs used to control allergic reactions. The antihistamine binds to the receptor and prevents histamine from affecting the cells (because it has to compete with the antihistamine that is already bound).

 

Autoimmune Disorders (self-sensitivity)

Autoimmune disorders occur when the immune cells are unable to recognise the body’s antigens as “self-antigens”. Instead, they are seen as foreign, and therefore a threat. This leads to the immune system attacking healthy cells.

T cells will attack body cells and B cells will produce autoantibodies (antibodies that bind and to and damage self-antigens). This causes organ damage and inflammation.
It is also thought that the disorder is triggered by a viral or bacterial infection – it is thought that during the infection, B Cells mutate to respond to the infection and these mutations can result in B Cells attacking healthy cells.For unknown reasons, autoimmune disorders affect women more than men, with 2/3 sufferers being female.i

 

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The Modern History of China – Part 4 – The Chinese Communist Party

The Chinese Communist Party

 

During WW1, China started supporting the allies by sending labouuntitledrers to Europe to help the war effort. Through this, they hoped to regain parts of China held by Germany following their defeat. However, there was a pre-existing agreement between the allies and Japan, promising the Shandong Province to them, as well as all other German Pacific territories/islands north of the equator (although Japan still wasn’t happy as they didn’t get given all of the requests they made over land).

When this was revealed in the Paris Conference (which created the Treaty of Versailles), it led to an outburst of student protests that culminated
in the May 4th Movement. To make matters worse, a Chinese warlord had been bribed by Japan into allowing the occupation. China was unhappy about this arrangement, and this resulted in them walking out of the Paris Peace Conference and refusing to sign the treaty.

 

Two men who had been involved in the protests, Li Dazhou and Chen Duxiu, then turned to Marxism for a solution, after seeing the success of Russia’s Bolsheviks in the Russian Revolution and from this, founded the Chinese Communist Party (1921, Shanghai) as both a revolutionary movement and a political party.

 

 

United to fight the Warlords

 

In 1924, Sun Yat Sen and the Nationalist Party formed an alliance (The United Front) with the Communist Party to build a republican army. A military academy was set up to train officers in fighting the warlords, and a man named Chiang Kai Shek / Jiang Jieshi took the role of first commander. When Sun Yat Sen died in 1925, Chiang took over as the leader. with the aid from the Soviet Union, and the next year saw him launch the Northern Expedition. This was an attempt to drive through the north of china, from Canton to the Yangtze River, overthrowing warlords in the process. With Soviet help, they gained control over most of south-east China (where the majority of China’s population and cities were located) within the year, and Beijing was taken in 1928 – ending the expedition. The country was reunited and a new capital was established in Nanjing.

 

However, there was unease within the Nationalist Party. Many members were unhappy with Communists being part of the party, especially nationalist businessmen and landowners who were threatened by the communists’ encouragement of strikes and peasant unrest. The left and right wings of the party became deeply divided in the 1920’s.

Sun Yat Sen had seen the communists as allies and friends, but the arrival of Chiang Kai gbShek brought along a new approach too. He saw them as a threat and enemy of the party. However, their alliance was crucial for getting support from the Soviet Union.

 

When the Nationalist forces reached Shanghai in April 1927, they had no need to keep up the façade anymore and the nationalist troops massacred anyone suspected of communist connections in what was known as The Shanghai Purge (or the White Terror [April 12th, 1927]).

Hundreds suspected of Communism (or communist connections) were killed with a further 5,000 missing and 1,000 arrested. 

After the massacre, the communists continued to be suppressed and most were driven out of cities and forced to go into hiding in the countryside.

 

Posted in China, interesting, learn something new, Post, Posts, Uncategorized

A Modern History of China – Part 3 – Changing Governments and the Warlord Era

Changing Governments

When Sun Yat Sen returned from America (where he had been fundraising), the republicans finally pulled everything together. Sun Yat Sen was elected as the provisional (temporary) president before a compromise was agreed to between him and Yuan Shikai, arranging for him to become president in return for military recognition of the republic and help getting the Qing Dynasty to step down.fgdsg.jpg

The Qing dynasty was left without a military and, when the Guangxu Emperor and Empress Dowager Cixi died, in the hands of the 2 year old Emperor Xuantong (Henry Puyi). It was also weak from years of losing wars and the recent reforms which, by trying to regain support, had reduced their power over the country.     Yuan Shikai persuaded Puyi to abdicate when he was only 6 years old, and came to power on the 13th of February, 1912.

However, the China Shikai inherited was weak and over in the provinces, warlords started to fight for influence. Elections in early 1913 also saw the Kuomintang (nationalist party/government) and their leader, Sun Yat Sen, gain huge support. Shikai started targeting his opposition and, after the suspicious death of the party’s chairman (all links leading to Yuan Shikai), Sun Yat Sen fled to Japan, where he called for a second revolt – this time against Yuan Shikai.                                                                                                              Yuan crushed the revolt along with any hopes for democracy. Two years later, in 1915, he declared himself president for life and announced the start of a new Hongxian dynasty with him as emperor.

However, the citizens of China, who had spent so long trying to get rid of the dynasty, and even Shikai’s former generals, were unhappy with the idea of another dynasty, and widespread opposition forced Shikai to step down after just 86 days of dynasty. Many demanded he resigned from his role as president after this, but his death three months later removed the need for it.

 

The Warlord Era (1916 – 1928)

The death of Yuan Shikai brought a whole new problem to China. In his wake, he left a huge power vacuum and, due to the lack of a united, national army (see The New Army), Untitled.jpgit was easy for local generals to seize control of provinces and use their power to challenge the authority of the republic. These generals were known as warlords, and the 12 years of fighting between them for influence of other provinces became known as the Warlord Era.

The era saw a lot of fighting over provincial influence, and many warlords were corrupt and reckless, seeking personal gain through opium trade, tax, printing money, stealing and violence.

That said, some warlords had a positive impact on China, like Yan Xishan – who tried to reform China for good, improving and modernising his area via changes such as education for girls and banning foot binding.

There was technically still a central government in Beiyang / Beijing – but in reality this was just a front for whichever Warlord had control so that they could benefit from foreign trade and tax (it was recognised as legitimate by foreign powers!).

 

 

Posted in China, interesting, learn something new, Post, Posts, Uncategorized

A History of Modern China – Part 2

The end of the Qing dynasty

BOX 2.jpgThe people living in China started to grown weary of the outdated and incompetent (The Opium Wars, the Sino Japanese War) dynasty and they craved the modernization of the west. The dynasty was also revealed as corrupt to its citizens during The First Sino-Russian War.

A revolutionary, called Sun Yat Sen (or Sun Yixian) organised these feelings by setting up the Revive China Society whilst exiled in Honolulu (Hawaii) in 1894. He later joined forces with other anti-monarchy groups to form the Tongmenghui (1905) – a group dedicated to overthrowing the Qing Dynasty.

 

Reform

The failing dynasty made several attempts to regain BOX 3.jpg
support, such as “The 100 Days Reform”, initiated by Empress Dowager Cixi through the rule of her nephew, Zaitian (Guangxu Emperor). It brought many of the changes that Cixi had previously stood in the way of, such as:

  • new departments to oversee police, education, law , communication and foreign affairs
  • economic reforms, encouraging capitalism
  • a westernised criminal code
  • lifted bans on ManchuHan marriages
  • banned slavery, foot binding and opium smoking

However, it was too little, too late, too insincere– and the reforms did little to quell dissent, and instead made it easier for it to increase.

 

Railway Protests

The spark that ignited the fire came in 1911, when it was announced that two privately owned railways would be nationalised to help finance the Boxer Protocol Reparations.

Many local businessmen had invested their own money in these railways, and they would have huge losses if it became nationalised, so the news triggered heavy protesting across Sichuan, with The Railway Protection Movement organising strikes and demonstrations.

The Sichuan government tried to quell BOX 1.jpgdissent via military intervention, but this worsened the situation and Beijing was forced to back down and remove the Sichuan governor for his actions. However, another load of soldiers was sent in shortly after, this time from the New Army.

Unfortunately for the Qing dynasty, the New Army was compromised by republicans and their sympathisers – as well as large groups of radical students, workers unions and secret literary societies who were stockpiling weapons in preparation for an uprising in nearby Wuchang (in the Hubei province). On the 10th of October, 1911, one of the bombs being stored accidently went off and, facing discovery, the Wuchang New Army regiment set the plan into action and rebelled against their superiors – a mutiny.

The rebels stormed government buildings, arresting loyalists and gaining control of Wuchang before declaring Hubei a republican government on the 11th of October.

Their success encouraged many other rebellions and many cities followed in their steps. Government forces reclaimed a few cities (including Wuchang), but the dynasty was fast falling apart.

Posted in interesting, learn something new, Uncategorized

The Modern History of China – Part 1

Hello!

I’ve spent the last few months making a project on Chinese History. I always remember my Mum being fascinated by China and so this was a way to fulfil my five-year-old self’s wish to be able to understand it. I’m going to go from the fall of the Qing dynasty right up to the end of Mao’s China. Hopefully it will be interesting!

Continue reading “The Modern History of China – Part 1”

Posted in Blog, Cats, Memories, Photos, Post, Posts, Rosie and Jim, Uncategorized

Klever Kitties – Part two – Rosie Stubington

Hello!

So it’s been awhile since my last post, but I mentioned a follow up to Jim’s Skills – so without further ado, here is Rosie’s section!

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When we first got Rosie, she was a lot shier than Jim, and she spent the first hours inside her carrier – where she had been kept all her life before the RSPCA found her. When she finally came out though, she got a bit braver everyday. Rosie was only 2 then, so she still had a lot of kittenish traits (she still does at five and a half!) and it wasn’t long before she wanted to explore.

 

The way that I connected with her was through playIMG_4924.JPG. Continue reading “Klever Kitties – Part two – Rosie Stubington”

Posted in Blog, News, Post, Posts, quick hello, Uncategorized

Making maps and offending countries

I will first make a disclaimer apologising for my abysmal lack of geographical skills and mistake of drawing maps in permanent pen.

I have a book where I try to teach myself about world history and geography. Today’s challenge was looking at the formation and breakup of Yugoslavia – something I have been curious about for a while. However, it turns out I am very bad at drawing maps…

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What I was aspiring to create… 

So far I have: literally boosted turkey (or at least the blob representing it) up in the world so that it sits next to Romania; completely removed about 4 countries, swapped over Slovenia and Slovakia (they had the same first 3 letters on my abbreviated map); turned Austria into what looks like a slipper (paired with a high-heeled Italy and you have an argument for renaming Europe “the international shoe shop”) and finally, and perhaps worst of all, completely forgotten about Moldova.

I think I may have just offended half of Europe.

My project is nearly done now but from this point onwards, you can be sure that my printer will be working a lot harder…

Posted in Uncategorized

Klever Kitties!

I will start by admitting how difficult it was for my perfectionist side to spell clever with a “K”… Moving on!

When my brother first met our cats, he point blank refused to call them by their names. Instead, Rosies ginger and black triangles earned her the name “Pizza Face”…pizza face.jpg

And Jim’s fabulous face accessories/eyebrows/forehead whiskers landed him with “Einstein”.

Einstein.jpgHowever, this got me thinking about how, in my opinion, they are both rather clever. Two little geniuses, if you like.

Now don’t get me wrong – I’m not claiming to be unbiased. In fact, I feel rather like a proud mother looking at their child vaguely human-like paint splodge and declaring them the next picasso. However, taking into account the difference in species and age, they are definitely intelligent.

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Jim Van Gogh’s  recreation of the Sunflower painting.

No – Jim has not recently sat me down and explained relativity. We both decided to leave that to the real Einstein, but he does have a knack for human emotions. If there’s a stressed groan or runaway tear in our house, he hunts down the owner in minutes and fixes the problem within seconds.

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Stress? Is that Human for relax?

I have had many a day where nothing has cured me of a bad mood, only to return home and have my frown melted off my face by a single “Mew”.

 

He is also good at recognising when he is the cause of the stress – i.e. when he eats the entire pot of stew or batch of brownies on the side.

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No worries! I’ve got a shoe ready to bring down!

This then triggers his “I’m sorry” act. A few minutes after his telling off, there will be a tell tale “Brow… Bruuuuuuuuow…..Brrrrrrroooooowwwww”.

Nope. Not a mouse thank goodness. Jim likes sorry slippers. If he has been naughty, we will be awarded a sock, shoe, slipper, teddy or various hygiene tool (toilet roll, face wipe, makeup brush, hair bobble). This will be dropped off in the sitting room as he sits and yells for attention. Of course, he is given a showering of praise and affection and all his wrongs are instantly forgotten.

The only problem is, he’s now started bringing things down as compensation for something naughty he will do. That way, he’s covered for later if opportunity arises. It’s quite an effective way of predicting a bolognese heist.

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As you can see, Jim was particularly naughty this day and did a lot of apologising.

The best present we have received so far is a five foot shark teddy which was so heavy that it got dropped at the top of the stairs instead of downstairs. His attempts to bring down a gorilla toy twice his size was also rather funny and required him to stop and hop over the top every now and again to get a better grip.

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I’m sorry for eating your pecan pie (and for spitting the pecans out onto the floor – they’re yucky).

 

Now if you can look me in the eye and tell me you could manipulate someone like that then I will eat my cat-themed hat and take back the “my cat’s a genius” claim.

I will also note that Rosie is a genius too! Keep an eye out for my next post which will be focused around her excellent success with human training.

 

 

Posted in Blog, Cats, Photos, Post, Posts, Rosie and Jim, The Sunday Treat, Update

Rosie’s week

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’tis my blog now

Hello! This is a Blog Takeover, by me – your supreme leader Rosie!IMG_3605.JPG

Some strange people visited this week (they were referred to as children) so I took it as an opportunity to recruit some new servants.i need.jpg

I’ve also been showing off my Bikini Belly as practice for the summer holidays.IMG_3697.JPG

I worked very hard to get that fluff, I deserve to flaunt it!

IMG_3714.JPGThat said, there’s been a few chilly days, haven’t there?

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Unfortunately, we have a bit of a Tom Cat infestation at the moment. Probably dragged here by my womanly wiles… I’ve been staying alert though.

 

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Watch duty is hard work! Good job I can do it horizontally.

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I still find time for a good bath though. Here I am drying off.

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Well, I’m off!