immunologe

Antibodies (Human)

  • The ‘foot’ (bottom) of the antibody is known as the Fc fragment - binds to cells, binds to complement = effector function (kills or removes antigen)
  • The top (antigen binding) is the Fab fragment
  • Chains are held together with disulphide binds
  • Associated molecules allow intracellular signalling 
  • Normally 3X constant heavy chain domains per chain and a hinge region (except μ and ε which have 4 and no hinge region)

Classes of Immunoglobulins

The five primary classes of immunoglobulins are IgG, IgM, IgA, IgD and IgE,  distinguished by the type of heavy chain found in the molecule. 

  • IgG - gamma-chains
  • IgMs - mu-chains
  • IgAs - alpha-chains
  • IgEs - epsilon-chains
  • IgDs - delta-chains.

Differences in heavy chain polypeptides allow different types of immune responses. The differences are found primarily in the Fc fragment. There are only two main types of light chains: kappa (κ) and lambda (λ), and any antibody can have any combination of these 2 (variation).

IgG 

  • monomer
  • Gamma chains
  • 70-85% of Ig in human serum. 
  • secondary immune response 
  • only class that can cross the placenta - protection of the newborn during first 6 months of life
  • principle antibody used in immunological research and clinical diagnostics
  • 21 day half life
  • Hinge region (allows it to make Y and T shapes - increasing chance of being able to bind to more than one site)
  • Fc strongly binds to Fcγ receptor on phagocyte - opsono-phagocytosis
  • Activates complement pathway

IgM

  • Serum = pentamer 
  • Primary immune responses - first Ig to be synthesised
  • complement fixing 
  • 10% of serum Ig 
  • also expressed on the plasma membrane of B lymphocytes as a monomer - B cell antigen receptor
  • H chains each contain an additional hydrophobic domain for anchoring in the membrane
  • Monomers are bound together by disulfide bonds and a joining (J) chain.
  • Each of the five monomers = two light chains (either kappa or lambda) and two mu heavy chains.
  • heavy chain = one variable and four constant regions (no hinge region)
  • can cause cell agglutination as a result of recognition of epitopes on invading microorganisms. This antibody-antigen immune complex is then destroyed by complement fixation or receptor mediated endocytosis by macrophages.

In humans there are four subclasses of IgG: IgG1, IgG2, IgG3 and IgG4. IgG1 and IgG3 activate complement.


IgD 

  • B cell receptor
  • <1% of blood serum Ig
  • has tail pieces that anchor it across B cell membrane
  • forms an antigen specific receptor on mature B cells - consequently has no known effector function (don’t kill antigens, purely a receptor) (IgM as a monomer can also do this)

IgE 

  • Extra rigid central domain
  • has the most carbohydrates
  • IgE primarily defends against parasitic invasion and is responsible for allergic reactions.
  • basophils and tissue mast cells express very high affinity Fc receptors for IgE - mast cells then release histamine
  • so high that almost all IgE is bound
  • sensitizes (activates) mucosal cells and tissues 
  • protects against helminth parasites

IgE’s main purpose is to protect against parasites but due to improved sanitation these are no longer a prevalent issue across most of the world. Consequently it is thought that they become over activated and over sensitive while looking for parasites and start reacting to eg pollen and causing allergies.

IgA

  • Exists in serum in both monomeric (IgA1) and dimeric (IgA2) forms (dimeric when 2 Fcs bind via secretory complex)
  • 15% of the total serum Ig.
  • 4-7 day half life
  • Secretory IgA2 (dimer) = primary defense against some local infections
  • Secreted as a dimer in mucous (e.g., saliva, tears)
  • prevents passage of foreign substances into the circulatory system


Isotype: class of antibody (IgD, IgM etc)

Allotype: person specific alleles 

Idiotype: (hyper) variable region - antibody specificity 

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18.03.16 | Busy, busy, busy ✨📚🌿 

Because I haven’t done as much as I should’ve this past week (mostly due to some unforeseen, very frustrating circumstances) I have to work really hard this weekend. 

Currently I’m struggling with some immunology, which, even though very interesting, proves to be an equally challenging subject- so please keep your fingers crossed for me 💪🏻 

Have a productive weekend everyone! ✨

olga

What Science is Launching to Space?

The tenth SpaceX cargo resupply mission launched to the International Space Station on Feb. 18, and is carrying science ranging from protein crystal growth studies to Earth science payloads. Here’s a rundown of some of the highlights heading to the orbiting laboratory.

The CASIS PCG 5 investigation will crystallize a human monoclonal antibody, developed by Merck Research Labs, that is currently undergoing clinical trials for the treatment of immunological disease. Results from this investigation have the potential to improve the way monoclonal antibody treatments are administered on Earth.

Without proteins, the human body would be unable to repair, regulate or protect itself. Crystallizing proteins provides better views of their structure, which helps scientists to better understand how they function. Often times, proteins crystallized in microgravity are of higher quality than those crystallized on Earth. LMM Biophysics 1 explores that phenomena by examining the movement of single protein molecules in microgravity. Once scientists understand how these proteins function, they can be used to design new drugs that interact with the protein in specific ways and fight disease.

Much like LMM Biophysics 1, LMM Biophysics 3 aims to use crystallography to examine molecules that are too small to be seen under a microscope, in order to best predict what types of drugs will interact best with certain kinds of proteins. LMM Biophysics 3 will look specifically into which types of crystals thrive and benefit from growth in microgravity, where Earth’s gravity won’t interfere with their formation. Currently, the success rate is poor for crystals grown even in the best of laboratories. High quality, space-grown crystals could improve research for a wide range of diseases, as well as microgravity-related problems such as radiation damage, bone loss and muscle atrophy.

Nanobiosym Predictive Pathogen Mutation Study (Nanobiosym Genes) will analyze two strains of bacterial mutations aboard the station, providing data that may be helpful in refining models of drug resistance and support the development of better medicines to counteract the resistant strains.

During the Microgravity Expanded Stem Cells investigation, crew members will observe cell growth and morphological characteristics in microgravity and analyze gene expression profiles of cells grown on the station. This information will provide insight into how human cancers start and spread, which aids in the development of prevention and treatment plans. Results from this investigation could lead to the treatment of disease and injury in space, as well as provide a way to improve stem cell production for human therapy on Earth.

The Lightning Imaging Sensor will measure the amount, rate and energy of lightning as it strikes around the world. Understanding the processes that cause lightning and the connections between lightning and subsequent severe weather events is a key to improving weather predictions and saving life and property. 

From the vantage of the station, the LIS instrument will sample lightning over a wider geographical area than any previous sensor.

Future robotic spacecraft will need advanced autopilot systems to help them safely navigate and rendezvous with other objects, as they will be operating thousands of miles from Earth. 

The Raven (STP-H5 Raven) studies a real-time spacecraft navigation system that provides the eyes and intelligence to see a target and steer toward it safely. Research from Raven can be applied toward unmanned vehicles both on Earth and in space, including potential use for systems in NASA’s future human deep space exploration.

SAGE III will measure stratospheric ozone, aerosols, and other trace gases by locking onto the sun or moon and scanning a thin profile of Earth’s atmosphere.

These measurements will allow national and international leaders to make informed policy decisions regarding the protection and preservation of Earth’s ozone layer. Ozone in the atmosphere protects Earth’s inhabitants, including humans, plants and animals, from harmful radiation from the sun, which can cause long-term problems such as cataracts, cancer and reduced crop yield.

Tissue Regeneration-Bone Defect (Rodent Research-4) a U.S. National Laboratory investigation sponsored by the Center for the Advancement of Science in Space (CASIS) and the U.S. Army Medical Research and Materiel Command, studies what prevents other vertebrates such as rodents and humans from re-growing lost bone and tissue, and how microgravity conditions impact the process. 

Results will provide a new understanding of the biological reasons behind a human’s inability to grow a lost limb at the wound site, and could lead to new treatment options for the more than 30% of the patient.

Make sure to follow us on Tumblr for your regular dose of space: http://nasa.tumblr.com

anonymous asked:

What do you do when you run into anti-vaccine dog/pet owners?

I don’t genuinely run into them often. If they’re profoundly anti-vaccine then often they’re anti-veterinarian as well, which means I don’t get to see them or their dogs until the last possible minute, if at all. Many of these people will seek out so-called ‘holistic vets’ who will quite happily tell them what they want to hear regardless of, and sometimes in spite of, actual evidence.

So most of the time I don’t have to converse with zealots.

The more common scenario is that I encounter a perfectly reasonable pet owner who has come across some article, blog post or meme which has mad them concerned about vaccines and we have a nice chat about what we vaccinate for, why, and how often. And then if they chose not to vaccinate, and the most common reasons we might recommend against vaccinating, what the relative risks and consequences are

At the end of that conversation, the pet owner either chooses to vaccinate on the recommended schedule, or skip kennel cough vaccination aware of the risks, or do titres for the core vaccines instead.

I can’t drag these people or their pets into the clinic. If they don’t come in, I don’t deal with them, and I don’t engage with them on social media any more because it never makes a difference. They are not there for a discussion or a debate, they are there to preach. And they think that because they colonic hydrotherapy for a living they have been mystically granted advance knowledge of immunology that a veterinarian, even a veterinarian that has been to immunology conferences to stay up to date, simply doesn’t have.

So in the vet clinic, we have a civil conversation.

Outside of the clinic, all bets are off.