immunology

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

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Proteus OX19 and the Polish Schindler,

Proteus OX19 is a strain of the bacterium Proteus vulgaris, a simple gram negative bacteria that is commonly found in dirt and water.  It is a fairly unremarkable bacteria, some exposed to it might suffer urinary tract infections or infections of wounds.  However, most infected with the bacteria will suffer few symptoms as the body’s immune system eradicates the invading microbe.  It does have one interesting reaction, however.  People exposed to Proteus OX19 often test false positive for typhus, a disease which is much deadlier and can cause terrible outbreaks and epidemics.

When Germany invaded Poland on Sept. 1st, 1939, Dr. Eugeniusz Lazowski served as an army doctor with the Polish Army.  After the occupation of Poland by Germany, Dr. Lazowski returned home to Rozwadow to continue his private medical practice.  However, he heard news of mass deportations of Poles and Jews by the Nazi’s.  Hundreds of thousands of Jews were being rounded up and deported to concentration camps.  Hundreds of thousands of Poles were also being deported to Germany as forced labor.  It was only a matter of time before the Germans demanded the deportation of Poles from Rozwadow, and Lazowski was determined that the Nazi’s would go empty handed.

Lazowski solution was ingenious and audacious; to keep the Germans away from Rozwadow by simulating a fake typhus epidemic. At the time, Germany was terrified of the prospect of a typhus outbreak spreading across the Fatherland, and strict protocols were in place to isolate and quarantine infected areas.  Inspired by the Proteus microbe, Lazowski informed German medical officials that Rozwadow was being ravaged by a terrible typhus epidemic.  With the help of his friend, Dr Stanisław Matulewicz, Dr. Lazowski injected the people of Rozwadow with proteus OX19, as well as the residents of several nearby Jewish ghettos, so that they would all test false positive for typhus.  He then sent blood samples to German medical officials.  As predicted, the samples all tested false positive for typhus.

In response, the Germans sent three medical inspectors to assess the seriousness of the epidemic.  The three inspectors were greeted cordially and plied with food and generous amounts of vodka.  They were then given a short tour of the town.  Due to fears of contracting the disease, the Germans only made a cursory examination of the town.  Then they were led to a fake medical ward filled with severely ill patients.  Dr. Lazowski claimed they were suffering from typhus, and again due to the German’s fear of contracting the disease, they made no medical assessments.  Instead they took Dr. Lazowski at his word and sped out of Razwadow, declaring the town and surrounding area to be in a state of quarantine.  Little did they know, the so called “patients” the German’s were led to were people with flu and pneumonia, told to act as sick as possible.

Due to the quarantine, the Germans never deported anyone from Razwadow or the ghettos.  As a result, he is credited with saving 8,000 Jews from certain death, and thousands of other Poles from deportation.  Throughout the rest of the war he lent his medical services to the Polish resistance, and worked to smuggle Jews to safety from the Nazi’s.  After the war he moved to the United States and worked as a pediatrician.  He died in 2006 at the age of 96.

Multiple Sclerosis (MS) is a disease in which the immune system eats away at the protective covering of nerves.

In MS, resulting nerve damage disrupts communication between the brain and the body.

Multiple sclerosis causes many different symptoms, including vision loss, pain, fatigue, and impaired coordination. The symptoms, severity, and duration can vary from person to person. Some people may be symptom free most of their lives, while others can have severe chronic symptoms that never go away.

Physical therapy and medications that suppress the immune system can help with symptoms and slow disease progression.