Target Health Blog

Convalescent Plasma

September 9, 2020

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Quiz
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Each antibody binds to a specific antigen; an interaction similar to a lock and key.
Graphic credit: by Fvasconcellos 19:03, 6 May 2007 (UTC) - Color version of Image:Antibody.png, originally a Work of the United States Government, Public Domain; Wikipedia Commons

An antibody (Ab), also known as an 1) _____ (Ig), is a large, Y-shaped protein produced mainly by plasma cells that is used by the immune system to neutralize pathogens such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the pathogen, called an antigen, via the fragment antigen-binding (Fab) variable region. Each tip of the “Y“ of an antibody contains a paratope (analogous to a lock) that is specific for one particular epitope (analogous to a key) on an antigen, allowing these two structures to bind together with precision. Using this binding mechanism, an antibody can tag a microbe or an infected cell for attack by other parts of the immune system, or can neutralize its target directly (for example, by inhibiting a part of a microbe that is essential for its invasion and survival). Depending on the antigen, the binding may impede the biological process causing the disease or may activate macrophages to destroy the foreign substance. The ability of an antibody to communicate with the other components of the immune system is mediated via its Fc region (located at the base of the “Y“), which contains a conserved glycosylation site involved in these interactions. The production of antibodies is the main function of the 2) _____humoral immune system.

Antibodies are secreted by B cells of the adaptive immune system, mostly by differentiated B cells called plasma cells. Antibodies can occur in two physical forms, a soluble form that is secreted from the cell to be free in the blood plasma, and a membrane-bound form that is attached to the surface of a B cell and is referred to as the B-cell receptor (BCR). The BCR is found only on the surface of B cells and facilitates the activation of these cells and their subsequent differentiation into either antibody factories called plasma cells or memory B cells that will survive in the body and remember that same antigen so the B cells can respond faster upon future exposure. In most cases, interaction of the B cell with a T 3) _____ cell is necessary to produce full activation of the B cell and, therefore, antibody generation following antigen binding. Soluble antibodies are released into the blood and tissue fluids, as well as many secretions to continue to survey for invading microorganisms.

Convalescent Plasma the blood plasma of a person who has recovered from an infectious illness, which contains antibodies to an infectious disease factor (such as viruses). For convalescent plasma therapy, the plasma can be transfused into an ill victim of that disease as a treatment.

The US FDA has issued an 4) _____ use authorization for convalescent plasma to treat Covid-19. However, the published research studies have not been peer-reviewed and do not describe a randomized clinical trial that proves Covid-19 convalescent plasma, or CCP, is effective. One of them presents pooled data drawn from CCP studies in multiple countries including China, Iran, Iraq and Mexico. In short, we need much more information than we now have.

The scientific basis of CCP therapy is giving an outside boost to a patient battling the virus. The plasma contains virus-neutralizing 5) _____ -- proteins that recognize the invading virus, bind to it at specific locations and prevent it from infecting human cells. They “neutralize“ the virus. CCP therapy is very soundly based on decades of experience with other infections. It's generally considered quite safe, but all blood products carry some risk, including rare but fatal transfusion reactions and transfusion-transmitted infections. But CCP therapy can only work well when the patient receives enough antibodies to make a difference. The amount of antibodies in the blood of Covid-19 patients depends on the severity of the infection and when the measurement is made. The sickest patients have the most antibodies, even those who go on to die. People with mild symptoms who recover at home usually have only very low levels of these antibodies. The best donors are seriously ill hospital patients who recover, are discharged and then give their plasma within the next month or two. Plasma donations from people who recover from mild infections are all too often not useful.

CCP therapy is not a simple procedure. Considerable efforts are being made to obtain suitable plasma units and then use them. There's enough knowledge already around, including preliminary information from randomized clinical trials, and the hints in the 6) ____ Clinic manuscripts, to know that it's best “to hit early, hit hard“. But to use CCP therapy effectively, only the most antibody-rich plasma should be used. And it should be given early, within the first week after the patient enters hospital, preferably the first three days..

Transferring purified and concentrated antibodies produced by the immune systems of those who have recovered from 7) ____ to people who need them is being investigated as a non-vaccine method of passive immunization. This strategy was tried for SARS with inconclusive results. Viral neutralization is the anticipated mechanism of action by which passive antibody therapy can mediate defense against SARS-CoV-2. The spike protein of SARS-CoV-2 is the primary target for 8) _____ antibodies. Other mechanisms, however, such as antibody-dependent cellular cytotoxicity and/or phagocytosis, may be possible. Other forms of passive antibody therapy, for example, using manufactured monoclonal antibodies, are in development. Antiserum is human or nonhuman blood serum containing monoclonal or polyclonal antibodies that is used to spread passive immunity to many diseases via blood donation 9) (_____). For example, convalescent serum, passive antibody transfusion from a previous human survivor, used to be the only known effective treatment for 10) _____ infection with a high success rate of 7 out of 8 patients surviving.

Antisera are widely used in diagnostic virology laboratories. The most common use of antiserum in humans is as antitoxin or antivenom to treat envenomation.

Dr. Sanjay Gupta takes a deeper look at the data and explains why controlled randomized trials are still necessary to fully understand the effectiveness of convalescent plasma.

Sources: nih.gov; CNN.com (Sanjay Gupta); Wikipedia

ANSWERS: 1) immunoglobulin; 2) humoral; 3) helper; 4) emergency; 5) antibodies; 6) Mayo; 7) COVID-19; 8) neutralizing; 9) plasmaphoresis; 10) ebola

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