B-cell response at re-infection

by Mohammad Hajighasemi-Ossareh, MD

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    00:02 An organism that is infected with an extracellular pathogen produces an increased amount of varying antibodies via T-helper cell-activated B cells in the germinal center of lymphoid tissues.

    00:16 If the same organism is later reinfected with the same pathogen, the macroorganism will respond with a much stronger response, producing antibodies specific to that antigen in a shorter amount of time.

    00:31 What is the term for this process, that allows B-cells to produce antibodies specific to that antigen? Answer choice (A) - Affinity maturation Answer choice (B) - Avidity Answer choice (C) - T-cell positive selection Answer choice (D) - Somatic hypermutation and answer choice (E) - T-cell negative selection Now take a moment to go through the answers by yourself before we come to a conclusion together.

    01:08 Okay let’s discuss the question.

    01:10 The first thing we need to do is determine the subject of this question.

    01:13 And in this case, we are dealing with an immunology question.

    01:17 We have infections of a cell, we have T-helper cells, we have B-cells, we have lumphoid tissues, we're talking about antibodies.

    01:24 This is classically immunology.

    01:26 Now this is a 2-step question.

    01:28 We first need to be able to identify the process that’s allowing the B-cells to produce specific antibodies and then we have to know the name of this process.

    01:37 And the stem is absolutely required in this case because it's going to the detailed process that we need to be able to interpret to properly answer the question.

    01:46 So let’s walk through this question together.

    01:48 Well for step 1, we need to determine what immunological step is being described in the process in the question stem.

    01:56 Now the vignette is referring to a stronger immunological response in the case of a reinfection.

    02:03 Now antibodies produced by B-cells are more specific at reinfection than when you had it at first exposure.

    02:11 Now the process is describing the increase of antibody specificity after first antigen exposure.

    02:18 So we have to be able to identify that first.

    02:20 Second, we have to know what that process is called.

    02:24 Now the increase of antibody specificity actually occurs at various stages during B-cell maturation.

    02:32 And that’s very elegantly depicted in our image.

    02:36 Now if you look at our image, it’s showing the maturation of B-cells in a germinal center.

    02:41 So if you look at where it says dark zone B-cell, what you see they’re after is what’s called clonal expansion.

    02:50 Really this is monoclonal expansion of the B-cell and then what happens is the B-cells undergo somatic hypermutation.

    02:58 Now this triggers gene recombination and the mutations that occur in this process actually increase the affinity for the given antigen.

    03:09 And you see that here in the image.

    03:11 You have the dark zone B-cells, it then undergoes monoclonal expansion then we have somatic hypermutation.

    03:18 And as the mutations are occuring in the somatic hypermutation, what we’re actually doing is increasing antigen affinity during this process.

    03:27 Now recall that the term affinity is antibody-antigen binding strength, so we’re actually increasing this.

    03:36 Now when we are undergoing somatic hypermutation, we’re actually creating multiple clones of B-cells and the next step is actually the selection of the highest affinity ones, Now you actually have apoptosis of the lower affinity ones which you also see on the image.

    03:53 Now somatic hypermutation and selection, when these two things are combined is a process known as affinity maturation, which is actually the answer to this question - answer choice (A).

    04:06 Now selected B-cells progress either to become plasma cells for antibody production or memory B-cells to further accelerate immune reaction at the time of reinfection.

    04:21 So the image here we see is extremely high-yield.

    04:24 We’re seeing B-cells undergoing monoclonal expansion, then we’re seeing somatic hypermutation, and then that process we’re actually increasing our antigen affinity.

    04:34 And then as they go on to become plasma cells or memory B-cells, we have an ability to produce specific antigen and also have memory B-cells available for reinfection later.

    04:44 So now let’s discuss some high-yield facts regarding this question.

    04:48 The first thing we need to discuss is the answer choice in this case, which is affinity maturation.

    04:54 Now production of antibodies with highest single-site binding strength to certain antigens occurs with affinity maturation.

    05:02 Now where this occurs is actually in the germinal center of lymph nodes.

    05:06 Which is what we've discussed earlier as being what we are seeing in our image which is the maturation of B-cells occuring in the germinal center of lymph nodes.

    05:15 If you actually look at what the word 'affinity maturation' means, it comprises of both somatic hypermutation and the selection of the highest affinity antibodies which is what the process is described in the question stem.

    05:29 Now let’s discuss a little bit more about somatic hypermutation.

    05:33 Genetic recombinations and mutations that create a wide variety of antibodies when the organism first encounters a foreign antigen is what occurs in somatic hypermutation.

    05:44 Now this actually provides a range of B-cells and antibodies for selection which is a great process.

    05:50 We get a lot of antibodies to pick from from our B-cells in this somatic hypermutation process.

    05:56 And this overall process is called affinity maturation.

    06:00 Now there is a term also discussed here in the answer choices which is called avidity.

    06:06 Now this refers to the overall binding strength across multiple affinities or binding sites.

    06:12 Now generally, we use this term when describing antibody-antigen interactions across mutiple binding sites.

    06:20 For example, IgM has low affinity but high avidity due to its 10-low affinity binding sites.

    About the Lecture

    The lecture B-cell response at re-infection by Mohammad Hajighasemi-Ossareh, MD is from the course Qbank Walkthrough USMLE Step 1 Tutorials.

    Author of lecture B-cell response at re-infection

     Mohammad Hajighasemi-Ossareh, MD

    Mohammad Hajighasemi-Ossareh, MD

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    By Hazazi M. on 30. September 2018 for B-cell response at re-infection

    this made my concept of germinal centre very strong! Thank you Mohammad