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USMLE Step 1: Immunology
  • 27 Sep 2021

In his latest blog, Elliott Campbell MD, Dermatology Resident at Mayo Clinic, Pastest question writer and high-scoring candidate, discusses the resources, the utilization of resources and must review concepts in relation to the Immunology section of the USMLE Step 1 exam.

Immunology is fundamental to medicine and eminently testable on all three of the Steps, especially Step 1. In many sections of the Steps, it is advisable to first master the clinically relevant details which make up the bulk of questions. In other words, if there isn’t a disease associated with content of another section, it is less important. The Immunology section breaks this rule. It is still important to give special attention to clinically relevant factoids; however, all the details are fair game. This is because these details are essential to the research that drives understanding of the pathophysiology of conditions which ultimately results in new pharmacotherapies. This article includes the resources recommended and how to best use them to master this section on test day. At the end, some absolute need to know concepts are provided. 

Resources for the Immunology section

The Immunology chapter in the front of First Aid is a helpful resource. This section requires a global understanding of how all these immunologic systems interrelate. USMLE Step 1 question banks are critical to global understanding of these factoids and apply this content to clinical scenarios. This is one of the few sections that I may consider referencing back to medical school course material to dive deeper into the details.

Approach to learning this content

The advice on how to approach this section significantly differs from the recommendations that I give for most other “First Aid front of the book” sections. When you initiate your Step studying plan, I would dive first into the First Aid chapter and additional content you plan to review for this section (medical school course material). Spend a solid day learning the fundamentals of the immune system.

Start with understanding the organs involved, then slowly work towards the physiology. For instance, understand the lymphatic system and relevant anatomy of lymph nodes. Master the histology of the lymph nodes and understand the major players and where they are located (high yield histology). Understand how this differs from the spleen/thymus and their different functions. Then you can start to understand how the innate and adaptive immune system plays out in these systems. From there, you get to the cytokine/HLA subtype/receptor brute memorization.

After you achieve a deeper understanding of these systems, it is time to jump into the question banks. If you have read my other articles, you will see that this contradicts my advice on other sections. For example, in Biochemistry, it is critical to hit the question banks first and then dive into the books. The reason why I recommend this for Immunology is that each question should be thought of in the context of the overall immune system. If you get a question about Ustekinumab and learn that it binds to the p-40 subunit of both IL-12 and IL-23, that is an important factoid. If you can’t place the fact into the overall context of the immune system (Th17 cells in psoriasis rely on IL-23 for stimulation which ultimately results in epidermal proliferation), it is more difficult to memorize and apply later. Question writers are trying to move away from simple factoids and require understanding of global systems when answering pathophysiological questions.

I still recommend the annotation approach for this section (see below); however, unlike other sections, you will have read the First Aid pages before starting this process.

The “annotation approach”

This is what I used for my Step 1 (for all sections) and has been used by many of my colleagues and mentees with great success. See the linked article for a general approach to the Step 1 curriculum. In this approach, questions are completed in tutor mode, untimed, and within categories (not on random mode). After each question, content is reviewed in First Aid. If content is missing in First Aid that was included in the question’s explanation, it should be quickly annotated into the book.

This is extremely helpful in this section as you can circle steps in pathways that repeatedly come up and/or are associated with well-known pathologic entities. I would recommend also having the online version handy to search for page numbers. Any memory devices should also be noted (“How do I remember this?”, or “Why does this make sense?”). If performing a second pass, all of the annotations are complete, but content with annotations should be reviewed again with each question. This results in a very organized framework. You will start to remember where content is located and which annotations were present. Regardless of whether you perform one or two passes through your question bank, learners should read their annotated section in First Aid all the way through at least once.

High Yield concepts

These are some of the most testable concepts; however, this only highlights some of the well-known, high yield content in this section. If you are not very familiar with the below concepts, it would be advisable to master them before test day.

  • Above all, you need to memorize the specific mechanism of actions of the biologic drugs and immune related pharmacotherapies. These are some of the easiest questions to write and have dominated the pharmaceutical industry, revolutionizing modern medicine. You will get multiple questions with specific mechanism of action questions. In some cases, you will have never heard of the drug. Therefore, a global understanding of the immune system is helpful and will allow you to narrow down answer choices (i.e., patient has psoriasis, mechanism of drug is IL-12/IL-23 inhibitor which makes sense in this disease).
  • The immunodeficiencies are also very easy questions to write. I can’t imagine a step without at least one of these present.
  • Know the different types of vaccines (killed vs live vs toxoid, etc.), when they are used, and when they are not used (live in immunocompromised).
  • Hypersensitivity reactions: specific pathophysiology but also associated diseases. They like to ask questions about diseases which have multiple types, depending on the specific manifestation (rheumatic fever).
  • Blood transfusion reactions.
  • Transplant rejection types.
  • Know the autoantibody – disease associations very well. There will be questions about this. Sometimes there are questions about the physiologic mechanism of targets and the sensitivity and specificity within conditions (ANA vs. dsDNA vs Smith in lupus).
  • Know the cytokines well, including which diseases and medication associations.
  • Be able to map out the differentiation of a T cell, in terms or location, timeline, cytokines required, and receptor profile.
  • Immunoglobulin isotypes, which ones cross the placenta/expressed in lactation, locations, pathogens they target.
  • Complement cascade, etiologies for deficiencies, and bacterial disease associations (Neisseria).
  • Know how a T-cell is activated and know the immunotherapies for neoplasms (PD-1 inhibitors) that are related.
  • HLA subtype and disease associations.
  • Know the specific subsets of T cells, their function, associated cytokines and disease associations (Th17 – psoriasis, Th1 – mycobacterial, Th2 – allergic response/helminth).

Hope you've enjoyed reading this blog and you're now immense at immunology!


Elliott Campbell - Pastest USMLE Writer

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  • 27 Sep 2021