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Innate and adaptive immunity

15 min

Skills you'll build4 skills
  • Tell innate from adaptive immune cells by their receptors and memory
  • Name where lymphocytes develop and where they first meet antigen
  • Match MHC class I and class II presentation to the CD8 or CD4 T cell they activate
  • Explain how a secondary antibody response differs from a primary response

Try first

Try first

Within hours of a first infection with a virus, a population of large granular lymphocytes kills infected cells. These cells carry no rearranged antigen receptor. Which cells are they, and which branch of immunity do they belong to?

Keep going to see the reasoning.

Keep going to see the reasoning.

Right. Keep going to follow the reasoning.

Keep going to see the reasoning.

Keep going to see the reasoning.

Get the idea

Use the explanation to check your first decision.

Two branches of the immune system

Innate immunity responds within minutes to hours. Its parts are epithelial barriers, phagocytes, natural killer (NK) cells, complement and cytokines. Its receptors are encoded in the germline and recognize patterns shared by many microbes or by injured tissue.1,2

B and T lymphocytes carry out adaptive immunity. Each clone assembles its own receptor by gene rearrangement, so it recognizes a narrow set of epitopes. Antigen selects the matching clones, which expand into effector cells and memory cells.1,2

NK cells come from lymphoid progenitors and look like large granular lymphocytes. They use germline-encoded activating and inhibitory receptors and keep no clonal memory, so they belong to the innate branch.1

Where lymphocytes develop

Primary lymphoid organs build lymphocytes without antigen. B cells develop in the bone marrow. T cells develop and are selected in the thymus. Mature lymphocytes first meet antigen in the secondary lymphoid organs: the lymph nodes, spleen and mucosa-associated lymphoid tissue.1,3

MHC class I and class II presentation

T cells see peptide displayed on major histocompatibility complex (MHC) molecules. B cells see intact antigen through surface immunoglobulin.1,4

  • MHC class I shows peptides from proteins made inside the cell, such as viral proteins, to CD8 T cells, which become cytotoxic cells.
  • MHC class II shows peptides from material captured outside the cell to CD4 T cells, which direct B cells and macrophages as helper cells.
  • In cross-presentation, a dendritic cell places captured antigen on class I. The responding cell is a CD8 T cell.1

The secondary response

Memory cells change the antibody pattern on a second exposure to the same antigen.4,5

FeaturePrimary responseSecondary response
Cells at the startRare naïve clonesMemory B and T cells
Antibody patternIgM often appears before class-switched antibodyClass-switched antibody, commonly IgG, rises sooner and higher
Average affinityLowerHigher, after affinity maturation

Many memory B cells have already switched class. The IgM of a secondary response can be small or absent, so a negative IgM does not rule out a recent reexposure.1

Follow the bench demonstration

Sources for this step
References
  1. Abbas AK, Lichtman AH, Pillai S, Henrickson S. Cellular and Molecular Immunology. 11th ed. Elsevier; 2025.
  2. National Institute of Allergy and Infectious Diseases. Overview of the immune system. National Institutes of Health. Reviewed December 30, 2013. Accessed September 27, 2026. https://www.niaid.nih.gov/research/immune-system-overview
  3. Janeway CA Jr, Travers P, Walport M, Shlomchik MJ. The components of the immune system. In: Immunobiology: The Immune System in Health and Disease. 5th ed. Garland Science; 2001. Accessed September 27, 2026. https://www.ncbi.nlm.nih.gov/books/NBK27092/
  4. Cano RLE, Lopera HDE. Introduction to T and B lymphocytes. In: Anaya JM, Shoenfeld Y, Rojas-Villarraga A, et al, eds. Autoimmunity: From Bench to Bedside. El Rosario University Press; 2013. Accessed September 27, 2026. https://www.ncbi.nlm.nih.gov/books/NBK459471/
  5. Schroeder HW Jr, Cavacini L. Structure and function of immunoglobulins. J Allergy Clin Immunol. 2010;125(2 suppl 2):S41-S52. doi:10.1016/j.jaci.2009.09.046

Watch one

Read each decision and its explanation.

A nurse who received two doses of measles vaccine in childhood was exposed to measles at work. Paired sera, drawn on the day of exposure and 10 days later, were tested together in one run by the same method.

What kind of antibody response do these results show?

TestResultPreviousReference intervalFlag
Measles IgMNegativeDay 0: NegativeNegativeDay 0NegativeNegative
Measles IgG, indirect immunofluorescence1:512 titerDay 0: 1:32 titer1:32 titerDay 0

Specimen: H 3, L 5, I 1. Paired serum, day 0 and day 10, tested in one run

  1. Confirm the pairing: both specimens were tested in the same run by the same method.

    Titers can be compared only when one method and one set of reading rules produced them.

  2. Read the IgM: negative on both days.

    IgM often appears first in a primary response. Its absence 10 days after exposure suggests a memory response.

  3. Size the IgG change: 512 ÷ 32 = 16, a 16-fold rise.

    Class-switched memory B cells make IgG quickly and in large amounts.

  4. Check the timing: the rise came within 10 days of the exposure.

    Memory cells are already present, so a secondary response starts sooner than a primary one.

  5. Check the history: two vaccine doses in childhood.

    Memory needs an earlier exposure to the same antigen, by infection or by vaccination.

The results show a secondary response. The IgG titer rose 16-fold, from 1:32 to 1:512, within 10 days, with no IgM. In a vaccinated person, the negative IgM does not rule out a recent exposure.

Practice this skill

Your turn

Problem 1 of 3 · Hints available

Which lymphocyte usually recognizes peptide presented on MHC class II?

Correct. MHC class II displays material captured from outside the presenting cell to CD4 T cells, which then provide help to macrophages, B cells, and other leukocytes.

Incorrect. CD8 T cells respond to peptide on MHC class I, usually from proteins made within the cell.

Incorrect. B cells recognize intact antigen through surface immunoglobulin. The T-cell receptor of CD4 T cells recognizes peptide on MHC class II.

Hint
  1. Each MHC class has one usual T-cell partner, marked by its coreceptor.
  2. Class II shows material the presenting cell captured from outside. Ask which coreceptor binds class II.

Review Antigen presentation and lymphocyte activation

Problem 2 of 3 · Hints available

Where do T cells develop and undergo selection before they leave as mature naïve T cells?

T-cell progenitors start in the bone marrow and then travel on. Their receptor rearranges, and selection takes place, in another primary organ.

A lymph node is a secondary lymphoid organ. Mature T cells meet antigen there after they have developed elsewhere.

Placed initial T-cell development in a lymph node

T cells develop and undergo selection in the thymus, a primary lymphoid organ, and later meet antigen as mature cells in lymph nodes and spleen. Placing T-cell development in a lymph node confuses primary with secondary lymphoid organs and leads to misreading a low TREC count, which measures thymic output.

The thymus is the primary lymphoid organ for T cells. Thymocytes rearrange their receptor there, and self-reactive cells are selected out before mature naïve T cells leave.

The spleen is a secondary lymphoid organ. It screens blood-borne antigen for lymphocytes that are already mature.

Hint
  1. Sort the organs into those that build lymphocytes and those where lymphocytes meet antigen.
  2. Recall where each kind of lymphocyte finishes its development.

Review Lymphoid organs and lymphocyte development

Problem 3 of 3 · On your own

A laboratory employee completed a tetanus toxoid series in childhood and receives a booster dose today. Which antibody pattern fits the weeks after the booster?

Memory B cells from the childhood series have already switched class and matured in affinity. They respond to the booster quickly with IgG.

That is the shape of a primary response. After the series, memory B cells respond mainly with class-switched IgG, and the IgM can be small or absent.

Expected IgM to lead the secondary response

Many memory B cells from the primary response have already class switched, so a secondary response raises class-switched antibody, commonly IgG, sooner, to a higher concentration, and with greater average affinity. The IgM response can be small or absent, so a missing IgM does not rule out a recent reexposure.

The antigen is the same. This time memory B and T cells from the series respond, so the response comes sooner and higher.

Memory B cells become plasma cells on reexposure and raise the antibody concentration quickly.

Review B-cell activation and antibody responses

Use it

Read the case evidence, then make each decision. The step is complete without it.

  • A lymphocyte subset panel by flow cytometry comes in for Theo Miller, 3 weeks old, MRN 4417023.
  • The requisition notes that imaging showed no thymic shadow.
  • The panel's controls and gating passed review, and the results are compared with the procedure's age-matched reference intervals.
TestResultReference intervalFlag
CD3 T cells40 cells/µL Low2,500–5,500 cells/µL2,500–5,500Low
CD19 B cells1,100 cells/µL300–2,000 cells/µL300–2,000
CD3-negative CD16/56 NK cells450 cells/µL170–1,100 cells/µL170–1,100

Specimen: H 2, L 4, I 1. EDTA whole blood, drawn 09:40

Decision 1 of 3

Which organ's missing output fits a CD3 count this low beside B and NK counts within their intervals?

The thymus builds T cells. B cells and NK cells come from the bone marrow and are present in normal numbers, so the defect is in the organ where only T cells develop.

The bone marrow also makes the B cells and NK cells on this panel, and both counts are within their intervals.

Lymph nodes are where mature T cells meet antigen. T cells are built and selected in the thymus before they reach a lymph node.

Placed initial T-cell development in a lymph node

T cells develop and undergo selection in the thymus, a primary lymphoid organ, and later meet antigen as mature cells in lymph nodes and spleen. Placing T-cell development in a lymph node confuses primary with secondary lymphoid organs and leads to misreading a low TREC count, which measures thymic output.

Review Lymphoid organs and lymphocyte development

Decision 2 of 3

Which population on this panel belongs to the innate branch?

NK cells look like lymphocytes and come from lymphoid progenitors. Their germline-encoded receptors and lack of clonal memory make them innate cells.

Placed NK cells in the adaptive branch

NK cells arise from lymphoid progenitors, and most appear on a blood film as large granular lymphocytes. They recognize stressed or infected cells through germline-encoded activating and inhibitory receptors and lack the rearranged antigen receptors and clonal memory that define adaptive B and T cells. Counting them as adaptive misplaces a rapid innate response.

B cells carry rearranged immunoglobulin receptors and form clonal memory, the marks of the adaptive branch.

T cells carry rearranged T-cell receptors and form clonal memory, the marks of the adaptive branch.

NK cells are CD3-negative with CD56 or CD16. They recognize stressed or infected cells through germline-encoded receptors and belong to the innate branch.

Review Innate and adaptive immunity

Decision 3 of 3

Antibody responses to protein vaccines need help from CD4 T cells. On which molecule does a B cell show a vaccine peptide to that helper cell?

Class I usually presents to CD8 T cells. A B cell shows internalized protein antigen to its CD4 helper on class II.

Reversed the class I and class II T-cell partners

Class I usually presents to CD8 T cells and class II to CD4 T cells. Cross-presentation places captured extracellular antigen on class I, so the responding cell is still a CD8 T cell. Swapping the partners assigns the wrong subset, helper or cytotoxic, to each presentation route.

Surface IgM binds the intact antigen and brings it into the B cell. The peptides that come from it go back to the surface on MHC class II.

The B cell takes in the protein through its receptor and presents a peptide on class II. A CD4 helper T cell that recognizes it responds with signals that drive the antibody response.

Review Antigen presentation and lymphocyte activation

Only the CD3 count is low:

  • CD3 T cells at 40 cells/µL, far below 2,500 cells/µL
  • CD19 B cells and NK cells within their intervals

B and NK cells from the bone marrow are present, so the missing output is from the thymus. With so few T cells, antibody responses to protein vaccines also lack CD4 help.

For reference

Sources checked