10.1 Immune Response, B and T Cells, Macrophages

10.1 Immune Response, B and T Cells, Macrophages

Quick Answer: The innate system is immediate and nonspecific — barriers, neutrophils, macrophages, complement, NK cells — and has no immunologic memory. The adaptive system is antigen-specific and remembers. B cells become plasma cells that secrete antibody or memory B cells. CD4 T-helper cells see peptide on MHC class II and license class switch; CD8 T-cytotoxic cells see peptide on MHC class I and kill. The primary humoral response lags 5–10 days, starts as IgM, then IgG. The secondary (anamnestic) response is faster, IgG-dominant, and higher titer — that is delayed hemolytic transfusion reaction, classically Kidd.

The June 9, 2026 BB outline parks immune response at III.A.1. This is not a general immunology lecture. Every cell on this page exists so you can explain why the first Kidd-positive unit may look silent and the second one hemolyzes three days later.

Innate versus adaptive

Innate immunity is already armed. Skin, mucosa, complement, neutrophils, macrophages, and NK cells respond in minutes to hours. Recognition uses pattern receptors (TLR, CR1, CR3), not a unique receptor for Kidd or D. There is no clone expansion and no memory. Complement punching holes in an ABO-incompatible unit is an innate effector cascade. The trigger is preformed antibody; the lysis itself is the membrane-attack complex, not a new adaptive response.

Adaptive immunity needs a first look. Lymphocytes with clonotypic receptors (BCR or TCR) expand, differentiate, and leave memory. Two arms matter on BB:

• Humoral: B cells and secreted antibody. This is almost the entire immunohematology exam.
• Cellular: T cells. Graft rejection, control of CMV in a transfusion recipient, and transfusion-associated graft-versus-host disease (TA-GVHD) if a cellular unit is not irradiated for an at-risk patient.

Innate cells are not spectators. Macrophages and dendritic cells are antigen-presenting cells (APCs). They digest antigen, load peptide onto MHC, and present it to naive T cells. Without that presentation, T-dependent protein antigens — Rh, Kell, Kidd, Duffy — never class-switch to the IgG you detect at AHG.

B cells become plasma cells or memory

B cells leave the marrow expressing CD19, CD20, and surface immunoglobulin as their antigen receptor. Antigen encounter, usually with CD4 help, produces two products:

1. Plasma cells — antibody factories. They down-regulate surface Ig and secrete immunoglobulin. Serum titer is a plasma-cell readout, not a memory-cell readout.
2. Memory B cells — long-lived sentinels. They persist after plasma-cell antibody has fallen below the antibody screen. That single fact is the delayed-HTR setup.

Antigen chemistry decides the pathway:

That table is why a never-transfused group O adult already has anti-A and anti-B (environmental bacterial sugars cross-react with A and B), while anti-K and anti-Jka require transfusion or pregnancy. Do not label ABO isoagglutinins “immune antibodies” in the Rh sense. They are naturally occurring.

B cells also present antigen. Internalized protein is processed onto MHC II and shown to CD4 cells, which return cytokines that drive class switch and affinity maturation. A carbohydrate that never enters that loop stays IgM.

T-helper, T-cytotoxic, MHC restriction

T cells do not agglutinate red cells in a tube. They bind processed peptide sitting in an MHC groove. That pairing is MHC restriction.

• CD4 T-helper cells recognize peptide on MHC class II — HLA-DR, DQ, and DP — displayed by professional APCs (dendritic cells, macrophages, B cells). Th2-leaning help (IL-4, IL-5, IL-6, IL-21) drives class switch and plasma-cell differentiation. Th1-leaning help (IFN-γ, IL-2) activates macrophages. The BB headline: no CD4 help, no durable IgG to a protein blood-group antigen.
• CD8 T-cytotoxic cells recognize peptide on MHC class I — HLA-A, B, and C. Class I sits on every nucleated cell and on platelets; mature red cells carry very little. CD8 cells kill virus-infected targets and are the cellular half of solid-organ and HPC graft rejection and of TA-GVHD.

Do not swap the pairs. CD4–MHC II–APC. CD8–MHC I–any nucleated cell. An item that says “which cell kills a CMV-infected leukocyte” wants CD8, not a plasma cell.

Macrophages wear three transfusion hats

1. Phagocyte. Fcγ receptors and complement receptors (CR1, CR3) clear IgG- or C3b-coated red cells. That is extravascular hemolysis: spleen prefers Fc/IgG-coated cells; liver Kupffer cells are efficient at C3b-coated cells.
2. APC. After phagocytosis of a mismatched unit, the macrophage presents peptide on MHC II to CD4 cells and starts the adaptive response.
3. Cytokine factory. IL-1, IL-6, and TNF-α produce fever, hypotension, and the inflammatory picture of acute hemolysis once Fc and complement are ligated.

NK cells (CD16, CD56) perform antibody-dependent cellular cytotoxicity. They are not the answer to “which cell secretes anti-D.”

Primary versus secondary (anamnestic)

Memorize the clocks.

Primary response — first exposure to a foreign protein antigen:

• Lag of 5–10 days while naive clones expand and some class-switch.
• IgM appears first, then IgG.
• Peak titer is modest.
• After antigen disappears, plasma-cell output falls. Antibody may become serologically undetectable.
• A first-time transfusion of Jk(a+) red cells to a Jk(a−) recipient is often clinically silent. The units have left the circulation before IgG arrives.

Secondary / anamnestic response — re-exposure when memory B (and memory T) cells already exist:

• Lag shrinks to hours to a few days.
• The burst is IgG, higher titer, higher affinity.
• That is delayed HTR: usually 3–14 days after transfusion (published range about 24 hours to 28 days), falling hemoglobin, spherocytes, a newly positive DAT, and an antibody that was absent on the pretransfusion screen.

Kidd is the textbook evanescent antibody — titer vanishes, dosage hides a heterozygous cell, complement is fixed, and the anamnestic wave hemolyzes. Rh, Duffy, and Kell use the same memory logic; Kidd is the name most stems want.

Memory is cellular. A negative screen means circulating antibody is below the method cutoff. It does not mean the patient was never immunized.

Mapping this to transfusion practice

• The type and screen is a snapshot of plasma antibody, not a memory assay.
• History of transfusion or pregnancy is the clinical proxy for possible memory.
• First exposure may be silent; second exposure hemolyzes. Write that on every Kidd, Duffy, and E item.
• ABO is the exception. Anti-A and anti-B are already present, so the first incompatible unit can destroy red cells with no lag.
• HDFN is maternal secondary-response IgG crossing the placenta (Chapter 12).
• Passenger-lymphocyte hemolysis after solid-organ transplant is donor B cells making antibody in the recipient — the same plasma-cell biology, different zip code.
• TA-GVHD is donor T cells attacking a recipient who cannot reject them. Irradiation or an approved pathogen-reduced cellular unit prevents it.

Exam traps

• Calling the primary response “IgG first.” IgM is first.
• Treating a negative antibody screen as proof of no prior exposure. Memory outlives titer.
• Labeling delayed HTR a primary response. It is anamnestic.
• Requiring prior transfusion before anti-A can exist. ABO antibodies are naturally occurring.
• Assigning antibody secretion to T cells or macrophages. Plasma cells secrete antibody.
• Swapping MHC I/CD8 with MHC II/CD4.
• Calling Kidd a cold IgM. Anti-Jka and anti-Jkb are warm IgG that often bind complement.