White cells and immunity
White cells, immunity, antibodies, hypersensitivity and allergy
What each white cell does, innate and adaptive immunity, antibody classes and hypersensitivity types, for FCPS Part 1. Covers neutrophil killing, CGD, lymphocyte subsets, the spleen, vaccination and anaphylaxis.
One of the most tested topics in past papers
Normal differential and lifespan
| Cell | Count (×10⁹/L) | Share | Main job |
|---|---|---|---|
| Neutrophils | 2.0–7.5 | 40–70% | Kill bacteria; hours in blood |
| Lymphocytes | 1.0–4.0 | 20–40% | Specific immunity; memory cells live for years |
| Monocytes | 0.2–0.8 | 2–8% | Become tissue macrophages |
| Eosinophils | 0.04–0.4 | 1–4% | Helminths, allergy |
| Basophils | below 0.1 | below 1% | Histamine, IgE receptors |
- Of blood lymphocytes, about 70–80% are T cells, 10–15% B cells and 10–15% NK cells. Young children have more lymphocytes than neutrophils.
Neutrophils
- Made in marrow under G-CSF (and GM-CSF); a large marginated pool lines vessels and a marrow reserve is released quickly. Steroids, adrenaline and exercise cause neutrophilia by demargination.
- Getting to the site: margination, rolling (selectins), firm adhesion (integrins such as LFA-1 binding ICAM-1), transmigration (diapedesis, PECAM-1), then chemotaxis towards IL-8 (the main early neutrophil chemokine), C5a, leukotriene B4 and bacterial peptides.
- Phagocytosis is helped by opsonins (IgG through its Fc region, C3b).
- Killing: the respiratory burst uses oxygen: NADPH oxidase makes superoxide, which becomes hydrogen peroxide; myeloperoxidase converts H₂O₂ and chloride into hypochlorous acid. Granule enzymes add oxygen-independent killing.
- Chronic granulomatous disease: NADPH oxidase defect, so no superoxide. Infections are with catalase-positive organisms (*Staphylococcus aureus*, *Aspergillus*, *Serratia*, *Nocardia*, *Burkholderia*). Catalase-negative bacteria such as streptococci make their own H₂O₂, which accumulates in the phagosome and lets myeloperoxidase kill them. Aspergillus is a leading cause of death. Screen with the nitroblue tetrazolium or dihydrorhodamine test.
- Leukocyte adhesion deficiency: CD18 integrin defect; delayed cord separation, neutrophilia without pus.
- Neutropenia: drugs (carbimazole, clozapine, chemotherapy), viral infection, B12 or folate deficiency, marrow infiltration. Below 0.5 ×10⁹/L, sepsis risk is high.
Eosinophils, basophils and mast cells
- Eosinophils are made under IL-5 (from Th2 cells); IL-5 also activates them. They kill helminths with major basic protein and drive late-phase allergy.
- Eosinophilia: tissue-migrating helminths (hookworm, Ascaris, Strongyloides, filaria), allergy, drugs, Addison disease, eosinophilic granulomatosis with polyangiitis, Hodgkin lymphoma. Steroids cause eosinopenia.
- Basophils and mast cells carry high-affinity IgE receptors (FcεRI) and release histamine, heparin, tryptase, leukotrienes and prostaglandin D2. Basophilia suggests chronic myeloid leukaemia.
Monocytes, macrophages and dendritic cells
- Monocytes become tissue macrophages: Kupffer cells (liver), alveolar macrophages (the first-line phagocytic defence of the lungs; "dust cells"), microglia, osteoclasts, histiocytes. They phagocytose, present antigen on MHC class II, release IL-1, IL-6 and TNF-α, and form epithelioid and giant cells in granulomas.
- Dendritic cells (including Langerhans cells of the skin) are the most potent antigen-presenting cells and the only ones that can activate naive T cells; they carry antigen to the lymph node paracortex.
Lymphocytes
| Cell | Matures in | Marker | Role |
|---|---|---|---|
| B cells | Bone marrow | CD19, CD20, surface Ig | Become plasma cells that secrete antibody |
| Helper T cells | Thymus | CD4 | See antigen on MHC class II; Th1 (IFN-γ, macrophages), Th2 (IL-4, IL-5, IL-13, antibody and allergy) |
| Cytotoxic T cells | Thymus | CD8 | Kill infected and tumour cells showing antigen on MHC class I (perforin, granzymes, Fas) |
| Regulatory T cells | Thymus | CD4, CD25, FOXP3 | Suppress autoimmunity |
| NK cells | Bone marrow | CD16, CD56 | Kill cells lacking MHC class I without prior sensitisation |
- T cells mature in the thymic cortex (positive selection) and medulla (negative selection). Thymic epithelial hormones (thymosin, thymulin) promote T-cell maturation; they have no metabolic role.
- In lymph nodes, B cells sit in follicles and germinal centres; T cells in the paracortex.
- Leukaemia markers: precursor B-cell ALL in a 2–5-year-old is TdT positive and CD10 (CALLA) positive and has a good prognosis.
- X-linked (Bruton) agammaglobulinaemia: BTK defect; boys after 6 months with recurrent sinus and chest infections from encapsulated bacteria, absent B cells and plasma cells, normal T cells.
Antibodies
Each antibody has two Fab arms that bind antigen and an Fc region that gives its biological activity (complement fixation, binding to phagocytes and mast cells, placental transfer).
| Class | Key facts | |
|---|---|---|
| IgG | Most abundant; crosses the placenta; main opsonin; dominates the secondary response | |
| IgM | Pentamer; first antibody of a primary response; strongest complement activator; does not cross the placenta | |
| IgA | Secretions and breast milk (dimer with secretory component) | |
| IgE | Bound to mast cells and basophils; allergy and helminths | |
| IgD | On naive B cells | |
| Feature | Primary response | Secondary response |
| Lag | 5–10 days | 1–3 days |
| Peak titre | Low | Much higher, longer lasting |
| Main class | IgM | IgG, with higher affinity (affinity maturation) |
Types of immunity
| Type | Natural | Artificial |
|---|---|---|
| Active (own antibodies, memory, slow onset) | Recovery from infection | Vaccination |
| Passive (preformed antibody, immediate, short-lived) | Maternal IgG across the placenta, IgA in milk | Immunoglobulin or antitoxin (human tetanus immunoglobulin, anti-rabies) |
- A contaminated wound in someone of unknown tetanus status gets tetanus immunoglobulin (artificial passive) plus vaccine (artificial active).
The spleen
The red pulp filters old and damaged red cells; the white pulp mounts antibody responses to blood-borne antigens, especially polysaccharide capsules (marginal-zone B cells, IgM), and splenic macrophages clear opsonised bacteria. After splenectomy the main risk is overwhelming infection with encapsulated bacteria: *Streptococcus pneumoniae*, *Haemophilus influenzae* type b and *Neisseria meningitidis*. Vaccinate (conjugate vaccines link polysaccharide to protein to recruit T-cell help) and give prophylactic penicillin.
Hypersensitivity (Gell and Coombs)
| Type | Mechanism | Examples |
|---|---|---|
| I Immediate | IgE on mast cells, histamine | Anaphylaxis, asthma, food and nut allergy, hay fever |
| II Cytotoxic | IgG or IgM against cell or matrix antigens | Haemolytic disease of the newborn, transfusion reaction, Goodpasture, Graves, myasthenia |
| III Immune complex | Antigen–antibody complexes deposit, fix complement | SLE, post-streptococcal glomerulonephritis, serum sickness, vasculitis |
| IV Delayed | T cells, macrophages | Tuberculin test, contact dermatitis, granulomas, chronic graft rejection |
- Rejection within minutes of transplantation (hyperacute) is due to preformed antibodies.
- C3a and C5a are anaphylatoxins: they degranulate mast cells and increase vascular permeability; C5a is also chemotactic.
Anaphylaxis
Sensitisation produces IgE through Th2 help (IL-4). On re-exposure, allergen cross-links IgE on mast cells; histamine and tryptase are released within minutes, followed by leukotrienes and prostaglandins, and a late eosinophil phase. Features: urticaria, angioedema, bronchospasm and hypotension. IM adrenaline is first-line (α1 vasoconstriction, β2 bronchodilation, mast cell stabilisation). Serum tryptase confirms mast cell degranulation.
Remember Neutrophils for bacteria, eosinophils for worms, mast cells for allergy, CD4 sees class II, CD8 sees class I.
Exam trap Steroids raise neutrophils but lower eosinophils and lymphocytes.
How FCPS asks about this
- Oxygen burst in neutrophils: needed for microbicidal killing; absent in CGD (NADPH oxidase).
- Why CGD spares streptococci: catalase-negative bacteria supply their own H₂O₂.
- Cytokine for eosinophils: IL-5; early neutrophil chemokine: IL-8.
- Tetanus immunoglobulin: artificial passive immunity; vaccination is artificial active.
- Secondary response: faster, higher titre, mainly IgG.
- Most potent antigen-presenting cell: dendritic cell.
- After splenectomy: encapsulated bacteria (pneumococcus, Hib, meningococcus).
Test yourself on this topic
5 of the 30 questions in our bank on this topic. Choose an answer to see why every option is right or wrong.
Which antibody is secreted as a dimer joined by a J chain and protected by a secretory component in breast milk and the gut?
Answer: IgA
Secretory IgA is a dimer linked by a J chain. It is transported across epithelium by the polymeric Ig receptor, part of which remains as the secretory component and protects IgA from digestion. It is the main antibody of tears, saliva, respiratory and gut secretions, and colostrum, and it neutralises microbes at mucosal surfaces. It is the most produced antibody overall, though IgG is the most abundant in serum. Selective IgA deficiency is the commonest primary immunodeficiency and can cause anaphylaxis with blood products.
Secretory IgA
- Dimer + J chain + secretory component
- Tears, saliva, gut, colostrum
- IgA deficiency: commonest primary immunodeficiency
Remember IgA guards the gates (mucosa).
Why the other options are wrong
- IgG Monomer.
- IgM Pentamer with J chain, no secretory component.
- IgE Monomer bound to mast cells.
- IgD Monomer on B cells.
A 70-year-old man has lymphadenopathy and a white cell count of 80 × 10⁹/L with mature-looking small lymphocytes and many smudge cells. What is the diagnosis?
Answer: Chronic lymphocytic leukaemia
CLL, the commonest leukaemia in older adults in the West, is a clonal proliferation of mature-appearing B cells (CD5+, CD19+, CD23+). Many patients are asymptomatic; others have lymphadenopathy, splenomegaly, infections (hypogammaglobulinaemia) and autoimmune complications (warm AIHA, ITP). Fragile lymphocytes are crushed when the film is made, giving smudge (smear) cells. It may transform into an aggressive lymphoma (Richter transformation). Staging uses Rai or Binet systems; early disease is observed. Hairy cell leukaemia has cytoplasmic projections, pancytopenia and splenomegaly, and is TRAP positive.
CLL
- Elderly; mature B cells (CD5+, CD23+)
- Smudge cells on film
- Complications: infections, warm AIHA, ITP
- Richter transformation
- Early: watch and wait
Remember Old man, many small lymphocytes, smudge cells: CLL.
Why the other options are wrong
- Acute myeloid leukaemia Blasts, Auer rods.
- Chronic myeloid leukaemia Granulocytes at all stages, basophilia.
- Infectious mononucleosis Atypical reactive T cells in young people.
- Hairy cell leukaemia Hairy projections, pancytopenia.
Children with chronic granulomatous disease get recurrent infections with catalase-positive organisms. Why are they not unusually prone to catalase-negative organisms such as streptococci?
Answer: The bacteria supply their own H₂O₂
In chronic granulomatous disease, NADPH oxidase is absent, so neutrophils cannot make superoxide and H₂O₂ (respiratory burst). Catalase-negative bacteria release H₂O₂ into the phagosome, which the neutrophil's myeloperoxidase can use to make bleach (HOCl). Catalase-positive organisms (Staphylococcus aureus, Serratia, Burkholderia, Nocardia, Aspergillus) break down their own H₂O₂, so they survive. Diagnosis: dihydrorhodamine or NBT test.
CGD and catalase
- No NADPH oxidase: no respiratory burst
- Catalase-negative bugs donate H₂O₂
- Catalase-positive: S. aureus, Serratia, Aspergillus
- Test: DHR flow cytometry
Remember Bugs without catalase hand over their own weapon.
Exam trap Aspergillus is a leading cause of death in CGD.
Why the other options are wrong
- Antibodies alone kill streptococci Antibodies alone do not explain it.
- Streptococci cannot enter neutrophils They are ingested normally.
- Myeloperoxidase is increased in CGD Myeloperoxidase is normal, not increased.
- Complement kills them without phagocytes Not the explanation.
A man with advanced cirrhosis has low albumin, low clotting factors and low transferrin. His total globulin, however, is raised. Which plasma protein is not made by the liver?
Answer: Immunoglobulin G
The liver makes most plasma proteins, including albumin, clotting factors, fibrinogen, transferrin and many complement factors. Immunoglobulins are made by plasma cells. In cirrhosis, gut antigens bypass Kupffer cell clearance through portosystemic shunts and stimulate antibody production, so immunoglobulins often rise while liver-made proteins fall. A reversed albumin:globulin ratio is therefore common.
Liver proteins
- Liver makes albumin, clotting factors
- Also transferrin, fibrinogen
- Immunoglobulins: plasma cells
- Cirrhosis: globulin rises
Remember Low albumin plus high globulin: think cirrhosis.
Exam trap A high total protein in cirrhosis does not mean good liver synthesis.
Why the other options are wrong
- Albumin Made by the liver.
- Fibrinogen Made by the liver.
- Transferrin Made by the liver.
- Prothrombin Made by the liver.
A 45-year-old woman with fatigue, weight loss and postural hypotension has sodium 128 mmol/L, potassium 5.6 mmol/L and an eosinophil count of 0.9 × 10⁹/L. Which hormone deficiency best explains her raised eosinophils?
Answer: Cortisol deficiency
Glucocorticoids lower the blood eosinophil and lymphocyte counts by moving these cells into tissues and promoting their apoptosis, which is why steroid treatment causes eosinopenia and lymphopenia. Loss of cortisol in Addison disease does the reverse, giving a mild eosinophilia and lymphocytosis. A normal or high eosinophil count in a very ill, stressed patient, who would normally have eosinopenia, should raise suspicion of adrenal insufficiency. Her hyperkalaemia reflects the accompanying aldosterone deficiency.
Cortisol and blood counts
- Steroids: eosinopenia, lymphopenia
- Addison: eosinophilia
- Ill patient with high eosinophils: check cortisol
- Low aldosterone: high K⁺
Remember Stress should clear eosinophils; if it does not, think adrenal.
Exam trap Eosinophilia is not always allergy or worms; in a hypotensive patient, consider adrenal failure.
Why the other options are wrong
- Aldosterone deficiency Explains the potassium, not the eosinophils.
- Adrenaline deficiency Adrenal medulla loss has little clinical effect.
- Thyroxine deficiency Not linked to eosinophilia.
- Growth hormone deficiency Not linked to eosinophilia.
Where this sits in the CPSP syllabus
- Paper 1: Blood and immunity, White cells, immunity and allergy
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