Human Immunity — and why it fails in ESRD
There are 2 main systems of immunity in humans, and each breaks down further. Here's the full picture.
1. Innate Immunity
Born with it. Fast, non‑specific, no memory. First line of defense. Responds in minutes to hours.
Key components
- Physical barriers: Skin, mucous membranes, stomach acid, tears, cilia in lungs
- Chemical barriers: Lysozyme in saliva/tears, defensins, complement proteins, interferons
- Cells:
- Neutrophils: First responders, eat bacteria, 60‑70% of WBCs
- Macrophages: “Big eaters” in tissues, clean up debris + pathogens
- Natural Killer (NK) cells: Kill virus‑infected cells and tumor cells
- Dendritic cells: Bridge to adaptive immunity — present antigens to T‑cells
- Eosinophils, basophils, mast cells: Parasites + allergic responses
- Inflammation & fever: Increases blood flow, recruits cells, slows bacterial growth
Main point: Same response every time. No memory. If it worked yesterday against E. coli, it fights Staph the same way today.
2. Adaptive Immunity
Learned. Slow at first — days — but specific and has memory. The reason vaccines work.
Two arms
|
Humoral Immunity = B‑cells → Antibodies |
Cell‑Mediated Immunity = T‑cells |
| Main cells |
B‑lymphocytes → Plasma cells |
T‑lymphocytes: CD4+ Helper T, CD8+ Cytotoxic T |
| Weapons |
Antibodies: IgG, IgA, IgM, IgE, IgD |
Kill infected cells directly, activate other cells |
| Targets |
Bacteria, toxins, viruses outside cells |
Virus‑infected cells, tumor cells, fungi, intracellular bacteria like TB |
| Memory |
Memory B‑cells → faster antibody response next time |
Memory T‑cells → faster killing next exposure |
| Location |
Blood, lymph, mucosa |
Tissues, lymph nodes |
Adaptive immunity can be acquired 2 ways:
| Active Immunity | Passive Immunity |
|---|
| Natural |
Get sick with measles → you make antibodies + memory cells. Long‑lasting |
Baby gets IgG antibodies from mom through placenta + IgA in breast milk. Lasts months |
| Artificial |
Vaccination: Give killed/weakened pathogen → you make your own antibodies. Long‑lasting |
Injection of antibodies: Rabies immunoglobulin, antivenom, monoclonal antibodies. Immediate but short — weeks |
Why this matters for dialysis patients
ESRD patients have immune dysfunction across both systems:
🛡️ Innate dysfunction
- Neutrophils don’t phagocytose well
- Complement is dysregulated
- Barrier function from skin/edema is poor
- That’s why access infections are deadly
🧬 Adaptive dysfunction
- Uremic toxins (p‑cresyl sulfate + indoxyl sulfate) suppress T‑cell and B‑cell function
- Poor vaccine response to Hep B, flu, COVID
- Memory cells don’t form well
🔥 Chronic inflammation
- High IL‑6, TNF‑α from LPS fragments in dialysate → paradoxically you get both immunosuppression + chronic inflammation
- That drives CV disease and ESA resistance
— based on immunology and ESRD pathophysiology —