Pathology in rhythm and rhyme

Immunity to usual and unusual offenders

The Immune system’s structure and function unlike most organ systems in the body, is distributed (for surveillance) yet united in cross-talk within its components and receptivity to adverse stimuli. With a phenomenal capacity for explosive growth and diverse antigen recognition (commensurate with the severity of provocation) it closely resembles the haemopoietic system, with which it shares a dynamic co-location and co-performance. Whether innate or acquired, in latency, controlled response or in excess, Immunity’s cellular and extracellular mediator components are stimulated in response to infections or anything identified as the other as opposed to the self. This controlling and eliminating function is supported by a memory function for sustained resistance to repeat encounters. In pathological terms, the inappropriate or excessive overdrive of precisely the same mechanisms, unchecked if regulatory controls fail, allow diseases with an immune basis to emerge. In this post, Hypersensitivity, is in focus. The original Gell and Coombs classification system of 1963 (with modifications) groups these aberrant hyper-immune reactions based on the predominant immune mechanism into 4 classes. The result is a transformation of physiological protection to pathological tissue destruction – local/systemic, single/multiorgan, acute/chronic – with potential for relapse and recurrence.

Insights and Impact

• Hypersensitivity reactions are not uncommon in clinical practice. Accurate diagnosis ensures timely control and directs preventative advice for future episodes
• Triggers range from infection to non-infective foreign antigens (exogenous or endogenous) but the response has immunogenetic determinants making family history important
• Established antigenic stimuli lend themselves to available testing. If established, protective and preventive actions reduce recurrence
• Whatever the initial trigger: unregulated immune stimulation is the target for immunomodulatory therapy for most, and emergency, life-saving measures for few
• Rarely, immune activation has been used as an adjunct biotherapy in cancers e.g. the local instillation of BCG in bladder cancers

Rhythm ’n rhyme

Hypersensitivity Highways

Diverse in function, distributed in location, the immune system ensures,
We remain protected lifelong from microbes, foreign substances, dead cells and more;
Innate-immunity, readymade, responds rapidly to adverse stimuli
Acquired-immunity, complex, capable, bespoke: lasts longer, but slower to fly…

Physiological immune protection, unfortunately, is not always perfect,
If unusually strong or poorly regulated, may excessive damage effect;
Hypersensitivity reactions - alone or in combination - may then manifest
Immediate or delayed, local or systemic, they induce bodily unrest…

Type I reactions mediated by IgE, mast cells, leucocytes, cytokines and their kin,
Asthma, allergic rhinitis, atopy, surface; beware! Anaphylaxis may do your patient in; 
Previous history of such episodes, recent food, environment, drug exposures: do enquire,
Manage with urgency, you are playing here with fire…

In Type II reactions, normal or cross-reacting tissue antigens are attacked,
RBC’s, platelets, skin cell junctions, GBM, acetylcholine receptors are hacked;
Antibodies the weapons; proteases, complement, Fc-receptors, the conduit
Reckless their progress, organ functions they outwit…

For SLE, poststreptococcal glomerulonephritis, PAN: just to mention a few
Antigen-antibody circulating complexes in Type III reactions, are the toxic brew;
Targeted tissues are innocent, sitting ducks to this onslaught
With vasculitis, fibrinoid necrosis, reduced C3 levels, the diagnosis can be caught…

Type IV reactions - T-cell-mediated - are characterized by onset delay
Initial triggers: self-antigens - intact or damaged or microbes are in play;
CD4+/CD8+ T cells, Th 1, Th 17 cytokines: leucocytes recruit, phagocytes activate
Tuberculin reaction, Multiple Sclerosis, Type-1 Diabetes and such-like they fabricate…	

Deep Dive

A. Classification of Hypersensitivity Reactions

Acknowledgement – placed on Image

Q. Analyze why Type I, II and III reactions produce vessel-centric lesions. Why does this phenomenon favor involvement of certain organs more than others?

B. Anaphylaxis (a Type I Hypersensitivity reaction) – a medical emergency

Acknowledgement – placed on Image

DIY. Use this opportunity to review penicillin sensitivity and its testing prior to use of this useful antibiotic in patients.

Read on:

1.Aster, J. C.  (2025-05-09). Robbins, Cotran & Kumar Pathologic Basis of Disease, 11th Edition. [[VitalSource Bookshelf version]].  Retrieved from vbk://9780443283932

2. https://www.osmosis.org/learn/Hypersensitivity_Reactions

3. Redelman-Sidi G, Glickman MS, Bochner BH. The mechanism of action of BCG therapy for bladder cancer–a current perspective. Nat Rev Urol. 2014 Mar;11(3):153-62. doi: 10.1038/nrurol.2014.15. Epub 2014 Feb 4. PMID: 24492433.