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🛡️Immunobiology

Key Immunological Disorders

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Why This Matters

Understanding immunological disorders is essential because they reveal what happens when the immune system's carefully balanced mechanisms go wrong. You're being tested on the fundamental concepts of self-tolerance, hypersensitivity reactions, autoantibody production, and immune deficiency—and these disorders are the clinical manifestations of those breakdowns. Whether the immune system attacks its own tissues, overreacts to harmless substances, or fails to function at all, each disorder category demonstrates a specific immunological principle.

Don't just memorize disease names and symptoms. Know what mechanism is failing in each disorder, which immune components are involved (T cells, B cells, antibodies, complement), and how the disorders relate to each other conceptually. Exam questions frequently ask you to compare disorders that share underlying mechanisms or to identify which immune pathway is disrupted based on clinical presentation. Master the "why" behind each condition, and you'll be ready for anything the exam throws at you.


Autoimmune Disorders: Loss of Self-Tolerance

These conditions occur when the immune system fails to distinguish self from non-self, producing autoantibodies or autoreactive T cells that attack the body's own tissues. The breakdown of central or peripheral tolerance mechanisms allows immune cells that recognize self-antigens to escape deletion or suppression.

Systemic Lupus Erythematosus (SLE)

  • Multi-organ autoimmune attack—the immune system produces autoantibodies against nuclear components (anti-dsDNA, anti-Smith), causing widespread inflammation
  • Type III hypersensitivity drives much of the pathology through immune complex deposition in kidneys, joints, and blood vessels
  • Female predominance (9:1 ratio) suggests hormonal influences on immune regulation, making this a classic example of sex-linked autoimmunity

Rheumatoid Arthritis

  • Symmetrical joint destruction—autoantibodies (rheumatoid factor, anti-CCP) target synovial tissue, triggering chronic inflammation and cartilage erosion
  • Pannus formation occurs when inflamed synovium invades and destroys joint structures, demonstrating how chronic inflammation causes tissue damage
  • Systemic manifestations including cardiovascular disease show that autoimmune disorders rarely affect just one organ system

Type 1 Diabetes

  • Organ-specific autoimmunity—autoreactive T cells selectively destroy insulin-producing beta cells in pancreatic islets
  • Molecular mimicry may trigger disease when viral antigens resemble beta cell proteins, activating cross-reactive T cells
  • Lifelong insulin dependence results because the immune system completely eliminates the body's capacity to produce insulin

Compare: SLE vs. Type 1 Diabetes—both involve loss of self-tolerance, but SLE is systemic with multi-organ involvement while Type 1 Diabetes is organ-specific, targeting only pancreatic beta cells. If an FRQ asks about autoimmune mechanisms, use these as contrasting examples of broad versus targeted immune attacks.

Multiple Sclerosis

  • Demyelination disorder—autoreactive T cells attack myelin sheaths in the central nervous system, disrupting nerve signal transmission
  • Relapsing-remitting pattern in most patients reflects cycles of immune attack followed by partial repair, a hallmark of many autoimmune conditions
  • Blood-brain barrier breakdown allows immune cells to enter the CNS, demonstrating how immune privilege can be compromised

Inflammatory Bowel Disease (IBD)

  • Mucosal immune dysregulation—includes Crohn's disease and ulcerative colitis, where the immune system attacks the GI tract lining
  • Th1/Th17 imbalance drives chronic inflammation, with excessive pro-inflammatory cytokines damaging intestinal tissue
  • Environmental triggers interact with genetic susceptibility (NOD2 mutations), illustrating the multifactorial nature of autoimmunity

Compare: Multiple Sclerosis vs. IBD—both feature relapsing-remitting courses and T cell-mediated tissue destruction, but MS targets immune-privileged CNS tissue while IBD attacks mucosal surfaces constantly exposed to foreign antigens. This distinction tests your understanding of tissue-specific immune environments.


Autoantibody-Mediated Disorders: When Antibodies Cause Disease

In these conditions, autoantibodies directly cause pathology by binding to cell surface receptors or tissue components. The mechanism involves Type II hypersensitivity, where antibodies either activate, block, or destroy their targets.

Graves' Disease

  • Stimulating autoantibodies—thyroid-stimulating immunoglobulin (TSI) binds TSH receptors and activates them, causing hyperthyroidism
  • Type II hypersensitivity (stimulatory)—unlike most autoantibodies that destroy targets, these antibodies mimic hormone action
  • Exophthalmos (bulging eyes) results from antibody cross-reactivity with orbital tissue, demonstrating how autoantibodies can affect multiple sites

Myasthenia Gravis

  • Blocking autoantibodies—antibodies target acetylcholine receptors at neuromuscular junctions, preventing nerve-muscle communication
  • Fatigable weakness worsens with repeated muscle use because fewer functional receptors remain available for neurotransmission
  • Thymus abnormalities (thymoma or hyperplasia) in many patients suggest the thymus plays a role in generating autoreactive B cells

Compare: Graves' Disease vs. Myasthenia Gravis—both are Type II hypersensitivity disorders involving receptor-targeting autoantibodies, but Graves' antibodies stimulate receptors (causing hyperfunction) while Myasthenia antibodies block receptors (causing hypofunction). This is a high-yield comparison for understanding antibody-mediated mechanisms.

Psoriasis

  • Keratinocyte hyperproliferation—T cell-derived cytokines (IL-17, TNF-α) drive rapid skin cell turnover, creating characteristic scaly plaques
  • Autoinflammatory component involves both adaptive immunity and innate immune activation, blurring the line between autoimmune and autoinflammatory
  • Psoriatic arthritis develops in ~30% of patients, demonstrating how skin-directed autoimmunity can extend to joints

Hypersensitivity Disorders: Inappropriate Immune Responses

These conditions result from exaggerated immune responses to external antigens that shouldn't trigger significant reactions. Type I hypersensitivity involves IgE-mediated mast cell degranulation, releasing histamine and other inflammatory mediators.

Allergies and Asthma

  • IgE-mediated Type I hypersensitivity—allergen exposure triggers mast cell degranulation, releasing histamine and causing immediate symptoms
  • Th2 polarization drives allergic responses, with IL-4 promoting IgE class switching and IL-5 recruiting eosinophils
  • Chronic airway remodeling in asthma demonstrates how repeated hypersensitivity reactions cause permanent structural changes

Compare: Allergies vs. Autoimmune Disorders—both involve inappropriate immune activation, but allergies target external antigens (pollen, food proteins) while autoimmune diseases target self antigens. Understanding this distinction is crucial for classifying immune dysfunction.


Primary Immunodeficiency: When the Immune System Fails

These disorders result from intrinsic defects in immune system development or function, leading to inadequate immune responses. Defects can affect B cells, T cells, phagocytes, or complement proteins, each producing characteristic susceptibility patterns.

Primary Immunodeficiency Disorders

  • Recurrent infections are the hallmark—the type of pathogen indicates which immune component is defective (bacteria suggest antibody/complement deficiency; viruses/fungi suggest T cell defects)
  • Genetic basis underlies most cases, including X-linked agammaglobulinemia (B cell defect) and SCID (combined T and B cell deficiency)
  • Secondary autoimmunity paradoxically develops in some patients, showing that immune regulation requires functional immune cells

Compare: Primary Immunodeficiency vs. Autoimmune Disorders—these represent opposite ends of immune dysfunction. Immunodeficiency means too little immune activity (increased infections), while autoimmunity means misdirected immune activity (self-attack). Some patients have both, demonstrating that immune regulation is about balance, not just strength.


Quick Reference Table

ConceptBest Examples
Loss of self-tolerance (systemic)SLE, Rheumatoid Arthritis
Loss of self-tolerance (organ-specific)Type 1 Diabetes, Multiple Sclerosis, IBD
Type II hypersensitivity (stimulatory)Graves' Disease
Type II hypersensitivity (blocking)Myasthenia Gravis
Type III hypersensitivitySLE (immune complex deposition)
Type I hypersensitivity (IgE-mediated)Allergies, Asthma
T cell-mediated autoimmunityType 1 Diabetes, Multiple Sclerosis, Psoriasis
Primary immunodeficiencySCID, X-linked agammaglobulinemia

Self-Check Questions

  1. Which two disorders both involve autoantibodies targeting cell surface receptors but produce opposite functional effects (stimulation vs. blocking)?

  2. A patient presents with recurrent bacterial infections but handles viral infections normally. Which branch of the immune system is most likely defective—humoral (B cell/antibody) or cell-mediated (T cell)?

  3. Compare and contrast SLE and Type 1 Diabetes in terms of their target tissues and hypersensitivity mechanisms. Why is one considered systemic and the other organ-specific?

  4. If an FRQ asks you to explain how the same immune mechanism (loss of self-tolerance) can produce different clinical outcomes, which three disorders would you use as examples and why?

  5. What distinguishes Type I hypersensitivity disorders (like allergies) from autoimmune disorders at the level of antigen recognition, even though both involve inappropriate immune activation?