Lecture 3 : Disorders Of The Immune System Hypersensitivity Diseases Flashcards
What defines a hypersensitivity reaction, and what are the common features of all types?
✅ Answer: A hypersensitivity reaction is an inappropriate or excessive immune response to an antigen that may be harmless. All types involve:
Adaptive immunity
Chronicity, due to failure to eliminate the stimulus
Can be triggered by autoantigens, microbial persistence, or environmental allergens
What are the four types of hypersensitivity reactions and their main immune mediators?
I: IgE, Th2 cells, Mast cells: Asthma, Anaphylaxis
II: IgG/IgM + cells or ECM: Graves’ Disease, Myasthenia Gravis
III: Immune complexes (IgG/IgM): SLE, Serum sickness
IV: T-cell mediated (CD4/CD8): TB, MS, Coeliac Disease
What cytokines and cells are involved in IgE-mediated Type I hypersensitivity?
✅ Answer:
IL-4, IL-5, IL-13 (from Th2 cells)
Drive IgE class switching, mast cell, and eosinophil activation
Common in asthma, rhinitis, and food allergies
Give two examples of antibody-mediated diseases caused by receptor stimulation or inhibition.
✅ Answer:
Graves’ Disease – stimulating antibodies to TSH receptor (↑ T3/T4)
Myasthenia Gravis – blocking antibodies to acetylcholine receptor (↓ muscle activation)
How does antibody-mediated opsonization lead to cell destruction in Type II hypersensitivity?
✅ Answer: Antibodies bind to cell surface proteins → opsonization → complement activation (C3b) → recruitment of phagocytes → cell lysis or phagocytosis (e.g., autoimmune hemolytic anemia)
What is serum sickness and how does it illustrate Type III hypersensitivity?
✅ Answer:
Reaction to foreign antibodies (e.g., horse serum or infliximab)
Formation of antibody-antigen complexes → deposited in vessels, kidneys, joints
Leads to vasculitis, nephritis, and arthritis
Why are immune complexes often deposited in glomeruli and synovial joints?
✅ Answer:
These sites undergo ultrafiltration under high pressure
Small complexes avoid phagocytosis and get trapped in capillary beds, triggering inflammation
❓Q8: Name two diseases associated with Type III hypersensitivity.
✅ Answer:
Systemic Lupus Erythematosus (SLE) – autoantibodies to dsDNA
Post-streptococcal glomerulonephritis – immune complexes in glomeruli
What distinguishes Type IV hypersensitivity from the other types?
✅ Answer:
No antibody involvement
Mediated by CD4+ Th1/Th17 cells and CD8+ cytotoxic T cells
Characterized by delayed onset (24–48h) and chronic tissue damage
What immune mechanisms underlie delayed-type hypersensitivity (DTH) in TB?
✅ Answer:
Macrophages detect M. tuberculosis via TLRs, trigger Th1 response (IFN-γ, TNF)
Mycobacteria resist ROS and lysosomal killing
Leads to granuloma formation to contain infection
Can result in necrosis and fibrosis
What is the histological hallmark of a TB granuloma?
✅ Answer:
Necrotic core (caseation)
Surrounded by Langhans giant cells, epitheloid macrophages, and Th1 lymphocytes
How is TB diagnosed using Type IV response?
✅ Answer:
Tuberculin skin test (PPD)
Injected antigen elicits delayed skin reaction (DTH) in previously sensitized individuals
Describe the mechanism behind rheumatic fever and why it’s considered “pseudo-autoimmune”.
✅ Answer:
Cross-reactivity (molecular mimicry): anti-GAS antibodies also bind to cardiac tissue
Not a failure of self-tolerance; instead, microbial epitopes resemble self-antigens
Leads to valvular inflammation and eventual fibrosis (e.g., mitral valve)
What cardiac pathology results from recurrent rheumatic fever?
✅ Answer:
Chronic inflammation causes valve thickening, commissural fusion, and shortened chordae
Impairs valve closure → leads to cardiomyopathy and heart failure
Why is RHD more common in Indigenous Australian populations?
✅ Answer: Due to limited healthcare access, overcrowding, and higher exposure to GAS — leading to recurrent infections and untreated acute RF.
What determines the pathogenicity of a microbe?
✅ Answer: A microbe’s ability to evade, resist, or modulate the host immune response, or cause pathological immune reactions (e.g., Hepatitis B causing immune-mediated liver damage).
Compare microbial strategies of persistence: extracellular vs intracellular bacteria vs viruses.
Microbe Type/// Persistence Strategy
Extracellular bacteria: Antigenic variation, decoy vesicles, IgA proteases
Intracellular bacteria: Inhibit ROS/phagolysosomes, escape to cytosol
Viruses: MHC downregulation, latency, antigenic drift/shift, immune modulators
List key innate and adaptive responses to extracellular bacteria.
✅ Answer:
Innate:
Complement activation (lectin pathway, MAC, C3 opsonization)
Phagocytes (neutrophils, macrophages)
Innate lymphoid cells (ILCs) → IL-17, IL-22, GM-CSF
Adaptive:
Antibodies (IgM, IgG, IgA) → neutralize, opsonize, agglutinate
Th17 cells → IL-17, IL-8 (neutrophil chemotaxis)
Th1 cells → IFN-γ (macrophage activation)
What are innate lymphoid cells (ILCs) and how do they differ from T cells?
✅ Answer: ILCs come from lymphoid lineage but lack antigen-specific receptors. They do not undergo clonal selection and act rapidly, producing cytokines (IL-17, IL-22) to shape innate responses, especially at mucosal surfaces.
Name three ways extracellular bacteria evade immune detection and give an example for each.
Strategy //Example
Antigenic variation E. coli pili antigen variability (pilin)
Membrane blebbing Neisseria gonorrhoeae sheds vesicles as decoys
IgA1 protease Neisseria cleaves antibodies
How does sialylation of LPS help bacteria evade immunity?
✅ Answer: Adding sialic acid to LPS mimics host glycans, reducing antibody recognition and complement activation.
Outline the innate and adaptive immune responses to intracellular bacteria.
✅ Answer:
Innate:
Phagocytes & NK cells
NOD-like receptors (NLRs) detect intracellular PAMPs
IL-12, IL-15 → activate NK cells to release IFN-γ
Adaptive:
Th1 cells (CD4) → IFN-γ activates phagolysosome killing
CD8+ CTLs → kill infected cells (when bacteria escape to cytosol)
What are three ways intracellular bacteria evade killing by host cells?
✅ Answer:
Block phagolysosome fusion
Escape into cytosol to avoid lysosomes
Produce catalase to detoxify hydrogen peroxide → reduce ROS generation
What is the role of Type I Interferons in viral infection?
✅ Answer: Produced by infected cells and DCs → bind neighboring cells → induce antiviral state (inhibit viral replication, degrade viral RNA, block protein synthesis).
