CPAT3201 - Lectures 9 + 10

What are the three major causes of hypersensitivity?

autoimmunity (self-antigens), excessive response to microbes, non-microbial environmental antigens (e.g., allergens)

What immune mechanisms underlie Type I hypersensitivity?

IgE binding to mast cells → histamine release; IL-4 for IgE switching, IL-5 for eosinophil recruitment, IL-13 for mucus production

Name 3 clinical examples of Type I hypersensitivity.

asthma, allergic rhinitis, anaphylaxis

What defines Type II hypersensitivity?

antibody-mediated cytotoxicity via IgG/IgM targeting cell surface or ECM antigens, causing inflammation or functional disruption

Give examples of diseases caused by Type II hypersensitivity.

Graves' disease, Hashimoto's thyroiditis, Myasthenia gravis, Rheumatoid arthritis, Pemphigus vulgaris

What is Type III hypersensitivity?

immune complex-mediated disease; antigen-antibody complexes deposit in tissues causing inflammation and damage

Name diseases associated with Type III hypersensitivity.

SLE, serum sickness, post-streptococcal glomerulonephritis, vasculitis

What distinguishes Type IV hypersensitivity?

T-cell mediated delayed response; CD4+ T cells → cytokine-driven inflammation; CD8+ T cells → cytotoxicity

List examples of Type IV hypersensitivity.

tuberculosis, multiple sclerosis, viral hepatitis

What is the mechanism of disease in rheumatic fever?

molecular mimicry - cross-reactive antibodies against GAS [Group A Streptococcus] antigens attack heart tissue (especially mitral valve)

What causes chronic inflammation in rheumatic heart disease?

recurrent immune activation causes valve remodelling → thickening, fibrosis

Why does M. tuberculosis resist killing by macrophages?

waxy cell wall and catalase production inhibit lysosomal degradation and oxidative burst.

What are Langhans giant cells and when do they form?

multinucleated macrophage fusion products formed in granulomas due to IFN-γ activation during TB infection

What is a tuberculin reaction?

delayed hypersensitivity skin test using PPD to detect prior TB sensitization

What cytokines are key in TB granuloma maintenance?

IFN-γ and TNF-α

What causes the necrotic core in TB granulomas?

hypoxia due to poor vascular supply in enlarged granulomas → central cell death

How does the immune system respond to extracellular bacteria?

innate: Complement, phagocytes, ILCs; Adaptive: Antibodies (IgG, IgA), CD4+ T cells (Th17 & Th1)

What are Innate Lymphoid Cells (ILCs)?

tissue-resident lymphoid cells lacking antigen-specific receptors; rapidly secrete cytokines (e.g., IL-17, IL-22)

How do bacteria evade immune responses?

surface antigen variation, bleb release, LPS sialylation, immune modulation (e.g., IgA1 protease, IL-10 induction)

How does the immune system respond to intracellular bacteria?

Innate: Macrophages, NK cells via NOD-like receptors; Adaptive: Th1 CD4+ T cells (IFN-γ), CD8+ T cells (cytotoxicity).

How do intracellular bacteria evade immunity?

inhibit ROS/RNS, phagolysosome fusion, escape to cytosol, catalase production to neutralize H₂O₂

What immune cells are essential for controlling intracellular bacteria?

CD4+ Th1 cells and CD8+ cytotoxic T cells

What role does IFN-γ play in bacterial infections?

activates macrophages to produce ROS, enzymes, and enhance phagolysosome fusion

What are the main components of antiviral innate immunity?

Type I interferons, NK cells, and early cytokine production by DCs and infected cells

How do viruses escape CTL-mediated killing?

downregulate MHC-I, inhibit proteasome or TAP transport, block MHC synthesis, or express decoy MHC-like molecules

What is antigenic drift vs shift?

Drift: Gradual point mutations in viral proteins (e.g., flu); Shift: Abrupt gene reassortment, new viral strains (e.g., H1N1)

How does HIV evade the immune system?

infects and depletes CD4+ T cells, crippling adaptive immunity

How do type I interferons protect against viral infections?

induce antiviral state in neighboring cells via STING pathway and IRF transcription factors

What is the role of CTLs in viral infections?

detect viral peptides on MHC-I → kill infected cells to control virus

Give examples of viruses that persist via latency.

HSV, EBV, varicella (VZV), HPV

How does EBV modulate immunity?

produces IL-10 mimic → suppresses macrophage and DC activation