Lecture 1: Recognition of Pathogens by the Innate Immune System

Flashcards covering barrier immunity, PRRs, PAMPs and DAMPs, functional redundancy, and the three complement activation pathways and outcomes.

What are the three levels of immune defence outlined in the lecture?

Barriers (skin, lungs and gut), Innate immunity (humoral components in plasma/serum and cellular components), and Adaptive immunity.

What protective features are present in the skin epidermis and underlying layers?

The epidermis contains keratinocytes that produce antimicrobial peptides, while underlying layers contain many immune cells.

What examples of breaches or disruptions are listed for the respiratory tract?

Chronic inflammation, excess mucus, cystic fibrosis, smoking, and COPD.

What are the main functions of dendritic cells in barrier tissues?

Immune surveillance, specialized antigen presentation, engulfing pathogens and processing them into peptides, and presenting these to lymphocytes to activate adaptive immunity (e.g., Langerhans cells in skin).

What is the difference between neutropenia and neutrophilia?

Neutropenia is having too few neutrophils, whereas neutrophilia is characterized by increased neutrophil numbers.

What are Pathogen-associated molecular patterns (PAMPs) and what are some examples?

PAMPs are structural or essential microbial molecules that alert the immune system to microbial material. Examples include bacterial cell-wall components, fungal cell-wall components, and viral nucleic acids.

What are Damage-associated molecular patterns (DAMPs) and what are some examples?

DAMPs originate from damaged host tissues to alert the immune system to tissue damage. Examples include mitochondrial DNA, histones, genomic DNA, uric acid, and ATP.

Where are PRRs located that recognize microbial DNA and RNA from intracellular pathogens?

Intracellular compartments, including endosomes.

What specific function do chemokines perform following PRR activation?

Coordinate cell movement.

What is functional redundancy in the context of PRR signaling?

The ability of multiple PRRs to activate the same intracellular signaling pathway, meaning loss of one PRR may be compensated for by other PRRs.

Which kinase is cited as an example involved in PRR intracellular signaling?

Syk.

What are soluble PRRs and what is an example of one involved in complement activation?

Receptors found in body fluids and concentrated at barrier tissues (not attached to cells) that bind microbial surfaces to trap microbes; an example is mannose-binding lectin (MBL).

What activates the classical pathway of complement activation and what component does it involve?

Antibody binding and immune-complex formation; involves C1q.

What activates the lectin pathway of complement activation and what component does it involve?

Soluble PRR binding to microbial carbohydrates; involves MBL.

What activates the alternative complement pathway?

C3b deposition on microbial surfaces.

What convertase is formed by all three complement activation pathways, and what active fragments does it produce?

C3 convertase, which cleaves C3 into C3a and C3b.

Which complement fragments are responsible for inflammation and immune-cell recruitment?

C3a and C5a.

How does C3b deposition contribute to pathogen elimination?

C3b attaches to microbial surfaces and acts as a marker that promotes recognition and phagocytosis by immune cells.

What proteins assemble to form the Membrane Attack Complex (MAC) and how do they damage microbes?

C5b, C6, C7, C8, and C9. C5b associates with C6 and C7 on the membrane, C8 inserts into the membrane, and C9 molecules bind and polymerize to form a pore that damages microbial membranes.