Innate community

Purpose of immune system

To protect the host from infectious pathogens

What is innate immunity?

The first line of defence that provides immediate, non-specific protection against pathogens without immunological memory.

What are the main features of innate immunity?

Rapid response, non-specific recognition, germline-encoded receptors, no memory, does not attack self.

What are the three lines of defence in innate immunity?

mechanical barriers

chemical barriers

microbiological barriers

Give examples of mechanical barriers.

Skin, mucous membranes, tight junctions, cilia, flow of urine and mucus.

What are mechanical epithelial barriers

Mechanical barriers physically prevent pathogen entry.:

• Intact epithelial surface

• Longitudinal flow of air or fluid

• Mucus movement by cilia

Give examples of chemical barriers?

Chemical barriers kill or inhibit microbes, e.g.:

• Fatty acids in skin

• Lysozyme in saliva and tears

• Pepsin and low pH in the gut

• Antibacterial peptides

Role of normal microbiota?

Competitive exclusion of pathogens by competing for nutrients, blocking adhesion, and producing antimicrobial substances.

What is phagocytosis?

The ingestion of foreign material by white blood cells

What is opsonisation?

Coating of pathogens with opsonins (IgG, complement) to enhance phagocytosis.

What are Pattern Recognition Receptors (PRRs)?

Germline-encoded receptors that recognise conserved microbial structures (PAMPs) and danger signals (DAMPs).

What are PAMPs?

Pathogen-associated molecular patterns such as LPS, peptidoglycan, lipoteichoic acid, viral RNA/DNA.

What are DAMPs?

Danger associated molecular patterns which are endogenous danger signals released from damaged or dying cells (e.g. ROS, ATP, K⁺).

What are Toll-like receptors (TLRs)?

PRRs on cell surfaces or endosomes that detect PAMPs and activate inflammatory gene expression.

Which TLR recognises LPS?

TLR-4 (with MD-2).

What happens after TLR activation?

Activation of transcription factors (e.g. NF-κB) → cytokine production → inflammation.

What are NOD-like receptors?

Cytosolic PRRs that detect bacterial products and activate NF-κB–mediated inflammation.

What is the inflammasome?

A cytosolic multiprotein complex that activates IL-1β and IL-18 during infection or cell injury.

What are RIG-like receptors?

Cytosolic receptors that detect viral RNA and induce type I interferon production.

What is the STING pathway?

Cytosolic DNA sensing pathway that induces type I interferons via cGAS–STING–TBK1–IRF3 signalling.

What is the role of type I interferons?

Inhibit viral replication and induce an antiviral state in cells.

What are natural killer (NK) cells and how do they contribute to innate immune functions?

Innate lymphocytes that kill virus-infected and tumour cells and secrete IFN-γ.

Once a pathogen has been marked with an opsonin:

a. Ingested and killed by an immune cell (phagocytosis)

b. Killed directly without ingestion

How do NK cells kill target cells?

Via perforin-mediated pore formation and granzyme-induced apoptosis.

What are the main functions of macrophages?

Phagocytosis, antigen presentation, cytokine secretion, tissue repair, debris clearance.

Name tissue-specific macrophages.

Kupffer cells (liver), alveolar macrophages (lung), microglia (brain), osteoclasts (bone).

What are macrophages derived from?

Monocytes that differentiate after entering tissues.

What is NETosis?

Release of DNA, histones, and antimicrobial proteins to trap and kill pathogens.

List four key functions of neutrophils.

Phagocytosis, degranulation, ROS production, NETosis.

Which innate immune cell is first at sites of acute inflammation?

Neutrophils.

What cells are involved in the second line of innate defence?

Neutrophils, macrophages, dendritic cells, NK cells.

what are defensins?

Amphipathic antimicrobial peptides that form pores in microbial membranes, causing lysis.

What are microbiological epithelial barriers?

Commensal bacteria prevent pathogen colonisation by:

• Competing for nutrients

• Blocking adhesion

• Producing antimicrobial substances

What are the main functions of immune cells at mucosal surfaces?

• Slow down invasion of pathogens

• Signal danger to other immune system components

What is the role of commensal bacteria in innate immunity?

• Crowd out pathogenic organisms

• Prevent pathogen adhesion

• Protect against pathogen penetration from the external environment into the body

Describe the morphology of neutrophils.

• Granular cytoplasm

• Multi-lobed nucleus

What are band neutrophils and what do they indicate?

• Neutrophils with poorly defined nuclear lobes

• Indicate rapid release from bone marrow due to acute stress or infection

What do hyper-segmented neutrophils indicate?

5 nuclear lobes

indicative of folate deficiency and slowed DNA synthesis

What do bright granules or vacuoles in neutrophils indicate?

• Toxic shock

• Severe infection or sepsis

Where are monocytes found?

In the blood

Where are macrophages found?

In tissues, where they act as phagocytes

Give three examples of PRRs and their ligands.

• LPS receptor → binds lipopolysaccharide on Gram-negative bacteria

• Mannose receptor → recognises yeast, bacteria, protozoa

• Scavenger receptors → bind ligands on Gram-positive and Gram-negative bacteria

What is the role of PRRs in innate immunity?

• Promote adhesion of pathogens to immune cells

• Enable elimination of microbes

What happens when a Toll-like receptor (TLR) binds its ligand?

• Recognises conserved microbial structures

• Activates immune signalling pathways

• Induces cytokine production

• Triggers inflammation and kinase activation

Name three antimicrobial peptides and their mechanisms.

• Lysozyme → digests bacterial cell wall proteoglycans

• Lactoferrin → binds iron, inhibiting bacterial growth

• Histatins → cationic peptides with antifungal and antibacterial activity

What is the function of salivary peroxidase?

• Bactericidal activity

• Destroys hydrogen peroxide produced by microbes

• Protects mucosal tissues (prevents mouth ulcers)