innate response

PART 1: INTRODUCTION TO ANTIBACTERIAL DEFENCES

Section 1: Overview of Antibacterial Defences (Page 1)

Immune defences against bacteria are determined by:

Their surface chemistry
Their mechanisms of pathogenicity
Whether they are predominantly extracellular or intracellular

Bacterial Infection Strategies:

Infect tissues and multiply (extracellular bacteria)
Release toxic substances (exotoxins, endotoxins)
Both – some bacteria do both

PART 2: FIRST LINE OF DEFENCE – BARRIERS

Section 2: Simple Physical Barriers (Page 2)

Skin and exposed epithelial barriers have non-specific or innate protective systems limiting entry.

Barrier Type	Examples	Mechanism
Physical Barriers	Skin, mucosal epithelia, cilia lining the respiratory tract	Represent effective mechanical barriers; cilia move mucus and trapped particles out of the respiratory tract.
Biochemical Mechanisms	Sebaceous gland secretions	Contain fatty acids, hydrolytic enzymes, and antibacterial defensins.
Enzymatic Barriers	Saliva, intestinal secretions	Contain enzymes capable of digesting bacterial cell walls (e.g., lysozyme).
Chemical Barriers	Stomach acid	Acidic pH of the stomach lumen kills many ingested bacteria.

PART 3: INNATE IMMUNE RESPONSE

Section 3: Acute Inflammation (Page 3)

The Four Cardinal Signs of Inflammation:

Tumor (swelling)
Calor (heat)
Dolor (pain)
Rubor (redness)

Section 4: Recognition of Bacterial Components (Page 3)

Innate immunity recognises bacteria through Pattern Recognition Receptors (PRRs) that recognise Pathogen-Associated Molecular Patterns (PAMPs) .

Three main receptor types that recognise PAMPs:

Toll-like receptors (TLRs) – on cell surfaces and endosomes
Complement system – soluble proteins that are activated by bacteria
Phagocytosis receptors – including scavenger receptors, lectin receptors

PART 4: THE COMPLEMENT SYSTEM

Section 5: Complement Activation and Inflammation (Pages 3-4)

5.1. Overview:
The complement system is a cascade of soluble proteins that are activated by bacteria. Activation produces anaphylotoxins (C3a, C5a) that induce acute inflammation and cell chemotaxis.

5.2. Effects of Complement Anaphylotoxins (Page 4):

Anaphylotoxin	Target Cell	Effect
C3a and C5a	Mast cells	Cause degranulation and release of vasoactive amines (histamine, 5-hydroxytryptamine/serotonin).
C5a	Monocytes, neutrophils	Acts directly on receptors to induce migration (chemotaxis) to sites of acute inflammation and subsequent activation.

5.3. Vasoactive Amine Effects (Page 4):

Histamine and 5-hydroxytryptamine enhance:
- Vascular permeability (leading to swelling)
- Local blood flow (leading to heat and redness)
- These contribute to the cardinal signs of inflammation.

5.4. Secondary Effects (Page 4):

The secondary release of chemokines from mast cells causes cellular accumulation (more immune cells recruited).
As inflammatory cells are phagocytosing, they release pro-inflammatory cytokines.

Section 6: Pro-inflammatory Cytokines (Page 5)

Cytokine	Source	Effects
TNF-α (Tumour Necrosis Factor-alpha)	Macrophages, others	Increase production of complement; promote inflammation; activate endothelium.
IL-1 (Interleukin-1)	Macrophages, others	Increase production of complement; promote inflammation; induce fever.
IFN-γ (Interferon-gamma)	NK cells (innate), then T cells (adaptive)	Activates macrophages – enhances their killing ability.

The Cascade:

Complement activation → inflammation
Phagocytes recruited and activated
NK cells are activated, releasing IFN-γ
IFN-γ activates macrophages – making them more effective killers

PART 5: PHAGOCYTOSIS AND BEYOND

Section 7: Phagocytosis is Not Enough (Page 5)

While phagocytosis is crucial, it is not sufficient to clear all bacterial infections.
A lymphocyte-dependent response (adaptive immunity) is often required for complete resolution.

Section 8: Linking Innate and Adaptive Immunity (Page 6)

8.1. Dendritic Cell Activation:

Contact with bacteria in the periphery causes Dendritic Cells (DCs) to mature.
Maturation increases their antigen-presenting capability.
This occurs in an area rich in cytokines following binding of Toll-like receptors.

8.2. Antigen Presentation:

Macrophages that act as Antigen Presenting Cells (APCs) are localised more at the site of infection.
Dendritic cells migrate to lymph nodes where they present antigens to naïve T helper cells.

8.3. Activation of T Helper Cells:

Activated T helper cells then stimulate:
- Cytotoxic T cells (to kill infected cells)
- B cells (to produce antibodies)

Section 9: Antibody Binding (Page 7)

Antibodies (produced by B cells) bind to bacteria.
This enhances opsonisation (making bacteria more susceptible to phagocytosis).
Antibodies can also neutralise toxins and activate the classical complement pathway.

Section 10: Most Bacteria Are Killed by Phagocytosis (Page 7)

Despite the complexity of immune responses, the ultimate killing mechanism for most bacteria is phagocytosis.
Antibodies and T cells help to enhance and target phagocytosis.

PART 6: REVIEW QUESTIONS

Section 11: Quiz (Page 8)

Question	Answer
What are some of the innate immune defences?	Physical barriers (skin, mucous membranes), chemical barriers (stomach acid, antimicrobial peptides), phagocytes (neutrophils, macrophages), complement system, inflammation.
Name 3 phagocytes that can communicate with the adaptive immune system?	Dendritic cells, macrophages, B cells (these are all Antigen Presenting Cells, APCs).
Where do the dendritic cells meet with immature T helper cells?	In the lymph nodes (or other secondary lymphoid tissues).
How long does it take for the resolution of a bacterial infection, in general?	Varies widely – from days (mild infections) to weeks or longer (more severe infections). The adaptive response takes 7-10 days to become fully effective.
Are antibodies the same as antibiotics?	No. Antibodies are proteins produced by B cells as part of the adaptive immune response. Antibiotics are chemical compounds (natural or synthetic) that kill or inhibit bacteria.

SUMMARY TABLE: KEY COMPONENTS OF ANTIBACTERIAL IMMUNITY

Component	Type	Function
Physical Barriers	Innate	Prevent bacterial entry (skin, mucous membranes, cilia).
Chemical Barriers	Innate	Kill bacteria directly or create hostile environment (fatty acids, enzymes, acid pH).
Phagocytes	Innate	Engulf and destroy bacteria (neutrophils, macrophages).
Complement	Innate	Opsonisation, direct killing (Membrane Attack Complex), chemotaxis, inflammation.
Inflammation	Innate	Increases blood flow, vascular permeability, and recruits immune cells to site of infection.
Cytokines	Innate/Adaptive	Signalling molecules that coordinate immune response (TNF-α, IL-1, IFN-γ).
Dendritic Cells	Innate/Adaptive	Bridge innate and adaptive immunity; capture antigen and present to T cells in lymph nodes.
T Cells	Adaptive	Help other cells (CD4+ T helper); kill infected cells (CD8+ cytotoxic).
B Cells / Antibodies	Adaptive	Produce antibodies that opsonise bacteria, neutralise toxins, activate complement.