Host Barriers to Infection

1. Immunity — Main Aim

To protect against pathogens, organisms must:

  1. Distinguish self from non-self

  2. Kill or disable pathogens

Important point:

  • ALL organisms experience pathogen attack

  • Even bacteria need immune systems against bacteriophages

2. Three Levels of Host Defence

A. Physical Barriers

First line of defence.
Passive prevention of infection.

Examples

  • Skin

  • Tight junctions

  • Blood-brain barrier

  • Respiratory cilia

  • Gut peristalsis

  • Saliva and tears

  • Stomach acid

B. Innate Immunity

  • Rapid response

  • Non-specific

  • No true adaptive memory

  • Uses:

    • phagocytes

    • antimicrobial peptides (AMPs)

    • complement proteins

C. Adaptive Immunity

  • Slower response (days/weeks)

  • Highly specific

  • Has memory

  • Uses:

    • B cells

    • T cells

    • antibodies

3. How Pathogens Evade Physical Barriers

Host Defence

Evasion Mechanism

Skin/tight junctions

Destructive enzymes, transmigration

Mucus + cilia

Adhesins

Stomach acid

Acid tolerance

Important Examples

Candida albicans

  • Produces destructive enzymes

  • Damages epithelial barriers

Shigella flexneri

  • Uses transmigration through epithelial cells

E. coli

  • Uses adhesins to stick to tissues

Helicobacter pylori

  • Acid tolerant

  • Uses urease to survive stomach acid

4. Antimicrobial Peptides (AMPs)

Key Features

  • Ancient immune defence system

  • Present in all living organisms

  • Broad-spectrum antimicrobial activity

  • Usually work by membrane pore formation (“hole punching”)

β-defensins

  • Human AMPs

  • Secreted by leukocytes and epithelial cells

Histatin-5

  • AMP found in saliva

  • Active against Candida

  • Creates membrane lesions

  • Disrupts ion balance → fungal death

Lysozyme

Found in:

  • saliva

  • tears

Function

Breaks bacterial peptidoglycan.

Cleaves:

  • β(1→4) linkage between NAM and NAG

5. Complement System

Large group of plasma proteins involved in:

  • opsonisation

  • inflammation

  • pathogen killing

6. Complement Activation Pathways

Classical pathway

Activated by antibodies.

Lectin pathway

Activated by lectin binding to carbohydrates.

Alternative pathway

Activated directly by microbial surfaces.

All pathways produce:

C3 convertase

7. Functions of Complement

C3 convertase cleaves C3 into:

C3a

  • Causes inflammation

C3b

  • Opsonin

  • Promotes phagocytosis

  • Helps form membrane attack complex (MAC)

Membrane Attack Complex (MAC)

  • Creates pores in pathogen membrane

  • Causes lysis

8. Complement Receptors

CR1

  • Phagocytic receptor

  • Found on macrophages and neutrophils

CR2

  • Found on B cells

  • Enhances activation

CR3

  • Major phagocytic receptor

CR4

  • Minor phagocytic receptor

9. Innate Immune Cells

Phagocytic Cells

  • Macrophages

  • Dendritic cells

  • Neutrophils

Non-phagocytic Cells

  • Natural killer cells

  • Mast cells

  • Eosinophils

  • Basophils

10. Macrophages

Main roles

  • Tissue-resident sentinels

  • First responders to infection

Functions

  • Phagocytose pathogens

  • Release cytokines and chemokines

  • Recruit immune cells

Recognition Mechanisms

PAMP recognition

Recognise pathogen-associated molecular patterns.

Opsonin recognition

Recognise complement or antibody-coated pathogens.

11. Cytokines vs Chemokines

Cytokines

General signalling proteins affecting nearby cells.

Chemokines

Specific cytokines that attract immune cells by chemotaxis.

12. Dendritic Cells

Major antigen-presenting cells (APCs).

Functions:

  • Phagocytose pathogens

  • Constantly sample surroundings

  • Activate T cells

  • Link innate and adaptive immunity

13. Neutrophils

Features

  • Fast responders

  • Recruited from blood

  • Follow chemotactic gradients

  • Phagocytose pathogens

  • Often die after killing pathogens

Important chemoattractants

  • C5a

  • IL-8

  • IFN-γ

  • ATP released from damaged tissue

14. Evasion of Innate Immunity

Strategies

  • AMP resistance

  • Avoid opsonisation

  • Prevent phagocytosis

  • Block phagosome maturation

  • Escape phagocytes

  • Hide PAMPs

  • Produce receptor antagonists

15. Examples of Immune Evasion

Cryptococcus neoformans

  • Capsule hides epitopes

Histoplasma capsulatum

  • Alpha-glucan layer masks β-glucans from dectin-1 recognition

Neisseria

  • Modifies LPS with sialic acid

  • Reduces immune recognition

16. Adaptive Immunity

Humoral Immunity

  • B cells produce antibodies

  • Targets extracellular pathogens

Cell-Mediated Immunity

  • T-cell based

  • Targets infected host cells

17. Key Features of Adaptive Immunity

Specificity

Based on:

  • immunoglobulins

  • T-cell receptors

  • clonal selection

Important point:

  • Small antigen changes can prevent immune recognition

  • Explains seasonal influenza variation

Memory

  • Faster and stronger secondary response

  • Due to memory B and T cells

Tolerance

Immune system avoids attacking self.

Failure causes:

  • autoimmune disease

Tolerance mechanisms include:

  • deletion of self-reactive cells in bone marrow and thymus

  • regulatory T cells

18. Important Adaptive Immune Cells

B cells

  • Plasma cells

  • Memory cells

T cells

  • CD8 cytotoxic T cells

  • CD4 helper T cells

  • Regulatory T cells

19. Evasion of Adaptive Immunity

Major Strategies

  • Leukocidins

  • Ig proteases

  • Capsules

  • Antigenic variation

  • Interference with antigen presentation

20. Antigenic Variation

Influenza — Antigenic Drift

  • Small mutations accumulate over time

  • Caused by error-prone RNA polymerase

  • Produces new seasonal strains

Influenza — Antigenic Shift

  • Major reassortment of viral genomes

  • Occurs when two strains infect same cell

  • Produces completely new variants

  • Can lead to pandemics

21. CTL Antigen Variation

Viruses can mutate internal proteins presented on:

MHC I

This reduces:

  • CD8 T-cell recognition

Allows:

  • immune escape

22. Leukocidins

Toxins that kill leukocytes.

Staphylococcus aureus produces:

  • PVL

  • LukED

  • Gamma haemolysins

LukED

Targets:

CCR5 receptor

CCR5 is also important in:

  • HIV infection

23. Non-Human Host Defence Example — Bdellovibrio

Predatory Gram-negative bacterium.

Lifecycle

  1. Locates prey bacteria

  2. Attaches to prey

  3. Invades periplasm

  4. Consumes prey contents

  5. Replicates

  6. Bursts host cell

Important concept:

  • Host–pathogen interactions occur even between bacteria

24. CRISPR — Bacterial Adaptive Immunity

CRISPR

Clustered Regularly Interspaced Short Palindromic Repeats.

Adaptive immune system of bacteria and archaea.

Mechanism

  • Bacteria survive phage infection

  • Integrate viral DNA spacers

  • CRISPR RNAs guide Cas proteins

  • Viral DNA destroyed during reinfection

Potential Viva Questions & Answers

Question 1

“Describe the three levels of host defence against infection.”

Answer

  • The first level is physical barriers such as skin, cilia, stomach acid and tight junctions which prevent pathogen entry.

  • The second level is innate immunity, which is rapid and non-specific.

  • Innate immunity involves antimicrobial peptides, complement proteins and phagocytic cells such as macrophages and neutrophils.

  • The third level is adaptive immunity, which is slower but highly specific and has immunological memory.

  • Adaptive immunity involves B cells, T cells and antibodies.

Question 2

“How does the complement system protect against pathogens?”

Answer

  • The complement system is a group of plasma proteins involved in innate immunity.

  • It can be activated through the classical, lectin or alternative pathways.

  • All pathways produce C3 convertase.

  • C3 convertase cleaves C3 into C3a and C3b.

  • C3a promotes inflammation.

  • C3b acts as an opsonin and promotes phagocytosis.

  • Complement activation also forms the membrane attack complex, which creates pores and lyses pathogens.

Question 3

“Explain how pathogens evade innate and adaptive immunity.”

Answer

  • Pathogens evade physical barriers using adhesins, destructive enzymes and acid tolerance.

  • Innate immunity can be avoided by resisting antimicrobial peptides, preventing opsonisation and avoiding phagocytosis.

  • Some pathogens hide PAMPs using capsules or altered cell wall structures.

  • Adaptive immunity can be evaded using antigenic variation, Ig proteases and leukocidins.

  • Influenza uses antigenic drift and antigenic shift to escape immunity.

  • Staphylococcus aureus produces leukocidins that kill immune cells.

Question 4

“Explain specificity, memory and tolerance in adaptive immunity.”

Answer

  • Specificity means adaptive immunity targets particular antigens using antibodies and T-cell receptors.

  • Memory means secondary responses are faster and stronger because memory B and T cells remain after infection.

  • Tolerance prevents the immune system attacking self tissues.

  • Self-reactive immune cells are removed in the thymus and bone marrow.

  • Failure of tolerance can lead to autoimmune disease.