Lecture 7a Flashcards
(18 cards)
Phagocytosis
Phagocytosis is the actin-dependent process by which a phagocytic cell engulfs particles >0.5 µm (like bacteria).
The process has two key stages:
Ingestion – taking in the particle.
Digestion – degrading it inside acidified compartments (phagosomes → phagolysosomes).
Phagocytes & Biofilms
- Human Biofilms (Immune context):
Key phagocytes: Macrophages, monocytes, neutrophils, dendritic cells.
Feed on sloughed biofilm debris or single pathogens.
Occasionally amoebae like Entamoeba coli may be involved (rare, low concentration).
- Environmental Biofilms:
Dominated by amoebae (e.g. Acanthamoeba, high concentration).
Feed directly on the biofilm using similar phagocytic mechanisms as immune cells
Phagocytosis step 1: chemotaxis
Phagocytes are attracted to the site of infection by chemical signals in a process called chemotaxis.
They respond to:
Formyl peptides (like fMLP) from bacteria
Complement proteins like C5a
Cytokines from other immune cells
These signals create a gradient that guides phagocytes to the bacteria.
Phagocytosis step 2: Recognition
Phagocytes use pattern recognition receptors (PRRs) to detect pathogen-associated molecular patterns (PAMPs) on microbes.
LPS = gram -ve
Peptidoglycan = gram +ve
microbes are coated with opsonins (molecules that “tag” microbes for destruction), such as:
Antibodies (IgG)
Complement proteins (C3b)
Phagocytes have receptors for these opsonins.
Phagocytosis step 3: engulfment
Once attached, the phagocyte:
Wraps its membrane around the microbe
Engulfs it into a vesicle called a phagosome
This step requires rearrangement of the actin cytoskeleton.
Phagocytosis step 4: Phagosome-Lysosome Fusion
The phagosome fuses with a lysosome to form a phagolysosome.
The lysosome contains:
Acid hydrolases - Digest proteins, lipids, DNA
Reactive oxygen species (ROS) - Cause oxidative damage
Nitric oxide (NO) - Toxic to bacteria
Lysozyme - Breaks down bacterial cell walls
The microbe is broken down into small pieces.
Phagocytosis Step 5: Waste Removal and Antigen Display
Waste products are exocytosed out of the cell.
In antigen-presenting cells (like macrophages and dendritic cells), fragments are displayed on MHC-II molecules to activate T cells. This connects to adaptive immunity.
Bacterial Immune Evasion Strategies
Avoiding detection and phagocytosis
Surviving inside phagocytes
Inhibiting immune cell function
Avoiding complement system attack
Bacterial Immune Evasion Strategies: Avoiding Detection and Phagocytosis: Capsule Production
Many pathogenic bacteria produce a capsule — a slippery layer of polysaccharides or proteins around the cell.
It masks PAMPs, making it harder for phagocytes to recognise the bacterium.
It also prevents opsonisation (binding by antibodies and complement), reducing phagocyte attachment.
✅ Examples:
Streptococcus pneumoniae
Neisseria meningitidis
Bacterial Immune Evasion Strategies: Avoiding Detection and Phagocytosis: Antigenic Variation
Bacteria change their surface proteins (antigens) to avoid detection by antibodies.
This confuses the immune system, which must constantly adapt to “new” bacteria.
✅ Example:
Neisseria gonorrhoeae switches its pili proteins
Bacterial Immune Evasion Strategies: Avoiding Detection and Phagocytosis: Phase Variation
Bacteria switch genes on/off (e.g. those coding for flagella or adhesins) to avoid immune targeting.
Bacterial Immune Evasion Strategies: Surviving Inside Phagocytes: Preventing Phagosome-Lysosome Fusion
The bacteria prevent fusion of the phagosome with the lysosome, avoiding exposure to degrading enzymes and ROS.
✅ Example:
Mycobacterium tuberculosis does this by interfering with phagosome maturation.
Bacterial Immune Evasion Strategies: Surviving Inside Phagocytes: Resistance to Oxidative Burst
Some bacteria produce enzymes like catalase or superoxide dismutase (SOD) to detoxify ROS inside the phagolysosome.
✅ Examples:
Salmonella enterica
Staphylococcus aureus
Bacterial Immune Evasion Strategies: Surviving Inside Phagocytes: Escaping the Phagosome
Some bacteria break out of the phagosome into the cytosol before lysosomal fusion occurs.
✅ Example:
Listeria monocytogenes uses listeriolysin O to disrupt the phagosome membrane
Bacterial Immune Evasion Strategies: Inhibiting Immune Cell Function: . Secretion of Effector Proteins
Using secretion systems (like Type III secretion), some bacteria inject proteins into host cells to block immune signaling or destroy actin.
✅ Example:
Yersinia pestis (plague bacterium) injects Yop proteins to paralyse macrophages.
Bacterial Immune Evasion Strategies: Inhibiting Immune Cell Function: Killing or Disabling Phagocytes
Some bacteria produce toxins that kill or impair immune cells.
✅ Example:
Streptococcus pyogenes produces streptolysin O, which lyses leukocytes.
Bacterial Immune Evasion Strategies: Avoiding the Complement System: Capsule and Surface Proteins
The complement system can directly kill bacteria (via MAC) or opsonise them for phagocytosis.
Capsules reduce complement deposition.
Surface proteins (like Protein A in S. aureus) bind antibodies backwards, preventing opsonisation.
Bacterial Immune Evasion Strategies: Avoiding the Complement System: Recruiting Host Proteins
Some bacteria bind host complement regulators (like Factor H) to their surface to inhibit complement activation.
✅ Example:
Neisseria meningitidis binds Factor H to reduce C3b deposition.
