L32&33 Immunity Flashcards
L32: Innate Immunity
What are the four main functions of the immune system?
- Recognising threats – Differentiates between self and non-self.
- Responding to threats – Utilises barriers, innate immunity, and adaptive immunity.
- Resolving the response – Controls inflammation and prevents excessive damage.
- Remembering the threat – Forms immune memory (adaptive immunity).
L32: Innate Immunity
What are the three main types of barriers in the immune system?
- Physical barriers – Skin, mucosal surfaces.
- Chemical barriers – Antimicrobial secretions, low pH.
- Biological barriers – Commensal bacteria competing with pathogens.
L32: Innate Immunity
How does the skin act as a physical barrier to infection?
Thick and dead outer layer (keratin).
Dry surface (prevents microbial growth).
Impermeable to pathogens.
Antimicrobial secretions (e.g., defensins, lysozymes).
L32: Innate Immunity
What role do mucosal surfaces play in immunity?
Thin single-cell layer allowing passage of molecules (e.g., O₂, CO₂, nutrients).
Mucociliary elevator in the lungs removes trapped microbes.
Antimicrobial peptides prevent infections.
Commensal bacteria prevent pathogen colonisation.
L32: Innate Immunity
What are the six major types of pathogens?
- Bacteria
- Viruses
- Fungi
- Protozoa
- Worms (Helminths)
- Flukes
L32: Innate Immunity
How many bacterial cells colonise the human body?
The human body contains 10¹⁴ human cells but is colonised by 10¹⁵ bacteria, meaning over 90% of cells in/on the body are non-human.
L32: Innate Immunity
What are the three levels of immune defence?
- Physical barriers – Skin, mucosa, antimicrobial secretions, commensal bacteria.
- Innate immunity – Immediate, non-specific response with no memory.
- Adaptive immunity – Specific, memory-based response taking 4-6 weeks to develop.
L32: Innate Immunity
What are the main humoral (soluble) components of innate immunity?
- Complement system – Plasma proteins (C1-C9) aiding pathogen destruction.
- Acute phase proteins – Produced by the liver in response to infection (e.g., C-reactive protein (CRP), Mannose-binding lectin (MBL)).
L32: Innate Immunity
What are the three complement activation pathways?
- Lectin pathway – MBL binds to sugars on the microbe, activating the complement system.
- Alternative pathway – C3b binds to the microbe, triggering complement activation.
- Classical pathway – Antibodies bind to the microbe, initiating the pathway.
L32: Innate Immunity
What does C3b do in the complement system?
Opsonisation – Tags microbes for phagocytosis.
Activates the alternative pathway.
C3a activates mast cells, leading to histamine release.
L32: Innate Immunity
What is the function of the Membrane Attack Complex (MAC)?
Formed by C5-C9.
Creates pores in bacterial membranes.
Causes bacterial lysis by allowing water to rush in.
L32: Innate Immunity
What are PRRs and what do they detect?
PRRs are receptors that detect Pathogen-Associated Molecular Patterns (PAMPs).
Toll-Like Receptors (TLRs) are key PRRs.
L32: Innate Immunity
Where are Toll-Like Receptors (TLRs) found?
Surface TLRs detect bacterial cell wall components (LPS, peptidoglycan).
Endosomal TLRs detect viral nucleic acids (RNA/DNA).
L32: Innate Immunity
What is the function of cytokines and chemokines?
Cytokines – Small proteins that mediate immune responses.
Chemokines – Attract immune cells to infection sites.
L32: Innate Immunity
What are the four main steps in inflammation?
- Sentinel Cells Detect Infection – Macrophages, dendritic cells, mast cells release cytokines and chemokines.
- Blood Vessel Changes – Increased permeability allows immune cells to enter tissues.
- Recruitment of Effector Cells – Neutrophils and monocytes migrate to the site.
- Pathogen Elimination – Phagocytosis, complement activation, NK cell killing.
L32: Innate Immunity
How does the interferon response protect against viruses?
Virus-infected cells produce interferons (IFN-α, IFN-β).
Interferons:
Activate antiviral genes in neighbouring cells.
Induce RNAse enzymes to degrade viral RNA.
Activate Protein Kinase-R, inhibiting viral replication.
L32: Innate Immunity
How do Natural Killer (NK) cells kill virus-infected cells?
- Recognise lack of MHC-I molecules.
- Release perforin and granzyme to induce apoptosis.
- Kill via Antibody-Dependent Cellular Cytotoxicity (ADCC).
L32: Innate Immunity
What are the key characteristics of innate immunity?
Always present and responds immediately.
No memory, relies on Pattern Recognition Receptors (PRRs).
Clears most infections before adaptive immunity is needed.
L32: Innate immunity
What are the three key mechanisms of innate immunity?
- Barrier defences – Skin, mucosa, antimicrobial secretions.
- Cellular defences – Neutrophils, macrophages, NK cells.
- Humoral defences – Complement system, acute phase proteins.
L32: Innate immunity
What are the three main roles of innate immunity?
- Immediate response – Recognises PAMPs and activates defences.
- Pathogen clearance – Phagocytosis, complement activation, NK cell killing.
- Inflammation – Recruits immune cells and initiates adaptive immunity.
L32: Innate immunity
What are the main innate immune cells and their functions?
- Neutrohils (60-70% WBCs) - Phagocytosis, oxidative burst, NETosis (trapping microbes in DNA nets)
- Monocytes/Macrophages (7%) - CIrculate in blood, differentiate into macrophages in tissues, phagocytosis, antigen presentation
- Natural killer cells (2%) - Recognise virus-infected/cancerous cells, release perforin and granzyme to induce apoptosis
- Mast cells - Release histamine, increase blood flow, recruit immune cells
- Dendritic cells - Bridge between innate and adaptive immunity, present antigens to T cells
L32: Innate immunity
What are the key functions of neutrophils?
Phagocytosis – Engulfs and destroys microbes.
Oxidative burst – Produces reactive oxygen species to kill microbes.
NETosis – Releases DNA traps to catch and kill microbes.
L32: Innate immunity
How do neutrophils find infection sites?
Follow chemokine signals (e.g., CXCL8/IL-8) to infection sites.
Recognise C3b-opsonised pathogens.
L32: Innate immunity
How do NK cells identify and kill infected cells?
Detect cells lacking MHC-I molecules (which are often infected or cancerous).
Release perforin and granzyme to induce apoptosis.
Can kill via Antibody-Dependent Cellular Cytotoxicity (ADCC) by recognising Fc receptors.
L32: Innate immunity
What are the two types of receptors NK cells use?
- Activating receptors – Detect stress signals from infected cells.
- Inhibitory receptors – Detect MHC-I; if absent, NK cells kill the target.
L32: Innate immunity
What role do mast cells play in the immune response?
Act as sentinel cells in tissues.
Release histamine, leading to vasodilation and increased permeability.
Recruit immune cells via cytokine release.
L32: Innate immunity
How does histamine contribute to inflammation?
Dilates blood vessels → increases blood flow.
Increases permeability → immune cells and plasma proteins enter tissues.
Causes swelling, redness, and heat at the infection site.
L32: Innate immunity
What are the three main functions of the complement system?
- Opsonisation – Coats microbes with C3b, making them easier to phagocytose.
- Inflammation – C3a and C5a recruit immune cells and promote inflammation.
- Lysis – C5-C9 form the Membrane Attack Complex (MAC), lysing bacteria.
L32: Innate immunity
What triggers each complement pathway?
Lectin pathway – Mannose-binding lectin (MBL) binds to microbial sugars.
Alternative pathway – C3b spontaneously binds to microbes.
Classical pathway – Antibodies (IgG/IgM) bind to pathogens.
What are the five steps of phagocytosis?
- Recognition & Attachment – PRRs (e.g., TLRs) recognise PAMPs or opsonised microbes.
- Engulfment – Pseudopodia extend and enclose the microbe in a phagosome.
- Lysosome Fusion – Phagosome fuses with a lysosome, forming a phagolysosome.
- Microbe Killing – Enzymes, ROS, and antimicrobial peptides kill the microbe.
- Antigen Presentation – Fragments of microbes are presented to T cells.
What are Toll-Like Receptors (TLRs) and what do they detect?
TLRs are Pattern Recognition Receptors (PRRs) that detect PAMPs.
Found on cell surfaces and endosomes.
What are acute phase proteins and where are they produced?
Produced by the liver in response to infection.
Upregulated by IL-6, IL-1, TNF-α.
What are key acute phase proteins and their functions?
- C-Reactive Protein (CRP) – Opsonises bacteria, activates the classical complement pathway.
- Mannose-Binding Lectin (MBL) – Binds to microbial sugars and activates complement.
How do interferons protect against viruses?
Virus-infected cells release Type I Interferons (IFN-α, IFN-β).
Interferons:
Activate RNAse enzymes to degrade viral RNA.
Induce Protein Kinase-R, blocking viral replication.
Enhance NK cell and macrophage activity.
What are the key differences between innate and adaptive immunity?
Innate immunity is immediate, while adaptive immunity takes days to weeks to develop.
Innate immunity is non-specific, recognising general pathogen patterns, while adaptive immunity is highly specific and recognises unique antigens.
Innate immunity has no memory, whereas adaptive immunity forms memory, leading to a faster response upon re-exposure.
Key innate cells include neutrophils, macrophages, dendritic cells, and NK cells, while adaptive immunity involves T cells and B cells.
Innate immunity relies on the complement system and cytokines, whereas adaptive immunity relies on antibodies and T cell receptors.
What are the three main roles of innate immunity?
- Immediate response – Recognises PAMPs and activates defences.
- Pathogen clearance – Phagocytosis, complement activation, NK cell killing.
- Inflammation – Recruits immune cells and initiates adaptive immunity.
What are the key functions of neutrophils?
Phagocytosis – Neutrophils engulf and digest microbes.
Oxidative burst – They produce reactive oxygen species (ROS) to kill pathogens.
NETosis – They release DNA strands to trap and kill microbes.
How do neutrophils find infection sites?
They follow chemokine signals like CXCL8 (IL-8) to infection sites.
They recognise C3b-opsonised pathogens, allowing for easier phagocytosis.
How do NK cells identify and kill infected cells?
They detect cells lacking MHC-I molecules, which are often infected or cancerous.
They release perforin and granzyme, inducing apoptosis (cell death).
They kill via Antibody-Dependent Cellular Cytotoxicity (ADCC) by recognising Fc receptors on antibody-coated cells.
What are the two types of receptors NK cells use?
Activating receptors detect stress signals from infected cells.
Inhibitory receptors detect MHC-I; if absent, NK cells kill the target.
What are the three main functions of the complement system?
- Opsonisation – Coats microbes with C3b, making them easier to phagocytose.
- Inflammation – C3a and C5a recruit immune cells and promote inflammation.
- Lysis – C5-C9 form the Membrane Attack Complex (MAC), lysing bacteria.
What triggers each complement pathway?
The lectin pathway is triggered when mannose-binding lectin (MBL) binds to microbial sugars.
The alternative pathway is activated when C3b spontaneously binds to microbes.
The classical pathway is activated when antibodies (IgG or IgM) bind to pathogens.
What are the five steps of phagocytosis?
- Recognition & Attachment – PRRs (e.g., TLRs) recognise PAMPs or opsonised microbes.
- Engulfment – The pathogen is enclosed in a phagosome.
- Lysosome Fusion – The phagosome fuses with a lysosome, forming a phagolysosome.
- Microbe Killing – Enzymes, ROS, and antimicrobial peptides kill the microbe.
- Antigen Presentation – Fragments of microbes are presented to T cells.
What are some key TLRs and their ligands?
TLR4 recognises Lipopolysaccharide (LPS) from Gram-negative bacteria.
TLR2 recognises peptidoglycan and lipoproteins from Gram-positive bacteria and fungi.
TLR3 recognises double-stranded RNA from viruses.
TLR7 and TLR8 recognise single-stranded RNA from RNA viruses.
TLR9 recognises unmethylated CpG DNA from bacteria and DNA viruses.
What are the main cytokines involved in inflammation?
IL-1 increases fever and activates endothelial cells.
IL-6 stimulates the production of acute-phase proteins.
TNF-α increases vascular permeability and recruits immune cells.
IL-8 (CXCL8) recruits neutrophils to infection sites.
IL-10 is anti-inflammatory and limits the immune response.
What is the difference between inflammation and fever?
Inflammation is a local response to infection or injury, involving redness, swelling, heat, and pain.
Fever is a systemic response, raising body temperature to slow pathogen growth.
Inflammation is driven by IL-1, IL-6, and TNF-α, while fever is triggered by IL-1, IL-6, and PGE₂.
