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Questions and Answers
What is the primary function of lysozyme in the immune system?
What is the primary function of lysozyme in the immune system?
Which components are classified as anti-viral interferons?
Which components are classified as anti-viral interferons?
What role does normal bacterial flora play in the immune system?
What role does normal bacterial flora play in the immune system?
What happens when physical and physiological barriers of the immune system are compromised?
What happens when physical and physiological barriers of the immune system are compromised?
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What are pattern recognition receptors (PRRs) responsible for in the innate immune system?
What are pattern recognition receptors (PRRs) responsible for in the innate immune system?
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What is one key characteristic of the innate immune response?
What is one key characteristic of the innate immune response?
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Which of the following is considered a physical barrier of the innate immune system?
Which of the following is considered a physical barrier of the innate immune system?
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Which statement about the innate immune response is true?
Which statement about the innate immune response is true?
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What role does the acidic pH of the stomach play in innate immunity?
What role does the acidic pH of the stomach play in innate immunity?
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What is a major limitation of the innate immune system?
What is a major limitation of the innate immune system?
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Which of the following is NOT a physiological barrier of the innate immune system?
Which of the following is NOT a physiological barrier of the innate immune system?
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What is the primary function of skin as part of the innate immune system?
What is the primary function of skin as part of the innate immune system?
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Which component is involved in the innate cellular response?
Which component is involved in the innate cellular response?
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Study Notes
Innate Immune Response
- Innate immunity is a crucial part of any immune response.
- It reacts quickly to invading microbes, keeping the host alive while adaptive immunity develops a specific response.
- Innate defenses are present at birth, ready to fight infections.
- They have limited diversity in antigen recognition and attack microbes with consistent vigor regardless of encounter frequency.
- Innate immunity acts fast, immediately within minutes to hours after infection.
- The response doesn't retain memory, so repeated exposure doesn't enhance it.
Learning Objectives
- Identify innate immune components/barriers.
- Identify cells of innate immunity and their functions.
Innate Immune Components/Barriers
- Physical (anatomic) barriers:
- Skin: Most pathogens cannot penetrate intact skin; its pH is slightly acidic, hindering pathogen growth.
- Respiratory tract: Lined with cilia that help remove microbes, along with saliva and mucus (rich in antimicrobial enzymes and chemicals).
- Gastrointestinal (GI) tract: Also a mucous membrane, requiring pathogens to survive a highly acidic stomach environment. Sticky mucus traps foreign material.
- Physiologic barriers:
- Temperature: Many microbial pathogens cannot survive human body temperature.
- pH: The acidic pH of the stomach prevents pathogen growth and transmission. Skin pH also hinders pathogen growth.
- -Chemical: Lysozyme in secretions (tears, saliva, breast milk, mucus) breaks down bacterial cell walls. Defensins in phagocytes form pores in bacteria and fungi. Interferons (IFN-α and IFN-β) are antiviral.
Skin and Mucous Membranes
- Stratified epithelium (skin, lining of mouth)
- Embedded keratin
- Columnar epithelium (respiratory and reproductive systems)
- Cilia
- Mucus-producing cells
Innate Cellular Response
- Phagocytic cells (monocytes/macrophages, neutrophils, dendritic cells) are part of the first line of defense against invading pathogens.
- They recognize shared pathogen molecules (PAMPs) not found on host cells.
- Receptors of the innate immune system are called Pattern Recognition Receptors (PRRs).
- PRRs recognize pathogen-associated molecular patterns (PAMPs). Examples are molecules shared by pathogens (e.g., bacterial LPS)
- Innate receptors are built into the germline genes. They are not created by recombination in lymphocytes.
- Innate immunity can recognize up to 1000 pathogen patterns. Adaptive immunity recognizes over 1 billion or more.
Cells of Innate Immunity
- Neutrophils: Circulating phagocytes with a short lifespan, providing rapid but not prolonged defense.
- Eosinophils: Circulating phagocytes.
- Monocytes/Macrophages: Circulate in blood and become macrophages in tissues, promoting prolonged defense. Produce cytokines (inflammation), phagocytose pathogens, and clear dead tissue, aiding in tissue repair.
- Dendritic cells (DCs): Found throughout tissues, processing and presenting antigens. Initiate inflammatory responses and stimulate adaptive immunity.
- Mast cells: Found in skin and mucosa, playing a role in innate immunity via two activation pathways (innate TLRs and antibody-dependent, IgE).
- Natural killer cells (NK cells): Found in blood and periphery. Directly lyse cells and secrete IFN-γ.
Killing Mechanisms
- 1-NK cell mechanism: NK cells make close contact with target cells, releasing granules containing substances to cause lysis and activate apoptosis.
- 2- Antibody-dependent cell-mediated cytotoxicity (ADCC): IgG antibodies bind to target cells and to Fc receptors on NK cells, directing NK cells to kill the target cell.
Phagocytosis
- Process of engulfment and destruction of particles (bacteria, cellular debris, etc.).
- Involves chemotaxis, attachment, engulfment (phagosome formation), fusion with lysosomes (phagolysosome formation) and intracellular killing. Killing involves a variety of mechanisms.
- Microorganisms are exposed to a potent array of microbicidal proteins and oxidizing agents, eventually killing and digesting the microbe.
- Oxygen dependent killing and oxygen independent killing.
Chemotaxis
- Phagocytes move purposefully towards microorganisms following a chemoattractant.
- Source of chemoattractants from microorganisms and injured tissues.
- Chemotatic factors attract phagocytic cells to the infection site.
Attachment
- Phagocytes have receptors on their surface that recognize and bind pathogen-associated molecular patterns (PAMPs).
- PAMPs are shared by microorganisms and not present on host cells. These provide a target for phagocytes.
Engulfment
- Phagocytic membrane surrounds and encloses the organism in a vacuole termed a phagosome.
- Phagosome moves inside the cell.
- Phagocytosis is a specific membrane fusion event.
Fusion of phagosomes with lysosomes
- Fusion of phagosomes with lysosomes (containing enzymes and killing substances) creates phagolysosomes.
- The contents of phagolysosomes are mixed.
- These enzymes and killing factors are responsible for killing ingested microorganisms.
Killing
- Once ingested, microorganisms are exposed to potent microbicidal proteins and oxidizing agents, causing their death and digestion.
- Intracellular killing involves both oxygen-dependent and oxygen-independent pathways.
Intracellular Killing
- Respiratory burst (a metabolic process) generates reactive oxygen metabolites (important in killing).
- Reactive nitrogen intermediates also play a role.
- Lysosomal contents (e.g., lysozyme, defensins, lactoferrin, hydrolytic enzymes) have degradative effects.
Evasion of Phagocytosis
- Some microorganisms lack pattern molecules or coat themselves to evade recognition.
- Attachment can still occur if these microorganism become coated with opsonins (proteins like antibodies or complement).
- The coating makes them more desirable targets for phagocytosis.
Cytokines
- Important in mediating innate immune response.
- Pro-inflammatory cytokines (e.g. IL-1, IL-6, and TNF-α) produced by macrophages are involved in fever, cachexia and production of acute phase proteins.
- IL-12 secreted by macrophages promotes the activation of NK cells and type II interferons (IFN-γ). This promotes more class I MHC gene expression in general, as well as NK cell activation.
- IFN-α and IFN-β, secreted by virus infected cells, block viral replication.
- IFN-γ, secreted by T lymphocytes and NK cells, can interfere with virus replication in uninfected cells. Interferons also increase the MHC I and II expression in different cells.
Interferons
- Group of proteins with antiviral activity.
- IFN-α and IFN-β are part of innate immunity. Produced by virus-infected cells.
- IFN-γ is part of adaptive and innate immunity. Produced by T lymphocytes and NK cells.
- Mechanism of action: Interferons block viral replication by stimulating the production of cellular antiviral proteins.
Acute Phase Proteins
- Proteins that increase in the blood during infections, often in response to cytokines (IL-6).
- Examples include C-reactive protein.
- Mechanism of action: Acute phase proteins can bind to bacteria, promote microbial elimination through different effector mechanisms, and increase the killing ability of phagocytes.
Complement
- Group of proteins that is normally inactive, but gets activated resulting in elimination of the organism.
- Activation leads to elimination of the organism.
- Complement plays a role in inflammation, phagocytosis and target cell lysis.
Inflammation
- Process of inflammation that leads to leukocytes and plasma proteins for defense.
- Important and needed in the battle against infection.
- Inflammation is accompanied by local swelling, pain and redness.
Innate Immunity Conclusion
- Innate immunity is effective and sufficient to kill invading microbes.
- When initial innate mechanisms fail, they activate adaptive immunity which takes over to provide a specific defense.
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Description
Test your knowledge of the innate immune system and its components. This quiz covers the essential roles of innate immunity, including its rapid response to pathogens and the various physical barriers that protect the body. Learn about the cells involved in innate immunity and their functions.
