42.1 Innate Immune Response
3 min read•june 14, 2024
The innate immune system is our body's first line of defense against pathogens. It includes physical barriers like and , as well as chemical barriers like stomach acid and antimicrobial proteins. These defenses work together to prevent pathogens from entering and spreading in our bodies.
Beyond barriers, the innate immune system has cellular and protein-based responses. These include that destroy infected cells, the that marks pathogens for destruction, and the inflammatory response that recruits immune cells to fight infection. These mechanisms act quickly to contain threats before they become serious.
Physical and Chemical Barriers
Identify key physical and chemical barriers in the innate immune system
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- Skin acts as a physical barrier preventing pathogen entry maintains an acidic pH that inhibits microbial growth and contains that secrete oils with antimicrobial properties (fatty acids, enzymes)
- Mucous membranes line the respiratory, digestive, and reproductive tracts secrete mucus that traps pathogens (dust, bacteria) and contain antimicrobial enzymes that break down bacterial cell walls ()
- Chemical barriers include saliva, tears, and sweat which contain lysozyme and other antimicrobial substances (, ) gastric acid in the stomach kills ingested microbes (bacteria, viruses) and in the intestines disrupt bacterial cell membranes (E. coli, Salmonella)
Innate Immune Responses
Immediate vs induced innate responses
- Immediate innate immune responses are always present and ready to act include physical and chemical barriers, , and (, ) respond quickly to pathogens without prior exposure
- Induced innate immune responses are activated by the presence of pathogens or tissue damage include , , and (, ) take several hours to days to become fully active
- on immune cells recognize specific pathogen-associated molecular patterns, triggering innate immune responses
Role of natural killer cells
- are that recognize and kill infected (viruses) or abnormal cells (tumors)
- NK cells contain granules with which forms pores in the target cell membrane and which enter through the pores and induce (programmed cell death)
- NK cells secrete like to activate other immune cells (macrophages, T cells)
Function of MHC I molecules
- are present on the surface of all nucleated cells display peptide fragments from intracellular proteins, including viral or abnormal proteins
- NK cells and cytotoxic T cells recognize cells with abnormal or missing MHC I, indicating infection or abnormality (viruses, cancer)
- Recognition of abnormal MHC I leads to the destruction of the infected or abnormal cell through apoptosis or cell lysis
Complement System
Complement system for pathogen destruction
- Complement system is a group of plasma proteins that work together to destroy pathogens
- Three pathways activate the complement system:
- activated by antibody-antigen complexes (IgG, IgM)
- activated by microbial surface components (lipopolysaccharide)
- activated by mannose-binding lectin recognizing pathogen carbohydrates (mannose, fucose)
- Complement activation leads to a cascade of reactions, resulting in:
- where complement proteins coat pathogens, enhancing phagocytosis ()
- where complement fragments attract phagocytic cells to the site of infection ()
- (MAC) formation where complement proteins create pores in the pathogen's cell membrane, causing lysis ()
- Complement system helps clear pathogens (bacteria, viruses) and enhances the effectiveness of other immune responses (antibodies, phagocytes)
Inflammatory Response
Key components of the inflammatory response
- such as histamine and prostaglandins are released by damaged cells and immune cells, causing vasodilation and increased vascular permeability
- Cytokines produced by various immune cells coordinate the inflammatory response and recruit additional immune cells to the site of infection or injury
- contribute to the inflammatory response by producing cytokines and mediating tissue repair
Key Terms to Review (54)
Acute-phase proteins: Acute-phase proteins are a group of proteins whose plasma concentrations increase or decrease in response to inflammation. They play a crucial role in the innate immune response by enhancing the body's ability to fight infections and promote tissue repair. These proteins are primarily produced by the liver and can act as markers for inflammation, helping to indicate the presence and severity of an immune response.
Alternative pathway: The alternative pathway is a mechanism of the innate immune response that activates the complement system in a manner that does not require antibodies. This pathway serves as a critical line of defense against pathogens by promoting inflammation, opsonization, and lysis of microorganisms, thereby facilitating their elimination. It acts independently of the classical pathway, allowing for a rapid response to infections.
Apoptosis: Apoptosis is a programmed cell death process that occurs in multicellular organisms, characterized by a series of tightly regulated events leading to the elimination of unwanted or damaged cells. This mechanism is crucial for maintaining tissue homeostasis, regulating the cell cycle, and ensuring proper development and functioning of organisms.
Basophil: Basophils are a type of white blood cell involved in the immune response. They release histamine and other chemicals during allergic reactions and inflammation.
C-reactive protein: C-reactive protein (CRP) is a substance produced by the liver in response to inflammation, particularly during infections or tissue injury. It plays a crucial role in the innate immune response by binding to phosphocholine on the surface of dead or dying cells and bacteria, marking them for destruction by immune cells. Elevated levels of CRP are often indicative of an inflammatory condition, making it a valuable biomarker for assessing disease activity and risk.
C3b: C3b is a crucial protein component of the complement system, which is part of the innate immune response. It plays a key role in opsonization, where it binds to the surface of pathogens, marking them for destruction by phagocytes. Additionally, C3b is involved in the formation of the membrane attack complex and promotes inflammation, further enhancing the immune response against infections.
C5a: C5a is a small peptide that plays a crucial role in the innate immune response as an anaphylatoxin, which is generated from the cleavage of the complement protein C5. This molecule is vital for promoting inflammation and recruiting immune cells to sites of infection or injury, thereby enhancing the body's ability to respond to pathogens and tissue damage.
C5b-9: C5b-9, also known as the membrane attack complex (MAC), is a critical component of the innate immune response that forms a pore in the membranes of target cells, leading to cell lysis and death. This complex is generated through the activation of the complement system, specifically through the cleavage of complement proteins C5 through C9, and plays a crucial role in defending against infections by bacteria and some viruses.
Chemotaxis: Chemotaxis is the movement of an organism or cell in response to a chemical stimulus, typically towards higher concentrations of beneficial substances or away from harmful ones. This behavior is crucial for various biological processes, such as nutrient acquisition, immune responses, and cellular communication. In single-celled organisms, chemotaxis allows them to navigate their environments effectively, while in immune responses, it helps direct immune cells to sites of infection or injury.
Classical pathway: The classical pathway is a part of the complement system, a crucial component of the innate immune response, that is activated when antibodies bind to antigens on the surface of pathogens. This pathway involves a series of protein interactions that ultimately lead to the opsonization of pathogens, recruitment of inflammatory cells, and lysis of target cells. By promoting inflammation and enhancing the ability of immune cells to clear infections, the classical pathway plays a vital role in protecting the body against infections and maintaining homeostasis.
Complement system: The complement system is a group of proteins in the blood that enhance the ability of antibodies and phagocytic cells to clear pathogens. It plays a crucial role in the innate immune response by promoting inflammation and attacking the pathogen's cell membrane.
Complement system: The complement system is a complex network of proteins that play a crucial role in the immune response, primarily by enhancing the ability of antibodies and phagocytic cells to clear pathogens. This system can be activated via three pathways: the classical pathway, the alternative pathway, and the lectin pathway. Each pathway leads to a cascade of reactions that ultimately result in pathogen lysis, inflammation, and opsonization, linking innate and adaptive immune responses.
Cytokine: Cytokines are small proteins that act as signaling molecules in the immune system. They regulate inflammation, immunity, and hematopoiesis by facilitating communication between cells.
Cytokines: Cytokines are small signaling proteins produced by various cells in the immune system that play a crucial role in cell communication and regulation during immune responses. They are vital for both the innate and adaptive immune responses, coordinating activities such as inflammation, cell growth, differentiation, and apoptosis. By acting on nearby cells or even distant ones, cytokines help orchestrate the body's defense against pathogens and maintain homeostasis.
Defensins: Defensins are small, cationic peptides that play a critical role in the innate immune response by exhibiting antimicrobial properties against bacteria, fungi, and viruses. These peptides are produced by various cells, including neutrophils and epithelial cells, and contribute to the first line of defense against pathogens. Their ability to disrupt microbial membranes makes them essential for protecting the host from infections.
Eosinophil: Eosinophils are white blood cells and a type of granulocyte involved in the immune response. They play a crucial role in combating parasitic infections and modulating allergic inflammatory responses.
Fever: Fever is an increase in body temperature that typically occurs as a physiological response to infection, inflammation, or other illness. It serves as a vital defense mechanism in the innate immune response, enhancing the body's ability to fight off pathogens by creating an unfavorable environment for their survival and boosting the efficiency of immune cells.
Fibrinogen: Fibrinogen is a soluble plasma glycoprotein produced by the liver, playing a crucial role in blood clotting by converting into fibrin during the coagulation process. It is essential for hemostasis, as it helps form a stable clot that prevents excessive bleeding. The presence of fibrinogen is vital in the innate immune response, as it also aids in trapping pathogens and facilitating wound healing.
Gigantism: Gigantism is a condition characterized by excessive growth and height significantly above average due to overproduction of growth hormone (GH) during childhood. It results from abnormal functioning of the pituitary gland.
Granzyme: Granzyme is a serine protease enzyme released by cytotoxic T cells and natural killer (NK) cells. It induces apoptosis in target cells by cleaving specific substrates within the cell.
Granzymes: Granzymes are serine proteases released by cytotoxic T cells and natural killer (NK) cells that play a vital role in the innate immune response. They are involved in inducing apoptosis, or programmed cell death, in target cells, particularly those that are infected or cancerous. By triggering cell death, granzymes help eliminate harmful cells, thus maintaining the integrity of the immune system and supporting overall health.
IgA: IgA, or Immunoglobulin A, is an antibody that plays a crucial role in the immune system by providing protection at mucosal surfaces such as those found in the respiratory and gastrointestinal tracts. It is primarily present in secretions like saliva, tears, and breast milk, serving as a first line of defense against pathogens entering the body through mucous membranes. This antibody helps prevent infections by neutralizing bacteria and viruses, highlighting its importance in both innate and adaptive immune responses.
Inflammation: Inflammation is the body's immediate response to injury or infection, characterized by redness, heat, swelling, and pain. It aims to eliminate the initial cause of cell injury, clear out damaged cells and tissues, and establish a repair process.
Inflammation: Inflammation is the body's natural response to injury or infection, characterized by redness, swelling, heat, and pain. It serves as a protective mechanism, helping to eliminate harmful stimuli and initiate the healing process. In the context of innate immune response, inflammation is essential for recruiting immune cells to sites of damage or infection, thereby facilitating the body's defense against pathogens.
Inflammation mediators: Inflammation mediators are chemical substances that are released during the inflammatory response to initiate and regulate the healing process. They play a crucial role in signaling to immune cells, causing blood vessels to dilate, and increasing vascular permeability, which helps deliver immune cells and nutrients to the site of injury or infection.
Innate immunity: Innate immunity is the body's first line of defense against pathogens, providing an immediate but non-specific response. It involves physical barriers, immune cells, and various proteins to protect the host from infection.
Innate lymphoid cells: Innate lymphoid cells (ILCs) are a group of immune cells that play a crucial role in the innate immune response, acting as key players in the body's first line of defense against pathogens. They are found in various tissues and are involved in the regulation of immune responses, tissue homeostasis, and inflammation. ILCs help bridge the gap between innate and adaptive immunity by producing various cytokines that influence the behavior of other immune cells.
Interferon-gamma: Interferon-gamma is a cytokine that plays a crucial role in the immune response, particularly in the innate immune system. It is primarily produced by T cells and natural killer (NK) cells and is important for activating macrophages, enhancing antigen presentation, and promoting the differentiation of T cells. Its actions help to protect the body against infections and are integral to the regulation of both innate and adaptive immunity.
Lectin pathway: The lectin pathway is a part of the innate immune response that activates the complement system through the binding of lectins to specific carbohydrates on pathogens. This pathway serves as a crucial first line of defense against infections, as it helps to identify and eliminate pathogens without the need for antibodies. The lectin pathway also enhances opsonization and promotes inflammation, making it an essential mechanism in immune surveillance.
Lymphocytes: Lymphocytes are a type of white blood cell crucial for the immune system. They play vital roles in both the innate and adaptive immune responses.
Lysozyme: Lysozyme is an enzyme that breaks down the cell walls of certain bacteria, leading to their destruction. It plays a crucial role in the innate immune response, serving as a first line of defense against bacterial infections by hydrolyzing the peptidoglycan layer in bacterial cell walls, thus promoting bacterial lysis and enhancing overall immunity.
Macrophages: Macrophages are a type of white blood cell that play a crucial role in the innate immune response by detecting, engulfing, and destroying pathogens and cellular debris. These large cells act as key players in the immune system's first line of defense, initiating inflammatory responses and helping to activate other immune cells. Macrophages are derived from monocytes and can adapt their function depending on the signals they receive from their environment.
Major histocompatibility complex (MHC) I molecules: Major histocompatibility complex (MHC) I molecules are proteins found on the surface of all nucleated cells that present endogenous antigens to cytotoxic T cells. They play a crucial role in the immune system's ability to recognize and destroy infected or malignant cells.
Major histocompatibility complex I: Major histocompatibility complex I (MHC I) refers to a set of molecules displayed on the surface of nearly all nucleated cells in the body, crucial for the immune system's ability to recognize and respond to foreign antigens. These proteins present peptide fragments derived from intracellular proteins, including those from pathogens, to CD8+ cytotoxic T cells, playing a pivotal role in the adaptive immune response and influencing how the innate immune response is activated.
Mast cell: Mast cells are immune cells found in connective tissues, especially in the skin, lungs, and digestive tract. They play a crucial role in the body's allergic and inflammatory responses by releasing histamines and other chemicals.
Membrane attack complex: The membrane attack complex (MAC) is a structure formed by the complement system, specifically the terminal complement proteins, which creates pores in the membranes of target cells, leading to cell lysis and death. This mechanism is a critical part of the innate immune response, serving to eliminate pathogens such as bacteria and some viruses by compromising their cell membranes. The formation of the MAC is a result of a cascade reaction initiated by immune recognition, emphasizing its role in enhancing the body's defense against infection.
MHC II molecules: MHC II molecules are proteins found on the surface of certain immune cells that present antigens to T-helper cells. They play a crucial role in initiating and regulating the adaptive immune response.
Monocyte: Monocytes are a type of white blood cell that plays a crucial role in the immune system by phagocytosing pathogens and presenting antigens to T cells. They circulate in the blood and migrate into tissues where they differentiate into macrophages or dendritic cells.
Mucous membranes: Mucous membranes are protective layers of tissue that line various cavities and internal organs, serving as a barrier against pathogens and environmental hazards. These membranes produce mucus, which helps trap foreign particles and microorganisms, playing a crucial role in the innate immune response by providing both physical and biochemical defenses against infections.
Natural killer (NK) cells: Natural killer (NK) cells are a type of lymphocyte in the innate immune system that can destroy virus-infected cells and tumor cells. They recognize stressed cells in the absence of antibodies, allowing for a faster immune reaction.
Natural killer cells: Natural killer (NK) cells are a type of lymphocyte in the innate immune system that play a crucial role in the body's defense against tumors and virally infected cells. These cells can recognize and eliminate compromised cells without prior sensitization, making them vital for early immune responses and bridging the innate and adaptive immune systems.
Neutrophil: Neutrophils are a type of white blood cell that play a crucial role in the body's innate immune response by engulfing and destroying pathogens. They are the most abundant type of white blood cells and act as first responders to infection.
Neutrophils: Neutrophils are a type of white blood cell that plays a crucial role in the body's innate immune response, primarily serving as the first line of defense against invading pathogens. These cells are characterized by their multi-lobed nucleus and granules filled with enzymes that help to digest bacteria and other harmful microorganisms. Neutrophils make up about 60-70% of the total white blood cell count, highlighting their significance in both blood components and immune function.
Opsonization: Opsonization is a process by which pathogens are marked for ingestion and destruction by phagocytes. This enhances the efficiency of the immune response by facilitating the binding of pathogens to immune cells.
Opsonization: Opsonization is the process by which pathogens are marked for destruction by immune cells, enhancing their recognition and uptake. This is crucial in both the innate and adaptive immune responses, as it allows phagocytic cells, like macrophages and neutrophils, to more effectively eliminate invading microorganisms. Opsonization can involve antibodies or complement proteins binding to the surface of pathogens, providing signals that promote their engulfment and clearance from the body.
Pathogen-associated molecular patterns (PAMPs): Pathogen-associated molecular patterns (PAMPs) are conserved molecular structures found on the surface of many pathogens. They are recognized by the innate immune system as foreign, triggering an immune response.
Pattern Recognition Receptors: Pattern recognition receptors (PRRs) are a class of proteins found on the surface of immune cells that recognize specific molecular patterns associated with pathogens, damaged cells, or stress signals. They play a critical role in the innate immune response by initiating signaling cascades that lead to the activation of immune defenses and the promotion of inflammation.
Pattern recognition receptors (PRRs): Pattern recognition receptors (PRRs) are proteins on or in cells that recognize and bind to specific molecular patterns found on pathogens. They play a crucial role in the innate immune response by detecting microbial invaders and initiating immune signaling pathways.
Perforin: Perforin is a protein released by cytotoxic T cells and natural killer (NK) cells that forms pores in the membranes of target cells. This action leads to cell lysis and death of the infected or malignant cells.
Perforin: Perforin is a protein that plays a crucial role in the immune response by forming pores in the membranes of target cells, allowing other cytotoxic molecules to enter and induce cell death. This action is vital for the innate immune system, particularly in the destruction of virally infected cells and tumor cells by cytotoxic T lymphocytes and natural killer (NK) cells.
Peroxidase: Peroxidase is an enzyme that catalyzes the oxidation of various substrates by hydrogen peroxide, playing a vital role in cellular processes such as defense against oxidative stress. This enzyme is crucial for the innate immune response, as it helps neutralize harmful reactive oxygen species produced during inflammation and microbial infection, thus protecting tissues from damage.
Phagocytic cells: Phagocytic cells are specialized immune cells that engulf and digest cellular debris, foreign particles, and pathogens through a process called phagocytosis. These cells play a crucial role in the innate immune response by acting as the body's first line of defense against infections and contributing to inflammation and tissue repair.
Sebaceous glands: Sebaceous glands are small, exocrine glands found in the skin that secrete an oily substance called sebum. This secretion plays a crucial role in maintaining skin and hair health, providing lubrication, and offering some antimicrobial protection, which ties into the innate immune response by acting as a barrier against pathogens.
Skin: Skin is the largest organ of the body, serving as a protective barrier between the internal environment and external threats. It plays a crucial role in the innate immune response by providing the first line of defense against pathogens, preventing their entry into the body. Additionally, skin contains various immune cells that contribute to the body’s overall defense mechanisms.