Hematopoietic Stem Cell
The origin point for all blood cells, a multipotent stem cell capable of differentiating into various blood cell types, including those that make up the immune system.
Name the different type of pathogens
Viruses (e.g. influenza)
Bacteria (e.g. Mycobacterium tuberculosis)
Fungi (e.g. Pneumocystis carinii)
Parasites (e.g. Trypanosoma brucei)
Myeloid Cells
A group of blood cells that arise from the common myeloid precursor; includes granulocytes (neutrophils, eosinophils, and basophils), monocytes (which can differentiate into macrophages and dendritic cells), megakaryocytes (platelet producers), and erythroblasts (precursors to red blood cells).
Lymphoid Cells
Cells derived from the common lymphoid precursor, crucial to the adaptive immune system; includes B cells (which can differentiate into antibody-producing plasma cells), T cells (which differentiate into various effector cells), and natural killer (NK) cells (which can destroy compromised host cells)
Innate vs. Adaptive Immune System Cells
Innate immune system cells (granulocytes, monocytes, NK cells) provide immediate defense with limited specificity. Adaptive immune system cells (B and T lymphocytes) are slower to respond but highly specific and can remember pathogens for a stronger response upon re-exposure.
Innate Immune System
Provides immediate defense against infection. Uses pattern recognition receptors encoded by germline DNA to identify common pathogens. It responds rapidly but with limited specificity and has limited memory capabilities.
Pattern Recognition Receptors (PAMPs)
Receptors in the innate immune system that can identify pathogen-associated molecular patterns (PAMPs) common to groups of pathogens, allowing for a quick response to infections.
Adaptive Immune System
Develops a slower, but more specific response to pathogens. Utilizes T- and B-cell receptors generated through somatic recombination, providing a wide array of specificities and producing a strong memory after initial exposure.
Somatic Recombination
The process by which T-cell and B-cell receptors are generated, allowing for a highly diverse set of receptors that can specifically recognize a vast array of antigens unique to different pathogens.
Immune Memory
A feature of the adaptive immune system. Once it responds to a specific pathogen, it creates memory cells that remember it, leading to a quicker and more effective response upon subsequent exposures.
Response Time
Innate immune system: Immediate to hours.
Adaptive immune system: Days (usually 4-7) to develop a full response.
Innate Immune System: 1st Line of Defense
The body's initial barrier against pathogens, consisting of physical and chemical defenses. Physical (mechanical) barriers include the skin and mucous membranes of the respiratory, gastrointestinal, and urogenital tracts. Chemical barriers include acidic environments, enzymes like lysozyme, and antimicrobial peptides that destroy or inhibit pathogens.
Skin
Acts as a mechanical barrier with the flow of fluid, perspiration, and shedding of skin cells. Chemically, it produces sebum containing fatty acids, lactic acid, and lysozyme for antimicrobial defense.
Respiratory Tract
Mechanical defense provided by mucus and cilia moving fluid and pathogens out. Chemical defenses include lysozyme in nasal secretions that destroys bacteria.
Gastrointestinal tract
Protected by epithelial cells with tight junctions. Mechanical defense includes the flow of fluid, mucus, and food, while chemical defense comes from acidity, digestive enzymes, and antimicrobial peptides like defensins.
Urogenital Tract
Mechanically cleansed by the flow of urine and mucus. Chemical defenses include the acidity of vaginal secretions, spermine, and zinc in semen with antimicrobial properties.
Eyes
Protected by the mechanical action of tears flushing out pathogens, and chemically by lysozyme present in tears that can lyse bacteria.
Innate Immune System - 2nd Line of Defense
When pathogens penetrate the initial physical barriers, the second line of defense engages. Immune cells recognize these pathogens, triggering inflammation—manifested by redness, heat, swelling, and pain. In this process, immune cells release cytokines, which not only help in coordinating the attack against the pathogens but also serve as a bridge to the adaptive immune system, signaling it to initiate a more specific immune response.
Monocytes
Circulate in the blood
Protect against bloodborne infections
Mature into macrophages in tissues
Can mature to macrophages or dendritic cells
Macrophages
Reside in tissues and organs, acting as scavengers.
Engage in phagocytosis of debris, microbes, and cancer cells.
Key players in inflammation, releasing cytokines to recruit immune cells.
Participate in antigen presentation, albeit less effectively than dendritic cells.
Dendritic Cells
Found mainly in tissues
Detect pathogens and induce inflammation
Phagocytose microorganisms
Professional antigen-presenting cells that process and present antigens to T cells
Excel at activating naive T-cells, initiating adaptive immune responses
Phagocytosis
Process by which cells engulf and digest pathogens and particles.
Involves opsonization, phagosome formation, and fusion with lysosomes.
Carried out by monocytes, macrophages, and dendritic cells.
Neutrophil
Most abundant white blood cell.
Quickly mobilized to infected sites.
Engage in phagocytosis and release antimicrobial substances.
Short-lived, often die at the infection site, forming pus.
Basophil
Involved in controlling immune responses to parasites.
Release histamine and other mediators during inflammatory reactions.
Eosinophil
Target antibody-coated parasites.
Destroy parasites by releasing cytotoxic granule contents.
Mast Cell
Play a role in expelling parasites from the body.
Release histamine and other active substances to recruit other immune cells and attack parasites.
T Lymphocytes (T cells)
Part of cell-mediated adaptive immunity
Respond to processed antigens presented by other cells
Have T-cell receptors with specific antigen-binding sites
B Lymphocytes (B cells)
Central to humoral immune response
B-cell receptors can bind directly to specific free-floating antigens
Upon activation, can differentiate into plasma cells that produce antibodies
Antigen
A substance (molecule, particle, cell) that is recognized and bound by specific B or T cell receptors.
Can be part of a pathogen or abnormal body cells.
Triggers an adaptive immune response when detected.
Naïve Lymphocyte
A mature B or T cell that has not yet encountered its specific antigen.
Activation of these cells initiates adaptive immune response.
Clonal Selection
Adaptive immune response
Initial recognition of a pathogen by specific naive lymphocytes.
Selected lymphocytes undergo clonal expansion.
Clonal Expansion
Rapid multiplication of lymphocyte clones specific to the pathogen.
Occurs over approximately 4-7 days post-infection.
Differentiation into Effector Cells
Cloned lymphocytes differentiate into effector cells.
B cells become plasma cells that produce antibodies.
T cells become cytotoxic T cells or helper T cells.
Pathogen Clearance
Effector cells act to eliminate the pathogen.
Antibodies neutralize pathogens; cytotoxic T cells kill infected cells.
Contraction Phase
Post-pathogen clearance, the number of effector cells reduces.
Prevents excessive immune activity.
Memory Cells
Some effector cells become long-lived memory cells.
Provide quicker, more effective response upon re-exposure to the pathogen.
Resting B Cell
Inactive state with B cell receptors (BCRs) on its surface.
Awaits encounter with a specific antigen.
B Cell Activation
Occurs when BCRs bind to their specific antigen.
Activation leads to clonal expansion and differentiation
Plasma Cell Differentiation
Activated B cells differentiate into plasma cells.
Plasma cells are specialized for antibody production.
Antibody Production
Plasma cells secrete antibodies, the soluble form of BCRs.
Antibodies circulate to bind and neutralize pathogens.
Antibodies
Produced by B cells and plasma cells.
Circulate in blood and tissue, targeting extracellular pathogens.
Neutralization
Antibodies bind to pathogens and toxins.
Neutralize their capacity to infect or intoxicate host cells
Opsonization
Antibodies coat pathogens, marking them for phagocytosis.
Enhance phagocyte ability to recognize, engulf, and degrade pathogens.
Complement System in Opsonization
Antibody-coated pathogens bind complement proteins.
Facilitate pathogen recognition by phagocytes via complement receptors.
Killer T Cells (Cytotoxic T Cells)
Recognize and bind to virus-infected cells. (sometimes also bacterial infected cells)
Induce apoptosis in infected cells to prevent virus spread.
Identified by CD8 marker on their surface.
Helper T Cells (Macrophage Activation)
Activate macrophages through cytokine release.
Result in more effective phagocytosis and antigen presentation by macrophages.
Identified by CD4 marker on their surface.
Helper T Cells (B Cell Activation)
Stimulate B cells to proliferate and differentiate.
Lead to the production of specific antibodies by plasma cells.
Essential for humoral immune response coordination.
Primary/Central Lymphoid Organs
Locations where lymphocytes are formed and mature.
Bone marrow: B cells mature here.
Thymus: T cells mature here.
Secondary/Peripheral Lymphoid Organs
Sites where mature lymphocytes become activated by antigens.
Include lymph nodes, spleen, Peyer's patches, tonsils, and adenoids.
Facilitate interactions between lymphocytes and antigens, leading to immune responses.
Lymphatic System
A network of vessels, nodes, and organs that maintain fluid balance and participate in immune surveillance.
Transports lymph, a fluid containing immune cells.
Includes primary organs where lymphocytes mature (bone marrow, thymus) and secondary organs where they become activated (lymph nodes, spleen).
Lymphocyte Recirculation and Circulation
Continuous movement of lymphocytes between the bloodstream and lymphatic system via High Endothelial Venules (HEVs) and efferent lymphatic vessels.
HEVs allow lymphocytes to enter lymph nodes from the blood, facilitating immune surveillance.
Efferent lymphatic vessels carry lymph and lymphocytes out of lymph nodes, leading to larger ducts that return them to the bloodstream.
This process maximizes the immune system's efficiency in detecting antigens and responding to pathogens throughout the body.
High Endothelial Venules (HEVs)
Specialized blood vessels in lymph nodes through which lymphocytes enter from the bloodstream
Characterized by a cuboidal endothelium, unlike the flat endothelium of other venules
Lymph Nodes and Lymphocyte Activation
Lymph nodes are key sites where lymphocytes may encounter and bind to their specific antigens
Activation leads to lymphocyte proliferation and differentiation into effector cells
How do lymphocytes return to the bloodstream?
Lymphocytes re-enter the bloodstream via the thoracic duct or right lymphatic duct, which drain into the subclavian veins.
Allows for the distribution of activated lymphocytes to sites of infection or inflammation.
Lymph Node Structure
Contains afferent lymphatic vessels for lymph entry.
Features lymphoid follicles (mostly B cells) and germinal centers for B cell activation.
T-cell areas for T cell activation.
Efferent lymphatic vessels for lymph exit.
Medullary sinuses where lymph is filtered.
Adaptive Immune Response in Lymph Node
Initiated when dendritic cells present antigens to T cells in T-cell areas.
B cells in lymphoid follicles are activated by helper T cells.
Plasma cells derived from B cells produce antibodies.
Antibodies and activated T cells leave the lymph node to engage pathogens.
Gut-associated Lymphoid Tissue (GALT)
Integral part of the mucosal-associated lymphoid tissue (MALT) located in the gut.
Composed of immune cells like B cells in follicles and T cells in the surrounding areas.
Contains M cells that sample antigens from the gut lumen and present them to immune cells.
Facilitates the immune response to ingested pathogens through specialized germinal centers.
Drains lymph through efferent lymphatic vessels after immune cell activation.
Spleen in Adaptive Immunity
Filters blood and provides an immune response to blood-borne pathogens.
White pulp is involved in the immune function, containing B-cell corona and germinal centers.
Red pulp is responsible for filtering out old red blood cells and pathogens.
Marginal zone acts as a site for antigen capture and presentation.
Central arterioles supply blood, and Periarteriolar Lymphoid Sheath (PALS) contains T cells for initiating immune responses.
Which are the types of barriers used in the immediate inate immune response?
Types of barriers of the immediate inate immune response:
Physical/Mechanical
Epithelia
Movement e.g. cilia/peristalsis
Chemicial
Antimicrobial peptides
Fatty acids
pH
Microbiological
What are epithelial barriers and where are they found?
Epithelial barriers are tissues that separate the body from the external environment. They cover outer surfaces like skin and line inner cavities, including the respiratory, gastrointestinal, and urogenital tracts. These barriers serve as the first line of defense in the immune system.
Epithelial cells are joined by tight junctions.
How does the skin act as a physical barrier?
The skin provides a physical barrier through its cornified layer, made up of dead cells that create a tough surface (stratum corneum). This 'brick and mortar' structure effectively prevents pathogen entry and adhesion.
Describe the defense mechanism of the respiratory tract.
The respiratory tract is lined with ciliated epithelial cells that move mucus along with trapped pathogens, which helps in clearing them from the airways and preventing infection.
What are the defense mechanisms of the gastrointestinal tract?
The gastrointestinal tract uses a layer of mucus to trap pathogens and antimicrobial peptides to destroy them, preventing them from penetrating the gut lining and entering the bloodstream.
What do Antimicrobial Proteins (Host Defense Peptides) do?
Antimicrobial proteins like defensins are crucial in killing bacteria, enveloped viruses, and fungi.
Defensins are amphipathic, which helps them integrate into and disrupt pathogen membranes.
They are considered broad-spectrum antibiotics and are a potential new therapeutic strategy.
Chemical Barriers of Epithelia
Antimicrobial peptides and enzymes, along with low pH and fatty acids, serve as chemical barriers.
Different areas of the body, such as skin, gut, lungs, and eyes/nose/oral cavity, utilize distinct chemical defenses like fatty acids and antimicrobial peptides to prevent pathogen entry.
Where are defensins synthesized, and what regulates their production?
Defensins are synthesized by epithelial cells and certain immune cells like neutrophils. Their production is either constitutive, meaning they are always being produced at a steady rate, or induced in the presence of pathogens.
Antimicrobial Peptides - Defensins
Inactive pro-form requiring proteolytic cleavage
Requires lower ions
Increase electrostatic interaction
Secreted by epithelia
Kill pathogen in the extracellular space
Granules of neutrophils
Kill phagocytized pathogens
What are antimicrobial enzymes and their functions in the immune system?
Lysozymes (Glycosidase): Break down peptidoglycans in bacterial cell walls, compromising structural integrity.
Lipases: Degrade phospholipids in bacterial membranes, disrupting membrane-based processes.
Nucleases: Degrade genetic material of pathogens, preventing their replication and spread.
Proteases: Break down foreign proteins, including those of invading pathogens, hindering their function.
What is the role of commensal bacteria in the innate immune system?
They compete with pathogens for nutrients and space, inhibit other bacteria through antimicrobial substances, and stimulate the immune system to express defense factors.
How can the commensal niche be disturbed, and what are the potential consequences?
The balance of commensal bacteria can be upset by antibiotics, infections, immune deficiencies, or dietary changes. This can allow pathogenic bacteria to dominate and potentially cause disease.
Role of extracellular vs. intracellular pathogens in immune response
Extracellular pathogens are targeted by plasma proteins while intracellular pathogens are combated by cell-mediated responses.
Function of opsonization in phagocytosis
Opsonization marks pathogens for phagocytosis, involving complement system, pentraxins like CRP, and antibodies.
How plasma proteins regulate tissue permeability and restrict infection
Plasma proteins regulate tissue permeability through coagulation and kinin systems, compartmentalizing infections and containing pathogen spread.
Role of pentraxins in immune response
Pentraxins are pattern recognition receptors that bind to microbial components, aiding in phagocytosis either directly or indirectly through the complement system.
Mechanism of immunothrombosis in pathogen containment
Immunothrombosis traps pathogens within thrombi, limits their movement, recruits leukocytes, and increases local concentration of antimicrobial peptides.
Impact of kinin system on blood vessels during infection
Kinin system increases blood vessel permeability to allow immune cells to access the site of infection and promote inflammation.
Function of protease inhibitors in immune response
Protease inhibitors like α2-Macroglobulins neutralize microbial proteases, preventing tissue damage and pathogen dissemination.
Role of tissue resident macrophages
Macrophages in tissues perform specific and non-specific phagocytosis and recruit neutrophils, playing a key role in tissue homeostasis and immune response.
What is the evolutionary arms race in the context of parasites and hosts?
The evolutionary arms race refers to the ongoing struggle between parasites and their hosts, where parasites evolve mechanisms to evade the immune system and hosts develop stronger immune responses.
What are some strategies used by parasites like malaria to evade the immune system?
Parasites use strategies like changing their surface proteins, having multiple genes for similar functions, and mimicking host molecules to evade the immune response.
What broader evolutionary questions are raised by parasite-host interactions?
Parasite-host interactions raise questions about how these relationships shape the evolution of both and why certain parasites evolve to be more or less harmful to their hosts.
What is the role of inhibitory antibodies in the processing of MSP-1?
Inhibitory antibodies interfere with the processing of MSP-1, which is a part of the malaria parasite's life cycle.
What is the role of blocking antibodies in the processing of MSP-1?
Blocking antibodies counteract the action of inhibitory antibodies, allowing the processing of MSP-1 in the malaria parasite.
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