Immunology

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.

Viruses (e.g. influenza)

Bacteria (e.g. Mycobacterium tuberculosis)

Fungi (e.g. Pneumocystis carinii)

Parasites (e.g. Trypanosoma brucei)

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).

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 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.

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.

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.

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.

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.

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.

• Innate immune system: Immediate to hours.

• Adaptive immune system: Days (usually 4-7) to develop a full response.

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.

• Innate Immune System: 1st Line of Defense

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.

• Innate Immune System: 1st Line of Defense

• Mechanical defense provided by mucus and cilia moving fluid and pathogens out. Chemical defenses include lysozyme in nasal secretions that destroys bacteria.

• Innate Immune System: 1st Line of Defense

• 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.

• Innate Immune System: 1st Line of Defense

• 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.

• Innate Immune System: 1st Line of Defense

• Protected by the mechanical action of tears flushing out pathogens, and chemically by lysozyme present in tears that can lyse bacteria.

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.

Monocyte - Mononuclear phagocyte

• Innate Immune System - 2nd Line of Defense

• Circulate in the blood

• Protect against bloodborne infections

• Mature into macrophages in tissues

• Can mature to macrophages or dendritic cells

Macrophage - Mononuclear phagocyte

• 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 Cell - Mononuclear phagocyte

• Innate Immune System - 2nd Line of Defense

• 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

• Innate Immune System - 2nd Line of Defense

• 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-Granulocytes

• Innate Immune System - 2nd Line of Defense

• 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-Granulocytes

• Innate Immune System - 2nd Line of Defense

• Involved in controlling immune responses to parasites.

• Release histamine and other mediators during inflammatory reactions.

Eosinophil-Granulocytes

• Innate Immune System - 2nd Line of Defense

• Target antibody-coated parasites.

• Destroy parasites by releasing cytotoxic granule contents.

Mast Cell-Granulocytes

• Innate Immune System - 2nd Line of Defense

• Play a role in expelling parasites from the body.

• Release histamine and other active substances to recruit other immune cells and attack parasites.

• Part of cell-mediated adaptive immunity

• Respond to processed antigens presented by other cells

• Have T-cell receptors with specific antigen-binding sites

• 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

• 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.

• A mature B or T cell that has not yet encountered its specific antigen.

• Activation of these cells initiates adaptive immune response.

• Adaptive immune response

• Initial recognition of a pathogen by specific naive lymphocytes.

• Selected lymphocytes undergo clonal expansion.

• Adaptive immune response

• Rapid multiplication of lymphocyte clones specific to the pathogen.

• Occurs over approximately 4-7 days post-infection.

• Adaptive immune response

• Cloned lymphocytes differentiate into effector cells.

• B cells become plasma cells that produce antibodies.

• T cells become cytotoxic T cells or helper T cells.

• Adaptive immune response

• Effector cells act to eliminate the pathogen.

• Antibodies neutralize pathogens; cytotoxic T cells kill infected cells.

• Adaptive immune response

• Post-pathogen clearance, the number of effector cells reduces.

• Prevents excessive immune activity.

• Adaptive immune response

• Some effector cells become long-lived memory cells.

• Provide quicker, more effective response upon re-exposure to the pathogen.

• Inactive state with B cell receptors (BCRs) on its surface.

• Awaits encounter with a specific antigen.

• Occurs when BCRs bind to their specific antigen.

• Activation leads to clonal expansion and differentiation

• Activated B cells differentiate into plasma cells.

• Plasma cells are specialized for antibody production.

• Plasma cells secrete antibodies, the soluble form of BCRs.

• Antibodies circulate to bind and neutralize pathogens.

• Produced by B cells and plasma cells.

• Circulate in blood and tissue, targeting extracellular pathogens.

• Antibodies bind to pathogens and toxins.

• Neutralize their capacity to infect or intoxicate host cells

• Antibodies coat pathogens, marking them for phagocytosis.

• Enhance phagocyte ability to recognize, engulf, and degrade pathogens.

• Antibody-coated pathogens bind complement proteins.

• Facilitate pathogen recognition by phagocytes via complement receptors.

• 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.

• Activate macrophages through cytokine release.

• Result in more effective phagocytosis and antigen presentation by macrophages.

• Identified by CD4 marker on their surface.

• Stimulate B cells to proliferate and differentiate.

• Lead to the production of specific antibodies by plasma cells.

• Essential for humoral immune response coordination.

• Locations where lymphocytes are formed and mature.

• Bone marrow: B cells mature here.

• Thymus: T cells mature here.

• 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.

• 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).

• 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.

• 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 are key sites where lymphocytes may encounter and bind to their specific antigens

• Activation leads to lymphocyte proliferation and differentiation into effector cells

• 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.

• 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.

• 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.

• 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.

• 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.

Types of barriers of the immediate inate immune response:

• Physical/Mechanical

  • Epithelia

  • Movement e.g. cilia/peristalsis

• Chemicial

  • Antimicrobial peptides

  • Fatty acids

  • pH

• Microbiological

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.

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.

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.

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.

• 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.

• 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.

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.

• 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

• 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.

They compete with pathogens for nutrients and space, inhibit other bacteria through antimicrobial substances, and stimulate the immune system to express defense factors.

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.

Extracellular pathogens are targeted by plasma proteins while intracellular pathogens are combated by cell-mediated responses.

Opsonization marks pathogens for phagocytosis, involving complement system, pentraxins like CRP, and antibodies.

Plasma proteins regulate tissue permeability through coagulation and kinin systems, compartmentalizing infections and containing pathogen spread.

Pentraxins are pattern recognition receptors that bind to microbial components, aiding in phagocytosis either directly or indirectly through the complement system.

Immunothrombosis traps pathogens within thrombi, limits their movement, recruits leukocytes, and increases local concentration of antimicrobial peptides.

Kinin system increases blood vessel permeability to allow immune cells to access the site of infection and promote inflammation.

Protease inhibitors like α2-Macroglobulins neutralize microbial proteases, preventing tissue damage and pathogen dissemination.

Macrophages in tissues perform specific and non-specific phagocytosis and recruit neutrophils, playing a key role in tissue homeostasis and immune response.

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.

Parasites use strategies like changing their surface proteins, having multiple genes for similar functions, and mimicking host molecules to evade the immune response.

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.

Inhibitory antibodies interfere with the processing of MSP-1, which is a part of the malaria parasite's life cycle.

Blocking antibodies counteract the action of inhibitory antibodies, allowing the processing of MSP-1 in the malaria parasite.