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66 Cards in this Set
- Front
- Back
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What categories of defense do epithelial surfaces provide?
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Mechanical defenses like liquid flow (mucus, perspiration, tears, urine, food)
Chemical defenses (degradative enzymes, lysozyme, sebum, acidity) Microbiological defenses (normal flora, compete with pathogens) |
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2 components of immune system?
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cellular and soluble
Solubles includes ABs, complement, cytokines, chemokines, leukotrienes, prostaglandins Cellulars include B and T cells of the adaptive immune response. Innate response mediated by granulocytes (neutrophils, basophils,eosinophils), dendritic cells, macrophage, mast cells, NK cells (lympocyte) |
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What is the largest component of the innate immune response?
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INFLAMMATION (Heat, redness, swelling, pain = hallmarks of inflammation).
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What are the steps of inflammation?
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infectious agent accesses tissue through a wound. resident effector cells (macrophage, mast cell, dendritic cell) release cytokines in response to sensing non-host invasion. Cytokines precipitate local vasodilation and leakiness of vessel, allowing fluid, immune soluble molecules, and cells to enter tissue. Local area becomes red, hot, painful, and swollen.
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What are the differences between innate and adaptive immunity and what cells and molecules execute their activity?
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Innate is fast and local (occurs at site of infxn) and always in action, has evolved to detect highly conserved pathogen antigens. Includes macrophages, neutrophils, complement pathway. Does not change or adapt over time. Like the local police.
Adaptive response is slow. Does not occur at site of infection but rather secondary lymphoid organs like LNs and spleen. T and B lymphocytes as well as their antibodies are major players. Improves over time and response is much faster upon reexposure to pathogen (memory). Like specialized army. |
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Examples of receptors of innate immunity?
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Toll-Like Receptors (TLRs) - recognize lipopolysaccharide (LPS) in gram- bacteria, and other TLRs recognize dsRNA, flagellin, peptidoglycan. TLR is a type of pattern recognition receptor.
Natural Killer receptors? |
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General structure of a T lymphocyte?
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T cell receptors on membrane recognize a peptide antigen/epitope bound to another cell's MHC.
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What is clonal selection?
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process of expanding the population of a specific lymphocyte, as would occur in response to a pathogen to which the lymphocyte has activity. Does not take away from the rest of the population of lymphocytes (memory cells).
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What do B cells do and how does this kill pathogens?
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B cells secrete antibodies when activated. Antibodies can bind pathogens or toxins and destroy them by neutralization (binding them up such that they cannot perform pathogenic activity), activate complement pathway (leading to lysis or phagocyte recruitment), opsonize pathogen such that phagocytes are recruited.
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3 functions of T lymphocytes?
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(1) CD8 T cells kill host cells that have been infected with viruses. Do this by recognizing viral peptides presented on infected cell surface by MHC.
(2) CD4 T cells activate macrophages and induce inflammation. Activated macrophages secrete more toxic compounds and have enhanced ability to kill microbes. (3) CD4 T cells activate or "help" activate B cells. Release cytokines that induce b cell proliferation and generation of antibody secreting plasma cells. |
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What is the function of dendritic cells?
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Dendritic cells are resident cells of innate immunity. When activated by a pathogen, dendritic cells carry the pathogen to nearest lymphoid that drains the tissue to activate adaptive immune response.
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Describe immune response to an acute viral infection
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innate cells produce large amounts of cytokines, specifically interferons (IFNalpha, beta). IFN inhibits virus replication and activates NK cells. These together control infection, but don't eradicate it. By day 5-7, T cell response has geared up, effectively eliminating the virus (CD8 cells do this mostly). Also get buildup of different immunoglobulins to fight against future infections.
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What is mannose binding lectin (MBL) and how is it clinically important?
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Type of collectin (col = collagen, lectin = sugar binding domains). Similar to a ficolin.
4-10% humans lack this, giving them a 6x increased risk of meningitis early in life. |
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Why do collectins bind microbes but not human cells when both contain sugars in their membranes? What is function of collectins?
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Microbial cells have much more densely packed carbohydrates allowing collectins like MBL to bind.
Collectins opsonize cells and activate complement. |
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What is opsonization?
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Preparing food. Makes microbes more appetizing to phagocytes by giving them handles to grab onto.
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What is complement?
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Series of 11 proteins that circulate in blood. They are inactive proteases. When activated by an infection, they initiate a cascade of cleavage that yields 2 pieces, an a unit that is inflammatory and b that binds the pathogen membrane as an opsin. Ultimately, complement can recruit phagocytes or form a complex that pokes a pore in the membrane, helping to lyse the pathogen cell.
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Describe the 3 complement pathways
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2 are innate: lectin and alternate pathways.
(1) Lectin - Collectins bind microbe, recruiting MASP proteases that cleave early complement proteins. (2) Alternate - C3 spontaneously cleaves and stabilizes. If C3b binds a pathogen membrane it stabilizes and activates complement cascade. (3) Classical pathway, adaptive immune system. Antibodies bound to pathogen recruit complement. After C3a, all steps are the same in the 3 pathways.(C3->C5->C6->C7->C8->C9) |
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3 families of innate immune response we need to know and what are 2 characteristics of this system to know in terms of what they target?
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Toll Like Receptors (TLRs) in cell surface endosome/phagosome.
Nod Like Receptors (NLRs) and RIG-like Receptors (RLRs) in cytosol. Focuses on features of microbes different from mammals (1) and shared by diverse microbes (requiring fewer receptors)(2). |
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What type of cell has many TLRs?
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Macrophages
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What are natural killer cells?
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granular lymphocytes that recognize certain abnormal cells, such as those infected by viruses. Become activated by interferon 1. Kill cells by releasing lytic granules.
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What is the reticuloendothelial system (RES)?
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Widespread "system" of mononuclear phagocytes, where they travel, such as macrphages, kuppfer cells in liver, microglia in brain, etc.Neutrophils, which are phagocytic, are not considered part of the RES. RES filters blood, want to rapidly clear bacteremias.
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What are mast cells?
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Landmine granulocytes. Basophilic staining granules. Degranulate with trauma and in some immune responses (in response to IgE, Complement fragments). Granules contain histamine. Can produce cytokines.
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What is a polymorphonuclear leukocyte?
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PMNs are neutrophils, or "polys." Abundant cytoplasm filled with granulocytes. Lifespan is 12-20 dhours. 1st recruited cell. basis of pus. End cell. First recruited cell in inflammation and can be used to diagnose infection.
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How are neutrophils bactericidal?
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Ingested bacteria killed with ROS. In granules there are antimicrobial mediators such as cationic proteins, lysozyme, proteases. Can release these onto pathogens to digest debris, can cause collateral damage.
low neutrophils almost always leads to severe infection. |
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What are eosinophils?
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bi-lobed granulocyte that stain pink on H/E. Involved in immune response to parasites and allergens. Scattered sparsely in tissues and circulate, respond to parasitic infection. Also seen in healing wounds and tumors.
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What are basophils?
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Similar to mast cells. Exact role unclear. May be important in allergy?
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What is the modern definition of inflammation?
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Inflammation is a response to injury of vascularized tissues whereby fluid and blood cells accumulate.
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What are the 2 categories of pathogens?
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extracellular: bacteria, fungi, worms, protozoa
intracellular: viruses, intracellular bacteria, intracellular protazoa |
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What is margination?
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accumulation and adhesion of leukocytes to the epithelial cells of blood vessel walls at the site of injury in the early stages of inflammation.
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How do the WBC weakly “anchor” and roll on endothelium at sites of inflammation?
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Injury or infection causes the local defenders like macrophages to make cytokines like TNF and IL-1 that stimulate endothelium in local venules to express adhesion molecules called selectins or selectin ligands that bind to the corresponding receptors or ligands on the WBC. This is rolling.
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What firmly adheres WBCs to endothelium during inflammation?
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Integrins (unlike selectins) are the strong binders (ICAM, for example). When WBCs are activated by cytokines like IL1 and TNF, integrin receptors activated. Binds ICAM tightly firmly anchoring cell to endothelium.
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What is diapedesis?
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the outward passage of blood cells through intact vessel walls.
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Where do rolling, firm adhesion, and diapedesis occur in the circulatory system?
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Venules, NOT capillaries or arterioles.
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What is pus?
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exudate that is rich in cells. Cells are creamy and white looking. typical of infections with strongly chemotactic bacteria like Staphylococcus.
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What is the order of cellular response in inflammation (which cells come first?)?
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Neutrophils are first responders within the first few hours. Then come macrophages (from circulating monocytes). Finally come lymphocytes within a few days.
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How do microbes avoid phagocytosis?
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Polysaccharide capsules, making them slippery, opsonization especially important. ex, Pneumococcus.
Biofilm formation, such as on catheters and other surfaces. |
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What are phases of phagocytosis?
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(1) Binding to pathogen, can be mediated by antibodies and opsins.
(2) Ingestion/Engulfment. Fuse with membrane to become a phagosome. (3) Killing. oxygen independent (lysosome mediated: bactericidal proteins and enzymes, lactoferrin, major basic protein), oxygen dependent (HOCL and O free radicals, ROS). (4) Demolition and collateral damage. Leukocytes die, phagosomes leak out, leaking toxic substances that digest dead material and cause collateral damage. (5) Further release of cytokines, recruit more reinforcements. |
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Clinical examples of acute leukocyte induced injury?
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ARDS, asthma, glomerulonephritis, reperfusion injury, NSAID ulcers, Vasculitis
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Possible outcomes of acute inflammation?
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Resolution, Abscess, Regeneration and scarring, chronic inflammation (from persistent injury)
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What causes chronic inflammation?
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This occurs because the stimulus – injury or infection – persists. This
causes the body to continue to respond in ways that leads to the picture of chronic inflammation. However, if the inciting problem clears then the inflammation will subside. |
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What are 3 outcomes of chronic inflammation?
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active inflammation, tissue damage/destruction, attempts at repair
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What are the predominant cells in acute vs chronic inflammation?
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acute = neutrophiles
chronic = macrophages, with some exceptions |
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What is a giant cell?
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Multinucleated cell composed of fused macrophages
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What are the two types of granuloma?
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Nonimmune (foreign body) - irritants like splinters or sutures
Immune - antigenic inflammation from hard to remove pathogens like TB or fungi. Granuloma stimulated as part of t cell immune response. |
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What is caseous necrosis?
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Central necrosis of a granuloma that grossly resembles cheese, oozy, pus.
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What is function of a granuloma?
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attempt to contain, destroy, wall off source of inflammation (the 'difficult' agent).
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Difference btw tuberculoid and lepromatous granulomas?
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Tuberculoid has many granulomas and few bacteria, granulomas control expansion.
Lepromatous has few granulomas and many bacteria. other factors prob contribute. |
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What is granulation tissue/
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Present in sites of chronic inflammation.
Surrounds granuloma (is DIFFERENT though) Leads to scarring. Composed of macrophages, fibroblasts, has new vascularization |
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What is a pannus?
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when granulation tissue forms in a joint, is called a pannus.
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What is meant by the "organization" process?
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Removal and replacement of dead tissue, fibrin, etc, by granulation tissue. A lesion is "organizing."
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What is an abscess?
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Collection of pus in a newly formed cavity. Typically in response to microbes. Walled off, gets a center of necrotic debris, dead neutrophils. Chronic inflammation in form of granulation tissue exists at the periphery.
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What are possible abscess outcomes?
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Sterilizes and resorbs leading to complete healing or a scar.
Continued infection leading to growing abscess. Continued infection leading to fistula formation (canal) that allows drainage to a surface or body cavity. |
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What is an abscess?
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Gap in a surface (skin or mucosa) that is inflamed and poorly healing and becomes surrounded by granulation tissue. Can be similar to an abscess (without closed cavity) or can become chronic with features like fibroblasts, vessels, mononuclear cells, fibrosis,etc.
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Describe inflammation at serosal surfaces eg pericardium, pleura
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Fluid and cells leak out onto outer body cavity surface, ie of the lung. Can be seous fluid, pus, or other exudate. If fibrinogen is present (from exudate) it can be cleaved to fibrin which can then either resorb and heal or become an adhesion. Fibrin provides scaffold for granulation tissue. Adhesions can be useful in that they obliterate potential space, but can also be pathological if interfere with organ function.
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What is exudate?
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An exudate is any fluid that filters from the circulatory system into lesions or areas of inflammation. I
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What are the 2 steps of Repair after inflammatory process?
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(1) Regeneration of Cells.
(2) Replacement by connective tissue leading to fibrosis or scarring. Sometimes both, sometimes one or the other. |
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What are required for regeneration of parenchyma?
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Growth factor mediators that stimulate cell division.
An intact basement membrane as a scaffold for growth. |
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Can there be healing and cell regeneration if both stroma and parenchyma are destroyed by chronic inflammation or necrotizing inflammation?
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NO, requires intact basement membrane scaffold (stroma). Only get regeneration if only parenchyma destroyed.
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What is contact inhibition?
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Fibroblasts (and other cells?) can sense surrounding cells and stop division when they form a monolayer.
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What are characteristics of fibrosis?
What can stimulate this process? |
-excess fibrous tissue
-white color (high collagen, like a tendon) -Hard (sclerotic) -End point of healing (failed regeneration) can be stimulated by injury, chronic inflammation, irritant particles like asbestos, silica. May do this by stimulating mediator release from macrophages which activates fibroblast |
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What is a scar?
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Dense collagen matrix. Remodeling of matrix over time. contracts and loses blood supply. increased collagen and cross linking.
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How can fibrosis be useful?
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Wall off an infected area like an abscess or granuloma. IT can also restore continuity of damaged tissues.
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Key points of inflammatory healing and fibrosis
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• Inflammatory mediators stimulate angiogenesis and the growth of fibroblasts
• Initially forms granulation tissue which can evolve into fibrosis • Collagen content & crosslinking increases, vascularity decreases and contraction may occur • Fibrosis walls off injury and fills in for lost tissue • Fibrosis can cause disease |
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Systemic factors influencing wound healing?
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nutrition (protein deficiency, scurvy)
metabolic disorders (diabetes) poor blood supply (atherosclerosis) hormones (glucocorticoids, suppress immune system) |
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Local factors influencing wound healing?
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INFECTION - must clear infection before granulation tissue can heal wound
foreign bodies - can lead to chronic irritation or be surface for infection mechanical stress and movement size and location |
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What are symptoms of systemic inflammation?
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Similar to flu - fatigue, fever, chills/rigors, malaise. Also leukocytosis from cytokines in blood. stimulates marrow and get leftward shift (immature white cells). Also get acute phase proteins (opsins, complement) from liver.
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