Chapter 14
Neutrophils (PMN)
"Foot Soldiers" 1st to show up in infection (w/in 1 to 2 min) Also called polymorphonuclear neutrophils (PMN) make 55-90% circulating leukocytes, lobed nuclei w/ lavender granules; phagocytes, active engulfers & killers of bacteria; cytoplasmic granules carry digestive enzymes & chemicals that degrade phagocytosed materials;
NK cells: general function
"security guards" destroys unwanted infected cells
Secondary lymphoid organs & tissues
-Circulatory based locations like spleen & lymph nodes -Lymph nodes have B cells in outer cortex & T cells in deep cortex. -They have B cells and macrophages in their medulla.
Interferon (INF) gamma modes of action
-Activates tumor destruction & killing of infected cells (also blocks virus replication by AVP synthesis) -Helpful & Nonselective b/c Lymphocytes & NK cells don't have to be infected w virus to synthesize
complement system
-A non-specific defense mechanism/innate immunity consisting of 30 blood proteins that work in concert to destroy bacteria & viruses (3 different pathways) -Proteins produced in liver & released in blood where proteins are activated by cleavage in cascade reaction
Lymphatic Fluid (Lymph)
-A plasma-like liquid carried by lymphatic circulation. -Formed when blood components move out of blood vessels into extracellular spaces. -Made of water, dissolved salts, 2-5% proteins. -Transports WBCs, fats, cell debris & infectious agents
Lymphatic vessels
-Lymphatic capillaries permeate all body parts except CNS, bone, placenta, & thymus -Thin walls easily permeated by ECF & then moved through contraction of skeletal muscles. -Functions to return lymph to circulation -Blind ended vessels that flow in 1 direction toward heart & eventually return to blood stream -As lymph moves in vessels it passes thru lymph nodes
Other lymphoid tissues
-Peyer's patches are lymphoid nodules, also called GALT (gut-associated lymphatic tissue) -BALT(bronchial), MALT (mucosal), VALT (vulvovaginal)
granulation tissue
-The fragile, reddish, grainy tissue seen at cut site (mainly areolar connective tissues w blood vessels). -When fibroblasts & fibers accumulate it replaces nerve & muscle tissues that cant regenerate & new epidermis replaces the part destroyed.
NK cells specific definition
-subtype of T cells derived from lymphoid lineage -a lymphocyte that kills nonspecifically (=innate immunity) -destroys bacterial-infected, viral-infected & tumor cells -makes physical contact w/infected cells, releases porins to put hole in membrane & granzymes that enter thru porin into infected cell and destroy it
Functions of Inflammation
1) to mobilize & attract immune components to injury site 2) set in motion mechanisms to repair tissue as well as localize & clear away harmful substances 3) destroy and block microbes from further invasion
physical & anatomical barriers (1st line of defense)
1)Skin and mucous membranes of respiratory, urogenital, eyes, and digestive tracts. 2)Outermost layer of skin is composed of epithelial cells compacted, cemented together, and impregnated with keratin; few pathogens can penetrate if intact. 3)Flushing effect of sweat glands. 4)Damaged cells are rapidly replaced. 5)Mucous coat impedes attachment and entry of bacteria 6)Blinking and tear production. 7)Stomach acid. 8)Nasal hair traps larger particles
functions of lymphatic system
1. Auxiliary route for return of extracellular fluid to the circulatory system 2. Acts as a drain-off system for the inflammatory response 3. Renders surveillance, recognition, and protection against foreign material
Benefits of Fever
1. Inhibits multiplication of temp-sensitive bad guys 2. Impedes bacteria nutrition by reducing available iron. 3. Increases metabolism/stimulates immune reactions & protective physiological processes (shortens infection) 4. Inactivates some microbial enzymes or toxins. 5. Phagocytosis is enhanced. 6. Causes patient to rest & use energy to fight infection. 7. The production of antiviral interferon is increased
4 stages of complement
1. Initiation: molecule or trigger (ex. antibodies, lectins, microbial surface receptors) starts process 2. Amplification & cascade: chain of action leading to C3 3. polymerization: rxs =half moon formation in membrane 4. Membrane attack complex (MAC): creates hole & lysis
Lymphoid organs
1. Thymus - high rate of growth & activity until puberty, then begins to shrink; site of T-cell maturation 2. Lymph nodes - small, encapsulated, bean-shaped organs stationed along lymphatic channels and large blood vessels of the thoracic and abdominal cavities 3. Spleen - structurally similar to lymph node; filters circulating blood to remove worn out RBCs & pathogens
Recognition stage of phagocytosis
1. Toll-like receptors (TLRs) & pattern recognition receptors (PRRs) =Protein receptors in cell membrane that recognize PAMPs (pathogen-associated molecular patterns) 2. microbes & damaged tissues release chemicals to attract phagocytes. 3. cytokines-released from phagocytes to initiate inflammation or in the case of chemokines to attract additional phagocytes infection site
Pathogenic Agents
1. bacteria 2. viruses 3. fungi 4. protozoa 5. multicellular parasites 6. prions
Immune Cell Homes
1. lymphatic tissues: that is lymph nodes, spleen, tonsils, MALT, GALT, lymphatic nodules. 2. select organs: alveolar of the lungs, brain, liver. 3. epithelial layer of the skin 4. connective tissue
Innate Defenses Summary
1. physical barriers: i.e, skin, mucous membranes 2. chemical barriers: i.e, antimicrobial substances in the body fluids such as saliva, mucus 3. cellular defenses: The cells of innate immunity = granulocytes (neutrophils,basophils, eosinophils) & macrophages. 4. inflammation 5. fever 6. molecular & genetic defenses: i.e, interferons, complement system.
Microbes that can resist phagocytosis
1.CAPSULES- ex. Yersinia pestis/plague, produces capsules not vulnerable to destruction by macrophages. 2. ACID FAST CELL WALLS of M. tuberculosis are resistant to lysosomal enzymes. 3. Some microbes, like staph & strep, produce TOXINS that kill phagocytes by causing release of phagocyte's own lysosomal enzymes into its cytoplasm.
steps/process of inflammation
1.cut lets bacteria get beneath surface of skin. 2.Damaged cells release histamine & bradykinin (9 amino acid long) both potent vasodilators. 3.Capillaries dilate (vasodilation), bring more blood to tissue. Skin gets red & warm. 4.Capillaries more permeable, fluids accumulate & cause swelling (edema). 5.Blood clotting occurs, scab forms (scabs made of blood clots & dried fluid from wound & dead tissues). 6.Bacteria multiplies in cut. 7.Phagocytes enter tissue (diapedesis). 8.Phagocytes move to bacteria (chemotaxis) & ingest them. 9. Larger vessels dilate, increasing blood flow & adding heat & redness. 10.dead cells & damaged debris removed, epithelial cells proliferate & begin to grow under scab. 11. normal or scar tissue replaces cells.
Defense Mechanisms of the host's immune system
3 Levels of defense that create network of physical barriers, immunologically active cells, and a variety of chemicals
basic inflammation definition
A reaction to any traumatic event in the tissues that restores homeostasis & helps clear away cellular debris. 1. RUBOR - redness from circulation & vasodilation 2. CALOR - warmth from increased blood flow 3. TUMOR - swelling from increased ECF 4. DOLOR - pain from pressure swelling puts on nerves [sometimes loss of function is considered #5]
Names of fixed macrophages in various tissue
Alveolar macrophage: in the lungs Histiocyte: connective tissue Kupffer cell: liver Microglial cell: neural tissue Osteoclast: bone Sinusoidal lining cell: spleen Langerhans: skin
Lymph nodes
Filtering organs located in the thoracic (chest), neck, armpits, & groin. Most infectious agents passing thru a node are trapped & destroyed by the defensive cells.
Nonspecific chemical barriers (2nd line of defense)
Include: 1)Sebaceous secretions 2)Lysozyme, an enzyme that hydrolyzes the cell wall of bacteria, in tears 3)High lactic acid & electrolyte concentration in sweat 4)Skin's acidic pH 5)Hydrochloric acid in stomach 6)Digestive juices and bile of intestines 7)Semen contains an antimicrobial chemical 8)Vagina has acidic pH
White Blood Cells (WBCs) or Luekocytes
Leukocytes are formed in the bone marrow and then enter the blood circulation as motile, migratory, defensive cells that wander through the body and have an innate capacity to recognize & differentiate any foreign material in the body. Able to distinguish between self & non self.
Fever
Most often, fever is initiated by circulating pyrogens which reset the hypothalamus to increase body temperature; signals muscles to increase heat production and vasoconstriction
Interferon (INF) alpha & beta modes of action
Mostly effective against viruses (especially RNA viruses) Once stimulated by virus infection of a cell, interferon alpha & beta are synthesized & released from the infected cells. The interferon then binds to cell surface receptors of nearby uninfected cells & induce expression of series of new proteins. Most of these proteins are enzymes & collectively called antiviral proteins (AVPs)
ingestion stage of phagocytosis
Once captured, phagocytes rapidly ingest (engulf) the microbes. The cell membrane of the phagocyte forms fingerlike extensions, called pseudopodia, that surrounds the microbe. These pseudopodia then fuse, enclosing the microbe w/in a cytoplasmic vacuole called a phagosome.
Adherence stage of phagocytosis
Once the infectious agent is reached able to attach /adhere to specific molecules on surface (ingestion occasionally made easier if microbes are coated w/Abs or complement system proteins)
division of leukocytes into two groups
Precursor= undifferentiated pluripotent/hematopoietic stem cells in bone marrow (areas recede w/aging) 1. GRANULOCYTES: have lobed nucleus & noticeably colored granules in cytoplasm. Includes: Neutrophils, Basophils,Eosinophils, Mast cells (from myeloid lineage/non-specific) 2. AGRANULOCYTES: lack visible granular cytoplasm w/light microscope & have unlobed, rounded nucleus. Includes: monocytes & lymphocytes (Monocytes from myeloid lineage/non-specific & lymphocytes from lymphoid lineage/specific)
TLRs (Toll Like Receptors)
Receptors that span the membran of a phagocyte that allow it to find and bind to the PAMP receptors of various microbes. 1st the exposed end of one TLR hooks onto the PAMP and then joins/merges w/ a second TLR to trap the molecule. This sends a signal to the phagocyte nucleus that stimulates the phagocytic processes & releases chemical mediators.
collective cytokines
Soluble products of immune cells that play various roles in defending the body against pathogens. Used to regulate, stimulate, suppress or control many aspects of cell development, inflammation & immunity Major cytokines: 1. interleukins (ILs) 2. tumor necrosis factor (TNF) 3. colony stimulating factors (CSFs) 4. Interferons (IFNs)
Interferon (INF) gamma
Sources: T cells & NK cells
Interferon (INF) beta
Sources: fibroblasts and epithelial cells
Interferon (INF) alpha
Sources: lymphocytes and macrophages
macrophages
The "big eater" or the clean up crew that arrives at the injured site late & stays longer.
classical complement pathway
Triggered by antibodies (activated by the presence of antibody bound to microorganism)
alternative complement pathway
Triggered by anything unusual (begins when complement proteins directly bind to normal cell wall and surface components of microorganisms, usually polysaccharides)
2nd Line of Defense
protective cells and fluids = nonspecific (innate immunity) Includes: inflammation, phagocytosis, interferon, fever
lysosome
a cytoplasmic organelle containing lysozyme (a destructive enzyme) & other hydrolytic enzymes that migrates & fuses to a phagosome in order to create a phagolysosome and destroy it's contents .
3rd Line of Defense
acquired with exposure to foreign substance; produces protective antibodies & creates memory cells = specific (adaptive immunity) Includes: T lymphocytes, B lymphocytes & antibodies
digestion stage #2 as a Phagolysosome
after lysosome fuses w/ phagosome death occurs in 20-30 minutes. (30+ different types of antimicrobial enzymes have been identified w lysosomes). Defensins place holes in cell membrane of microbes, allowing lysosomal enzymes to digest microbes in 20-30 min. -Other mechanisms used to kill ingested microbes=H2O2, NO, superoxide ions (-O2), hypochlorite ions (OCl-)
phagosome
an prey holding vacuole created when a phagocyte extends it's pseudopods to enclose and internalize cells or particles in a pocket
1st Line of Defense
any barrier that blocks invasion at the portal of entry = nonspecific(innate immunity) includes: Physical Barriers- tears, skin, coughing, sneezing Chemical Barriers- low pH, lysozyme, digestive enzymes Genetic Barriers- resistance inherent in genetic makeup of host (pathogen can't invade)
phagocytosis process
cells must: 1. Recognize 2. adhere to 3. ingest 4. digest
Erythrocytes
develop from bone marrow stem cells (myeloid line), lose nucleus, simple biconcave sacs of hemoglobin. Their job is to carry O2.
basophils/mast cells general function
engage in chemical warfare by releasing histamine, heparin, eicosanoids to stimulate inflammation.
Platelets
formed elements in circulating blood. In other words, they are not cells (don't have nucleus). They are cytoplasmic fragments from a large cell called megakaryocyte. Their job is forming blood clots.
endogenous pyrogens
liberated by monocytes, neutrophils, and macrophages during phagocytosis; interleukin-1 (IL-1) and tumor necrosis factor (TNF) are examples of endogenous pyrogens made by the body.
Lymphocytes
lymphoid lineage of bone marrow; 20-35% of WBCs; create specific/acquired immune response that includes: 1) B Cells (humoral immunity) = activated B cells produce that produce antibodies 2) T cells (cell-mediated immunity) = activated T cells modulate immune functions and kill foreign cells
Eosinophils
more numerous in spleen & bone marrow than circulation, 1-3% of WBC count; bilobed nucleus w/larger orange/red cytoplasmic granules; destroy eukaryotic pathogens such as parasitic worm & fungal infections; granules contain toxic proteins, inflammatory mediators, & digestive enzymes; among earliest cells near inflammation/allergic reactions where they attract other leukocytes and release chemical mediators
Innate Immunity
natural defenses present at birth that provide nonspecific resistance to infection
Monocytes
non-specific immunity from myeloid lineage of bone marrow; 3-7% of WBCs & largest w/kidney-shaped nucleus; main function phagocytosis followed by differ-entiation into macrophages & dendritic cells, also secrete several chemicals to moderate immune system functions MONOCYTES are mobile & floating in blood stream but once migrate into tissue areas become MACROPHAGE or DENDRITIC cells
Mast cells
nonmotile elements bound to connective tissue around blood vessels, nerves, & epithelia; trigger local inflamm-atory cells, RXs & allergic symptoms; 1st line defenders vs. local pathogenic invasion, directly responsible for histamine release (associated w allergies)
digestion stage #1 of phagocytosis
phagocytic cells have several mechanisms for digestion & destroying ingested microbes. One mechanism uses lysosome organelles. Lysosome bags containing digestive enzymes & defensins, fuse w phagosome membrane forming a phagolysosome.
Mast cell lineage
pluripotent/hematopoietic stem cell ~> Myeloid stem cell ~> myeloblast ~> granulocyte leukocyte ~> MAST CELL
B cell & T cell lineage
pluripotent/hematopoietic stem cell ~> lymphoid stem cell ~> lymphoblast ~> lymphocytes ~> T & B CELLS
Natural Killer (NK) cell lineage
pluripotent/hematopoietic stem cell ~> lymphoid stem cell ~>NK CELL (related to T cell, but displays no specificity; active against cancer & virally infected cells)
Monocyte lineage
pluripotent/hematopoietic stem cell ~> myeloid stem cell ~> monoblast ~> agranulocyte leukocyte ~> MONOCYTE (blood phagocyte 1st, then matures into macrophage or dendritic cell)
Neutrophils, Basophils, & Eosinophils cell lineage
pluripotent/hematopoietic stem cell ~> myeloid stem cell ~> myeloblast ~> granulocyte leukocyte ~> NEUTROPHILS, BASOPHILS, EOSINOPHILS
Macrophage/Dendritic cell lineage
pluripotent/hematopoietic stem cell ~> myloid stem cell ~> monoblast ~> agranulocyte leukocyte ~> monocyte (blood phagocyte) ~> MACROPHAGE/DENDRITIC CELL
exogenous pyrogens
products of infectious agents & include both exotoxins & endotoxins of bacteria
Basophils
scarcest leukocyte, less than 0.5% WBCs; constricted nuclei w/dark blue/black granules; granules release histamine, a chemical that initiates inflammatory response & prostoglandins/other chemical mediators of allergic response; similar to mast cell but motile
Primary lymphoid organs
sites of lymphocytic origin and maturation (thymus and bone marrow)
Adaptive Immunity
specific. Adaptive responses respond to particular agents called antigens. Adaptive defenses must be acquired.
MB-Lectin complement pathway
triggered by the presence of sugar mannose on the pathogen surface (MBL made in the liver & released in blood, then binds to glucose or mannose on surface of bacteria & activation occurs/ similar to classical)