Anatomy Lecture 12 (II)

pathogens

agents capable of producing disease, including viruses, bacteria, fungi, and other microbes

first line of defense

skin and mucous membranes, which serve as barriers

second line of defense

protections against pathogens that break the skin, mucous membrane barriers

example of second line defense

leukocytes and macrophages, antimicrobial proteins, natural killer cells, fever, and inflammation

third line of defense

adaptive immunity, mechanisms that defeat a specific pathogen and leave the body with a memory of it

immune system

widely distributed population of cells, diverse chemicals, physical barriers, and physiological responses

innate immunity

defenses we are born with; protect us from broad spectrum of disease agents; local effect, non-specific, and lacks memory

local effect

defends at point of invasion, but are exceptions (fever)

non-specific

defenses are against a broad spectrum of disease agents, rather than one particular pathogen

adaptive immunity

defenses against specific pathogens, developed only upon exposure to the pathogen and maintains immune memory

protective features of the skin

toughness of keratin, too dry and nutrient-poor to support microbial growth, microbes adhered to skin are continualy shed with dead keratinocytes of the stratum corneum of epithelium; presence of acid mantale

acid mantle

thin film of lactic acids and fatty acids from sweat and sebum that inhibits bacterial growth

what peptides does the skin contain that kill microbes?

dermcidin, defensins, and cathelicidins

what is protected by the mucous membranes?

digestive, respiratory, urinary, and reproductive tracts

protective features of mucous membrane

sticky mucus physically traps microbes and presence of lysozyme

lysozyme

enzyme that destroys bacterial cell walls

subepithelial areolar tissue of skin and mucous membranes

contain a viscous barrier of hyaluronic acid and pathogens can release hyaluronidase

what does hyaluronic acid do?

slows pathogens from invading quickly through barriers

hyaluronidase

an enzyme to make hyaluronic acid less viscous

phagocytes

cells that engulf foreign matter

five type of leukocytes

neutrophils, eosinphils, basophils, monocytes, and lymphocytes

which leukocytes are phagocytic?

neutrophils and monocytes

neutrophils

wander in connective tissue, functions to kill bacteria; can ensnare bacteria by releasing a neutrophil extraceullar trap; can kill by phagocytizing and digesting microbe or by releasing bactericidal chemicals to create a killing zone

neutrophil extraceullar trap

web of nuclear chromatin and proteins

eosinophils

found especially in mucous membranes, guard against large parasites (tapeworms, roundworms), participate in inflammation, and react to allergens and participate in allergic reactions

basophils

secrete chemicals that aid mobility and action of other leukocytes like histamine and heparin

leukotrienes

activate and attract neutrophils and eosinphils

histamine

a vasodilator; increases blood flow and speeds delivery of leukocytes to the area

heparin

inhibits clot formation that would impede leukocyte mobility

mast cells

secrete histamine and heparin; similar to basophils but found in connective tissue

lymphocytes

includes T cells and B cells which participate in adaptive immunity; also includes NK cells which are part of the innate immunity

monocytes

emigrate from the blood into connective tissues and transform into macrophages

macrophage system

all the body’s avidly phagocytic cells, except leukocytes; includes monocytes, macrophages, dendritic cells, and others

inferferons

proteins secreted by virally infected cells and immune cells; serves as an alarm to nearby cells; bind to receptors on nearby cells, stimulating their synthesis of defensive antiviral proteins to prevent their infection; activate NK cells and macrophages to better destroy infected cells

complement system

group of 30 or more globular proteins that contribute to both innate immunity and adaptive immunity; circulate in the blood in inactive form

where is the complement system mainly synthesized?

liver

activated complement contributes to C3a

inflammation

activated complement contributes to C3b

immune clearance, phagocytosis, and cytolysis

classical pathway

faster than alternative; requires antibody binding to microbe, which changes the antibody’s shape and exposes complement-binding sites on the antibody

complement fixation

binding of the complement C1 to the antibody sets off a reaction cascade

alternative pathway

complement C3b binds to microbe surface, activating reaction cascade

four outcomes of complement activation

inflammation, immune clearance, phagocytosis, and cytolysis

inflammation

c3a stimulates mast cells and basophils to secrete histamine and other inflammatory chemicals which activates and attracts

immune clearance

c3b binds the antigen antibody complexes to red blood cells that then circulate the liver and spleen where macrophages strip off and destroy the ag-ab complexes leaving the RBCs unharmed

phagocytosis

c3b coats microbial cells and serves as binding sites for phagocyte attachment

cytolysis

complement c3b initiates formation of c5b; electrolytes leak out, water flows in rapidly, and the target cells ruptures

what does c5b do?

aggregates with other complement proteins within plasma membrane of microbe which forms the membrane attack complex

NK cell functions

immunological surveillance; attack and destroy microbes, transplanted cells, cells infected with viruses, and cancer cells

what do NK cells do when they recognize infected cell?

bind to it and release perforins

perforins

proteins which form a ring to create a hole in the target’s plasma memebrane

granzymes

protein-degrading enzymes which enter through the pore and degrade intracellular enzymes and induce apoptosis

tumor specific antigens

cancer cells may exhibit these and these are identified as abnormal by NK cells

immunological escape

some cancer cells avoid NK cells; either destroy NK cells that detect them or avoid detection by not displaying tumor specific antigens or masking them

viral infections

cells infected with viruses present abnormal proteins on their plasma membranes; allows NK cells to identify and destroy them

fever (pyrexia)

an abnormal elevation of body temperature

what is a fever caused from?

trauma, infections, drug reactions, brain tumors, etc..

why can a fever be helpful?

promotes interferon activity, elevated metabolic rate and accelerates tissue repair, and inhibits reproduction of bacteria and viruses

antipyretics

fever reducing medications

stages of a fever

onset, stadium, defervescence

reye syndrome

serious disorder in children younger than 15 following an acute viral infection such as chickenpox or influenza

how can reye syndrome be triggered?

use of aspirin to control fever

effects of reye syndrome

swelling of brain neurons, pressure of swelling brain (nausea, vomiting, disorientation, seizures, and coma), some suffer intellectual disabilities, and fatty infiltration of liver and other viscera

inflammation

local defensive response to tissue injury including trauma and infection

general purpose of inflammation

limit spread of pathogens and destroys them; remove debris from damaged tissue and initiate tissue repair

four cardinal signs/symptoms of inflammation

redness, heat, swelling, and pain

cytokines

involved in inflammation; small proteins that function in chemical communication between cells; alter physiology of receiving cells

cytokine examples

interferon, interleukins, tumor necrosis factor, chemotactic factors, and others

mobilization of defenses to inflammation

most immediate requirement after tissue injury is to get defensive leukocytes to site quickly which is achieved through hyperemia; local vasodilation due to vasoactive chemicals; vasoactive chemicals stimulate endothelial cells to contract, widening gaps between them; cell adhesion molecules made by endothelial cells aid in the recruitment of leukocytes

hyperemia

increasing blood flow and washes toxins and metabolic waste from the site more rapidly

vasoactive chemicals stimulate endothelial cells to contract, widening gaps between them

increases capillary permeability fluid, leukocytes, and plasma proteins leave the bloodstream and into tissue

cell adhesion molecules made by endothelial cells aid in the recruitment of leukocytes

make membranes sticky so leukocytes adhere to vessel wall, diapedesis, and extravasated

margination

make membranes sticky so leukocytes adhere to vessel wall

diapedesis (emigration)

leukocytes crawl through gaps in the endothelial cells and enter tissue fluid

extravasated

term for cells and chemicals that have left the bloodstream

heat

results from hyperemia

redness

due to hyperemia and extravasated RBCs in tissue

swelling

due to increased fluid filtration from capillaries

pain

from direct injury to nerves, pressure on nerves from tissue edema, stimulation of pain receptors by prostaglandins, bacterial toxins, and bradykinin

containment and destruction of pathogens

fibrinogen filters into tissue fluid, activates fibrin and forms clots in adjacent areas to the damage; heparin; neutrophils accumulate at the injury site

heparin function for containment and destruction of pathogens

pathogens are in a fluid pocket surrounded by clot; attacked by antibodies, phagocytes, and other defenses

neutrophil function in containment and destruction of pathogens

exhibit chemotaxis after leaving the bloodstream; phagocytosis; respiratory burst; secrete cytokines

chemotaxis

attraction to chemicals that guide them to the injury site

respiratory burst

neutrophils absorb O2 and form H2O2 and release hypochlorite → both are highly toxic and from a killing zone around cell

neutrophilia

5000cells/uL to 25000 cells/uL in bacterial infection

eosinophilia

elevated eosinophil count in allergy or parasitic infection

tissue clean up and repair

primarily involves monocytes, edema contributes; hyperemia delivers oxygen, amino acids, and other necessities for protein synthesis; increased heat increases metabolic rate, speeds mitosis and tissue repair; fibrin clot forms a scaffold for tissue reconstruction

how does edema contribute to tissue cleanup?

swelling compresses veins and reduces venous drainage; forces open valves of lymphatic capillaries, promoting lymphatic drainage of bacteria, dead cells, and debris

pus

yellow accumulation of dead neutrophils, bacteria, cellular debris, and tissue fluid

abscess

accumulation of pus in a tissue cavity

platelet derived growth factor

secreted by blood platelets and endothelial cells in injured area; stimulates fibroblasts to multiply, synthesize collagen

adaptive immunity

serves as the third line of defense; has 3 characteristics to distinguish it

3 characteristics of adaptive immunity

systemic effect, specificity, and memory

systemic effect

acts throughout the body

specificity

generates protection and immunity to specific pathogens on an individual basis

memory

when re-exposed, the body reacts so quickly that there is no noticeable illness

cellular immunity

T lymphocytes directly attack and destroy foreign cells or diseased host cells; rids the body of pathogens that reside inside human cells where they are inaccessible to antibodies; and act against parasitic worms, cancer cells, and transplanted cells

humoral (antibody-mediated) immunity

mediated by B lymphocytes that become plasma cells that release antibodies, do not directly destroy a pathogen but tag it for destruction; effective against extracellular viruses, bacteria, yeasts, protozoans, and molecular disease agents such as toxins, venoms, and allergens

natural active immunity

production of one’s own antibodies or T cells as a result of infection or natural exposure to antigen; ex produced when you catch the flu

artificial active immunity

production of one’s own antibodies or T cells as a result of vaccination against diseases

vaccine

consists of dead or attenuated pathogens that stimulate the immune response without causing the disease