Chapter 12: Host defenses

what are host defenses?

a multilevel network of innate nonspecific protections & adaptive

• specific protections commonly referred to as:

  • first line of defense

  • second line of defense

  • third line of defense

first line of defense (overview)

any barrier that blocks invasion at the portal of entry

• limits access to the internal tissues of the body

• not considered a true immune response because it does not involve recognition of foreign substances

• very general in action

second line of defense (overview)

innate internalized system of protective cells & fluids

• includes inflammation & phagocytosis

• acts rapidly at the local & systemic levels once the first line of defense has been overcome but lacks memory

third line of defense (overview)

acquired on an individual basis as each foreign substance is encountered by lymphocytes

• the reaction w/each different microbe produces unique protective substances

• remembers microbes to provide long-term immunity

Immunology

the study of all features of the body’s second & third lines of defense

• its response to infectious agents

• allergies & cancer

immune system

a large complex diffuse network of cells & fluids that permeate every organ & tissue

• they communicate their activities to other compartments

lymphatic system

a compartmentalized network of vessels, cells, & specialized accessory organs

• transport lymph through an increasingly larger tributary system of vessels & lymph nodes, leading to major vessels that drain back to the circulatory system

functions of lymphatic system

provide a route for the return of extracellular fluid to the circulatory system

• act as a “drain off” system for the inflammatory response

• render surveillance, recognition & protection against foreign materials through:

  • lymphocytes

  • phagocytes

  • antibodies

• contain lymphatic fluid

lymphatic fluid

transports WBCs & other materials

lymphatic organs

• primary lymphatic organs

• secondary lymphatic organs

primary lymphatic organs

sites of immune cell birth & maturation

• red bone marrow

• thymus

secondary lymphatic organs

sites of immune cell activation, residence & functioning

• lymph nodes

• spleen

• various lymphoid tissues

red bone marrow (primary lymphoid tissues)

found in the internal matrix of long bones & is the site of all blood cell production

• B cells are generated & mature here

thymus (primary lymphoid tissues)

originates in the embryo as 2 lobes in the lower neck region & fuse into a triangular structure

• T cells mature here after migrating from the red bone marrow

lymph nodes (secondary lymphoid tissues)

small, bean-shaped organs clustered along lymphatic channels & large blood vessels

• contain WBCs & filters pathogens & WBCs from lymph

spleen (secondary lymphoid tissues)

found in the abdominal cavity

• filters pathogens from blood instead of lymph & removes old RBCs

associated lymphoid tissue (secondary lymphoid tissues)

bundles of lymphocytes at many sites or just beneath the skin & mucosal surfaces

• positioned as first-strike potential against the microbes & other foreign materials in food & air

• ex: tonsils, SALT, MALT, Peyer’s Patches

  • immune sensors of the intestine (PPs)

blood

• blood cells

• plasma

• serum

• stem cells

• white blood cells

hematopoiesis

production of blood cells

blood cells

formed elements suspended in plasma

plasma

clear, yellowish fluid

serum

essentially the same as plasma, except that it is the clear fluid from clotted blood

• used in immune testing & therapy

stem cells

primary precursor of new blood cells maintained in the bone marrow

• during development, stem cells proliferate & differentiate into the specialized form & function of mature cells

• become red blood cells, platelets, & white blood cells

white blood cells (leukocytes)

granulocytes & agranulocytes, depending on their staining patterns when viewed w/a microscope

• these cells are vitally important to nonspecific & specific immunity

cytokines: critical for cell communication

hundreds of small active molecules secreted to regulate, stimulate, suppress & otherwise control many aspects of cell development, inflammation & immunity

• produced by monocytes, macrophages, lymphocytes, fibroblasts, mast cells, platelets & endothelial cells

• effects may be local or systemic, short-term or long-term lasting, specific or nonspecific, protective or pathologic

first line of defense: our barriers

inborn, nonspecific

• physical & chemical barriers that impede the entry of microbes & foreign agents whether living or not

• consists of:

  • skin

  • mucus membranes

  • microbiota

skin (first line of defense)

tough outer layer that is impervious & waterproof

• constant sloughing off of the outer layers of skin removes microbes

• hair shaft & follicle cells are periodically shed

• flushing effect of sweat removes microbes

• slightly acidic pH

• subject to periodic dryness

mucous membranes (first line of defense)

these membranes of the digestive, urinary & respiratory tracts & the eye

• mucous coat impedes entry & attachment of bacteria

• blinking & tear production flush the eye’s surface

• constant flow of saliva carries microbes to the harsh conditions of the stomach

• vomiting & defecation evacuate noxious substances or microorganisms from the body

• antimicrobial secretions/compunds

respiratory tract (mucus membrane)

mucus & cilia come together

• trap things to move them out

• alveolar macrophages (in the lungs)

digestive tract (mucus membrane)

we have mainly the stomach acid (pH = 2)

• mucus lines the stomach

• the microbiota in the large intestine; provides competition between the pathogens (if present)

urinary tract (mucus membrane)

there is an acidic pH

• we also have secretions here

microbiota/microbiota (first line of defense)

forms a type of structural barrier

• can block the access of pathogens to epithelial surfaces

• creates an unfavorable environment for pathogens by competing for limited nutrients & by altering the local pH

• Crohn’s disease & ulcerative colitis may be the result of attempts to free our environment of microbes & over treatment w/antibiotics, resulting in an ill-trained gut

second line of defense (innate immunity)

generalized, nonspecific defenses that support & interact w/specific immune responses

• phagocytosis

• complement cascade

• fever & inflammation

phagocytosis

survey the tissue compartments & discover microbes, particulate matter & injured or dead cells

• ingest & eliminate these materials

• extract immunogenic information (antigens)

• types of phagocytes:

  • neutrophils

  • monocytes/macrophages

  • dendritic cells

neutrophils

short-lived phagocytes in blood

• active engulfers & killers of bacteria

monocytes/macrophages

blood pathogens that rapidly leave the circulation

• mature into macrophages

  • large phagocytic cells

  • high capacity for killing microbes & cleaning up dead cells

  • antigen-presenting cells

dendritic cells

reside in tissues (in skin & lymphoid organs) & MPS (mononuclear phagocytic system)

• process foreign matter & present it to lymphocytes

• antigen-presenting cells

phagocyte

“eating cell”

• the physical process of engulfment

• attack & dismantling of foreign cells

• can be an isolated event or as part of the orchestrated events of inflammation

• phagocytes recognize pathogen-associated molecular pattens (PAMPS)

  • which help know if inflammation, phagocytosis needs to begin

chemotaxis (1st step of phagocytosis)

PAMP is recognized & it binds

ingestion (2nd step of phagocytosis)

grab

phagolysosome formation (3rd step of phagocytosis)

phagosome & lysosome fuse

destruction (4th step of phagocytosis)

kill it & breakdown in little pieces

excretion/presentation (5th step of phagocytosis)

phagocytose goes back to the cell membrane

• phagocytes keep little pieces of bacteria (antigen presentation)

  • not all can do this (like neutrophils)

the complement cascade

named for its property of “complementing immune reactions”

• consists of over 30 blood proteins that work in concert to destroy bacteria & certain viruses, parasites & nearby cells

• cascade reaction:

  • sequential physiological response

  • first substance in a chemical series activates the next substance, which activates the next & so on

  • has 4 stages

initiation (1st stage of complement cascade)

C3 protein (either free or bound to a pathogen membrane) is hydrolyzed into 2 fragments

• C3b & C3a

activation & cascade (2nd stage of complement cascade)

further enzymatic action

• C3b protein cleaves the protein C5

• C5 turns into C5a & C5b

polymerization (3rd stage of complement cascade)

C5b fragment is now free to form a complex w/C6, C7 & C8

• called the membrane attack

membrane attack (4th stage of complement cascade)

MAC is positioned on & forms pores in the offending cell’s membrane, causing it to lose structural integrity

• leads to inappropriate flow of water & ions in & out of the cell

• eventual of the lysis of the cell

inflammatory response

a powerful defensive mechanism that helps the body maintain stability or restore itself after injury

• has the potential to cause tissue injury, destruction & disease

• easily identifiable by a classic series of signs & symptoms

  • rubor

  • calor

  • tumor

  • dolor

  • loss of function

rubor

redness caused by increased circulation & vasodilation in the injured tissue

calor

warmth caused by the heat given off by the increased flow of blood

tumor

swelling caused by fluid escaping into the tissues

dolor

pain caused by the stimulation of nerve endings

inflammation: chronic diseases

such as cardiovascular disease are caused by chronic inflammation

• can be local or systemic

• factors that elicit inflammation:

  • trauma from infection

  • tissue injury of necrosis due to physical or chemical agents

chief function of inflammation

to mobilize & attract immune components to the site of injury

• to set in motion mechanisms to repair tissue damage & localize & clear away harmful substances

• destroy microbes & block their further invasion

stages of inflammation

fever

abnormally elevated body temperature

• nearly universal symptom of infection

• associated w/certain allergies, cancers & other organic illnesses

• if cause is unknown, its called fever of unknown origin (FUO)

• body temperature is maintained around 37 C (98.7 F) by the hypothalamus

  • low grade: 37.7 - 38.3

  • high grade: 40.0 - 41.4

pyrogens

substances that reset the hypothalamic thermostat to a higher setting:

• exogenous pyrogens

• endogenous pyrogens

exogenous pyrogens

products of infectious agents such as viruses, bacteria, protozoans, fungi, endotoxin, blood, blood products, vaccines

• or injectable solutions coming from outside of the body

endogenous pyrogens

liberated by monocytes, neutrophils & macrophages during phagocytosis such as interleukin-1 & tumor necrosis factor

• induces fever by acting in hypothalamus