inflammation, infection, and fever

N351

physical/chemical barriers to infection

* skin
* mucous membranes
* secretions

inflammatory response

(non-specific) fever and inflammation

* occurs after tissue injury or infection
* IMMEDIATE/GENERAL protection against invasion by a wide range of pathogens
* involves phagocytic WBCs, antimicrobial substances, natural killer cells

immune response

(specific) antigen-antibody response

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* identifies self from non-self (host vs. foreign)
* recognizes and eliminates altered host cells
* develops more SLOWLY and involves SPECIFIC CELLS to combat a PARTICULAR pathogen

first line of defense

non-specific resistance to disease; either mechanical or chemical factors

mechanical factors

* skin
* mucous membranes
* mucus
* hairs
* cilia
* lacrimal apparatus
* saliva
* urine
* defecation
* vomiting

cilia

fine hairlike structures in the nose, nasopharynx, lungs

lacrimal apparatus

tear ducts

chemical factors

* acidic pH of skin: prevents entry through orifice or cut
* unsaturated fatty acids: maintain fluidity of phospholipid bilayer
* lysozymes found in saliva, sweat, tears
* gastric juice to break down ingested food
* vaginal secretions

second line of defense

non-specific resistance to disease; internal

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* antimicrobial proteins
* natural killer cells
* phagocytes
* inflammation
* fever

antimicrobial proteins

involves interferons and complement system

interferons

microproteins with anti-viral proteins

complement system

group of 20 different proteins in blood that play a vital role in killing substances in the blood

immune system structure

• lymph nodes

• thymus

• spleen

• tonsils

• red bone marrow

lymph nodes

* distributed along lymphatic vessels
* filter lymph fluid + remove bacteria, toxins from circulation
* drainage for particles too big in the nervous system
* proliferation of immune cells

\

thymus

located in mediastinum and produces T-lymphocytes

spleen

* largest lymph organ and reservoir for blood
* contains macrophages
* plays important role in fighting off infection

tonsils

* produce lymphocytes
* guard against airborne and ingested pathogens

red bone marrow

houses stem cells that develop into lymphocytes

primary lymphatic organs

provide environment for stem cells to divide and mature

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ex:

* red bone marrow
* thymus gland

secondary lymphatic organs/tissues

sites where most immune responses occur

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ex:

* lymph nodes
* spleen
* lymphatic nodules

pathogen

(agent) disease-producing microbes

* bacteria, viruses, parasites

microbial factors

virulence, dose, portal of entry, organ preference

resistance

ability of the body to ward off disease

susceptibility

vulnerability or lack of resistance to disease

host factors

responsible for degree to which the individual is able to adapt to the stressor produced by the agent OR maladapt

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ex: eldery, neonates and immunocompromised have a higher susceptibility to infection due to poor immune system

examples of host factors

* age
* immunity
* genetics
* nutrition
* underlying/pre-existing disease
* health habits
* stress
* psychological factors

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environment

extrinsic factors that affect the agent and the opportunity for exposure

\
influences the probability and circumstances of contact between host + agent

\
* sanitation and living conditions
* pollution
* social, political and economic factors

agent

aka the infectious microorganism; can be biologic, chemical, physical

biologic agents

* allergens
* viruses, bacteria, mycoplasma, Rickettsiae, fungi, parasites
* vaccines

chemical agents

* toxins
* dusts

physical agents

* kinetic energy
* bullet wounds, blunt trauma, vehicular injuries
* radiations
* chemotherapy
* thermal
* heat, cold
* noise

infection

host organism’s response to a pathogen

• tissues destroying microorganisms enter and multiply in the body

• categorized by severity

  • minor (cold, ear infection)

  • life-threatening (sepsis)

sepsis

infection and contamination

bacteremia

presence of bacteria in the blood

viremia

presence of virus particles in the blood

septicemia

systemic infection in which pathogens present in the blood have spread from an infection in any part of the body

viruses

* microscopic genetic parasites
* consist of a protein coat that surrounds a nucleic acid core which may contain RNA/DNA
* no metabolic capability → most require a host to replicate
* some reproduce outside of a living cell
* capable of remaining dormant for long periods of time
* replicate/produce symptoms month or years after initial infection

bacteria

* single celled microorganisms
* no true nucleus
* reproduce by cell division
* pathogenic ones contain cell damaging proteins
* endotoxins, exotoxins

endotoxins

released when bacterial cell wall decomposes

can cause fever; are not affected by antibiotics

exotoxins

released during cell growth

bacteria classification

based on

* shape
* coccus, spirillum, bacillus
* growth requirements
* motility
* oxygen requirements
* gram stain

gram positive

stains purple (positively purple!!)

gram negative

does not retain stain/color in gram stain

mycoplasmas

* 1/3 the size of bacteria
* capable of reproducing independently
* NO rigid cell wall
* some cause pneumonia

Rickettsiae

* depend upon host cell for nutrients
* multiply by cell division
* rigid cell wall
* human infection caused by bite of an infected arthropod

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* cause Typhus, Rocky Mountain spotted fever

fungi

* non-photosynthetic microorganisms that reproduce asexually
* relatively large and contain a TRUE nucleus
* either yeasts or molds

yeasts

round, single-celled facultative anaerobes (can live w/ or w/o oxygen)

molds

filament-like, multinucleated, aerobic microorganisms

mycotic infections

(mycoses) infections caused by fungi that release mycotoxins

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most are mild until they become systemic or patient’s immune system is compromised (opportunistic)

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ex: thrush, commonly caused by asthma inhaler

parasites

* depend on a host for food and protective environment
* can’t survive outside of host
* includes
* protozoa
* helminths
* arthropods
* ectoparasites

protozoa

* minute unicellular animals
* transmitted by arthropod vector or contaminated food/water
* ex: malaria, amebic dysentery

helminths

* worm like parasites
* transmitted by ingested of fertilized eggs/larva penetration through skin

\
* most common in developing countries

arthropods

* have jointed exoskeleton and paired jointed legs
* serve as vectors for other diseases
* ex: ticks, mosquitoes, biting flies

ectoparasites

* organism that lives on the outside of body
* transmitted through contact with infected clothing, bedding, grooming articles
* ex: mites, lice, chiggers

normal body flora

harmless microorganisms that reside in/on body

\
found on skin, in nose, mouth, pharynx, distal intestine, colon, urethra, vagina

intestinal flora

synthesizes vitamin K which is important for blood clotting

chain of infection

model to conceptualize the transmission of a communicable disease from its source to a susceptible host

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pathogen → reservoir → portal of exit → transmission → portal of entry → new host

reservoir

the habitat in which an infectious agent normally lives and grows

* humans
* animals (aka zoonoses)
* environment (soil, plants, water)

portal of exit

the path by which an agent leaves the source host

transmission

how pathogens are passed; modes include direct and indirect

direct transmission

agent is passed through direct contact

\
ex: droplet spread

indirect transmission

* airborne
* vehicleborne (non living)
* vectorborne (bit by arthropod)

portal of entry

agent enters susceptible host through:

* respiratory, oral, skin, IV, GI

new host

final link of chain of infection, susceptible host

peripheral smear

laboratory test that takes a drop of blood → examine WBCs and RBCs

granulocytes

* neutrophils
* bands
* basophils
* eosinophils

agranulocytes

do not granulate during inflammation response

• lymphocytes

• monocytes

hematopoiesis

production of blood cells

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starts with hematopoietic stem cell from bone marrow → differentiates → either common lymphoid progenitor OR myeloid progenitor

common lymphoid progenitor

precursor cell to B and T cells → become plasma cell and activated T cell respectively

myeloid progenitor

give rise to either

* polymorphonuclear leukocytes
* megakaryocytes → platelets
* erythroblast → erythrocytes

macrophages

* phagocytic effector cells in both humoral and cell mediated responses
* lack surface receptor for specific antigens
* but have receptors for Fc region and complement

macrophage function

ingest and process antigen → deposit antigen on its surface with MHC II → present antigen-MHC complex to T lymphocytes → activate T-lymphocytes

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secrete cytokines: TNF and IL-1 (produce fever)

MHC

group of genes that code for membrane bound proteins that help the immune system recognize foreign substances

dendritic cells

(mononuclear phagocytes) type of antigen presenting cell

• communicates with innate/adaptive immune systems

• central role in fighting infection and maintaining organ integrity

dendritic cell function

activate naive T cells not previously subjected to an antigen

reticuloendothelial system

designed to filter out and kill foreign substances out from where it doesn’t belong

tissue macrophage examples

* lung → alveolar macrophages
* liver → Kupffer’s cells
* spleen
* lymph nodes
* intestine → Peyer’s pathces
* CNS → microglial cells
* skin → Langorhans’ cells
* connective tissue → histiocytes

white blood cells

protect body against harmful bacterial and infection

neutrophil

primary phagocyte, arrive early

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* either polymorphonuclear (PMNs) or segmented (segs)

neutrophil function

* bacterial infections
* inflammatory disorders
* stress
* certain drugs

bands

immature neutrophils (make up 1-3% of neutrophils)

shift to the left

increase in the number of bands

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occurs when mature neutrophils die fighting a severe infection for 48+ hours → more bands needed to replace the dead ones

eosinophil function

* allergic disorders
* parasitic infestations
* release heparin and histamine → inflammation

basophil function

* located in tissue’s mast cells
* inflammation (mediated by histamine)
* allergic reaction

lymphocyte function

fight against viral infections

B cells

(lymphocyte) mature into plasma cells and release antibodies

T cells

(lymphocyte) regulate mediated immunity and work in both innate/adaptive immune responses

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ex:

* T4 cells secrete cytokines that amplify cell response
* T8 cells amplify killing infected and tumor cells through inducing apoptosis

monocyte function

phagocytosis; fight severe infections

absolute WBC count

• actual number of WBC, preferred

• equal to relative value (%) * total WBC

• ↑s or ↓s cell counts IMPORTANT

relative WBC

* percentage (%)
* sum of values will always total 100%
* if one type cell ↑ then the other types MUST ↓
* ↑s or ↓s cell counts NOT important 

calculating absolute counts

relative (%) \* 12.8 \* 10^3 cells/mm3

absolute neutrophil count

= WBC x (% neutrophils + % bands)

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critical value < 1000

increased WBC conditions

(osis, ilia)

* leukocytosis
* neutrophilia
* lymphocytosis
* monocytosis
* eosinophilia
* basophilia

decreased WBC conditions

(penia) haha penis

* leukopenia
* neutropenia
* lymphopenia
* monocytopenia
* eosionpenia
* basopenia

significance of increased WBC count

can be indicative of the following:

* infection
* inflammation
* tissue necrosis
* leukemic neoplasia
* trauma
* emotional/physical stress

significance of decreased WBC count

can be indicative of

* chemotherapy
* radiation therapy
* marrow infiltrative deficiencies
* overwhelming infections
* dietary deficiencies
* autoimmune diseases

persistent WBC increase

response to worsening of an infection

drastic WBC decrease

indicative of bone marrow failure and risk of infection

WBC critical values

< 2500 cells/mm3

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> 30000 cells/mm3

WBC values and age

normal newborns/infants → higher WBC values

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elderly → low WBC values (even in presence of severe bacterial infection)