351 second lecture

physical and chemical barriers to infection

skin

mucous membranes and secretions

inflammatory response (non specific) = fever and inflammation

occurs after tissue injury or infection

immediate and general protection against invasion by a wide range of pathogens

involves phagocytic WBCs, antimicrobial substances, natural killer cells

immune response (specific) = antigen-antibody repsonse

identifies self from nonself (host V foreign)

recognizes and eliminates altered host cells

develops more slowly and involves specific cells to combat a particular pathogen

mechanical factors

Skin

Mucous membranes

Mucus

Hairs

Cilia

Lacrimal apparatus

Saliva

Urine

Defecation & vomiting

chemical factors

Acid pH of skin

Unsaturated fatty acids

Lysozyme

Gastric juice

Vaginal secretions

internal defenses

Antimicrobial proteins

- Interferons

- Complement system

Natural killer cells

Phagocytes

Inflammation

Fever

lymph nodes

Distribute along lymphatic vessels

Filter lymph fluid & remove bacteria & toxins from circulation

Proliferation of immune cells

thymus

Located in mediastinum

Produces T-lymphocytes

spleen

Largest lymph organ

Reservoir for blood

Macrophages clear cellular debris & process hemoglobin

tonsils

Produce lymphocytes

Guard against airborne and ingested pathogens

red bone marrow

Houses stem cells that develop into lymphocytes

primary lymphatic organs function

provide environmet for stem cells to divide and mature

example of primary lymphatic organs

red bone marrow

thymus gland

secondary lymphatic organs and tissues

sites where most immune responses occur

example of secondary lymphatic organs and tissues

lymph nodes

spleen

lymphatic nodules

lymphatic flow

Remove excess fluid from tissue spaces

Right lymphatic duct empties into right subclavian and drains right side of head and neck

Thoracic drains rests of body and empties into left subclavian

pathogen (agent)

Disease-producing microbes

- Bacteria, viruses, parasites

Microbial Factors

- Virulence, dose, portal of entry, organ preference

host

Resistance

- Ability of the body to ward off disease

Susceptibility

- Vulnerability or lack of resistance to disease

Host Factors

- Age, immunity, genetics, nutrition, underlying or pre-existing diseases, health habits, stress, psychological factors

environment

Humidity, poor sanitation, crowded living conditions, pollution, dust

epidemiologic triangle

Infectious agent, host, and environment.

agent = originally referred to an infectious microorganism,

environment = extrinsic factors that affect the agent and the opportunity for exposure

host = intrinsic factors that influence an individuals exposure

biologic agent

Allergens

Infectious organisms

Viruses

Bacteria

Mycoplasma

Rickettsiae

Fungi

Parasites

Vaccines

physical agent

Kinetic energy

- EX: bullet wounds, blunt trauma, vehicular injuries

Radiation

Thermal

Heat (burns)

Cold (frostbite)

Noise

chemical agent

toxins

dusts

social and psychological stressors

anxiety and depression

infection

Host organism's response to a pathogen (substance capable of causing disease)

Tissue destroying microorganisms enter and multiply in the body

Categorization by severity

Minor: colds, ear infections

Life-threatening: sepsis

- Results in widespread vasodilation & multi-organ failure

emia

its in the blood

sepsis

infection; contamination

bacteremia

presence of bacteria in the blood

viremia

presence of virus particles in the blood

septicemia

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

infection causing microbes: viruses

Microscopic genetic parasites

Consist of a protein coat that surrounds a nucleic acid core which may contain RNA or DNA

Have no metabolic capability most require a host cell to replicate (obligate intracellular parasites)

Some can reproduce outside of a living cell

Capable of remaining dormant for long periods of time & replicate / produce symptoms months or years after initial infection

infection cuase microbes: bacteria

Single-celled microorganisms

No true nucleus

Reproduce by cell division

Pathogenic bacteria contain cell-damaging proteins

Endotoxins - released when the bacterial cell wall decomposes; can cause fever and are not affected by antibiotics

Exotoxins - released during cell growth

Classified based on

Shape: coccus (spherical), spirillium (helical), bacillus (elongated)

Growth requirements

Motility (flagellated)

Oxygen requirements (aerobic vs anaerobic)

Gram stain: positively stains purple, negative do not retain stain

microorganisms: bacteria

Staphylococcus aureus- frequently found in the human respiratory tract and on the skin. Escherichia coli- rod-shaped bacterium that is commonly found in the lower intestine of warm-blooded organisms. Spirochete, staphylococcus aureus, clostridium tetani

mycoplasmas

1/3 the size of bacteria

Capable of reproducing independently

Do NOT have a rigid cell wall

Some cause pneumonia

rickettsiae

Depend upon host cell for nutrients

Multiply by cell division

Have a rigid cell wall

Human infection caused by bite of an infected arthropod

EX: Typhus, Rocky Mountain spotted fever

fungi

Non-photosynthetic microorganisms that reproduce asexually (cell division)

Relatively large microorganisms

Contain a true nucleus

Classified as

Yeasts

- Round, single-celled facultative anaerobes (can live with or without oxygen)

Molds

- Filament-like, multinucleated, aerobic microorganisms

mycotic infections or mycoses

Infections caused by fungi that release mycotoxins

most infections are...

mild (athlete's foot, candidiasis) unless they become systemic or the patient's immune system is compromised ---> opportunistic infection

infection causing microbes: parasites

depend of host for food and protective environment

protoza

Minute unicellular animals

Transmission by arthropod vector or contaminated food / water

EX: malaria, amebic dysentery

helminths

Worm-like parasites

Transmitted by ingestion of fertilized eggs or larva penetration of the skin

Most common in developing countries

arthropods

Have jointed exoskeleton & paired jointed legs

Can serve as vectors for other diseases

EX: ticks, mosquitoes, biting flies

Ectoparasites

organism that lives outside the body

Transmitted through contact with infected clotting, bedding or grooming articles

EX: mites, lice, chiggers

normal body flora

Harmless microorganisms that reside in or on the body

Found on skin and in the nose, mouth, pharynx, distal intestine, colon, distal urethra & vagina

Skin contains ~100,000 microorganisms per square centimeter

Trillions of microorganisms are secreted from the GI tract daily

Many provide useful functions

Intestinal flora help synthesize vitamin K

host factors

Responsible for the degree to which the individual is able to adapt to the stressor produced by the agent (resistance)

Influenced by

Genotype / phenotype

Nutritional status

Immune system

Social behaviors

chain of infection

pathogen, reservoir, portal of exit, mode of transmission, portal of entry, susceptible host

granulocytes

Neutrophils

- Bands

Basophils

Eosinophils

agranulocytes

lymphocytes

monocytes

other cellular elements

red blood cells

platelets

white blood cells

Protect body against harmful bacteria & infection

Granulocytes "polys" or "segs"

Neutrophils ---> phagocytosis

"pyogenic" infections

bands --> immature neutrophils (~1-3% of neutrophils)

"shift to the left" is an ↑ in the number of bands

Basophils

involved in allergies and inflammatory responses

Eosinophils

release heparin and histamine, involved in delayed allergic reaction, also has role in parasitic infections

Agranulocytes

Monocytes --> phagocytosis --> severe infections

Lymphocytes --> viral infections

B-cells = mature into plasma cells & release antibodies

T-cells = regulate cell mediated immunity

types of white blood cells

neutrophils, eosinophils, basophils, monocytes, lymphocytes

macrophages

Lack surface receptors for specific antigens

Have receptors for Fc region and for complement

Ingest and process antigen & deposit it on its own surface in association with MHC II present antigen-MHC complex to T-lymphocytes activate T-lymphocytes

Secrete cytokines: tumor necrosis factor (TNF) & interleukin-1 (IL-1) which produce fever

Phagocytic effector cells in both humoral & cell-mediated responses

dendritic cells

Also mononuclear phagocytes that are another type of antigen presenting cell

Different function than dendritic cells in the nervous system

Also communicate with the innate and adaptive immune systems with central role in fighting infection and maintaining organ integrity

Main function of dendritic cells is activation of naïve T cells not previously subjected to an antigen

reticuloendothelial system

Tissue macrophages

Lung: alveolar macrophages

Liver: Kupffer's cells

Spleen

Lymph nodes

Intestine: Peyer's patches

CNS: microglial cells

Skin: Langerhans' cells

Connective tissue: histiocytes

neutrophil function

bacterial infections, inflammatory disorders, stress, certain drugs

eosinophils

allergic disorders and parasitic infestations

basophils

inflammation and allergic reaction

lymphocytes

viral infections

monocytes

severe infections

neutrophil WBC relative %

55-70%

neutrophil absolute

2500-8000

eosinophil relative

1-4%

eosinophil absolute

50-500

basophil relative

0.5-1%

basophil absolute

25-100

lymphocyte relative

20-40%

lymphocyte absolute

1000-4000

monocyte relative

2-8%

monocyte absolute

100-700

total WBC relative

100%

total WBC absolute

5000-10000

WBC absolute vc relative

Absolute = Actual Number (#)

Relative = Percentage (%)

Absolute value = Relative value (%) x Total WBC

The RELATIVE values will ALWAYS total 100% ... Soooo ... if one type of cell ↑'s the other types MUST ↓

RELATIVE ↑'s or ↓'s in cell counts are NOT important ... ABSOLUTE ↑'s or ↓'s ABSOLUTELY ARE!

calculating absolute counts in WBC

Total WBC Count = 12.8 x 103 cells/mm3

increased value

Leukocytosis

Neutrophilia

Lymphocytosis

Monocytosis

Eosinophilia

Basophilia

decreased value

Leukopenia

Neutropenia

Lymphopenia

Monocytopenia

Eosinopenia

Basopenia

significance of WBC values

An increased WBC count infection, inflammation, tissue necrosis, or leukemic neoplasia

Increases also observed in trauma, emotional/physical stress

A decreased WBC count chemotherapy, radiation therapy, marrow infiltrative diseases, overwhelming infections, dietary deficiencies, autoimmune diseases

Serial WBC & differential counts have diagnostic & prognostic value

EX: persistent increase worsening of an infection

EX: drastic decrease bone marrow failure & risk of infection

Critical Values: < 2500 cells/mm3 or > 30,000 cells/mm3

WBC values tend to be age-related

Normal newborns & infants - have higher WBC values

Elderly - may not develop increased WBC even in the presence of severe bacterial infection

absolute neutrophil count (ANC)

ANC = WBC x (% neutrophils + % bands) Critical value < 1000

EX: WBC = 12.8 x 103 cells/mm3 Neutrophils aka segs or polys = 50% Bands or stabs = 15% ANC = (12.8 x 103) x (50% + 15%) = 8320

EX: WBC = 1.3 x 103 cells/mm3 Neutrophils aka segs or polys = 50% Bands or stabs = 5% ANC = (1.3 x 103) x (50% + 5%) = 715

Erythrocyte Sedimentation Rate (ESR)

rate that RBC's settle out of anticoagulated blood in 1 hour

Inflammatory & necrotic processes cause an alteration in blood proteins --> RBC's tend to clump together in a column-like manner (Rouleaux formation) and thus are heavier and settle out faster when placed in a vertical tube

Is NOT diagnostic but provides information about disease processes that need to be investigated

In acute infections the ESR usually does not elevate for 6-24 hours and peaks after several days.

C-reactive protein (CRP)

An abnormal protein synthesized by the liver & present in blood during any process that involves tissue necrosis, trauma, inflammation, or infection

Appears rapidly in response to injurious stimulus

CLASSIC & MOST dramatic ACUTE PHASE reactant, levels ↑ up to 1000 x normal --> rapidly declines when inflammatory process regresses --> provides good indicator of healing and response to Tx

NON-SPECIFIC test for evaluating inflammatory disease course & severity

Serum levels ↑ w/in 18-24 hrs (rises earlier) and starts to decrease earlier as well

culture and sensitivity

Saliva, blood, urine, CSF, or other specimens may be sent for testing

Specimen sample placed in special culture media to allow organism to grow and then be identified

Antimicrobial effectiveness determined by placing various antibiotic disks on the culture medium

REMEMBER: In vitro tests do NOT reflect plasma concentrations or attainable concentrations at the site of infection & do NOT take into account local factors (pH) that may affect the activity of drug

serial dilution

Used to obtain a culture plate that yields a countable number of separate colonies

From this, a calculation of viable cells in the original suspension can be made

gram negative

Describing the group of bacteria that have a cell wall that is structurally more complex and contains less peptidoglycan than the cell wall of gram-positive bacteria. Gram-negative bacteria are often more toxic than gram-positive bacteria. PINK

gram positive

Describing the group of bacteria that have a cell wall that is structurally less complex and contains more peptidoglycan than the cell wall of gram-negative bacteria. Gram-positive bacteria are usually less toxic than gram-negative bacteria. PURPLE

urinalysis: markers of infection

Appearance & color

- Cloudy urine may be caused by the presence of pus (necrotic WBCs), RBCs, or bacteria

- Pseudomonas may produce green urine

Odor

- Foul odor may indicate presence of a urinary tract infection

pH

- Bacteria may increase urinary pH

- Urea-splitting bacteria cause the urine to be alkaline

Leukocyte esterase

- A screening test used to detect leukocytes in the urine (90% accuracy)

Nitrites

- Screening test for identification of urinary tract infections Bacteria produce an enzyme called reductase which can reduce nitrates to nitrites (50% accuracy)

- False positive if contaminated with vaginal secretions

stool culture

Normally stool contains many bacteria & fungi (indigenous)

Bacteria that act as pathogens: Salmonella, Shigella, Campylobacter, Yersinia

Presence of urine in the sample may inhibit bacterial growth false negative culture

Performed on patients with unrelenting diarrhea, fever & abdominal bloating

The normal stool flora can become pathogenic if the host is immunocompromised

WEAR GLOVES!

acute inflammatory response

Response

Rapid & non-specific

Protective response to cellular injury from any cause

Can only occur in vascularized tissue

Results in

Accumulation of fluid & cells at the inflammatory site

"-itis" = Inflammation

hallmarks of inflammation

Redness

- Rubor

Swelling

- Tumor

Heat

- Calor

Pain

- Dolor

Loss of function

- Functio laesa

itis = inflammation

The reaction of vascularized tissue to local injury

Active

Aggressive

Nonspecific

Is NOT synonymous with infection

Colonization (presence of microorganisms) alone does NOT produce inflammation

Infection is only one activity that can cause cell injury & inflammation

The tissue response is the same regardless of cause

Cell injury initiates the inflammatory process

Any cellular injury will produce a non-specific inflammatory response

Generally localized but may be systemic

causes of inflammation

Infection by microorganisms

Heat (burns) & cold (frostbite)

Radiation

UV, infrared or radioactive

Trauma

Abrasions, lacerations, bruising, crushing

Chemicals

Strong acids or bases, insect bites, allergens, toxins produced by microorganisms

Ischemic damage

hypoxia

Lack of sufficient oxygen

Ex: decreased amount of oxygen in the air, loss of hemoglobin or hemoglobin function, decreased production of red blood cells, diseases of the respiratory & cardiovascular systems, poisoning of the oxidative enzymes within the cells

ischemia

Reduced blood supply (gradual progressive vs. sudden acute)

Ex: arteriosclerosis (gradual narrowing of the arteries), thrombosis (complete blockage of an artery by a blood clot), embolus (a blood clot that has traveled from a distant site)

anoxia

total lack of oxygen

infarction

cell death

vascular response

Immediate arteriolar vasoconstriction followed by vasodilation swelling (edema) & erythema (redness) hyperemia

Increased capillary permeability allows fluid to escape into tissue swelling (edema) [fluid dilutes toxins!]

Pain & impaired function d/t tissue swelling & release of chemical mediators

cellular response

WBCs move toward damaged cells --> phagocytosis of dead cells & microorganisms

Platelets move toward damaged cells --> control any excess bleeding in the area

Mast Cells --> release heparin to maintain blood flow to area