BIOL 217 Exam 3

pathology

the study of disease

etiology

the cause of disease

pathogenesis

the development of disease

symptoms

body function response (what is felt by patient as result of disease); subjective

signs

changes in body (can be measured/observed as result of disease); objective

syndrome

determined by specific signs and symptoms that accompany a disease (often confirmed with lab tests)

communicable disease

spread from one human host to another

noncommunicable disease

*NOT* spread from one human host to another (often microbes outside of body that only cause disease when enter body)

reservoir

habitat of infectious agent (*CAN* live here, but may not be atm)

- living = humans, animals, etc.

- nonliving = soil, water, etc.

carrier

living organism with the pathogen reproducing inside them and being shed into environment (can have NO symptoms OR obvious symptoms)

contact (person-to-person) transmission types

1) direct transmission: transmission through physical contact (touch, kiss, exchange bodily fluids, etc.)

- ex: rhinovirus and influenza (touch) or gonorrhea (sexually transmitted)

2) droplet transmission: microbes spread from respiratory droplets over short distances (coughing, sneezing, etc.)

- ex: rhinovirus and influenza

3) indirect transmission: transmission via nonliving organism

- fomite: inanimate objects (bedding toys, surgical instruments, etc.) that transmit disease

vehicle transmission types

1) airborne transmission: infectious agents in droplets, but dispersed via dust and travel >1 meter

2) waterborne transmission: untreated water allows pathogens to replicate

3) food borne transmission: undercooked, poorly refrigerated, unsanitary preparation

- ex: cholera, foodborne illness, etc.

4) vectors: living organisms that transfer pathogen from one person to another

- arthropods: fleas, ticks, mosquitos, vertebrates (dogs, rats, etc.)

- mechanical transmission: passive transport (from insects feet and land on food then human consume food)

- biological transmission: active transport (arthropod bite and take blood of infected person and then infect another person when feeding)

epidemiology

study of occurrence, distribution, and determinants of health and disease in population

types of epidemiology

1) descriptive: collection and analysis of data (more general)

2) analytical: analyze disease for probable cause

3) experimental: hypothesis and experiment

- clinical trial: test and control group

3 scientists and type of epidemiology

Snow: mapped occurrence of cholera in London (descriptive)

Semmelweis: tested improved sterilization of doctor's hands prior to exams would reduce the death rate (experimental)

Nightingale: noticed that individuals with a lower incidence of typhus (bacterial infection) were treated at hospitals with better sanitation (analytical)

outbreak

numerous cases over a short period of time (often occurs where cases are minimal)

incidence vs prevalence

incidence: # of new cases of a disease during a time (indicates spread of disease)

prevalence: # of new AND existing cases at a particular time (indicates how long a disease can persist in population)

mortality and mortality rate

deaths in a population

mortality rate = deaths/population * 100%

endemic

disease that is constantly at low incidence in population (ex. common cold)

epidemic

disease that infects unusually high # of individuals in population (ex. influenza)

pandemic

worldwide epidemic (ex. covid)

classifications of epidemics by transmission modes

human host-to-human host epidemics: an infected individual (considered *patient zero*) infects susceptible person (ex. chicken pox, influenza, etc.)

- slow, steady progression followed by gradual decline (often variable incubation periods)

common-source epidemics: originate from common source (ex. food, water, etc.)

- rapid increase in infected individuals over short time

- common result: intestinal diseases (ex. cholera (vibrio cholera), etc.)

how one is infected/types

infection: organism invades, colonizes, and grows in host

primary infection: infection that causes initial illness

secondary infection: opportunistic infection after primary infection

stages of disease

1) infection: organism invades, colonizes, and grows in host

2) incubation: duration between infection and appearance of symptoms

3) prodromal period: short period after incubation; early, mild symptoms

4) acute (illness) period: disease is most active; most severe symptoms

5) decline period: symptoms subside

6) convalescent period: patient regains strength and returns to normal

predisposing factors

factors that increase disease susceptibility (gender, inherited traits, weather, lack of vaccination, fatigue, age, lifestyle, nutrition, chemotherapy, etc.)

types of disease based on severity/duration

1) acute disease: symptoms develop rapidly (often with dramatic onset of symptoms) but disease lasts short time

- ex. influenza

2) chronic disease: symptoms develop slowly and often last a long time

- ex. tuberculosis, mononucleosis, etc.

3) subacute disease: between cute and chronic

4) latent disease: causative agent is inactive for a time but then activates resulting in symptoms

enterohemorrhagic E. coli

- major cause of food borne illness

- transmission: contaminated food/water

- incubation: 2-5 days

- symptom duration: >8 days

- shiga toxins: targets and damage intestinal lining ; can result in bloody diarrhea

- O157:H7 is the predominant strain

o-antigen (advantages and disadvantages)

- in contact with the environment

advantage: caries among bacterial strains -- ensures bacteria are unique

disadvantage: target for human immune response and location for viral attachment

lipid A

- can release toxins

- can negatively affect humans (ex. food poisoning symptoms)

infection vs disease

infection: the growth of microbe in a host

disease: when the pathogen affects the normal functioning of the host

pathogenicity vs virulence

pathogenicity: the *potential* ability to cause disease in a host

virulence: the *actual* ability of a pathogen to infect or damage a host

number of invading microbes vs. virulence (ID50?)

low number of invading microbes can often be stopped by host immune system

ID50: number of microbes/viruses required to produce an infection in 50% of healthy humans

- lower ID50 = "easier" for infection to occur

1) portals of entry?

mucous membranes

- linings of respiratory tract (inhalation)

- GI tract (consumption of contaminated food)

- genitourinary tract (sexual contact)

skin

- via hair follicles or sweat pores (unbroken skin is impermeable to microbes)

parenteral

- deposit directly into tissues (cuts, bites, injections, etc.)

mechanism of entry

adherence (adhesion): adhesins on bacteria bind to complementary receptors on host

- adhesins often located on glycocalyx (polysaccharide layer on outside of ALL bacteria)

- adhesins can also be on pill or flagella

process host uses to destroy microbes

phagocytosis: cells recognize invading microbes, engulf them, and destroy them

- lysozyme break down peptidoglycan layer

- lysosome is cell vesicle that has digestive enzymes

- exocytosis: release digestion products from cell

2) how can microbe penetrate or evade host defenses

1) capsule formation:

- glycocalyx released by bacteria can form capsule around bacteria

- advantage: reduce phagocytosis effectiveness bc cannot bind to receptors on phagocytic cells

- ex. streptococcus pneumonia (cause pneumonia), bacillus anthraces (cause anthrax), yersinia pestis (cause plague)

2) enzyme release:

- bacteria can gain protection from phagocytosis inside a clot so...

- *coagulase*: binds/interacts w/ clotting factors which convert fibrinogen --> fibrin = blood clot (ex. used by some staphylococcus species)

- when microbes ready to release, excrete *kinase* to digest fibrin clots (ex. used by some streptococcus species)

- body cannot recognize bacteria bc it thinks that the blood clot is needed (does not know bacteria in clot)

3) antigenic variation:

- some microbes can alter surface antigens so host antibodies cannot bind and inactivate these microbes

3) how can microbe to damage to host cell

1) use host nutrients

- siderophores: microbial proteins that bind to iron more tightly than host cells and bacteria take up iron when siderophore bind to siderophore receptor on bacteria

2) toxins: microbial produced substances that negatively affect host

- exotoxins: produced internally but excreted into environment (gram negative AND gram positive)

- endotoxins: part of bacterial cell (lipopolysaccharide layer) which can be released (gram *negative* ONLY)

- ex. of responses: fever, cardiovascular issues, diarrhea, shock

- LD50: # of toxins required to kill 50% of healthy humans (lower # = higher potency)

exotoxin characteristics and treatments

characteristics:

- production is coupled to growth/metabolism during log phase (just happens during growth/metabolism, they don't know they are actively producing exotoxins)

- soluble in bodily fluids and can diffuse into blood

- function: enzymes that destroy host cell and/or inhibit metabolic functions

treatment:

antitoxin injections: antibodies against specific exotoxins

toxoid vaccines: inactivated exotoxins (result in immune response)

how are exotoxins named?

- type of host cell attacked (ex. neurotoxins attack nerve cells)

- type of disease they cause (ex. tetanus toxin cause tetanus)

- species that produce them (ex. botulinum toxin produced by clostridium botulinum)

A-B toxin

A-B toxins:

- contain active (enzyme component) and binding (B part) components

- ex. diphtheria toxin inhibit host cell protein synthesis

- 1) bacterium produce A-B toxin

- 2) B bind to host cell receptor

- 3) host cell fold inward to take in toxin

- 4) exotoxin enter cell by endocytosis

- 5) A and B separate (A alter host cell function and B is released and put receptor back on host)

ex. genotoxin: cause damage to host cell DNA

endotoxins and human reaction

- part of bacterial cell

- produced by gram-negative bacteria on lipid A layer (can release endotoxins IF cell wall lyses or during binary fission)

- human rxn: chills, fever, weakness, aches, shock (dec. BP), and/or death

endotoxin mechanism and host response

1) macrophage ingest gram-negative bacteria

2) bacterium degraded in vacuole releasing endotoxins and macrophage produces cytokines

3) cytokines released (like asking for help bc panic due to toxin release) into bloodstream and travel to somewhere (ex. hypothalamus)

4) cytokines induce set in body (ex. for hypothalamus, hypothalamus produce prostaglandins and reset body thermostat)

4) portals of exit

- respiratory tract (coughing/sneezing)

- gastrointestinal tract (feces)

- genitourinary tract (urine)

- skin

- blood (arthropods that bite; needles or syringes)

what is the immune system?

body's defense against disease causing organisms, malfunctioning cells, and foreign particles

what is innate immunity?

defenses that a human obtains from birth

- host's early warning system

- first (and second) line(s) of defense when microbe enters host

- not microbe specific

no memory component

what is adaptive immunity?

responses to a specific causative agent (after innate immunity has been breeched)

first line of defense of innate immunity

- physical factors (skin and mucous membranes)

- chemical factors (perspiration, lysozyme, earwax, alive, gastric juices)

second line of defense of innate immunity

- phagocyte production

- inflammation, fever

what is a macrophage?

phagocytic white blood cell (host)

what are cytokines?

proteins taht mediate communication w/in "immune system" (host)

how do endotoxins and exotoxins vary?

- toxicity (ability to cause disease) is higher in exotoxins

- endotoxins are better at producing fever

- lethal dose is smaller for exotoxins (more toxic)

how does innate immunity work?

- innate response is initiated by protein receptors in the host cell membrane defensive cells

- host defensive cells = macrophages and dendritic cells

- host protein receptors = toll-like receptors (TLRs)

1) host TLRs attach to pathogen-associated molecular patterns (PAMPs) in pathogens (ex. lipopolysaccharide layer (gram neg.), flagella (all), peptidoglycan (gram pos.), DNA (all), and genetic info in viruses)

2) when TLRs contact PAMPs -- cytokines (proteins) are released to regulate/inform the immune response

- role of cytokines: (1) recruit more defensive cells (macrophages and dendritic cells) to isolate and destroy microbes (inflammation) (2) can initiate the adaptive immunity response

skin composition and why is it so hard for microbes to penetrate? (first line of defense)

composition:

- epidermis: comprised of tightly packed epithelial cells containing keratin (protective protein)

- dermis: inner portion made of connective tissue (connective tissue provides support and aids in tissue repair)

why is it so hard for microbes to penetrate?

- top layers of skin are shed (40-50k skin cells everyday)

- extreme dryness of skin inhibits microbial growth (bc they need water)

mucous membranes and why so hard to penetrate? (first line of defense)

- mucous membranes consist of epithelial layer and underlying connective tissue and line the gastrointestinal and respiratory tracts

why is it hard for microbes to enter?

- secretes mucus: glycoproteins that prevent tracts from drying out (traps microbes preventing entry)

chemical factors of first line of defense?

- lysozyme break down peptidoglycan in bacterial cell walls (cause lysis) and present in saliva, perspiration, tears, and urine

many secretions release low pH substances to inhibit microbial growth:

- gastric juices in stomach (pH ~1-3)

- vaginal secretions (pH 3-5)

- ear wax secretions (pH 3-5)

- urine (pH~6)

other physical factors of first line of defense

ciliary escalator: cilia transport trapped microbes away from lungs

earwax: physically prevent microbes from entering

urine: cleans out urethra via flow

vaginal secretions: move microbes out of

vaginal tract

defecation and vomiting: expel microbes from body

wbc counts

wbc counts measure leukocytes in blood

- high wbc = bacterial infections, autoimmune diseases, or side effects of medication

- low wbc = viral infections, pneumonia, autoimmune diseases, or cancers

wbc types (2)

granulocytes: contain large granules that can be viewed w/ light microscope after staining

agranulocytes: granules are not visible w/ light microscope after staining

types of granulocytes

neutrophils: phagocytic; involved during early stages of infection (kill and digest pathogens)

eosinophils: phagocytic; produce toxic proteins that target parasites

basophils: communicate w/ other cells when pathogens are in the blood (release histamine; involved in allergic responses)

types of agranulocytes

monocytes: phagocytic (mature into macrophages in tissues)

dendritic cells: phagocytic (located in skin, mucous membranes)

lymphocytes: involved in adaptive immunity (create antibodies ex. T cells, B cells, NK cells)

types of phagocytes

free (wandering) macrophages: roam tissues and gather at sites of infection

fixed macrophages: residents in tissues and organs (liver, lungs, etc.)

mechanism of phagocytes

1) chemotaxis

- chemical signals (microbial products, damaged host cells, cytokines) attract phagocytes to the microbes

2) adherence

- attachment of a host phagocyte receptor (TLRs) to the surface PAMPs

3) ingestion

4) digestion

- lysozyme fuses with the phagosome and enzymes break down the bacteria

- microbes are digested and released

symptoms/signs of inflammation

- pain (often due to pressure or chemical release)

-redness (response to increased blood in affected region)

- heat (increased blood flow)

- swelling (accumulation of fluids)

- immobility (local loss of function if inflammation is severe)

purpose of inflammation

- destroy microbes

- limit effects of microbes on body

- repair/replace damaged tissue

what is fever?

abnormally high body temperature

- cytokines are released increasing your body's temperature set point (achieved by vasoconstriction and shivering)

- fever persists until cytokines are eliminated

- body temp decreases back down (achieved by vasodilation and sweating)

adaptive immunity

defenses that target a specific pathogen inside and outside of the host cell (acquired through infection or vaccination)

two types of adaptive immunity

humoral and cell-mediated

antibodies

- proteins (produced by plasma or attached B cells) that bind to, damage, clump, and/or slow foreign particles (antigens) in the body

- each antibody binds to only one specific binding site, known as an antigen

antibody structure

fab (fragment, antigen, binding) region = arms of the Y

- constant region: "light" (~215 AA's) chain

- variable region: binding sites to antigens made of variable "heavy" (450-550 AA's) chain in regards to AA sequence (allows it to bind to one specific antigen)

Fc region/constant region: base of the Y

- contains two heavy chains that are identical for a particular Ig class (ex. IgG, IgM, IgA, etc.)

- can bind to B cell receptors at base

IgM (class, response, structure, proportion in serum antibodies, location, function)

class: 5

response: first antibody to appear after initial exposure to an antigen

structure: pentamer

proportion in serum antibodies: 6%

location: blood vessels

function: largest in size; cause clumping of RBCs if blood is not compatible with human blood type

IgG (class, response, structure, proportion in serum antibodies, location, function)

class: 1

response: second type of antibodies to respond to antigens

structure: monomer

proportion in serum antibodies: 80%

location: in blood, lymph, intestine

function: cross placenta and protect fetus (passive immunity); enhance phagocytosis

IgA (class, response, structure, proportion in serum antibodies, location, function)

class: 4

response: typically produced after IgM and IgG

structure: monomer in serum; dimer in secretions

proportion in serum antibodies: 13%

location: common in mucous membranes and body secretions (saliva, tears, breast milk, etc.)

function: prevent microbial attachment to mucous membranes; protects infants from GI infections when breastfed (in breast milk)

antigens

substances (proteins or large polysaccharides) that cause the production of antibodies (or a substance that elicits an immune response) [i.e. a humoral (antibody response) or cell-mediated immune response]

where can antibodies bind to on pathogens

antibodies bind to epitopes or antigenic. determinants on antigenic sites located on surface of pathogens (ex. flagella, LPS, etc. (PAMPs))

ex. pollen, egg whites, etc.

antigen-antibody complex

binding of an antigen to an antibody (i.e. antibody recognizes the AA sequence in antigen epitope)

antibody binding results in...

agglutination: clumping of antigens resulting in easier attack by phagocytes

neutralization: IgG blocks attachment to host cells = inactive pathogens (facilitates increased phagocytosis)

humoral immunity

fights invaders and threats *outside* of the cells (in extracellular fluid)

- produce antibodies (Ig) that combat foreign molecules known as antigens

overview of humoral immunity response

- carry immunoglobulins on their surface

- when activated, B cells produce plasma cells and memory cells (clonal expansion) --> produce antigen specific antibodies

- T-dependent antigens require a T helper cell to activate a B cell (both T helper and B cell must recognize/interact with epitope on antigen for antibodies to be produced)

- some antigens (T-independent antigens) only require a B cell

T-dependent antigen process

1) host APC receptors recognize and attach to antigen

2) antigen is phagocytized (digested)

3) antigen fragments are displayed on B cell surface on MHC class II, attracting a matching T helper cell

- MHC = major histocompatibility complex: formed inside B cell and embedded in plasma membrane

- MHC combine w/ antigenic fragments on B cell surface which will attract specific T helper cells

4) T helper cell binds to fragment and secretes cytokines, activating a B cell

5) activated B cell begins clonal expansion, producing an army of antibody-producing plasma cells (plasma cells produce antibodies) and memory cells

6) production of antibody specific to the antigen

immunological memory/secondary response

secondary response = memory response:

- quicker response (2-7 days vs ~2 weeks for peak antibody production)

- antibody concentrations remain higher for longer

- difference in response is driven by activated B cells not only becoming antibody-secreting plasma cells but also becoming memory cells

immunological memory/secondary response steps

1) pathogen X exposure

2) memory B cells (specific for pathogen X) locate pathogen X

3) B cells differentiate into plasma cells

4) pathogen X-specific antibodies are released

memory cells

- these cells have long lifespan (years to decades)

- when exposed to repeat antigen they can differentiate into plasma cells (producing antibodies)

antibody titer (primary vs. secondary response)

relative amount of antibodies in serum (reflects intensity of humoral response)

primary: IgM first produced by B cells

secondary: B cells may decide to produce IgG or IgA first instead of IgM (*class switch*)

cellular immunity

attacks antigens that have already entered cells

how long does active immunity last?

depends on antigen:

- some pathogens constantly mutate into forms that initial antibodies no longer recognize (this is why we need annual flu vaccinations/booster shots)

- other causative agents, such as DNA viruses hide within the host for life (ex. varicella/chicken pox)

naturally acquired active immunity

unplanned exposure to actual antigen

artificially acquired active immunity

planned exposure to a modified form of the antigen -- deactivated pathogen parts or extremely weakened pathogen

naturally acquired passive immunity

mom passes immunity to a baby during pregnancy or after birth

- provides antibodies to protect fetus/baby for a host period while the immune system develops

artificially acquired passive immunity

antibodies injected into patient