MCB exam IV

pathogen

microbe that can cause disease

ID50

dose that infects 50% of hosts

colonization

microorganisms show up, not possible without membrane receptors or pili/fimbriae or adhesin

infection

microorganisms establish themselves and multiply

disease

host is damaged or functions are inhibited

in the gut

goblet cells (make mucus), paneth cells (make defensins), epithelial cells (signaling)

on the skin

Staph. epidermis, Corynebacterium, Cutibacterium acnes, Malassezia (yeast); must resist cool, dry, salty, acidic conditions; shedding controls G+ pop., dryness controls G- pop.

in the nose

S. epidermis, S. aureus

in the nasopharynx

Streptococcus, Neisseria, Haemophilus

in the throat

normal alpha-hemolytic strep, beta causes strep throat

in lower respiratory tract

mucociliary “escalator” of cilia that sweep up bacteria, alveolar macrophages eat what gets through

in the mouth

plaque, periodontitis, calculus/tartar

plaque

biofilm on teeth, carries Streptococcus mutans that turns sugar into acid

periodontitis

anaerobic Porphyromonas live under the gums

calculus/tartar

plaque hardened with calcium

in the stomach

pH 2 acid kills most; Helicobacter pylori neutralizes urea with urease, can cause gastritis and ulcers

in the genitourinary tract

no bacteria in kidneys, bladders flushes out microbiota through urine, Lactobacillus make vagina acidic

immunity

ability to resist a disease

innate immunity

non-specific, fast, no antigen-specific memory; recognition via germline-encoded receptors; works via neutrophils, macrophages, DCs, NK cells, complements

adaptive immunity

specific, slow, antigen-specific memory; recognition via specific antigens; works via B cells, T cells, antibodies

defensins

peptides that punch holes in microbes

lysozymes

cut peptidoglycan, part of saliva/tears/mucus

mucus

traps microbes, contain antimicrobials

intrinsic defenses

defensins, lysozymes, mucus, skin, stomach acid, urine flow, cilia

PRR

pattern recognition receptor, induce cytokines and chemokines and antimicrobial responses

TLRs

toll-like receptors, main type of PRRs; 4 senses LPS, 5 senses bacterial flagellin

PAMP

molecular pattern that microbes have but not your cells; includes LPS, peptidoglycan, flagellin, nucleic acids

innate immune cells

carry PRRs; include macrophages, neutrophils, mast cells, dendritic cells, NK cells

macrophages

eat and clean via phagocytosis

neutrophil

first responder, throws DNA NETs

NETs

neutrophil extracellular traps for phagocytosis (engulfing and digesting) and degranulation (releasing antomicrobial substances)

mast cell

histamine, inflammation, local vascular response

dendritic cell/DC

sense and process antigens, activates T cells, bridge to adaptive immunity; travel through lymph vessels to draining nodes, present antigens to naive T cells

NK cell

kills infected cells and tumors using perforin and granzymes

lymphatic system

includes DCs, lymph vessels, lymph nodes

lymph vessels

immune cell highway

lymph nodes

cell and antigen meeting spot, 400-450 in the body; swelling indicates immune response

complements

blood proteins C1-C9; C3b coats microbe (opsonization); C5a reports inflammation, C5b-C9 form MAC membrane pore

how adaptive immunity works

cell activates defense → makes messengers to recruit innate immune cells → macrophages, neutrophils, DCs move in and make more → response triggered when there’s enough cytokines

natural immunity

from getting the germ itself or antibodies from mom

artificial immunity

from vaccine (active) or antibody shot (passive)

microfold (M) cell

part of gut/airway linings; transcytose antigens from lumen and release antigens to DCs, B cells, T cells → DCs process them and transfer to lymph nodes → nerves release neuropeptides, limit pathogen entry and make more protective bacteria → cytokines recruit more immune cells

humoral immunity

antibody clears infection, T cells activate B → B produce antigen-specific antibody and memory B

cell-mediated immunity

CD4 helper T that activate Bs and macrophages, CD cytotoxic that kill cells with intracellular pathogens and tumor cells, regulatory T cells that turn off response when done

antigen

any molecule that induces antibody production, binds to antibodies and signal immune response; strongest antigens are large complex proteins; weakest are lipids and nucleic acids

epitope

antigenic determinant, the numerous parts of an antigen that are actually bound

hapten

attaches to carrier proteins to trigger a big enough response

molecular mimicry

microbial epitopes mimic host molecules, trigger autoimmunity

immunoglobin (Ig)

antibody secreted by B cells, consists of FAB binding sites, Fc tail to “type” antibody; M is 1st and largest; A in mucus and breast milk; G is most specific and systemic

B cell receptor (BCR)

membrane-bound antibody, 1st signal

helper T

responsible for class switching between Ig types, affinity maturation (better fit for each round), memory

T-dependent antigen

bacterial polysaccharides, give IgM, little memory

antibody functions

• neutralization (block stuff from attaching to cells)

• opsonization (Fc tail tags for phagocytosis)

• agglutination/precipitation (clump cells/antigens for clean up)

• complement activation (inflammation + MAC pore formation)

  • ADCC (NKs grab tagged cell’s Fc and kills it)

primary response

1st exposure, 5-14 day lag, IgM then IgG, low titer

secondary response

re-exposure and recall, 1-4 days, IgG, high titer and affinity, lasts longer

T cell receptor (TCR)

binds peptide sitting in MHC

CD4 helper T

MHC class II, found on APC, presents peptides from eaten antigens; secrete cytokines IL-2, IL-4, IFN-y

CD8 cytotoxic T

MHC class I, found on all nucleated cells, presents peptides from endogenous antigens; NK cells catch whatever it misses

suppressor T

suppress antibody production, cause autoimmune response if not turned on

contamination

microbes are present where not expected

pathogenicity

ability of a microbe to cause disease

virulence

degree of pathogenicity via pathogen’s host defenses and disease severity, measured relative between strains or host

disease

= pathogen (virulence, dose, site, strain) x host (barriers, immunity, age, microbiota, physiology, prior exposure) x environment (exposure, sanitation, crowding, medical devices, treatment, season)

Ebola reston

silent infection, antibodies appear, no illness

Ebola zaire

25-90% fatality, virus lives in semen/eye for a year

primary pathogen

causes disease in otherwise healthy host

opportunistic pathogen

causes disease only when defenses, microbiota, or barriers change/fail

endemic

constant, expected presence of a disease in an area/pop

epidemic

sudden rise in cases, more than expected

pandemic

epidemic across countries/continents

morbidity rate

new cases of a disease/total pop

mortality rate

deaths from a disease/pop. at risk

case fatality rate

deaths from disease/people diagnosed with disease

common source (A) curve

everyone exposed to the same source/event, sharp spike, quick fall

propagated (B) curve

person-to-person, gradual rise and fall

communicable

transmitted between people

noncommunicable

acquired from common source, not transmitted between people (EX: vector-borne)

chain of infection

infectious agent → reservoir → exit portal → mode of transmission → entry portal → susceptible host

reservoir

where pathogen typically lives and multiplies

exit portal

respiratory secretions, feces, urine, blood, skin lesions, genital secretions, etc.

mode of transmission

direct contact, droplets, aerosol, indirect contact

direct contact

skin-skin or mucosa-mucosa

droplets

larger than 5 um; from coughing, sneezing, talking

aerosol

smaller than 5 um, airborne, stay suspended and travel farther

indirect contact

vehicles (food, water, soil, blood), fomites (inanimate objects/surfaces), vectors, parenteral (needles, bites), vertical

entry portals

mucous membranes, skin (cracks, hair follicles, etc.), parenteral, mouth/plaque, implants and joints, chronic inflammation

R0

basic reproduction number, average number of people that 1 infected person infects in a fully susceptible pop; > 1 means it grows, < 1 means it dies

herd immunity threshold

1-1/R0, number of people needed to vaccinate to stop spread

infection requires microbe to

• attach to tissue (adhesin, capsule, adherence proteins, fimbriae/pili)

• colonize (nutrients, temp., pH, growth factors)

• generate local infection

• reach circulation

  • damage host (secrete toxins, have LPS, trigger cytokine storm)

invasinveness

spread across tissue, impair function or migrate towards blood

invasins

surface proteins that trick host cells into taking microbe in

collagenase

exoenzyme that digests collagen

hyaluronidase

exoenzyme that digests hyaluronic acid between cells

coagulase

exoenzyme that builds fibrin clot for pathogen to hide in

streptokinase

exoenzyme that dissolves fibrin clots so microbe can continue

lipase

exoenzyme that dissolves membranes, enables breaching blood-brain barrier

protease

exoenzyme that degrades antibodies

nuclease/DNase

exoenzyme that digests DNA NETs made by neutrophils

quorum sensing

G- release AHLs, G+ release peptides, both are autoinducers; virulence factors turned on when there’s enough

direct tissue damage

caused by microbe; replication, cell lysis, toxins, degrading enzymes