Micro Final New Content

normal flora

• diverse communities of microorgs consistently living on and inside the healthy human body

• mutualistic/ communalistic

nosocomial infection

• infections that occur in institutions

• Ex: hospitals (geriatrics, ICU, post-op)

pathogen

microorganism that causes disease

virulence

• degree of pathogenicity

• inc. virulence = pathogens very potent (high mortality)

opportunistic pathogen

microrog that does not cause disease in healthy host but can cause an infection when the host’s immune system is weakened or when it enters an unusual body site

• ex: e. coli, staphylococcus aureus

bacteremia

presence of viable bacteria in the blood streams

viremia

• presence/detection of viruses in the blood stream

  • can travel to initial infection site to other organs/tissues

septicemia

infection pathogenic microorgs in the blood, organs or tissues

Four things must pathogens do to cause disease

a.       Gain entrance/attach into/onto host

b.       Resist (or not stimulate) host defense mech.

c.       Multiply in/on host (tissues)

d.       Cause a pathology, i.e. damage to host tissue

four routes of entry of bacterial/viral pathogens into the human body

a.       Respiratory Tract – inhalation

b.       Skin/Gastrointestinal tract – urinary

c.       Fecal – Oral (4 F’s)

d.       Parenteral (trauma): direct introduction into the skin

• Wound, burn, injection with contaminated needle

what are the four “F’s”

• finger

• food

• feces

• fomites (any inanimate object that can harbors disease)

  • primary pathways for fecal-oral disease transmission

spiderophores virulence factor

iron-scavenging molecules produced by microbes (bacteria, fungi) to capture essential ferric iron (Fe3+) from iron poor environments

lysogenic strains (lysogens) virulence factor

integrate a bacteriophage’s DNA (prophage) into their own chromosome, allowing the viral genome to replicate passively with the host cell without immediately causing harm

pili virulence factor

attachment to surface, such as host tissue or other bacteria, crucial for colonization

intracellular growth virulence factor

microorg actively multiply inside the living cells of a larger organism, using the cell’s resources for replication and survival, often escaping the host defense

antigenic variation virulence factor

• Happens in parasites and viruses – disguise themselves to look like host antigens by constantly changing their surface proteins; immune evasion

  • two types: antigenic drift and antigenic shift

antigenic drift (small)

evade host by accumulating to small point mutations

• need new vaccines every year (seek major strain of bacteria)

antigenic shift (large)

major change in antigenic profile; mix genetic material from different strains; bypass immunity

capsules virulence factor

resist host mechanisms (antibodies); stick to other capsules that produces a glob that is more resistant

toxins (plasmids/lysogens) virulence factor

• potent molecules microbes used for war fare (killing competitors, evading immune cells) and survival (inducing dormancy)

  • Endo toxins vs. exotoxins

How old are plagues in the course of human history

a.       Great Plague of Athens:  430-427 BCE

b.      Tuberculosis: 18^th and 19^th centuries

c.       Leprosy:  Ancient times - Middle Ages

d.      Smallpox: 16 century

e.       Black Death: 1347-1351

f.         Typhus (1847), Cholera (1817), Typhoid Fever

g.       Influenza – Spanish flu - 1918

h.      Polio: 1916

i.         AIDS : 1981

j.         EBOLA: 2014-2016

Recurrent and Emergent Infections: SARS, MERS, SARS-CoV-2/COVID- 19

Who are some of the first scientists credited with proposing the “germ theory of disease”; who actually proved it?

• Louis Pasteur: showed microbes cause fermentation and spoilage (pasteurization) and developed early vaccines, disproving spontaneous generation

• Robert Koch: ID specific bacteria causing antharax, cholera, and tuberculosis, establishing criteria to link microbes to specific diseases, thus proving the theory

• Joseph Lister: applied Pasteur’s ideas to surgery, using carbolic acid to kill germs and prevent infection, revolutionizing surgical practice

Name, in order, Koch's postulates. What did these postulates enable Koch to do?

• M.O. should be present in diseased but not healthy animals

• M.O. must be grown in pure culture outside the host

• Pure culture will produce disease when inoculated into a animal host

• M.O. must be re-isolated from infected host and should be identical to the original

• four tenants to prove germ theory of disease

reservior

in which an infectious agent lives and multiplies (living = organisms; inanimate = surfaces)

carrier (accute, chronic)

• A: displays symptoms of disease; communicable

• C: asymptomatic; don’t know they have disease

  •   Many are chronic carriers of mersa

vector

insects that harbor/transmit disease; may or may not (usually done) show symptoms of disease

morbidity

state of being diseased or the amount of illness in a populations, measuring the burden of disease (how many get sick), not death

mortality

the number or rate of deaths in a population, typically caused by pathogens

What is the connection between "Typhoid Mary " (Mary Mallon) and typhoid fever? What kind of a carrier was she? What was the significance of the 4 "F's" in this case?

• Mary Mallon = chronic carrier of typhoid fever (1900)

  • Typhoid bacillus—>salmonella typhi (g-) in her gall bladder

    • Shed it in her feces (route for fecal-oral disease transmission)

• “Chief cook & bottle washer” for boarding houses in Manhattan & long island, NY

• Responsible for >50 cases & 3 death; WAS NOT only carrier

epidemic

• on the people; Epi = on; demi - people

pandemic

worldwide epidemic

endemic disease

• appears suddenly in a community or region in numbers exceeding what’s normally expected,

• spreads rapidly via pathogens through person-to-person contact, contaminated sources

• vectors, causing widespread illness in a short time (ex: ebola or measles)

What kind of public health measures are used to control or eliminate the spread of a contagious disease?

• Eliminate Reservoir (or vector)

• Eliminate pathogen

• Immunize susceptible

• Quarantine diseased individuals

When was the ‘Great Plague of Athens’; what caused the disease (do we know, why or why not?)

• The Plague of Athens 430 B.C.

• We are still certain as to its cause, perhaps it was due to typhus or due to typhoid fever or possibly something else

  • Took lives of Pericles, and his two son’s sister

What disease was recently eradicated in 1975 due to a worldwide immunization program; why was this possible (there are numerous reasons)?

• small pox

• human only virus, visible symptoms, no asymptomatic carriers, inexpensive heat-stable vaccines

What are some problems associated with research concerning a disease that has been eradicated like smallpox?

What are the two main groups of pathogenic E.coli?

• Diarrheagenic E. coli (DEC)

• Extraintestinal Pathogenic E. coli (ExPEC)

exotoxins

• protein

• Heat labile = destroyed by heat

• Specific – binds to specific receptors

• Low LD50 – lethal dose that would kill 50% of experimental population; high toxicity = low LD50

• Toxoid potential – the rate to inactivate toxicityàtoxoid; maintaining protein structure but don’t have toxin abilities; body still recognizes and reacts to toxoids

• Classes:

  • Neurotoxins (Bo toxin, Tetanospasmin)

  • Cytotoxins (Diptheria toxin, streptolysins)

endotoxins

• LPS = lipopolysaccharide; can with stand 2 rounds of autoclaving

• Heat stable

• High LD50 – if present can send ppl into anaphylactic shock

• Relatively non specific systems

•   Endotoxin LPC Schmatic & Effects

  • IL_1 (endogenous pryegen) inc. prostaglandin syn. & fever production

  • TNF-a (cytokine release) capillary damage, how B.P and eventual shock

  • Production of NO (Nitric Oxide)

What are some of the physiological consequences of LPS to the host?

List three classes of exotoxins. Name the functions of the following toxins: botulinum toxin, and tetanus toxin.

• Nuerotixins (Bot toxin, Tetanospasmin)

  • Bot: blocks release of neurotransmitter at the junctionà if exposed you will go limp (From limbs to interior)

  • Tetanospasmin: blocks relaxation pathway; causes muscle spasms/tremors

• Cytotoxins (Diphtheria toxin, Streptolysin)

• Enterotoxins: causes massive dehydration; degrade bases in ribosomal RNA’s in ribosome

specific host defense mech

• binds to specific receptors (3^rd line of defense)

  •   Humoral immunity – four classic body humors

    • Circulating Ab produced by B cells/lymphocytes

  • Cellular, Cell-mediated immunity

    • Produced by T cells/lymphocytes

non-specific (innate immunity)

• the body's immediate, built-in defense system that attacks broad categories of microbes using general mechanisms like skin barriers, inflammation, and phagocytic cells (macrophages, neutrophils),

List five different nonspecific defense mechanisms.

•   Physio-chemical barriers – (1^st line of defense)

  •   Ex: lysozyme, skin, cilia, mucous membranes

•   Phagocytosis – phagolysosome (2^nd line of defense)

  • Ex: macrophages & neutrophils

• Blood components –complement cascade

  • 9 serum protease that cause lysis of bacterial cells

• Inflammation – ‘classic sings/symptoms’

  • Ex: heat, pain, redness & swelling

• Interferon – antiviral glycoproteins (a, B, y)

What is complement; what type of a defense mechanisms is it?

• acting as a first-line defense by using a cascade of plasma proteins to identify, tag (opsonize), and destroy pathogens like bacteria, or tag them for destruction, and trigger inflammation, all without needing prior exposure

• non specific host defense mechanism

leukocytes (WBC)

immune system cells produced in bone marrow, crucial for defending body against pathogen and disease by migrating the blood to infection sites, identifying threats and destroying invaders through process like phagocytosis and antibody production

granulocytes (PMN’s)

• class of leukocytes characterized by visible granules in their cytoplasm

• contain enzymes and chemicals to fight pathogens

• key players in innate immune systems, rapidly deploying the infection sites of engulf (phagocytosis) or release substances to destroy invaders

monocytes (& macrophages)

-mono: leukocytes from bone marrow that patrol blood, acting as key innate immune cells; differentiate macrophages and dendritic cells in tissue

-macro:  process, then display antigen on surface; has specific cell surface protein (glycoproteins); have foreign AND self-antigen in order to recognize a  foreign invader

lymphocytes

key white blood cells that orchestrate adaptive immunity, identifying and destroying pathogens like viruses and bacteria, and forming immune memory, primarily consisting of B cells (antibody production) and T cells (cell mediated killing/help) plus Natural Killer (NK) cell

thrombocytes (platelets)

tiny, a nuclear cell fragments in the blood, crucial for stopping bleeding by forming clots (hemostasis) at injury sites, sticking to vessel walls, and creating a fibrin mech for wound healing

serum

passive version of artificial acquired immunity (blood transfusion)

plasma

• the liquid component of blood (blood plasma), a yellowish fluid carrying cells, nutrients, hormones, and proteins, vital for transport and immunity

How does the process of phagocytosis destroy microorganisms; what chemical/enzymatic processes are involved ?

• Phagocytosis (2^nd line of defense) – phagolysosome

  • destroys microorganisms by engulfing them in a vesicle (phagosome), which then fuses with a lysosome to form a phagolysosome

  • creates a toxic environment with enzymes (like proteases, lipases, lysozyme) and reactive species (ROS/RNS) that break down the pathogen through oxygen-dependent (respiratory burst) and independent pathways, effectively digesting it. 

 

What is a phagolysosome?

Lysosome + phagosome

How do some microorganisms evade destruction by phagocytic cells?

a.       Create physical barrier (capsules)

b.       Interfering with immune signals

c.       Killing phagocytes

List the four classical symptoms of inflammation; (what are the ‘Latin’; designations?)

• heat (calor): increase enzyme velocity for repairing

• pain (dolor): prevent harming area again

• rubor (redness): increased blood flow

• swelling (tumor): concentrating/immobilizing on one place so body and focus repair mechanisms

What is histamine and what function does it serve?

a.       Principle inducer: histamine (primary mediator of inflammatory response)

b.       Histamine = modified histidine

What kind of a defense mechanism is interferon and how does it work?

• innate immune system, acting as an early warning system,

• signaling infected cells to warn neighboring cells, triggering antiviral states, and activating other immune cells like natural killer (NK) cells and T-cells to fight infection

  What interactions between interferon and SARS-CoV-2 have led to severe COVID disease?

Dysregulated interferon (IFN) response – body either fails to produce enough early IFNs or produce too much later, causing damaging inflammation, with SARS CoV-2 actively blocking IFN signals

What is an antigen

Antigen (Ag) = antigenic determinant (hapten) + carrier molecule

Autoimmune disease = luppus

what bacterial structures or products are recognized as antigens by host defense mechanisms?

• LPS - on G(-) cells

• peptidoglycan

• teichoic acids - on G(+) cells

• flagella

• exotoxins - potent antigens

What is an antibody?

• large glycoprotein approx.. belongs to class of immunoglobulins called gamma globulins

• made in response to a specific Ag

• function is to combine with the Ag and immobilize it by forming Ag-Ab complexes

• Antibody structure look like tuning fork

What are the five major classes (i.e. isotypes) of antibodies; what are their functions?

• IgM: first antibody formed; surveillance function

• IgG: major circulating antibody in blood; represent 80% of total blood circulation; Crosses placenta: baby protected by maternal antibodies

• IgA: secretory antibody (tears, saliva, G.I)

• IgD: plays a role in how antibodies develop; differentiation of antiB

• IgE: mutant antibodies, allergic reactions; responsible for allergic receptors

                                                                         

humoral immunity

• B cells produce and secrete AB that circulate body’s humors to neutralize and eliminate extracellular pathogens

cellular immunity

• aka cell mediated immunity

  • produced by T cells/lymphocytes

B Cell

• key white blood cells in the adaptive immune system, crucial for humoral immunity, primarily by producing antibodies (immunoglobulins) that target specific pathogens like viruses and bacteria, marking them for destruction

T (tissue) Cell

• crucial white blood cells that orchestrate and execute the adaptive immune response, recognizing specific foreign invaders (antigens) and coordinating attacks

  • ex: Helper T cells

What is the function of a macrophage?

engulfing pathogens, dead cells, and debris (phagocytosis) to clear infections and damaged tissues, while also initiating inflammation and presenting antigens to T cells to kickstart the specific (adaptive) immune response.

What is a ‘PMNL’?

Polymorphonuclear leukocyte – type of white blood cell crucial for immunity, known fir its multi-lobed nucleus and granular cytoplasm, primarily consisting of neutrophils, eosinophils, and basophils, which fight infections and inflammation by releasing enzymes

What specific roles do B cells & T cells play in the immune system?

What is an APC?

• APC (professional antigen presenting cell)

  • Ex: macrophages, dendritic cells

• 1 of 3 parts of adaptive immune system

What is the difference between a ‘Natural Killer Cell’ and a ‘Cytotoxic T-cell? (Hint: think about the cell line from which they derive.)

• (NK = first responders) cells are innate, acting fast without prior sensitization, killing stressed/missing MHC-I cells

• (CTLs = special forces) are adaptive, requiring antigen presentation (MHC-I) to become specific killers, forming memory, and are highly targeted

What is the function of MHC molecules in terms of specific immunity?

act as display platforms, presenting processed antigen fragments (peptides) from pathogens or abnormal cells on the surface of host cells to T cells, initiating tailored immune responses

What is a monoclonal antibody?

  Lab made proteins from single B-cell clone, engineered to target and bind to one specific antigen (like on a pathogen or diseased cell), caused for precise detection (diagnostic) and treatment (therapeutics) by mimicking the immune system to neutralize infections, ID pathogens, or deliver drugs directly to target cells

  What type of antibodies are found in your blood serum?

• Blood Components – Complement cascade

  • 9 serum protease that cause lysis of bacteria/ foreign invaders

  What does the ‘clonal selection’ theory of antibody formation help explain?

how the adaptive immune system creates a massive, specific response to any pathogen

  What is the difference between an immunization and a vaccination?

• act of introducing a weakened/dead pathogen (or parts of of it) to the body via a shot

• broader process where body develops protection (immunity) against disease, either from vaccination or natural infection, creating cells and antibodies for future defense

innate/native immunity

due to species, racial, individual differences in genetic makeup; this type of immunity is inherited, even deficiencies

Acquired immunity

• deliberate protection against disease created by medical intervention, either by exposing the body to weakened pathogens (vaccines) to build its own defenses (active) or by injecting ready-made antibodies (immune globulins/antisera) for immediate, temporary relief (passive)

natural acquired immunity

artificial acquired immunity

Natural Acquired Immunity

• protection developed after a person naturally encounters and fights off a pathogen; immune system to create specific antibodies and memory cells, leading to long-term defense against future infections

  • active: body makes its own antibodies from infection

  • Passive: mother to baby via placenta/breastmilk

artificial aquired immunity

• Active – “VACCINATION” (three types)

  • Attenuated vaccine – e.g. Sabin, oral, live polio vaccine

  • Killed vaccine – e.g. Salk killed, dead, polio vaccine

• Toxoid vaccine – e.g. DPT (diptheria, pertussis, tetanus) vaccine

  •   DPT: high dose for children <7 years of age

  •   Toxoid: doesn’t have toxicity but still contains antigenicity

• Passive – receive Ab via serum, blood transfusions or antiserum or antitoxin injection – fluid with antibodies

attenuation

• virulence factors lessened; type of vaccine

•   in vaccines, a process of weakening disease-causing bacteria or viruses so they can trigger immunity without causing illness, making them safe to use.

toxoid

• doesn’t have toxicity but still contains antigenicity

• Toxoid potential – the rate to inactivate toxicityàtoxoid; maintaining protein structure but don’t have toxin abilities; body still recognizes and reacts to toxoids

• Protection against diphtheria, pertussis, tetanus

antitoxin/antiserum

• passive artificial acquired immunity

• Antiserum/antitoxin injection – fluid with antibodies

Describe the 4-5 different types of vaccines in terms of their composition.

• Live/Attenuated – MMR (measles, mumps, repellents), Rotavirus, Smallpox, Chickenpox, Yellow fever, Polio (oral**)

• Inactivated/Dead – Hep A, Influenza, Polio, Rabies

• Toxoid – Diphtheria, Tetanus

• DNA/RNA – Covid-19/SARS-CoV-2 spike protein mRNA

•  Capsid & Subunit/Recombinant/Polysaccharide/Conjugate – Hib, Hep B, HPV, Whooping Cough, DTaP, Pneumococcal, Meningococcal, Shingles

                                                                            

DPT vaccine

  high dose for children <7 years of age; protects children against diphtheria, tetanus and pertussis

MMR vaccine

measles, mumps, repellents

Hib vaccine

capsid & subunit/recombinant/polysaccharide/conjugate

Salk vaccine

(1953), killed (cannot reproduce/still contain antigen), dead Polio vaccine (polio – oral; spready by fecal oral route)

sabinn pilio vaccine

• (1961), attenuated (virulence factors lessened), live Polio vaccine

• Danger: back mutationàrevert back to og strain,

• Advantages: can shed live virus that can be spread by fecal routes (or other F’s – secondary immunity route)

What is R0? What is the R0 for measles, for Influenza, for COVID-19?

• ‘Basic Reproduction Number’: Large portion of population becomes immune that protects small portion of population will die if get infection or cannot be immunized

  • 12-18

  • 0.9-2.1

  • 1.5-3.5

What is ‘herd immunity’ and how is it achieved?

• also called population immunity — often results from a combination of people getting vaccinated and people getting infected with the germ (natural immunity).

Describe what type of new vaccine technology is being used by Moderna and Pfizer-BioNTech in their COVID-19 vaccines, and explain how these vaccines work.

• Pfizer-BioNTech COVID-19 mRNA Vaccine (‘COMIRNATY’)

  • BNT162b2, Two doses, 21 days apart (three weeks)

  • 91-95% efficacy

• Moderna mRNA Vaccine

  • 94.5% effective, called “mRNA-1273”

  • Two doses, 28 days apart (four weeks)

•   Janssen (Johnson & Johnson) Ad26.CoV2.S recombinant

  •   adenovirus-based vaccine, ChAdOx1 nCoV-19,

  • one-dose; 72% efficacy

• Oxford-AstraZeneca recombinant adenovirus*

  • ChAdOx1 nCoV-19

• Novavax Protein Adjuvant *Not yet available in the U.S.

What virus causes Influenza, AIDS, COVID-19?

• All RNA viruses; constantly mutating

  •  H1N1 = (-) RNA (8 segments)

    • causes influenza

  • HIV = Retroviral (+) RNA Dimer

    • reverse transcriptase

  • SARS-CoV-2 = (+) RNA

Hemagglutinin

• a viral surface glycoprotein, especially on influenza viruses, that binds to sialic acid on host cells, initiating infection, and causes red blood cells (RBCs) to clump (agglutinate)

neuraminidase

• ta crucial viral enzyme, especially on influenza viruses, that cleaves sialic acid (neuraminic acid) from host cell surfaces, allowing newly formed virus particles to detach, spread, and infect new cells

• sub-types of influenza NA, N1-9

nucleocapsidasid

an influenza virus

‘cap snatching’

Nuclear Localization Signal

allows the virus to enter the nucelus

antigenic drift

small; due to small point mutations; why we need new vaccines every year