Micro Final Exam

Carbon Cycle

-Carbon enters a common pool of organic matter that can be oxidized back to CO2

-Cycle begins with carbon fixation

-1/2 of earth’s carbon is fixed aerobically and anaerobically by microbes

Mircoorganisms that do carbon fixation

-cyanobacteria, which are photosynthetic bacteria

-certain types of archaea found in extreme environments such as hot springs

Nitrogen Cycle

-N2 fixation

-Nitrification: ammonia and nitrate oxidation

-Denitrification

-DNRA

-Anammox

Nitrogen Fixation (Diazotrophy)

-N2→NH4+→Organic N

-Energy-demanding process

-Catalyzed by the enzyme nitrogenase (sensitive to O2)

-Widespread in Bacteria and Archaea

-EX: cyanobacteria heterocyst

-EX: Alphaproteobacteria, Rhizobiales: motile rods, grow symbiotically as nitrogen-fixing bacteria within root nodule cells of legumes, most successful plant family on earth.

Nitrification: N-Oxidizing Bacteria

-Nitrifying bacteria

-Oxygen as electron acceptor

-Convert NH3→NO2- ; nitrosomonas of betaproteobacteria

-Convert NO2- → NO3- ; nitrobater of alphaproteobacteria

Denitrification

-multiple steps of reduction of N species from nitrate to dinitrogen gas

-several gas intermediates are involved

-NO3- → NO2- → NO → N2O → N2

-Anaerobic respiration: N as electron accepter

-Chemoorganoheterotrophs: widely distributed among bacterial phyla

-most facultative anaerobes

Anammox

-Anaerobic Ammonia Oxidation

-also produces N2, loss of N from the system

-NH4+ +NO3- →N2 + 2H2O

-phylum planctomycetes: gram -, cell walls lack peptidoglycan, having compartmentalized cells

-chemolithoautotrophs: may contribute 70% of nitrogen cycling in oceans

-Role of N2: Catabolic: NO2- + NH4+ → N2 + 2H2O Anabolic: 2NO2 +CO2 +H2O → CH2O +2NO3-

The Microbial Loop

-transfer of nutrients between trophic levels

-autotrophs are primary producers

-heterotrophic microbes consume dissolved organic matter (DOM)

-particulate organic matter (POM)

-Algae→Small Fish→Large Fish

Viruses in Microbial Loop

Types of Microbial Interactions

-Symbiosis: Mutualism, Commensalism/Cooperation, Parasites, Amamensalism

-Predator-prey/parasitism

-Ammensalism

-Competition

Symbiosis

-a physical association of two or more different species of organisms

Ectosymbiont

organism located on surface of another organism, usually larger

Endosymbiont

organism located within another organism

Consortium

-hosts have more than one associated symbionts

-relationships can be intermittent and cyclic or permanent

Mutualism

-reciprocal benefit to both partners

-relationship with some degree of obligation

-often partners cannot live separately

-mutualist and host are dependent on each other

Zooxanthellae

-marine invertebrates harbor them

-dinoflagellates

-provide organic C to host

-coral has pigments that protect algae from UV radiation

-provide N compounds, phosphates, and CO2 to endosymbionts

-Coral bleaching: caused by temp increase, results from loss of photosynthetic pigments or expulsion of the zooxanthellae

Tube Worm-Bacterial Relationship

Cooperation

-along with commensalism is a positive but NOT OBLIGATE form of symbiosis which involves syntrophic (cross-feeding) relationships

-beneficial to both organisms

-differs from mutualism because cooperative relationship is not obligatory

Commensalism

-one organism benefits and the other is neither harmed nor helped

-commensal: organism that benefits

-can also involve modification of environment by one organism, making it more suited for another organism

-skin or surface microbes on plants or animals

-host plant/animal releases volatile, soluble, and particulate organic compounds, which are used by commensals

-nitrification: carried out by two different bacteria together (nitrosomonas and then nitrobacter)

Microbial Predation

-Bdellovibrios

-gammaproteobacteria

-”wolf pack” predation

Parasitism

-one host organism gains (parasite) and the other is harmed (host)

-outcome of long-term parasitic relationship: genome reduction, parasite loses unused genomic information

-successful parasites have evolved to co-exist in equilibrium with their hosts

-Lichen: green bacteria and fungi

Ammensalism

-negative impact of one organism on another based on release of a specific compound

-EX: antibiotic production by fungi and bacteria; use of antibiotic-producing streptomycin by ants to control fungal parasites

Human-Microbe Interactions

-the human body is a diverse environment; specific niches at different parts of the body; dynamic conditions

-microbiome: all the genes of the host and microbiota

-superorganisms: host genes become integrated with those of the symbionts; co-metabolize various substrates, resulting in unique products

-pathogen/pathogenicity

Normal microbiota for the human body

-microbes regularly found at an anatomical site, different at different regions

-relationship begins at birth; humans are born without any microorganisms; varies with environment and food source

-Bifidobacteria: found in breastfed babies; prototrophic: can synthesize all amino acids and growth factors from simple carbs

-microbes found on surface tissues of human skin and mucous membrane

The human microbial metagenome

-colonization of skin, oral/respiratory tract, genitourinary system and gastrointestinal tract begins immediately at birth

-our adult bodies contain 10 times more microbial cells than human cells

-human colon contains 100 trillion bacteria

-comparative metagenomic studies have suggested that shifts in the populations of microbial communities may be associated with a number of important acute and chronic diseases: IBD, obesity, heart disease, eczema, vaginal infections

Adaption of microbiota to human body

-Skin: transient or resident; dry, moist, oily

-Mouth, oral cavity: nutrient rich but subjected to mechanical forces

-Stomach: low pH

-Small/large intestine: nutrient rich, suitable pH

-Urinary track: frequent flush

What organ hosts the largest amount of normal microbiota in humans?

Large intestine

What organ hosts the smallest amount of normal microbiota in humans?

Lungs

Immunity

-host’s ability to resist infectious diseases

Nonspecific (innate, natural)

-first line of defense

-no specificity, no immunological memory

Specific (acquired, adaptive)

-resistance to a particular foreign agent

-has “memory”

Level 1: Barriers

-microbial (commensal organisms)

-physical (epithelium, mucous membrane)

-chemical (AMPs, APRs, cytokines)

1.1: Microbial

-the relationship between normal/commensal microbiota and the host

-can offer mutual benefits: normal microbiota often prevent colonization by pathogens; bacterial produces e.g. vitamins B and K are beneficial to the host

-opportunistic pathogens: members of normal microbiota that produce disease under certain circumstances

-compromised host: debilitated host with lowered resistance to infection

1.2: Physical Barriers

-interface between human and microorganisms are guarded

-skin & mucous membranes: mouth, resp. system, gastrointestinal tract, genitourinary tract

Skin

-inhospitable environment for microbes

-shedding of outer skin cells

-high NaCl

-periodic drying

-strong mechanical barrier to microbial invasion: keratin produced by keratinocytes in outer layer; hard to penetrate

Mucous Membrane

-mucous: slippery, flushing, acidic, special structure (ciliated epithelial cells), antimicrobial chemicals (lysozyme, degrade peptidoglycan)

-lungs don’t have normal microbiota

-cells are alveolar sponges

Mucous Membranes by Part

-mouth: biofilm on teeth, transitional (flush away)

-stomach: unfriendly env., gastric acid pH 2-3

-small/large intestine: microbe number increases from small to large, fluid like pancreatic enzymes and bile, pH becomes more alkaline, most bacteria at the end

-genitourinary tract: urine flushing and kill bacteria (low pH and toxic compounds), normal microbiota

Opsonization-Enhanced Phagocytosis

-microbes are coated by opsonins in preparation for recognition/ingestion by phagocytic cells

-opson: to prepare victims for…

Chemical Mediators: Cytokines

-cytokines: cell movement; works in both innate and adaptive immunity

-chemical messages between cells

-soluble proteins or glycoproteins act as intercellular mediators (signaling molecules)

-synthesis is inducible from nonspecific stimuli

-3 functional groups as regulators of: innate resistance, adaptive immunity, and hematopoiesis

Level 2: Cells of the Immune System

-Leukocytes: white blood cells, involved in both specific and nonspecific immunity, granulocytes vs agranulocytes

Granulocytes

-Eosinophils: active in worm and fungal infections, allergy and inflammatory reactions

-Basophils: function in inflammatory events and allergies

-Neutrophils: essential blood phagocytes; active engulfers and killers of bacteria

Arganulocytes

-ALL are phagocytotic plus Neutrophils

-Monocytes: blood phagocytes that rapidly leave the circulation; mature into macrophages and dendritic cells

-Macrophages: largest phagocytes that ingest and kill foreign cells; strategic participants in certain specific immune reactions

-Dendritic cells: reside in the tissues; responsible for processing foreign matter and presenting it to lymphocytes

-Lymphocytes: primary cells involved in specific immune reactions to foreign matter

-T-cells: lymphocyte, perform a number of specific cellular immune responses like assisting B cells and killing foreign body cells (cell-mediated immunity)

-B-cells: lymphocyte, differentiate into plasma cells and form antibodies (humoral immunity)

Lymphocytes

-natural killer cells-innate

-no phagocytic granular lymphocytes

-important role in innate immunity

-kill malignant cells and cells infected with pathogens by releasing cytotoxic enzymes

-NK cells DO NOT kill foreign particles, but neutrophils and macrophages do

B-cell: Adaptive Immune System

-bone marrow

-circulate in blood and can settle in lymphoid organs

-plasma cells and produce antibodies

-humoral immunity: antibody-mediated immunity

T-cell: Adaptive Immune System

-thymus

-circulate in blood or reside in lymphoid tissue

-differentiated tissue helper (TH) and cytotoxic lymphocytes (CTLs)

-major role in B-cell activation

- cellular immunity: cell-mediated immunity

Primary B and T cell location

-bone marrow

-thymus

Secondary B and T cells locations

-axillary lymph node

-spleen

-MALT (mucosal-associated lymphoid tissue)

-afferent lymphatic vessels

-involved in skin and mucous membrane immunity

Level 3: Processes-Phagocytosis

-the process of cell eating

-the lysosomes fuse with the phagosomes containing the ingested microbes and the microbes are destroyed

-recognize: pattern recognition molecules (PRM)

-ingest

-digest

-microbe-associated molecular patterns (MAMPs): LPS for G -, peptidoglycan for G +

-intracellular digestions and exocytosis: secretory vesicles expel out or build membrane

Level 3: Processes-Inflammation

-innate immune defense reaction but also combined with adaptive defense

-bring all the host defense together in response to injury or infection

-localized to tissue infection/injury: can be used by pathogen or physical trauma, acute inflammation is the immediate response of body to injury or cell death

-cardinal signs: redness, warmth, pain, swelling, altered function

-acute or chronic inflammation

Specific (Adaptive) Immunity

-recognize nonself

-respond to nonself

-remember nonself

Acquired Immunity

-Natural immunity: is acquired though normal life experiences and is not induced through medical means

-Artificial immunity: is produced purposefully through medical procedures (immunization)

Natural Immunity

-active immunity: the consequence of a person developing his or her own immune response to a microbe (ex: infection)

-passive immunity: the consequence of one person receiving preformed immunity made by another person (ex: maternal antibody)

Artificial Immunity

-active immunity: the consequence of a person developing his or her own immune response to a microbe (ex: vaccination)

-passive immunity: the consequence of one person receiving preformed immunity made by another person (ex: immune globulin therapy)

Antigens

-self and nonself substances that elicit an immune response and react with products of that responses

-antigenic determinant sites (epitopes)

-antibody affinity: strength with which antibody binds to its antigen at a given antigen-binding site

-most are large, complex molecules

Haptens

-small organic molecules

-not antigenic, but may become antigenic when bound to larger carrier molecules

-ex: penicillin, may elicit hapten-specific and carrier-specific responses

Recognize non-self (antigens)

-major histocompatibility complex (MHC): collection of genes that code for self/nonself recognition potential of a vertebrate

-present antigens to activate T-cells

T-cell Development

-antigen-presenting cells (APC)-dendritic cell

-T-cell receptors (TCR) complexes: bind to MHC

-endocytosis

-degrade by lysosomal process

-bind with MHC receptor

-presentation on the cell surface

Major Histocompatibility Complex (MHC)

-a collection of genes in vertebrates for self/nonself recognition

-human version: human leukocyte antigen (HLA) complex

-binding and presenting foreign peptides (antigen)

Mature T-cells

-mature T-cells are naive until they are activated by antigen presentation

-once activated, they proliferate into effector cells and memory cells

-effector cells carry out specific functions to protect host

-regulatory (Treg) cells

-T-helper (TH) cells: help with activation CTL

-cytotoxic lymphocyte (CTL): matured from cytotoxic t-cells, destroy infected host cells

-memory T-cells

B-cell Activation/Functioning

-B-cells must be activated before functioning

-2 mechanisms for antigen-specific activation: T-dependent where B-cell binds with T-helper cell, or T-independent (minor)

-activation leads to proliferation and differentiation into plasma cells (secrete antibodies)

-antibodies neutralize or recognize antigens

-also called immunoglobulin (Ig)

-in blood serum, tissue fluids, and mucosal surfaces of vertebrate animals; an antibody can recognize and bind antigen that caused its production

Ig Structure

-Y-shape

-stalk: crystallizable fragment (Fc) and constant region (C)

-top: binding fragments (Fab) and both constant and variable regions (V)

-four polypeptide chains: two identical heavy chains (H) and two identical light chains (L) connected by disulfide bonds

Ig classes: gamma and mu

-IgG: heavy chain gamma, 9 mg/ml mean serum concentration, 80-85% of total serum antibody, most abundant in body fluids, neutralizes toxins, opsonizes bacteria

-IgM: heavy chain mu, 1.5 mg/ml mean serum concentration, 5-10% of total serum antibody, first to appear after antigen stimulation, very effective agglutinator, expressed as membrane-bound antibody on B-cells

Ig Primary Response

-latent (lag) period: several days to weeks after initial exposure to antigen; no antibody detectable in blood

-IgM appears first, followed by IgG

-log phase: plasma cells/antibodies production

-plateau phase: antibody titer stabilize

-decline phase: antibody binds to antigen

Ig Secondary Antibody Response

-upon secondary exposure to same antigen, B-cells mounted a heightened memory response

-shorter lag

-rapid log phase

-longer persistence

-a higher IgG titer

-production of antibodies with a higher affinity for the antigen

Comparing Phases 1 and 2

-antigen exposure: first vs. re-exposure

-lag phase: long vs. short

-log phase: antibody concentration low vs. high; production time of IgM and IgG: IgM earlier than IgG vs. similar time

-persistence of antibody: shorter vs. longer

-antigen affinity of produced antibodies: low to moderate vs. high

Specific Immune Response

-vaccine

-antibody diversity

-each human can synthesize antibodies that can bind to more than 10^13 antigens

Immune Disorders

-hypersensitivities

-autoimmune diseases

-transplantation (tissue) rejection

-immunodeficiencies

The Chain of Infection

Agent: Pathogen

-any parasitic organism causing infectious disease

Pathogenicity

-ability of a parasite to cause disease

Primary (frank) Pathogen

-causes disease by direct interaction with healthy host

Opportunistic Pathogen

-may be part of normal flora and causes disease when it has gained access to other tissue sites or host is immunocompromised

Time Course of Infectious Disease

-Incubation period: no obvious signs and symptoms

-Prodromal stage: onset of signs and symptoms, not clear enough for diagnosis

-Period of illness: disease is most severe, signs and symptoms

-Convalescence: signs and symptoms begin to disappear

Signs

-objective changes in body that can be directly observed

Symptoms

-subjective changes experiences by the patient

Disease Syndrome

-signs + symptoms

Virulence

-degree or intensity of pathogenicity

-toxic to the host

-resist host defense

-largely determined by genes on pathogenicity islands: genes for toxin production, bacterial attachment, intracellular survival; HGT

Virulence Factors

-determine the degree to which the pathogen causes damage, invasion, infectivity

Virulence: Attachment and Colonization

-pili and fimbriae bind to complementary receptor sites on host cell surface

Virulence: Invasion

-invasiveness

-penetration

Invasiveness

-ability to spread to adjacent tissues

Peneetration

-active: occurs through lytic substances which disrupt host cell surface

-passive: skin lesions, insect bites, wounds; spread by body fluid/chemicals

Virulence: Exotoxins

-soluble

-heat liable

-proteins

-could be lethal

- highly immunogenic

-mostly produced by G -

-easily spread out

-various types: AB exotoxins - A subunit is responsible for toxic effect, B subunit binds to specific target cell

-botulinum toxin

Virulence: Endotoxins

-heat stable

-weakly immunogenic

-generally similar, despite source

-cause general system effects: fever, diarrhea, inflammation, intestinal hemorrhage

-bring about these effects indirectly

-interacts with host molecules and cells, activating host systems; coagulation, complement, fibrinolytic, and kininogen system

-ex: LPS: G-bacteria (leads to septic shock)

Virulence: Biofilm Development

-physiologically different from planktonic growth

-may cause chronic infection

-increases virulence

-becomes less sensitive to antibiotics

-make cells in biofilm more resistant to host defense (“frustrates” phagocytes)

Virulence: Resisting Host Defenses

-numerous mechanisms for both viral and bacterial pathogens

-infection of immune system cells, diminishing function

-fuse with adjacent cells to prevent exposure to antimicrobial proteins in host

-capsules prevent phagocytosis

Pathogen Transmission

-direct contact → less virulent

-vector-borne → highly virulent in human host, relatively benign in vector

-greater ability to survive outside host → more virulent

Epidemiology

-science that evaluates occurrence, determinants, distribution, and control of health and disease in a defined human population

Sporadic Disease

-occurs occasionally and at irregular intervals

Endemic Disease

-maintains a relatively steady low-level frequency at a moderately regular interval

Hyperendemic Disease

-gradually increase in occurrence frequency above endemic level but not to epidemic level

Outbreak

-sudden, unexpected occurrence of disease

-usually focal or in a limited segment of population

Epidemic

-sudden increase in frequency above expected number

Index Case

-first case in an epidemic

Pandemic

-increase in disease occurrence within large population over a wide region (usually worldwide).

COVID-19

-disease name: Coronavirus disease

-transmission: primarily airborne (zoonotic origins)

-agent name: SARS-CoV-2 virus (severe acute respiratory syndrome coronavirus 2)

-agent structure: enveloped (spikes), ssRNA, huge for a virus

-virulence factors: multiple (ACE2-binding, FURIN, etc)

-signs and symptoms: fever, chills, cough, fatigue, difficulty breathing, cytokine storm (hyperactive innate immune response)

-treatment and prevention: antiviral drug, antibody treatment, mRNA vaccine

Treatment, Prevention, and Control of Viral Infection

-rapid immunologic tests

-antivirus drugs (target the replication cycle)

-symptomatic/supportive therapy

-major way: vaccine (inactivated virus vaccine)

Other Airborne Viral Diseases

-pathogen suspended in air and travels less than 1 meter

-droplet nuclei: small particles (1-4 micro m), can remain airborne for long time, can travel long distances, usually propelled from respiratory tract (source)

-dust particles

-ex: chicken pox, flu

Chicken Pox

-varicella-zoster virus

-transmission: acquired by droplet inhalation into respiratory system

-susceptible population: children 2-7 yo

-signs and symptoms: 10 day incubation period, like a common cold (runny nose, couch, stomach ache), rash appears after 1-2 days

-become immune after recovery

-still a carrier, latent