Bio207 E4

Summarize some of the mechanisms used by pathogens to determine their location within a host.

- 2-component signal transduction systems to sense Mg and Fe concentrations and pH - Quorum sensing to detect exotoxins made by other cells- delays toxin synth, avoids tripping host cell alarms, coordinates attack

Define virus.

- A noncellular particle that infects a host cell and directs it to produce progeny particles (more viruses), the virion (virus particle) consists of viral genome (DNA or RNA) within protein capsid - Usually infect a specific host but a range of cells within that host, bacteriophages= viruses that infect bacteria, replication observed as a plaque of lysed cells on host lawn in petri dish

Assess the role of antigen-presenting cells.

- APCs part of first stage in adaptive immune response- degrade pathogen proteins, attach to MHC, travel to lymph nodes to interact w B/T cells for antibody production -Dendritic (APC) cells engulf microbe and places antigens on its surface and initiates both pathways - Also includes macrophages and B cells - Travel to lymph nodes to activate helper T cell that links to B cell through same antigen, which stim to generate plasma cell that secretes antibody against antigen

Categorize innate chemical defenses against infection.

- Acid from skin, gut, vagina - Mucin forms mucus in respiratory tracts and digestive pathways - Lysozymes in saliva, mucous, and eye fluid - Defensins- antimicrobial proteins (small, cationic) that insert into and create channels to destroy the invading cell membrane, produced by many human cells (Paneth cells)

Cite examples of how the gut microbiome aids human digestion.

- Akkermansia muciniphila- G-, anaerobic, inner intestinal lining; anti-inflammatory effects, can control diet-induced obesity, thicker inner intestinal mucus - Bacteriodes thetaiotaomicron- G-, anaerobic in the gut and opportunistic pathogen; breaks down complex carbs into ones the body can digest (genomes encode starch utilization systems), directly influence function of human immune system by inducing Paneth cells (spec secretory epithelial cells, in SI that secrete antimicrobial peptides and immunomodulating proteins (Ang4- can kill pathogenic organisms) that function to regulate the composition of the intestinal microbiome, produce bactericidal lectin (binds to peptido of G+ orgs)

Recall examples of benefits provided by gut microbiota.

- Akkermansia muciniphila- G-, anaerobic, inner intestinal lining; anti-inflammatory effects, can control diet-induced obesity, thicker inner intestinal mucus - Bacteriodes thetaiotaomicron0 G-, anaerobic in the gut and opportunistic pathogen; breaks down complex carbs into ones the body can digest (genomes encode starch utilization systems), directly influence function of human immune system by inducing Paneth cells (spec secretory epithelial cells, in SI that secrete antimicrobial peptides and immunomodulating proteins (Ang4- can kill pathogenic organisms) that function to regulate the composition of the intestinal microbiome, produce bactericidal lectin (binds to peptido of G+ orgs)

Name different types of T cells and recall their functions.

- All develop in the thymus and contain surface antigens different from B cells, activation requires interaction of surface TCRs w MHC complexes on host cells or APCs, can recognize antigens on MHC (B cells recognize on free-floating too) - Helper T cells display CD4 (recognize antigens on class 2 MHC) and assist in activation of B cells and other T cells - Cytotoxic T cells have surface protein CD8 (rec antigens on class 1 MHC) and destroys bacteria and infected host cells- killer T cells - Th0- helper T cells that differentiate into other types based on cytokines present - Th1- assist in activation of cytotoxic T cells - Th2- recruit eosinophils to combat parasitic infections, activate B cells, and inhibit Th1 proliferation - Th17- cells stim inflammation by secreting IL-17 - Tfh (follicular helper)- derive B cell differentiation into antibody secreting plasma cells - Treg (regulatory)- dampens inflammatory response

Describe the structure and function of the immune system.

- An integrated system of organs, tissues, cells, and cell products - Differentiates self from nonself and neutralizes potentially pathogenic organisms or substances - Capable of responding to almost any foreign molecular structure

Assess how the structure of an antibody relates to its function.

- Antibodies are large glycoproteins members of immunoglobulin superfamily of proteins (Ig) (MCH proteins and B-cell receptors also belong in fam), made by body in response to antigen, lock and key analogy (key to immunological specificity), antibody Igs indv circulate through blood ignoring all antigens except one they were designed for - Structure is Y-like, w 4 polypeptides: 2 large heavy chains and 2 smaller light chains, connected by disulfide bonds- usually has 2 antigen binding sites, each of which binds identical antigens at F(ab) site, F(c)= cell surface binding site (easily crystalized) - Have constant (highly conserved AA- CH for long side, CL for short side) regions and variable regions with different AAs (on the tips of the Y, so four sections, labeled VH and VL same as C regions) - 5 types of heavy chains (alpha, mu, gamma, delta, and epsilon) and are classified as such (IgA, IgM, IgG, IgD, and IgE) - Isotypes are shared by all members of species (Ig classes); allotypes are shared by some but not all members of a species (individual specific), have differences in antigen-binding sites, AA changes in constant regions (usually light chain); idiotypes have changes within same antibody class, in same individual and each idiotype binds a different antigen - IgG: monomer w 4 subclasses, most abundant antibody in blood/ tissue fluids, opsonin, can cross placenta, activates complement - IgA: dimer, secreted across mucosa, abundant in secretions like tears and breast milk - IgM: monomer (on B cells) or pentamer, 1st antibody detected in an immune response - IgD: monomer, found abundantly on B cells, rare in blood) - IgE: monomer on mast cells and basophils, mediates inflammatory response and allergic reactions - IgM and IgA can have more than 2 antigen binding sites (IgM can have up to 10)

Explain the meaning of immunological specificity.

- Antibody made to one epitope won't bind to other epitopes, cross-binding to similar epitopes can happen (cowpox and smallpox viruses, used in vaccinations (Edward Jenner)- now administer live attenuated strains of microbe or virus) - Depends on efficiency of activating immune response via cell-cell communication

Differentiate among antigen, epitope, hapten, and immunogen.

- Antigen: substance that induces the immune system to produce antibodies (portion of pathogenic bacteria or virus, chemicals, toxins, pollen) - Immunogen: molecule capable of eliciting an immune system response (immunogen is an antigen but an antigen isn't necessarily an immunogen- hapten) - Epitope: each segment of an antigen that elicits an immune response (also antigenic determinant), the specific molecular structure of an antigen recognized by the immune system- humoral pathway response is B-cell responses to different epitopes of their cells, response to each indv epitope is clonal- gives rise to pop of immune cells that originate from 1 B-cell - Haptens: small molecules not immunogenic on their own bc too small to bind to MHC (incomplete antigens), have to be attached to large carrier protein or other molecule - Immunogenicity: effectiveness by which an antigen elicits an immune response, larger and more complex antigens more immunogenic, proteins effective, nucleic acids not

List factors that contribute to dysbiosis.

- Associated with lower microbial diversity, loss of beneficial microbes, increase in pathogens - Emotional stress, changes in diet, antibiotics - Dysbiosis= poor digestion/ IBD- imbalance in or perturbation of microbiome composition- short chain fatty acids impacted (metabolites) - C.diff can cause pseudomembranous enterocolitis (result of dysbiosis in antibiotic treatment) - Probiotics help (lactobacillus, bifidobacterium)- modulate microbiomes

Summarize the differentiation of naïve B cells into plasma and memory B cells via clonal selection.

- B-cell receptor is complex of IgM, plus IgA and IgB in the membrane, each naive mature B cell in body programmed for specific epitope, and once bound, it proliferates and differentiates into antibody-producing plasma cells and memory B cells - Clonal selection an invading antigen selects which will proliferate (randomly) and differentiate into memory and plasma cells - B-cell receptors undergo capping process, signals DNA recombination events for isotope switching (M->G), 2 B cell receptors can bind 2 identical epitopes on a single pathogen, B- cell receptor clustering initiates signal cascade, activating proliferation and differentiation, IgB initiates phosphorylation signal cascade - Capping requires antigen possess multiple repeating epitopes (like poly saccharides, but unlike protein antigens which would need a T-cell dependent route for B-cell activation) - Purpose of isotope switching is for antibody diversity (each person can make 10^11 antibodies with only 1000 genes, genes can move and rearrange within the genome of a differentiating cell- pathogens constantly mutate and antigenic factors change, so we're able to quickly generate recombinant clones - During differentiation, DNA segments deleted in gene switching, heavy and light chain genes both have separations with recombination signal sequences (RSS)- can generate 5x10^6 antibody specificities, rest are from somatic mutation in V regions, and recombination splicing ay VJ and VDJ junctions - CAN STILL MAINTAIN ANTIGEN RECOGNITION DOMAIN W DIFFERENT BASE

Explain how the microbiome develops.

- Begins to develop before birth- and source may be placenta which may have its own microbiome - After birth, exposed to very high number of bacteria (in birth canal and outside world) - Human babies have less diverse microbiomes than adults, but an adult microbiome is fully assumed by age 3

Define superantigen.

- Bind directly yo outside of TCR and MHC on APC, t-cells immediately actvated without undergoing APC processing and surface presentation, massive amounts of inflammatory cytokines released from T-cells and APCs to make cytokine storm- staphylococcal toxic shock syndrome toxin, evidence that covid is superantigen

List the cells of the immune system and recall their functions.

- Blood: RBCs (erythrocytes), WBCs (leukocytes- many types differentiate from stem cells formed in bone marrow), and platelets - White blood cells from hematopoietic (pluripotent) stem cells in bone marrow- myeloid stem cells usually for innate immunity - Myeloid cells develop into myeloblasts to Leukocytes (polymorphonuclear/ PMNs- have multi lobed nuclei) which include eosinophil, basophil, and neutrophil- basophiles and eosinophiles release products toxic to microbes; they also develop monoblast to monocyte to macrophage or dendritic cell (both monocytes)- neutrophils and macrophages engulf and destroy microbes via phagocytosis - Neutrophils: engulf via phagocytosis and throw neutrophil extracellular traps (NETs) around nearby pathogens, after interacting w bacteria undergo NETosis by spewing latticework of DNA/ chromatin w antimicrobial compounds into immediate area (pus in infections) - Monocytes: migrate into tissues and differentiate into macrophages (cells most likely to make first contact) and dendritic cells (don't take up w phagocytosis) and both function as APCs (antigen-presenting cells)

State the different forms viral genomes can exist.

- Can be DNA or RNA; ss or ds; linear, circular, or segmented (genome sizes ssDNA < RNA < ds DNA, and viruses for eukaryotes longer than bacteria or archaea) - Viral genomes used for virus classification using Baltimore system- looks at nucleotide classification and host-domain classification - Smaller virus= smaller genome, w less than 10 genes that may overlap in sequence, large viruses can be size of bacteria with 300-2500 genes and some can be infected by other viruses- usually have large number of enzymes with housekeeping functions- likely that virus evolved from parasitic cell

Recall mechanisms used by viruses and bacteria to attach to host cells.

- Can use adhesins: pili or fimbriae in G- bacteria, non-pilus adhesins in G-/+ bacteria - Pilus: Type 1 (adhere to carbs on most membranes) and Type 4 (involved in twitching motility) - Non-pilus: M-proteins, biofilm (usually w chronic infections by enabling persistent adherence, resistance to host defenses, and tolerance to anti-microbial agents)

Recognize the nine functional categories of bacterial exotoxins.

- Categories: plasma membrane disruption, cytoskeleton alterations, protein synth disruption, cell cycle disruption, signal transduction disruption, cell-cell adherence, vesicular traffic, inhibit exocytosis, and superantigens

Summarize how activated T cells influence both humoral and cellular immunity.

- Cell mediated: T lymphocytes recognize antigens, control antibody production, destroy host cells infected by microbes with antigen (intracellular pathogens and viruses) - Helper T cells are directed by cytokines to differentiate to killer T cells (Cell-mediated possibly with IL-4 cytokines) or B cells (Humoral with IL-12 cytokines)

Describe the process and function of T-cell education.

- Cell-mediated: Virus makes peptides to MHC1, CD8 recognizes and guides docking to TCR, T cell turned into Tc to kill infected cells in infected area via perforins and granzymes (proteases) - Th1 cells activate signal to Tc cells with IL-2, which causes Tc cell to replicate, have cytotoxic activity to kill those w same MHC 1 complex as APC; can also activate macrophages with intracellular microbial parts by binding to MHC 2 antigen and secretes IFN-gamma which helps macrophages kill intracellular bacteria- mostly produces cytokines - Th2 makes IL-4, IL-5, IL-6, and IL-10 to attack extracellular pathogens, cytokines also help determine pathway (Th1 or Th2), activates B cells, when Th2 cells attach to APC B cells, use CD40 and CD 154 to connect, triggers intracellular signaling to activate, releases IL-4 for B cells to proliferate, IL-6 to become plasma cells

List the three different ways the complement pathway can be activated.

- Complement is heat-liable component of blood that enhances killing effect of antibodies on bacteria, consists of 20 proteins naturally in serum (mostly proteases that form and cleave other factors), can form pores in bacterial membranes, attract leukocytes, and facilitate phagocytosis; main source in liver; pathways result in MAC (membrane attack complex) that creates pores in target membranes - Classical pathway: depends on antibodies produced during adaptive immune response - Lectin pathway: requires synth of mannose-binding lectin by liver in response to macrophage cytokines (then connects to classical) - Alternative pathway: involves cascade starting w complement factor C3 and ends w pore formation by MAC - Last two are nonspecific and don't depend on antibodies

Explain how differences in host susceptibility occur.

- Depends on immunocompetence and receptor availability, pathogens rely on very specific surface structures (Rs) to rec and attach to appropriate host cells (person to person differences possible- HIV binds CD4 and CCR5, so ppl w CCR5 are resistant to HIV infection)

Identify ways virions can differ from each other.

- Different viruses make different types of capsids, which can be symmetrical (icosahedral- polyhedral w 20 triangular faces, rotational symmetry found in herpesvirus- sometimes enclosed in envelopes (from cell membrane of host) with glycoprotein spikes encoded by virus; also filamentous- long tube of protein with helical symmetry, capsid surrounds genome which winds helically in tube and includes bacteriophages and animal viruses) or asymmetrical (complex, can have extra structures like protein tails, outer walls- influenza asymm, has RNA segments coated w nucleocapsid proteins, poxvirus is DNA stabilized by hairpin loops; also tailed viruses= structures w elaborate delivery devices- T4 has icosahedral head, helical neck, baseplate, and tail fibers for host recognition)

Explain why most vaccines are administered during childhood in multiple doses

- Diseases are more devastating when younger, allows for rapid and strengthened adaptive immune response

Explain how evolution of the virus is making it harder to contain

- Diverged from coronaviruses infecting bat and pangolin - Mutations to S RBD impact transmissibility, virulence, and immune escape of variants - Constantly mutating= immune system struggles to keep up with, has to add more antibodies for different proteins with different mutations-- coevolution

Assess how climate change affects emerging diseases.

- Drives range shifts for reservoir species, affects transmission and susceptibility, and affects geographical range of vectors

Distinguish among endemic, epidemic, and pandemic diseases and between prevalence and incidence.

- Endemic: consistently present but limited to particular region, disease spread and rates are predictable (malaria), effective reproductive number =1 - Epidemic: high frequency over a short time, unexpected increase in number of disease cases in a geographical area, can be contagious (hep C) or not (obesity), effective reproductive number > 1, if less than 1 it will disappear - Pandemic: epidemic that occurs over a wide geographic area, crossing international borders, with less predictable spread - Prevalence: total number of active cases of a disease in a location (no differentiation between new and old cases, impacted by duration of disease (acute vs chronic) - Incidence: refers to number of new cases of a disease in a location over a specified time, reflects risk someone has of acquiring disease

Distinguish between exotoxins and endotoxins.

- Exotoxins: proteins produced and secreted by bacteria, kill host cells and unlock nutrients - Endotoxins: part of LPS outer membrane (lipid A) of G- bacteria, hyperactivate host immune systems to harmful levels- as bacteria die, release endotoxin (MAMP) that binds to Rs on macrophages or B cells, binding triggers cytokine storm (fever, inflammation, shock, death) - Cholera toxin is an AB5 endotoxin, B subunit binds to intestinal cell membranes to trigger endocytosis of cholera toxin complex, A subunit ADP-ribosylates host cell target leads to inc in cAMP levels, which act ion TP to cause water to leave cell (diarrhea)

Recall how pathogens can avoid extra- and intracellular immune detections.

- Extracellular: thick capsule, proteins that bind to antibodies, apoptosis of phagocytes, alteration of surface antigens, become intracellular pathogens - Intracellular: growing inside phagolysosome (inclusion bodies), preventing phagosome-lysosome fusion (engulfed by macrophage, spread to lymph nodes and disseminate via circ system), escaping phagosome before phagosome- lysosome fusion by making lysins (break out of phagosome and move into adjacent cells by forming actin tails)

Explain why interventions that reduce a moderate fever caused by infection may be counterproductive.

- Fever designed to help kill off microbes, as internal T is important to survival. Reducing moderate fevers can allow infections to proceed and spread, and moderate fevers don't cause any damage

Summarize the alternative complement pathway.

- First line of innate defense system 1. In blood, C3 spontaneously cleaves slowly into C3a and C3b ...... more cascades (C3a and C5a are anaphylatoxins that trigger chemotaxis, C3b is potent opsonin, promotes phagocytosis) END: C5bC6C7 complex binds to membrane, C8 and C9 join to form MAC, becoming destructive pore in membrane of target cells - G+ more resistant to complement- lack outer membrane and have thick peptidoglycan layer- no LPS and no start to cascade (LPS important for binding C3b onto membrane)

Describe how human technology can aid infectious disease emergence and spread.

- Global changes: increased travel (air and high speed rail), coming in to work, living in dense populations - Improved global surveillance, vaccination affects dynamics, range and pace of spread with TP

Recall how natural killer cells recognize target cells and kill them.

- Healthy cells have major histocompatibility complexes (MHC) molecules, but infected and cancer cells lose this and become "foreign" - NK cells meet host cell w/o MHC, secretes perforin to form pores in target cell which allows for entry of granzymes (induce apoptosis)

Explain why it is important to determine the index case (patient zero) of an infectious disease.

- Helps with identifying spread and reducing it based on people they gave it to- ID everyone they had contact with so they can be treated or quarantined - To ID: when virus first appeared in community, sequence viral genomes to establish root of viral genetic tree

Evaluate the role of horizontal gene transfer in pathogen evolution.

- Horizontal gene TF from one host to another in same generation, can be direct or through inanimate objects (formities), can take up other genes and continues to evolve

Distinguish the two different types of adaptive immunity.

- Humoral Immunity: antibody-based, (related to body fluids= humoral) uses antigens (any molecule that induces antibody production), antigens stim B lymphocytes to produce antibodies that directly target invaders, circulate in blood and recognize antigens (best for extracellular bacterial pathogens) - Cell-mediated: killer T-cell based, T lymphocytes recognize antigens, control antibody production, destroy host cells infected by microbes containing antigen (best for intracellular pathogens/ viruses) - Both from lymphoid stem cells in bones, form T cells (thymus) which modulate a specific immune response, and B cells (bone marrow) which produce antibodies to bind antigens

State how the hypothalamus controls body temperature.

- Hypo regulates body temp by modulating vasodilation- when T is too high, increased blood to skin to accelerate heat release, when body T too low, blood flow dec. to conserve heat and shivering occurs to generate heat - Pyrogens cause fever (exogenous induce endogenous like IFN, TNF, IL-6) - Cytokines are a type of pyrogen that interact w Rs on neurons, stim prod. of prostaglandins, turn up thermostat

Define "compromised host" and "opportunistic pathogens."

- Immunocompromised hosts are at risk of being repeatedly infected by opportunistic pathogens which are part of normal healthy microbiome, but can cause disease following perturbation of a compromised host (via disease, wound, medication, prior infection, immunodeficiency, or ageing)

Define and state the functions of extravasation, opsonization, and autophagy.

- In acute immune response: - Extravasation: neutrophils circulate freely in BVs and squeeze between walls in a capillary to site of infection (cytokine signaling from damaged cells activate synth of endothelial cells, selectins capture neutrophils, white-cell integrins bind to ICAM1 and VCAM1 for adhesion, neutrophils squeeze between endothelial cells) - Osponization- process whereby innate and adaptive immune systems work collectively to permit phagocytosis of encapsulated microbes (enhances phagocytosis- antibodies on microbes facilitate uptake by macrophage, antibodies bind to bacteria, Fc on antibody binds to Fc on bacteria) -Autophagy: the natural, conserved degradation of the cell that removes unnecessary or dysfunctional components through a lysosome-dependent regulated mechanism.

Recall the ways that complement helps rid the body of pathogens.

- Inflammation causes release of cytokines from macrophages, which travel to the liver and stim synth of C-reactive protein, which binds to components of bacterial cell surfaces (not host membranes), once bound, converts C3 to C3b (starts cascade), presence in serum is general indicator of inflammation, elevated levels= inc. risk of CVD, daily aspirin reduces inflammation and C-reactive protein levels - CRP not specific, tests monitor for flares

Differentiate between innate and adaptive immunity.

- Innate immunity is present at birth and includes physical barriers, chemical barriers, and cellular defenses- nonspecific responses - Adaptive immunity includes active and passive and is a reaction to a specific antigen and retains memory of that antigen, with a faster response when exposed again

Recognize the main SARS-CoV-2 structural components and the virus classification

- Is an ss RNA virus, virion structure with envelope around capsule - Has E and M proteins on membrane and surface, Hemagglutinin-esterase (HE) dimer that connects with some spike proteins, and Spike glycoproteins

State the functions of the structures that are present in all virions.

- Keeps viral genome intact, enables infection of host cell- genomes can be different- capsid packages genome and delivers to host cell,

Outline the steps toward recognition that an epidemic is underway.

- Look at reportable diseases, required to notify WHO/CDC, allows incidences to be tracked, emerging disease detected as cluster of pts w unusual symptoms; upsurges in either set off institutional alarms, initiate efforts to determine source and cause - Look at herd immunity and R0- threshold= 1-1/R0 - Higher transmission rate= lower virulence - Emerging and reemerging diseases

Explain how interferons aid in innate immunity.

- Low MW cytokines, host-species specific for VIRUSES - Type 1: high direct antiviral potency, made by almost all cells, bind to Rs on uninfected host cell to increase resistance (alpha, beta, omega) - Type 2: (gamma) indirectly antiviral, modulates adaptive immune response (act WBCs to produce more MHC surface antigens) - Type 3: directly antiviral, but mostly in epithelial cells

Distinguish the lytic, lysogenic, and slow-release viral cycles.

- Lytic: both lytic and temperate phage- once ready to exit cell, DNA recircularizes out of host genome, host DNA cleaved, capsid proteins made and phage enzyme lyses cell ready to infect more host cells - Lysogenic: only temperate phage, doesn't cause lysis, phage attaches to host, DNA circularized, integrates into host (prophage), then phage genome replicates with host cell- generates lytic burst of phage- via env cues (will host cell survive and continue to propagate- host cell threatening env= lytic burst) - Slow release: I'm assuming lysogenic?-- check 6.4

Distinguish between class I and class II MHC proteins.

- Membrane proteins w variable regions that bind antigens, differ between species and among individuals, help determine whether antigen is recognized as self or nonself - Class 1: on all nucleated cell, presents intracellular antigens from microbial proteins degraded in cytoplasm, peptides imported from ER and loaded into MHC 1, antigens on MHC 1 recognized by CD8 T cells; interact with fragments of antigens synth w/in cell translocated into ER for degradation, antigen peptides then TP to cell membrane to be loaded onto C1 MHCs - Class 2: found only on APCs, presents extracellular antigens rec by CD4 T cells, presents antigens from microbial proteins from outside the cell that are first phagocytosed then degraded in an endosome, degraded peptides placed on MHC2 molecules- assembly starts in ER, antigen is degraded by proteases in endosome, peptide antigens loaded onto MHC 2 and complex exported to cell surface

Describe the impact of bacteriophages in the human intestinal tract.

- Mental health, break up biofilms, modulate immune system, limit bacterial numbers to tolerable level - NOT sugar regulation

Explain how gut microbial catabolism may enable host niche adaptation.

- Microbes encode carbohydrate active enzymes (absent from human genome) to break down the plant matter humans can't digest (target polysaccharides from plants that dominated early human diets, bacteroidies thetaiotaomicron has lots of SUS genes) - Marine microbes digest seaweed glycans (porphyrans), ability to digest only in humans in Japan, enzymes absent in microbes of north americans-- bacteroides acquired via horizontal gene TF, diversity allows host to fill new nutritional niche (indicated by phylogeny and genome sequencing)

Distinguish between Toll-like and NOD-like pattern recognition receptors.

- Microbes have unique structures that ID them as foreign, have microbe-associated molecular patterns (MAMPs) which are recognized by recognition receptors (PRRs) which include Toll-like (TLR) or NOD-like (NLR) that serve as alarm systems that activate when encountering an intruder - TLR on cell surface and compartment and NLR in the cell (inflammasome), they both induce cytokine production inflammasomes to activate cytokine precursors - TLRs conserved cell-surface glycoproteins present on euk cells, humans have many TLRs which recognize different MAMPs; once bound TLRs trigger intracellular regulatory cascade to cause host cell to release cytokines (that bind to various immune cells and direct to invader) - NLRs are cytoplasmic sensors, bind intracellular MAMPs, some NLRs activate txn of cytokines, other trigger assembly of inflammasomes, some precursors to cytokines cleaved by inflammasomes before release - High diversity of recognition

Describe the concept of the 'Gut-Brain Axis'

- Microbes interact w immune cells in gut, cells make cytokines that circulate from blood to brain - Interact w enteroendocrine cells of SI that sense/detect microbiota and metabolites, secrete peptide hormones and cytokines to immune cells to modulate adaptive and innate systems - Produce NTs and metabolites, circulate to brain where some cross BBB and others alter activity at barrier

Name regions of the human body that harbor a microbiome and regions that are normally sterile.

- Microbiomes in the nose, stomach, mouth, lung, skin, intestines, and vagina and anywhere the outside touches, essentially. - Sterile regions include: internal organs, blood, CSF

Propose how the microbiome influences obesity.

- Microbiomes influence by harvesting energy from foods, triggering intestinal inflammation - Microbes make short chain FAs that are used by cells, amounts and ratios of SCFAs influence obesity, hunger, fat production, inflammation, nervous and endocrine systems-- cascading signals from SCFAs - Archaea may also play a role

Assess whether viruses are living or non-living.

- Non-living: virion lacks metab/ ability to reproduce independent of host - Living: virion assembly process is evidence for living, large viruses show reductive evolution from cellular origin, vs others built up from just parts of cells

Evaluate the evidence for the influence of the microbiota on obesity.

- Obesity long term- testing uses germ-free animals, and these are generally more unhealthy compared to those with microbiota - Look at microbes from genetic twins, TF microbes from twins to gnotobiotic mice (fecal TP)- found clear link between obesity in humans and microbiomes- impact on obesity in mice (matching which twin they got microbiome from) - Co-housed mice- lean invaded obese and protected against weight gain, when germ free co-housed, initially gain a lot of weight, then lost dramatically - Obese mice: firmicutes > bacteroides vs lean mice: firmicutes < bacteroides

State the hygiene hypothesis.

- Our microbiota are far less diverse than they used to be (evolutionarily) due to increased sterility, less time outside, and cleanliness (may contribute to inflammatory and autoimmune disease)

Distinguish parasites, primary pathogens, opportunistic pathogens, reservoirs.

- Parasites: an organism that receives benefits at the expense of a host- usually refers to disease-causing protozoa and worms (ectoparasites on body surface, endoparasites inside the body); bacterial, viral, fungal parasitic agents of disease are pathogens- infection when a pathogen enters and grows, disease when host cell damage has occurred and symptoms assoc w disease observed - Primary pathogens: cause disease in healthy hosts - Opportunistic pathogens: cause disease in immunocompromised hosts or following entry into unprotected sites (fungus causes life-threatening disease in pts w HIV/AIDS), some have latent state during infection (organism can't be found by cultures- herpes) - Reservoirs: mammal, bird, arthropod that harbors a pathogen without exhibiting disease

Summarize how microbial amino acid decarboxylation can affect animal hosts.

- Peptides and AAs in diet, important but also cat. by microbes, exported amine "waste products" of AA cat serve as hormones and NTs (DA, serotonin, histamine, GABA- major inhib, decreased levels assoc w depression/ anxiety)

Recall the causes and consequences of chronic inflammation.

- Permanent damage (persistent presence of foreign object) caused by persistent pathogens that resist host defenses, nonliving irritant material, autoimmunity (RA, Crohn's)failure of immune system to distinguish from self) - walls off site of inflammation by forming granuloma (deposit fibroconnective tissue around lesion)

Categorize killing mechanisms as oxygen independent or oxygen dependent.

- Phagosome-lysosome fusion has O2 independent (involve compounds that disrupt microbial existence- lysozymes destroy cell walls, lactoferrin takes iron, defensins poke holes in cytoplasmic membranes) and O2 dependent (production of oxygen radicals- phagosome membrane has enzymes that make- NADPH oxidase- (superoxide ion, hydrogen peroxide, hydroxyl radicals), myeloperoxidase, nitric acid synthetase that cause oxidative burst large increase in O2 consumption during phagocytosis) killing methods - Phagocytosis- requires macrophages and neutrophils recognize surface of particle as foreign (human cells have glycoprotein CD47, which prevents phagocytotic attack and needs presence of MAMPs)

Differentiate between the primary and secondary antibody responses.

- Primary starts w B cell proliferation, and antibodies with in days, B cells that bind antigen make antibodies, IgM first then IgG, some B cells become memory cells - In booster injection or new exposure, immediate secondary response occurs due to memory B cells, so antibodies in the blood within hours, mostly IgG response, but bigger

Justify the use of probiotics.

- Prom=biotics help to modulate the gut microbiome and ensure there are enough good bacteria available to prevent the growth of bad bacteria. This includes synbiotics, prebiotics, microbial consortia, GMOs - Also used in personalized medicine

Recall examples of prophages or endogenous viruses contributing to host cell physiology.

- Prophage: CTS phage adds cholera toxin - Endogenous: HERV-W and HERV-FRD form Syncytin 1 and 2 (retroviral proteins) for placental fusion; HERV makes INSL4 for insulin-like protein in fetal development, and HERV-E has endothelin type B receptor for placental fusion

List the five major signs of acute inflammation.

- Redness - Warmth - Pain - Swelling - Altered function at affected site

Describe how SARS-CoV-2 replicates in our cells

- S binds to ACE protein in host cell, membrane fuses for entry, viral genome released, translation of virus polymerase protein, replicated, transcribed, translated- S, E,M proteins made in ER, combine with nucleocapsid with viral genome inside, exocytosis

Compare and contrast physical barriers against infection at different bodily surface sites.

- Skin, lining of lungs, GI tracts, oral cavity, all have tight junctions preventing foreign cells from moving between body cells - Skin: made of keratinocytes, oil from sebaceous glands-- under skin there is skin-associated lymphoid tissue (SALT) cells that activate adaptive immune system that phagocytose invading cells and travel to lymph nodes to become APCs (acting in both immune systems) - Mucous membranes: trap and destroy pathogens, host cells rec. conserved structures (Microbe-associated molecular patterns or MAMPs), mucous layers slough off and are removed, and cilia remove microbes from the lungs - Lungs: ciliated mucociliary escalator in trachea, bronchi, and bronchioles sweeps foreign particles up and out, microbes >100 micrometers trapped in hair and cilia in nasal cavity expelled w sneezing, alveolar macrophages ingest and kill microbes in alveoli _ GALT: gut- associated lymphoid tissue (similar to skin)- includes tonsils and Peyer's patches, specialized M (microfold) cells take up microbes from intestine and release them on other side for macrophages

Compare the skin, eye, oral and nasal cavities, respiratory tract, genitourinary tract, stomach, and intestine with respect to their microbiomes--identify habitats expected to be sterile versus not; consider sources for the colonization of the different body sites.

- Skin: difficult habitat for microbes (dry, salty, acidic, secretes oil and sweat which makes environment acidic and secretes lysozyme which destroys peptidoglycan); microbes only in moist areas, mostly gram-positive; staphylococcous epidermidis, cutibacterium acne (causes acne, inflames sebaceous glands, degrades skin oil) - Eye: has its own immune system, colonization inhibited by lysozyme, tears continuously rinse, some skin bacteria can rest there temporarily without causing damage - Oral/ nasal cavities: staph in nose- can enter wounds to cause infection but otherwise not harmful, newborns cavities colonized w microbes assoc w mom and surroundings (Neisseria (G-), Streptococcous, lactobacillus, actinomyces (G+)), when teeth emerge new bacteria colonize between gums and teeth and in tooth enamel; nasopharynx and oropharynx are also populated- can be anaerobic or aerobic) - Respiratory tract: (thought to be sterile, but not true)- ciliated mucous lining of trachea, bronchi, and bronchioles make up mucociliary escalator- movement pushes particles up and out of lungs, when too high of a load hits, infection can occur - Genitourinary tract: thought to be microbe free, but urethra contains species (UTI when migrate to bladder); vaginal changes during woman's lifetime and within each cycle, acidic secretions favor lacto, antibiotics can lead to overgrowth of candida albicans (yeast infection) - Stomach: high acidity and very few microbes survive, decreased acidity by hypochlorydia (malnourishment), cholera passes through, but est. infection in intestines; helicobacter pylori in mucous, creates a higher pH microenvironment by generating ammonia via urease (causes ulcers or cancer) - Intestine: long with unique microbial ecosystems, contains most of our bacteria/g feces, generally anaerobic , small amounts of O2 diffuse into lumen consumed by facultative bacteria, infant intestines colonized by ecoli and strep that generate reducing env that supports growth of anaerobic species

Recall the innate immune cells present in the skin, gastrointestinal tract, and lungs (these are referred to in the "To Summarize" section).

- Skin: made of keratinocytes, oil from sebaceous glands-- under skin there is skin-associated lymphoid tissue (SALT) cells that activate adaptive immune system that phagocytose invading cells and travel to lymph nodes to become APCs (acting in both immune systems) - Mucous membranes: trap and destroy pathogens, host cells rec. conserved structures (Microbe-associated molecular patterns or MAMPs), mucous layers slough off and are removed, and cilia remove microbes from the lungs - Lungs: ciliated mucociliary escalator in trachea, bronchi, and bronchioles sweeps foreign particles up and out, microbes >100 micrometers trapped in hair and cilia in nasal cavity expelled w sneezing, alveolar macrophages ingest and kill microbes in alveoli _ GALT: gut- associated lymphoid tissue (similar to skin)- includes tonsils and Peyer's patches, specialized M (microfold) cells take up microbes from intestine and release them on other side for macrophages

List the roles viruses play in ecosystems (coral reefs, algal blooms, human gut)

- Sum of viral pops in ecosystem is virome, viruses influence global nutrient balance by cycling organic food molecules between species and trophic levels when hosts lyse, when viruses kill hosts it works as population control - Dissolved organic molecules and particles settle in sediment for coral reefs, limits to pop can cause algal blooms to crash, resulting in increased host diversity - White algae in England algal bloom crashed because of virus - In human gut: phages limit bacterial numbers so human immune system can tolerate, can suppress T-cell activation and tumor formation, phages may attack biofilms- intestinal lumen has phages that infect host cell, lysogenized bacteria have enhanced traits, or host population dist changes, phage can stim immune system, lysogenized bacteria express virulence (toxins) - COLON CANCER- etiology marked by bacterial community perturbations- Fusobacterium nucleatum induces carcinogenesis by promoting inflammation and down-regulating anti-tumor Tcell-mediated immunity- knowlegde of gut virome improves predictions on colon cancer (specifically F. nucleatum, Pophyromonas spp., peptostreptococcus spp., and parvimonas spp.) - Altered human virome associated with several diseases

Judge whether herd immunity will protect against a particular disease (covered in previous class).

- Susceptible individuals indirectly protected by vaccinated individuals - Use 1- 1/R0 to determine percent that need to be immune for a disease to work- usually around 75%

Outline T-cell activation; include the role of APCs.

- TCRs on T-cell surfaces bind antigens, TCRs associate w CD3 proteins, bind antigens only when attached to MHC, then complex transduces signal into cell, triggers T-cell proliferation - APCS take in antigens and create MHC complex, presents antigen, Th0 recognizes antigen via T-cell receptor, has CD4 recognition (Th1 (macrophage, Tc cell, some B cell) for humoral immunity, CD8 for cell mediated- Th2 (which makes B cells))

Explain why live vaccines are better than component vaccines at producing antibody responses.

- They replicate at the normal body sites, generating the most appropriate immune response - Activate both innate and adaptive immune systems, results in more affective adaptive response - BUT more risky, esp for immunocompromised

Explain what tropism is and what determines tropism for SARS-CoV-2

- Tropism is the ability to infect a specific tissue type in a host, receptors determine tropism- SARS-CoV-2 has broad tissue tropism (Lung is primary, but also in liver, kidneys, and neural cells)

Justify the diagnostic value of white blood cell ratios.

- Uses relative amounts to make diagnoses of different types of infections- neutrophils normally most abundant, then lymphocytes - Use flow cytometer creates plot based on cell features

Compare and contrast the different types of vaccines.

- Vaccines work through adaptive immune response, some given for individual disease yearly, others grouped together (MMR) - Killed or inactivated pathogens: (hep A, polio) - Live attenuated: (BCG for Tb, MMR) - Purified subunits: includes capsular antigens (like from strep pneu. and haemophilus flu B. HPV, pertussis, hep B), variant includes toxoid vaccine that introduces inactive variant of toxin produced by pathogen - Viral vector: use harmless virus to deliver genetic code of antigen to hosts (ebola) - Intracellular mRNA delivery: instructs host cells to make specific antigen unique to pathogen, but doesn't induce illness (Moderna/pfizer covid)

Compare the three forms a virus can assume.

- Virion (virus particle) with nucleic acid genome in protein capsid - Intracellular rxn complex- viral gene products direct host enzymes to assembly progeny virions - Viral genome integrated into host DNA- prophage in bacteria, provirus in eukaryotic, permanently integrated transmitted vertically in germ line is endogenous virus

Contrast virions, viroids, and prions.

- Virions are viral particles that infect animals - Viroids are RNA molecules that infect plants - Prions are infectious proteins that have no nucleic acid component and abnormal structure that alters conformation of other normal proteins

Define pathogenicity islands and describe how researchers recognize them.

- Virulence factors usually on pathogenicity islands plasmids, or phage genomes- ctx gene required to produce cholera toxin on CTX phage that infects other vibrio cholerae - Horizontally transmitted, have a unique CA/AT ratio, near sequences assoc w transposition (tRNA genes, direct repeats, integrase gene, insertion sequences), and assoc w genes homologous to phage/plasmid genes - Bacteria that causes stomach ulcers uses type 4 secretion system that translocates toxin into gastric cells and causes inflammatory response - Bacteria for MRSA has high number of enterotoxins - Bacteria for salmonella enterica has type 3, effector proteins, and reg proteins - HPI of yersinia has genes for high-affinity iron uptake system needed for growth during colonization

State the roles of virulence factors.

- Virulence= severity of disease (increased death rate, decreased host growth, decreased host reproduction- ex. Ebola) - To cause disease, pathogens have to enter host, find niche, avoid host defenses, multiple, and transmit to new host- virulence factors help with these (from virulence genes) and include toxins, attachment proteins, and capsule proteins (also flagella, exotoxins, secretory enzymes, type IV secretion systems, effectors, urease, lipopolysaccharides, outer proteins)

List some strategies microbes use to evade the adaptive immune system.

- Viruses produce proteins that down-regulate production of class 1 MHCs on infected cell surfaces - Helicobacter pylori expresses proteins that trigger apoptosis of T cells - Bacteria and viruses disrupt or up-regulate cytokine synthesis to make cytokine storm- Yeresinia enterocolitica inhib signal transduction pathway to make TNF, IL-1, and IL-8

Name and state the functions of primary and secondary lymphoid organs.

- Where lymphocytes are found, spend most time there (not in bloodstream) - Primary organs: where lymphocytes mature and grow into B cells and T cells (from Bone marrow and Thymus) - Secondary Organs: Where B and T cells differentiate into antigen-specific cells (tonsils, lymph nodes, appendix, spleen, Peyer's patches)

Explain how bacteria defend themselves against viruses.

- genetic resistnce: altered receptor proteins - Restriction endonucleases: cleave viral DNA lacking methylation - CRISPR (clustered regularly interspaced short palindromic repeats): integration of phage DNA sequences (adaptive immunity)- piece of phage copied as spacer into host genome, spacer repeat region is history of infections so reinfection causes txn of spaces into crRNA which joins Cas complex to cleave phage DNA (making bacteria immune)

Explain how mRNA vaccines work and why they are considered a promising innovation

- mRNA transcribed and translated by host and protein antigen produced, protein triggers immune response with generation of antibodies that recognize it, so when exposed to virus in the future, body has antibodies to combat

Recall the benefits and risks of the microbiome.

-Microbes only need to find food- not inherently bad - Risks: can spread to other organs and cause infection, especially in immunocompromised people - Benefits: aids in digestion, competes with bad bacteria, make vitamins, promote host tissue development

Outline the series of steps leading to acute inflammation.

1. Infection 2. Resident macrophages engulf pathogens and release cytokines and chemokines 3.Vasoactive factors and cytokines help deliver additional phagocytes 4. Some cytokines initiate healing as pathogens destroyed - Infection releases microbes to tissue, macrophages phagocytose bacteria by releasing cytokines (IL-1, TNF-alpha) which cause capillary cells to express selectins or integrins which are adhesion molecules (slow down rolling neutrophil mvmnt), neutrophils extravasate, squeeze between endothelial cells, leave capillary, and attack bacteria - Damaged tissues release bradykinin (promotes more extravasation, stim mast cells to degranulate (release histamine), histamine stim BVs to open more, blood plasma and platelets release into area (swelling), prostaglandin is released (stim nerve endings to signal itching or pain)

stem cells

A cell that can develop into a variety of other cell types. Stem cells in the bone marrow can develop into immune cells and red blood cells.

Antigen-presenting cells (APCs)

A cell with an antigen bound to an MHC protein on its surface. APCs interact with T cells to trigger an immune response. The most common APCs are dendritic cells.

immunocompromised

A condition in which the immune system is "weakened" and less effective at fighting pathogens. A person could become immunocompromised due to certain medications, medical conditions, viral infections, etc.

autoimmune disease

A condition in which the immune system mistakenly attacks the body's healthy, normal cells.

lymph

A fluid similar to blood that circulates throughout the body. Lymph contains immune cells but not red blood cells.

lymph nodes

A fluid similar to blood that circulates throughout the body. Lymph contains immune cells but not red blood cells.

lymphoid organs

A group of organs that produce or contain large numbers of immune cells. Examples include the bone marrow, thymus, lymph nodes, spleen, and tonsils.

immune system

A group of organs, tissues, cells, and molecules that protect the body from pathogens.

complement proteins

A group of proteins in the blood that help destroy pathogens and infected cells. They can damage pathogens directly or attract other immune cells to the site of an infection.

pathogen

A microbe that causes disease. Can include bacteria, viruses, fungi, or parasites.

activation

A process by which a cell changes or gains functions in response to a stimulus.

apoptosis

A process by which a cell destroys itself. Involves several chemical reactions that make the cell change appearance and then die. Apoptosis is often used to kill cells that are unneeded or abnormal.

Neutralization

A process by which antibodies bind to a pathogen and block it from interacting with and infecting the body's cells.

Phagocytosis

A process by which immune cells called phagocytes engulf and destroy pathogens and abnormal cells. Parts of the destroyed pathogens or cells may be absorbed by the phagocyte, released, or displayed on the phagocyte's MHC proteins.

inflammation

A process in the innate immune response that helps the body fight pathogens and repair tissue damage. Inflammation is triggered by injury or infection and can result in redness, pain, and swelling.

engulf

A process in which certain cells, called phagocytes, surround and take in large particles (such as pathogens).The phagocyte extends its outer membrane around the particle, forming an enclosed structure called a vesicle that brings the particle into the cell.

differentiation

A process that switches a cell from one type to another, typically more specialized type. Differentiation is caused by changes in gene expression that are often triggered by chemicals, including cytokines and hormones.

B-cell receptor

A protein on the surface of a B cell that binds to a specific antigen. Plays a major role in B cell activation.

t-cell recptor

A protein on the surface of a T cell that binds to a specific antigen (but only when the antigen is bound to an MHC protein on an antigen-presenting cell). Plays a major role in T cell activation.

Major Histocompatibility Complex (MHC)

A protein that binds to antigens and "displays" them on the surface of a cell. Phagocytes use MHC proteins to "display" antigens from pathogens.

histamine

A small molecule released by mast cells to trigger inflammation. Histamine makes blood vessels "leaky," which allows immune cells and fluid to move from the blood vessels into body tissues.

antigen

A small piece of biological material (protein, carbohydrate, lipid, or nucleic acid) that can be recognized by the immune system. Antigens from pathogens or abnormal cells trigger an immune response.

antibody

A small protein that binds to a specific antigen. Antibodies are made by plasma cells and help the immune system fight pathogens in various ways. The human immune system can generate billions of types of antibodies.

Bone marrow

A spongy tissue in certain bones. Contains stem cells that develop into immune cells and red blood cells.

mucus

A sticky, slimy substance produced by certain cells. Protects tissues by trapping pathogens and contains antimicrobial enzymes and antibodies.

vaccine

A substance that triggers an immune response against a pathogen without causing an infection. If the immune system encounters the same type of pathogen later, it can destroy the pathogen more quickly and efficiently than if the individual had not had a vaccine.

mucus membrane

A thin tissue containing cells that make mucus. Mucous membranes line the digestive system (gut), respiratory system (airways), and urogenital tract.

helper t-cell

A type of T cell that activates other immune cells, including B cells and cytotoxic T cells.

cytotoxic t-cell

A type of T cell that kills infected cells by making themundergo apoptosis.

plasma cells

A type of adaptive immune cell that produces antibodies. Each plasma cell makes an antibody for a specific antigen and makes several thousand copies of this antibody per second. Plasma cells come from activated B cells.

lymphocyte

A type of immune cell. Includes T cells, B cells, and natural killer (NK) cells.

dendritic cell

A type of phagocyte (innate immune cell that engulfs and destroys pathogens). Dendritic cells "display" antigens from the pathogens it engulfs in order to activate other immune cells.

B-cell

An adaptive immune cell that helps target and destroy specific pathogens. After being activated by T cells, B cells differentiate into plasma cells to produce antibodies.

t-cell

An adaptive immune cell that helps the body respond to specific pathogens. Upon recognizing a specific antigen, T-cells differentiate into helper T cells and cytotoxic T cells.

antigen- MHC complex

An antigen bound to an MHC protein on the surface of a cell. T cells must bind to a specific antigen-MHC complex in order to activate.

adaptive immune cell

An immune cell involved in the adaptive immune response. Includes B cells and T cells.

innate immune cell

An immune cell involved in the innate immune response. Includes phagocytes (macrophages, neutrophils, dendritic cells, etc.), mast cells, and natural killer (NK) cells.

monocyte

An innate cell that differentiates into macrophages. Like macrophages, monocytes are phagocytes that engulf and destroy pathogens and abnormal cells.

basophil

An innate immune cell that circulates in the blood and is involved in inflammation.

esonophil

An innate immune cell that destroys large pathogens, such as parasites, by releasing damaging molecules and chemical signals (cytokines).

phagocyte

An innate immune cell that engulfs and destroys pathogens and abnormal cells. Includes neutrophils, monocytes, macrophages, and dendritic cells.

natural killer cell

An innate immune cell that kills infected and abnormal cells. Can release chemical signals (cytokines) that cause other cells to undergo apoptosis.

mast cells

An innate immune cell that plays a major role in inflammation. Releases chemical signals (histamine) that help fluid and immune cells move from the blood vessels into tissues.

macrophage

An innate immune cell that plays many roles. Macrophages are phagocytes that engulf and destroy pathogens and abnormal cells. They can also release chemical signals (cytokines) to attract other immune cells.

neutrophil

An innate immune cell. Typically the first cell type to respond to pathogens, particularly bacteria and fungi. Chemical signals (cytokines) can attract neutrophils and make them multiply.

thymus

An organ in the chest where immune cells called T cells develop.

immune cells

Cells that are part of the immune system. Sometimes also called white blood cells or leukocytes.

progenitor cells

Cells that come from stem cells and can then differentiate into other cell types. Lymphoid progenitor cells differentiate into lymphocytes, and myeloid progenitor cells differentiate into other immune cells and red blood cells. Both types of progenitor cells come from stem cells in the bone marrow.

toxin

Harmful substances (typically small molecules or proteins) produced by living organisms, including some pathogens.

primary immune response

How the immune system responds the first time it encounters a specific pathogen.

secondary immune response

How the immune system responds the second (or any subsequent) time it encounters a specific pathogen. This response is faster and more powerful than the immune system response when it first encounters the pathogen.

memory cells

Long-lived B and T cells that are made the first time a pathogen infects the body. If the body is reinfected by the same type of pathogen, memory cells provide a faster, stronger adaptive immune response.

innate immune response

One of the two main ways in which the immune system responds to pathogens. Provides immediate protection but cannot target specific pathogens.

adaptive immune response

One of the two main ways in which the immune system responds to pathogens. Provides long-lasting protection against specific pathogens but may take longer to start.

receptors

Proteins in and on the membranes of cells. Receptors bind to specific molecules, such as antigens, to send signals between or within cells.

tonsils

Small organs at the back of the throat that contain immune cells. These cells destroy inhaled or ingested microbes and warn the immune system about potential infections.

cytokines

Small proteins released by cells to communicate with other cells. Some cytokines alert immune cells to an infection or activate certain immune cells.

skin

The body's thick outer layer. Acts as a physical barrier to pathogens and also makes some antimicrobial substances.

humoral immune response

The processes of the adaptive immune response that involve antibodies (also known as the antibody-mediated response). These processes make and use antibodies to fight specific pathogens. They include B cell activation and differentiation into plasma cells, which produce antibodies.

cell-mediated immune response

The processes of the adaptive immune response that playa major role in destroying infected cells through cytotoxic T cells.

immune response

The processes that the immune system uses to fight pathogens. Includes two main parts, the innate and adaptive immune responses, and involves many cells and organs.

lymphatic vessels

Thin "tubes" that carry a fluid called lymph throughout the body. Lymphatic vessels are similar to blood vessels but do not contain red blood cells.

Describe the immune response to vaccination

_ Vaccine injected into muscle, protein antigen taken up by dendritic cells (act. through PRRs by MAMPs) in adjuvant then to draining lymph node - Presentation of peptides of vaccine protein by MHC on dendritic cell act. T cells through TCR, T cells drive B cell development in lymph node (maturation of antibody response to increase antibody affinity and induce different isotypes - B cells make short-lived plasma cells that secrete antibodies specific to antigen and serum ab levels inc over next 2 weeks, Memory B cells produced (immune memory- Long-lived plasma cells that can produce antibodies for decades travel to bone marrow - CD8+ T cells proliferate when they encounter a pathogen, Tc cells eliminate infected host cells (tell from MHC 1)