0763 - Microbiology & Parasitology Midterm PDF

MICROBIOLOGY & PARASITOLOGY Midterms Reviewer – Lecture BACTERIAL GENETICS - Chromosome is looped or folded and Genetics – science of heredity attached at one several points to the Study of genes...

MICROBIOLOGY & PARASITOLOGY Midterms Reviewer – Lecture BACTERIAL GENETICS - Chromosome is looped or folded and Genetics – science of heredity attached at one several points to the Study of genes plasma membrane 1. How they carry information - Chromosomes take up only about 10% 2. How they are replicated and passed to of the cells volume because DNA is subsequent generation of cells twisted and supercoiled 3. How the expression of their information within an organism determines the particular characteristics of that organism Gene – unit of heredity, segment or sequence that produces proteins Genome – the total genetic information in a cell, includes both chromosomes and plasmids Chromosomes – contains the majority (but not Key Features of Bacterial Chromosome all) of the genes - Most but not all bacterial species Plasmids – small circles of double stranded contain circular chromosomal DNA DNA that can replicate in bacterial cells - A typical chromosome is few million independently of the bacterial chromosome base pairs in length hence are commonly used cloning vectors - Most bacterial species contain a single DNA – composed of nucleotides that carry the type of chromosome, but it may be hereditary materials present in multiple copies - In bacterial cell, it is single molecule, - One origin of replication is required to double stranded and circular initiate DNA replication Genomics – is the molecular characterization - Repetitive sequences may be of genome interspersed throughout the Bacterial Chromosome chromosome - Every plasmid has its own origin of - Several thousand different genes are replication – a stretch of DNA that interspersed throughout the ensures it gets replicated by the host chromosome. The short regions bacterium. between adjacent genes are called - Plasmids can intergenic regions copy themselves Intergenic regions – non-coding regions of the independently bacterial chromosome that is not used in of bacterial translocation and transcription. chromosome; - Also called as junked chromosome multiple plasmids region – even hundreds - This region in important for controlling E. coli – has a gene activity and protein assembly circular DNA Key Features of Eukaryotic Chromosomes about 4.6M bp - Eukaryotic chromosomes are usually and is linear approximately - A typical chromosome is tons of millions 1000 times to hundreds of millions of base pairs in longer than the length cell - Genes are interspersed throughout the chromosomes. A typical chromosome  contains between a few hundred and 1. The linear sequence of bases provides several thousand different genes the actual information - Each chromosome contains many Genetic Codes – the set of rules that origins of replication that are determines how a nucleotide sequence is interspersed about every 100,000 base converted into the amino acid sequence of a pairs protein. - Each chromosome contains a 2. Complementary structure allows for the centromere that forms a recognition site precise duplication of DNA during cell for the kinetochore proteins division. - Repetitive sequences are commonly RNA STRUCTURE found near centromeric and telomeric - Form a complicated 3-dimensional regions, but they may also be structures where strands can loop back interspersed throughout the and form intra-strand base pairs chromosome Differences of RNA to DNA - Telomeres contain specialized 1. Sugar – ribose sequences located at both ends of 2. One Strand – instead of 2 linear chromosomes 3. Has Uracil – instead of thymine Telomeres - present at the end part of the Base Pair: GC and AU instead of AT chromosomes 3 Types of RNA - Non-coding part of the chromosome 1. mRNA (messenger RNA) that protects the chromosomes and - template for protein synthesis maintain chromosomal ability - messenger and carrier of genetic Centromere – constricted region of the information for protein synthesis from chromosome that aids to the attachment of DNA to ribosomes the spindle fibers. 2. rRNA (ribosomal RNA) Structure of DNA and RNA - forms an integral part of ribosomes - Made up of polynucleotide - bind the mRNA and specific enzyme for 1. Sugar Group – instead of OH in RNA, in protein synthesis DNA only H 3. tRNA (transfer RNA) 2. Phosphate Group - recognize the specific codons and 3. Nitrogenous Bases – is attached to the transport the required amino acid sugar group CENTRAL DOGMA OF MOLECULAR BIOLOGY - The coiling of the DNA is due to the - a theory proposed by Francis Crick hydrogen bonds in between - stated that sequence of nucleotides in nitrogenous bases. DNA determines the sequence of amino DNA STRUCTURE acids in proteins - Discovered by James Watson and - flow of the genetic information Francis Crick Major Information Pathways Nucleotide – the building block 1. DNA Replication – information is Composed of the following: transferred from one DNA molecule to a. Sugar (deoxyribose) another b. Phosphate - Happens in the synthesis phase prior to c. Nitrogenous bases the cell division Types of Nitrogenous Bases 2. Transcription – information is transferred 1. Pyrimidines – have one ring from DNA to an RNA molecule - Cytosine and Thymine, Uracil-RNA (CTU) - Conversion of DNA to mRNA 2. Purines – have two rings 3. Translation – information is transferred - Adenine and Guanine (AG) from RNA to a protein through a code Complementary base pairing by Chargaff’s that specifies the amino acid sequence Rule: G-C and A-T - mRNA to proteins or amino acids Primary Features of Biological Information Special Information Pathway Storage: - only happen in microorganisms that has an enzyme, reverse transcriptase  1. Reverse Transcription – in some viruses, information is transferred from RNA to DNA 2. RNA replication – information is transferred from RNA to another RNA molecule thus producing protein. DNA REPLICATION - One “parental” double-stranded DNA molecule is converted to two identical offspring molecules. Overview of DNA Structure Bacterial DNA Replication Enzymes 1. Topoisomerase or Gyrase - Supercoiling of the DNA is relaxed by this enzyme 2. Helicase – unwinds the parental double helix at replication forks 3. Single Stranded Binding Protein – - Each side of the double helix runs in regulates the unwinding opposite (anti-parallel directions) from - Binds to and stabilizes single-stranded 3’-5’ and 5’-3’. DNA until it is used as a template - Semiconservative replication because 4. Topoisomerase – relieves overwinding one strand of the DNA is used to strain ahead of replication forks by synthesized new DNA. breaking swiveling, and rejoining DNA - DNA does not unzip entirely. It unzips in a strands small area called a replication fork, 5. RNA Polymerase or Primase – which then moves down the entire synthesized an RNA primer at 5’ end of length of the molecules leading strand and at 5’ end of each Leading Strand – oriented from 3’-5’ (template Okazaki fragment of lagging strand strand and upper) - Where the DNA polymerase III attach Lagging Strand – oriented from 5’ – 3’ 6. DNA Polymerase III – adds nitrogenous (produced strand and lower) bases - The DNA replication always start in 5’. - Using parental DNA as a template, - Bases along the two strands of double- synthesizes new DNA strand by adding helical DNA are complementary. nucleotides to an RNA primer or a pre- - The bond between the complementary existing DNA strand bases is called as hydrogen bond. 7. DNA Polymerase I, II, IV, and V – - Adenine and Thymine – 2H bond counter checks the DNA polymerase III - Guanine and Cytosine – 3H bond - Removes RNA nucleotides of primer - The leading strand is continuous from 5’ end and replaces them with - The lagging strand is discontinuous, DNA nucleotides these strands are short sequences and 8. Exonuclease – removes the primer called as Okazaki fragment. 9. DNA Ligase – seal or joins the Okazaki - DNA replication requires the presence fragments of lagging strand: on leading of several cellular proteins that direct a strand, joins 3’ end of DNA that replaces particular sequence of events. primer to rest of leading strand DNA  - There are five different know types of - Ribo-nucleotides can only be added to DNA polymerases found in bacteria and the 3’ end of a transcript, thus human cells. elongation is in 5’-3’ direction - In E. coli, polymerase III is the main 3 Steps of Transcription replication enzyme, while polymerase I, 1. Initiation II, IV, and V are responsible for error - RNA polymerase binds to the promoter checking and repair. of a gene - Therefore, during replication, DNA Promoter – serves to target and orient RNA polymerase III binds to the strand at the polymerase site of the primer and begins adding - Once docked at the promoter, RNA new base pairs complementary to the polymerase unzips DNA strand 2. Elongation - In eukaryotic cells, polymerase alpha, - Only 1 strand of the DNA is used as a delta, and epsilon are the primary template in creation of mRNA polymerases involves in DNA replication, 3. Termination because replication proceeds in the 5’ - Triggered by a specific DNA sequence to 3’ direction, the newly formed strands in the gene called the terminator. is continuous. The transcription process allows the cell to REPLICATION produce shot-term copies of genes that can Prokaryotes Eukaryotes be used as the direct source of information for One point of origin Multiple points of protein synthesis. origin mRNA – acts as an intermediate between the Replication occurs in Unidirectional permanent storage form (DNA), and the two opposing replication process that uses the information (translation). directions at the - In prokaryotes, all of the nucleotides in same time the mRNA are part of codons for the (bidirectional) new protein. Takes place in the Takes place within - In the eukaryotes, there are extra cytoplasm the nucleus of the sequences in the DNA and mRNA that cell do not code for proteins called introns. Posses one or two Have 4 or more - This mRNA us then further processed: types of polymerases polymerases 1. Introns get cut out Faster rate of Longer Rate (400hrs) 2. The coding sequences get spliced replication (40 mins) together Have no ends to Have distinct process 3. A special nucleotide cap gets synthesize for replicating the added to one end telomeres at the 4. A long tail consisting of 100 to 200 ends of their adenine nucleotides is added to the chromosomes other end. Short replication Cells only undergo DNA TRANSLATION occurs almost DNA replication - Also called as protein synthesis continuously during the S-phase of - Codons of mRNA are converted into the cell cycle protein DNA TRANSCRIPTION - Involves decoding the language of - Copying process or synthesis of nucleic acids and converting it into the complementary strand of RNA from a language of proteins DNA template Codon – language of mRNA - Copy is mRNA - Group of 3 nucleotides that coded for - Happens in cytoplasm for prokaryotes, particular amino acid such as AUG, UAA nucleus for eukaryotes Genetic Code – the set of rules that determine - Performed by RNA polymerase how a nucleotide sequence is converted into Transcription is unidirectional the amino acid sequence of proteins  - Happens in ribosomes in prokaryotes - Translation also involves tRNA, each of and ER for eukaryotes which is attached to 1 of the 20 amino AUG – is the start codon in bacteria that codes acids. for formyl methionine rather than methionine - Ribosomes math the right tRNA via (eukaryotes) anticodon, with the right codon in the - There are 64 codons but only 20 amino mRNA, then add its amino acid to the acids growing protein Type of Codons Step by Step Process of Translation 1. Sense Codons – 61 including the AUG or Initiation the start codon 1. Components needed to begin 2. Nonsense Codons – 3 stop codons translation come together (UAA, UAG, UGA) 2. On the assembled ribosome, a tRNA - These nonsense codons do not produce carrying the first amino acid is paired proteins, the stop the process of with the start codon on the mRNA. A translation. tRNA carrying the second amino acid Workers in Translation approaches 1. Ribosomes (rRNA) Elongation - Is made in the cytoplasm in the 3. The place on the ribosome where the prokaryotes and nucleolus in the first tRNA sits is called the P site. In the A eukaryotes site next to it, the second codon of the A site – holds the next codon mRNA pairs with a tRNA carrying the P site – holds the first codon second amino acid. E site – holds the deacylated tRNA before it 4. The first amino acid joins to the second leaves the ribosome by a peptide bond, and the first tRNA is Functions of Ribosomes released - To direct the orderly binding of tRNAs to 5. The ribosome moves along the RNA until codons the second tRNA is in the P site, and the - To assemble the amino acid brought process, continues there into a chain producing proteins 6. The ribosomes continue to move along 2. tRNA the mRNA, and new amino acids are - each has a binding site for an amino added to the polypeptide acid Termination - each tRNA is specific for a single amino 7. When the ribosome reaches a stop acid, it must be able to recognize the codon, the polypeptide is released. codon on the mRNA that codes for that 8. Finally, the last tRNA is released and the particular amino acid ribosome comes apart. The release - has specific three-nucleotide sequence polypeptide forms a new protein. anticodon Summary of Translation - example if the mRNA is UUU, its Initiation anticodon is AAA. - Ribosome assembles at specific AUG of Anticodon - a sequence of three bases mRNA complementary to a codon - Ribosome binds 2 tRNA-amino acids, 2 - matches up with the appropriate mRNA codons at a same time; matching codon like a lock and key complementary anti-codons with mRNA Overview of Translation codons The building of polypeptide, 1 amino acid at Elongation time, by ribosomes using information in mRNA - Ribosome catalyzes peptide bond - ribosomes bind directly to mRNA, read formation between amino acids codon by codon attached to each tRNA - ribosomes always start at AUG (formyl - Ribosome shifts 3 nucleotides (1 codon) methionine rather than methionine) on mRNA and repeats the process Termination - Stop codon causes translation to end Table of the Genetic Code - Enables the initiation of protein synthesis by aligning the ribosome with the start codon - Generally located around 8 bases upstream of the start codon - The RNA sequence help recruit the ribosome to mRNA to initiate protein synthesis by aligning the ribosome with start codon - Once recruited, tRNA may add amino acids in sequence as dictated by the codons, moving downstream from the translational start site Kozak Consensus Sequence - Occurs on eukaryotic mRNA - Plays a major role in the initiation of the translation process - The sequence is recognized by the ribosome as the translation site from which protein is coded by mRNA molecule GENE REGULATION, MUTATION, AND GENETIC TRANSFER If the DNA sequence is The regulation of Bacterial Gene Expression CATGCCTGGGCAATAG Bacterial Cell -> Enzymes -> Metabolic Reax (transcription) Bacterial Cell to Metabolic Reaction is The mRNA copy is regulated by feedback inhibition. Genetic Control Mechanisms CAUGCCUGGGCAAUAG 1. Repression (translation) - The regulatory mechanism that inhibits The polypeptide is gene expression and decreases the Met-Pro-Gly-Gln-(stop) The initiating methionine is often removed later, synthesis of enzymes Repressor – block the ability of RNA so not all proteins contain methionine. Comparison of Bacterial and Eukaryotic polymerase to initiate transcription from the Translation repressed gene 2. Induction Bacterial Translation Eukaryotic - The process that turns on the Translation transcription of gene or genes AUG – N- AUG – unformylated - Inducer and inducible enzymes formylmethionine methionine OPERON MODEL OF GENE EXPRESSION Transcription and Transcription inside - Francois Jacob and Jacques Monod translation occur nucleus; translation in - Induction of enzymes of the lactose simultaneously cytoplasm catabolism of E. coli Short-lived mRNA Long-lived mRNA - Structural genes determine the Smaller, less dense Larger, denser structures of the protein ribosomes ribosomes - Control regions are two relatively short Shine-Dalgarno Kozak sequence DNA sequence Promoter – the region of the DNA where RNA Less initiation factors More initiation factors polymerase initiates transcription Shine-Dalgarno Sequence Operator – act as a go and stop signal for - Ribosomal binding site in bacterial transcription of the structural genes messenger RNA Regulatory Gene – encodes repressor proteins that switches and repressible operons on or off. Operon – the site of operator and promoter sites and structural genes Lac Operon – the combination of the three lac and promoter sites and the adjoining regions Lac Operon – inducible operon - In the absence of lactose, the repressor binds to the operator site preventing transcription - If lactose is present, the repressor binds to a metabolite of lactose instead of the  operator, and lactose, digesting - on either side of the promoter are 2 enzymes are transcribed special sequences, the CAP site which Trp Operon binds the activator CAP, and the - Repressible operon operator which binds the lac repressor - Structural genes are transcribed until Lac Z – beta-galactosease they are turned off or repressed - catabolize lactose to galactose or - The structural gene are transcribed and glucose translated leading to tryptophan Lac Y – permease synthesis - enzyme that transports lactose inside of - Excess tryptophan is present, the the cell tryptophan acts as a corepressor Lac A – transacetylase binding to the repressor protein - degrades disaccharides - The repressor protein can now bind to Only Lac Z and Y metabolizes the lactose. the operator stopping tryptophan 1. Lactose is Absent synthesis - the lac repressor protein by default Gene E – code for the production of bound to the operator sequence, thus anthranilate synthase component 1 blocking part of the promoter and Gene D – anthranilate synthase component 2 preventing RNA polymerase from Gene C – anthranilate isomerase binding and initiating transcription of Gene B – tryptophan synthase beta Lac Z, Lac Y, and Lac A genes Gene A – tryptophan synthase alpha - The lac operon is OFF since there is no POSITIVE REGULATION need for these gene products in the - Regulation of lactose operon depends absence of lactose on the level of glucose which in turn No lactose, With Glucose (low cAMP), no controls the intracellular level of the mRNA transcription small molecule cAMP 2. Lactose is Present with Glucose Cyclic Adenosine Monophosphate – is a - Lactose binds to the lac repressor, substrate derived from ATP that serves as a inducing a change in shape that cellular alarm signal prevents its binding the operator - When glucose in no longer available, sequence cAMP accumulates in the cell - With the operator no longer occupied, - cAMP binds to the lac promoter which the RNA polymerase can bind promoter initiates transcription by making it easier and initiate a low level of transcription. for RNA polymerase to bind to the - Since glucose (a preferred energy promoter source) is present, the lac operon is ON - Transcription of the Lac operon requires “low” both the presence of lactose and the With Lactose, With Glucose (low cAMP), low absence of galactose mRNA transcription - cAMP is an alarmone, a chemical alarm 3. Lactose is Present without Glucose signal that promotes a cells response to - The lac repressor is bound by lactose environmental or nutritional stress. and inactive, and low glucose levels Catabolite Repression – the inhibition of activate CAP, a transcriptional activator metabolism of alternative carbon sources by which binds the CAP site and enhances glucose binding of RNA polymerase to the - when glucose is available, the level of promoter cAMP in the cell is low and - Since lactose is a much more important consequently CAP is not bound. source of energy in the absence of Lac Operon of E. coli glucose the lac operon is ON “high” Lac Operon – is a module of 3 genes involves in With Lactose, No Glucose (high cAMP), high lactose metabolism; lac Z, lac Y, and lac A, transcription. that are transcribed In a single mRNA from a cAMp – inducer of CAP single promoter - Regulates the transcription MUTATION 2. FRAMESHIFT MUTATION - Change in the genetic material - Deletion or insertion - A change in the base sequence of DNA - a change in the DNA which one or – sometimes cause a change in the few nucleotide pairs are deleted or product encoded by that gene inserted in the DNA Ex. Gene for enzyme mutates – inactive or - Translational reading frame less active enzyme Results - can be advantageous or lethal a. Incorporation of the wrong amino acid Simple mutations (Neutral) downstream from the mutation - the change in DNA base sequence b. Production of an inactive protein causes no change in the activity of the 3. TRANSPOSONS/ INSERTION SEQUENCE product encoded by the gene. - Jumping genes or transposons can move or - Commonly occur when one nucleotide transfer that may result to frameshift is substituted for another in the DNA at mutation 3rd position of the mRNA codon. 4. SPONTANEOUS MUTATION - Even if the amino acid is charged, the - Combination of base substitution and function of the protein may not change frameshift mutation (nonvital portion of the protein or - Occurs in the absence of any mutation- chemically very similar to the original causing agents amino acid) Mutations result in resistance to antibiotics or MUTATIONS – a change that occur in DNA altered pathogenicity. sequence Example: - either due to mistakes when the DNA is Mutation in a gene encoding the outer copied or as the result of environmental membrane may increase factor. pathogenicity. Transition – from pyrimidine to a pyrimidine; Mutation in a capsule encoding gene purine to purine may result in decreased pathogenicity. Transversion – from purine to pyrimidine and Mutagens – agents in the environment that vice vers directly or indirectly bring about mutations. TYPES OF MUTATION Chemical mutagens 1. BASE SUBSTITUION 1. Nitrous acid - Occurs when one base is inserted in the 2. Nucleoside analog place of another 3. Benzopyrene - Takes place at the time of DNA 4. Aflatoxin replication CAUSES OF MUTATION - It can either be due to: A. Chemical Factors 1. DNA polymerase makes an error 1. Nitrous oxide and alkylating agent alter 2. A mutagens alters the hydrogen existing base bonding of the base Ex. Adenine would no longer pair with a. Missense mutation – a single base is thymine but the tyrosine instead replaced with a different one 2. 5-bromouracil is a base/nucleoside - One different amino acid formed analogue cause from a based substitution - Can be inserted in place of adenine - replacement since adenine and 5-bromouracil have - Example: Sickle cell disease the same structure (glutamic acid ➔ valine) - It can bind guanine with greater b. Nonsense Mutation – a base substitution frequency resulting in a nonsense codon - The antiviral drug iododeoxyuridine acts - Prevent the synthesis of the as a base analogue of thymine complete functional protein. - Antiviral and antitumor drugs (AZT- - Stop codon azidothymidine – primary drugs used to treat HIV infection  3. Benzopyrene – present in smoke and Frequency of mutation soot - mutation rate is the probability that a - binds to existing DNA base and gene will mutate when a cell divides causes frameshift mutation - the rate is expressed as 10 to a negative 4. Aflatoxin – produced by Aspergillus power (1/10000) Flavus – a mold that grows in peanuts - usually occur randomly along a and grains. It causes frameshift mutagen chromosome B. Physical Factors - occur at a very low rate/ very rare due Radiations: to the DNA polymerase I, II, IV, and V a. X-rays and Gamma rays that counterchecks the nitrogenous - Ionize atom and molecules bases - Ion can combine with base in DNA, BACTERIAL GENETIC TRANSFER AND resulting errors in DNA replication RECOMBINATION - Breaks covalent bond in the sugar- Bacterial Recombination - exchange genes phosphate backbone of DNA which between two DNA molecules to form new causes physical breaks in combinations of genes on a chromosomes chromosome Genetic Transfer – result in genetic genes - Penetrating rays of ionizing radiation variation cause electron to pop out of their 1. Vertical Gene Transfer – occur when gne usual shells. These electrons bombard are passed from an organism to its other molecules and cause more offspring damage such as these ions can - Transfer to the next generation combine with base in DNA, resulting in - Plants and animals errors in DNA replication 2. Horizontal Gene Transfer – occurs when b. UV radiation (260nm) genes are passed from an organism to - Causes cross linking of adjacent other organism of the same generation pyrimidine bases to form dimers (bacteria) - Thymine dimers – may cause damage - Intracellular gene transfer or death to the cell - transfer within the same - The effect of direct UV light on DNA generation causes the formation of harmful - Occur in only 1% or less an entire covalent bonds between certain population bases METHODS OF GENE TRANSFER - Enzymes for repair of UV induced damage. - Bacteria can acquire DNA (i.e., a. Photolyases use visible light energy to new genes) in 3 basic ways: separate the dimer back to original. 1. Transformation b. Nucleotide excision repair - Uptake and retention of external DNA - Methylases an enzyme that adds a molecules methyl group to selected bases soon 1) Recipient cell takes up donor DNA after DNA strand is made. 2) Recombination occurs between donor - Enzymes (endonucleases) cut out the DNA and recipient DNA incorrect base and exonuclease 3) Gene transferred from one bacterium to removed the damaged DNA and another as naked DNA DNA polymerase fill in the gap with 4) Transfer of DNA itself from one cell to newly synthesized DNA that is another complementary to the correct strand In nature, dying bacteria may release their of DNA ligase seals the remaining gap DNA, in the lab, DNA is extracted and by joining the old and new DNA. transferred to another bacteria Examples: Xeroderma Pigmentosum Griffith’s Transformation Experiment 3. Transduction - the transfer of DNA between bacteria by a virus 2. Conjugation - Direct transfer of DNA from one The following are encoded by bacteriophages bacterium to another and can be transformed by transduction: Diphtheria, botulinum, cholera and erythrogenic toxins The ability to secrete toxins can be transferred via DNA transduction from one bacterial cell to another Types of Transductions 1. Generalized – occurs when the virus carries a segment from any part of bacterial chromosomes - The bacteriophages can pick up any portion of the host’s genome 2. Specialized – occur when the bacterial virus DNA that has integrated into the cell DNA is excised and carries with it an adjacent part of the cell DNA - Since most lysogenic phages integrate at specific sites in the bacterial DNA, the  adjacent cellular genes that are Conditions: transduced are usually specific to that a. Introduction of normal microbiota into virus unusual site in the body - The bacteriophages pick up only b. Immune suppression specific portion of the host’s DNA c. Changes in the normal microbiota Opportunistic pathogens – ordinarily do not HOST-MICROBE RELATIONSHIP cause disease in their normal habitat in a Historical Information healthy person but may do so in a different Antoni van Leeuwenhoek – discovery of environment. microorganisms - Escherichia coli, Pneumocystis jirovencii, - These microorganisms can cause echoviruses, Neisseria meningitidis, diseases based on Robert Koch’s Streptococcus pneumoniae postulate. Contamination - mere presence of microbes in Germ Theory of Disease – showed Bacillus or on the body anthracis cause anthrax Portals of Entry – sites through which pathogens - Formalized criteria for establishing cause can enter to the body of disease known as Koch’s Postulates Major Pathways Normal Microbiota in Host 1. Skin 1. Resistant Microbiota/Normal Flora 2. Mucous membrane - Are microorganisms that normally reside - Respiratory tracts, breaks in the skin, in the human body through nose or eyes, gastrointestinal - Mostly are commensals tract, urinary and reproductive tract. 2. Transient Microbiota 3. Placenta - May be present for several days, weeks, 4. Parenteral – not a true portal of entry, months and disappear pathogens deposited directly into tissues - Cannot persist in the body because of beneath the skin or mucous membrane a. Competition from other microbes Portals of Exit – means to escape the host b. Elimination by the body’s defense reservoir cells Preferred Portal of Entry c. Chemical or physical changes in the - Many microorganisms can cause body infections only when they gain access Acquisition of Normal Microbiota through their specific portal of entry. - Development in womb free of Salmonella typhi – produce all the signs and microorganisms (axenic) symptoms when swallowed but if rubbed on - Microbiota begin to develop during the skin, no reaction occurs. birthing process Streptococci – when inhaled caused - Much of one’s resident microbiota pneumonia, those that are swallowed do established during first moths of life not produce signs and symptoms. Microbial Antagonism – is the phenomenon Number of Invading Microbes wherein normal microbiota prevent the - Few microbes enter the body, overcome overgrowth of harmful microorganisms by host’s defenses - Candida albicans, Escherichia coli, - Large numbers of microbes gain entry, Clostridium difficile the stage is probably set for disease Pathogens ID50 – infectious dose for 50% of the test - Microorganisms that can cause harm to population its host LD50 – lethal dose of a toxin for 50% of the test 1. Primary – cause disease upon infection population not normally associated with the host Bacillus anthracis – ID50 in skin is 10-50 2. Opportunistic – normal microbiota that endospores, Inhalation is 10,000 – 20,000, and can cause disease under certain ingestion is 250,000 – 1,000,000 endospores conditions Adhesion in Infection - Imbalance between normal microbiota 1. Uses adhesion factors: and pathogenic microbes a. Specialized structures Etiology of Infectious Diseases b. Attachment proteins and adhesins Diseases can be caused by many 2. Creation of Biofilm factors: - Some bacteria attach to each other infection, genetics, degeneration, and others. - Biofilm is a thin membrane secreted by Koch's Postulates bacteria that coats surfaces Developed by Robert Koch in 1877 to establish - It is estimated that biofilms are involved cause of infectious diseases: anthrax and TB in 65% of all human bacterial infection 1. Same pathogen must be present in Adherence every case of the disease. - The attachment of pathogens to their 2. Pathogen must be isolated from host tissues portal of entry. diseased host and grown in pure Adhesin or Ligand – the surface molecules culture. on the pathogens 3. Pathogen from pure culture must cause 1. Streptococcus mutans – glycocalyx, disease when inoculated in healthy, tooth decay, surface of the teeth susceptible laboratory animal. - Has the enzyme glucosyltransferase 4. Pathogen must be isolated from converts glucose into a sticky inoculated animal and shown to be the polysaccharide called dextran. original organism 2. Actinomyces – bacterial cell walls fimbriae adhere to the glycocalyx of S. mutans that causes dental plaque and dental carriers Receptors – complements the adhesin - Mannose is the most common receptor INFECTIOUS DISEASE AND ITS EPIDEMIOLOGY Principles of Epidemiology Term Definition Pathology scientific study of disease Exceptions to Koch’s Postulates Etiology study of the cause of disease 1. Some microbes cannot be cultured in Pathogenesis the manner in which disease artificial media. develops Treponema pallidum (syphillis) Pathogenicity ability of microbes to cause a Mycobacterium leprae (leprosy) disease Ricketsias, chlamydias, and viruses only Virulence degree of pathogenicity multiply within cells. Virulence features of microbes that help 2. One disease may involve several factors it infect and cause disease different Infections – invasion or colonization of pathogens. microbes in the body by pathogenic microbes Diarrhea Pneumonia Invasion – entry and spread throughout Meningitis Peritonitis and Nephritis the cells of host 3. Some pathogens may cause several Colonization – successful occupation of different diseases. new species not normally found in its niche Streptococcus pyogenes: Scarlet fever, Multiplication – ability of microbes to sore throat, skin infections, bone infections, etc. reproduce during infection Mycobacterium tuberculosis: Causes Diseases – abnormal state in which a part or all disease of lungs, skin, bones, and internal parts of the body is capable of performing its organs. function due to external factors or pathogens Difficulties in Satisfying Koch’s Postulate Disease Occurrence 1. Diseases can be caused by more than Disease Incidence: Percentage of population one pathogen that contracts a disease in a given time period. 2. Pathogens that are ignored as potential Disease Prevalence: Percentage of population cause of disease that has the disease during given time period. Ecological Models of Disease Causation 1. Sporadic Disease: Occurs only Host occasionally. Example: Polio in U.S. 2. Endemic Disease: Constantly present in the population. Disease Examples: Common cold or ear infections. Triad 3. Epidemic Disease: Many people acquire disease in short time period. Agent Environmen Examples: Influenza, gonorrhea, chlamydia, Disease Sequence t and AIDS. a. Reservoir of Infection 4. Pandemic Disease: Worldwide b. Transmission to a Susceptible host epidemics. c. Invasion by entering the host Examples: Influenza and AIDS. d. Microbial multiplication Disease Duration e. Pathogenesis causing injury - Acute Disease: develops rapidly, lasts a - The occurrence of disease ultimately short time. depends on the resistance if the host to - E.g., Flu and common cold. the activities of the pathogen - Chronic Disease: develops more slowly, Classifying Infectious Disease and reactions are less severe. Tend to Term Definition recur for long periods or to be continual. Symptoms -any changes in body function - E.g., Tuberculosis, hepatitis B, and -subjective changes infectious mononucleosis. - Subacute Disease: Intermediate Signs objective changes the between acute and chronic. physician can observe and - Subacute bacterial endocarditis measure. (streptococci). Syndrome specific group of symptoms or - Latent Disease: Causative agent signs of a particular remains inactive for a time, but then disease. becomes active and produces disease 1. Communicable Disease – is any disease symptoms. that spreads from one host to another, - E.g., Shingles, genital and oral herpes. either directly or indirectly AIDS. - E.g., chickenpox, measles, genital herpes, typhoid fever, tuberculosis 2. Contagious Diseases - are easily spread from one person to another. - E.g., chickenpox and measles 3. Noncommunicable Disease - is not spread from one host to another. - E.g., Clostridium tetani, produces disease only when it is introduced into the body via abrasions or wound  MIDTERMS GENERAL MICROBIOLOGY 1ST AND PARASITOLOGY SEMESTER HOST DEFENSES PHYSICAL FACTORS MIDTERMS LECTURE 5 1. SKIN ® Extremely important components of the first line of defense TERMS ® Two distinct portions: IMMUNOLOGY is the scientific study of immune systems that serves protection a. Dermis, made up of connective tissue against pathogens b. Epidermis, made up of compact epithelial cells IMMUNE SYSTEM refers to the complex network of organs cells and proteins that ® Periodic shedding of the skin, the dryness of the skin, and normal work together and serves as a defense against infection. microbiota helps remove microbes on the surface IMMUNITY ability of our body to protect inhibition of pathogen/ resistance to 2. MUCOUS MEMBRANES pathogen ® It lines the entire gastrointestinal respiratory, and genitourinary tracts ANTIGEN is any substance that is capable of stimulating the immune response of ® Mucus is a slightly viscous glycoprotein secreted by goblet cells bacteria, fungi, or any foreign substances. 3. LACRIMAL APPARATUS ® A group of structures that manufactures and drains away tears 4. SALIVA CAUSES OF IMMUNITY ® Helps dilute the numbers of microorganisms and washes them from 1. Natural is acquired from exposure of disease (bacterial infection) and allows teeth and gums our body to create antibodies 5. MUCUS 2. Previous attack of the disease ® Traps microorganisms that enter the respiratory and gastrointestinal 3. Artificial means (vaccines) is acquired through the introduction of a killed or tract weakened form of the disease organism through vaccination. 6. EPIGLOTTIS ® Prevent microorganisms from entering lower respiratory tract DEFENSE AGAINST DISEASES 7. URINE Body Defenses ® Prevents microbial colonization in the genitourinary tract ® The body is constantly in contact with bacteria, fungi, and viruses 8. PERISTALSIS, DEFECATION, VOMITING ® The body has two defense systems for foreign materials 1. Nonspecific defense system/ Innate Immunity CHEMICAL FACTORS 2. Specific defense system/ Adaptive Immunity (targets 1. SEBUM specific antigen) ® Contains unsaturated fatty acids which inhibit the growth of pathogenic bacteria and fungi 2. PERSPIRATION ® Contains enzyme capable of breaking down cell walls 3. SALIVA ® Contains salivary amylase, lysozyme. Urea, uric acid, and immunoglobulin A. 4. GASTRIC JUICE ® The high acidity of gastric juice prevents microbial growth in the stomach o Clostridium botulinum o Helicobacter pylori 5. VAGINAL SECRETION a. Glycogen produced by vaginal epithelial cells 1. NONSPECIFIC DEFENSE SYSTEM (INNATE IMMUNITY) b. Cervical mucus 6. URINE ® General response to any antigen ® Has an acid pH of 6 that inhibits microbes ® Defense that are present at birth ® Urea, uric acid, hippuric acid, and indican ® Rapid response to invaders (physical and chemical factors) ® Present and available for protection NORMAL MICROBIOTA AND INNATE IMMUNITY ® Does not involve specific recognition of microbe ® Normal microbiota and host cells relationship help prevent the ® Does not have a memory response (ability of the immune system to overgrowth of pathogens recognize a pathogen) § Normal microbiota in the vagina alters pH preventing population of C. albicans § E. coli produces bacteriocins that inhibit the growth of FIRST LINE DEFENSE Salmonella and Shigella SECOND LINE OF DEFENSE – INTERNAL DEFENSES A. ANTIMICROBIAL SUBSTANCES 1. Interferons ® produced by macrophages, fibroblasts, infected with viruses. ® Terminate replications of viruses 2. Complement system ® Inactive proteins in blood plasma and on plasma membrane ® Causes cytolysis of microbes, promotes phagocytosis, and contributes to inflammation 3. Iron binding proteins ® Reduce the amount of available iron Examples: o Transferrin (found in blood and tissue fluids) o Lactoferrin (found in milk, saliva, and mucus) 1  MIDTERMS GENERAL MICROBIOLOGY 1ST AND PARASITOLOGY SEMESTER o Ferritin (found in liver, spleen, and red bone marrow) T cells o Hemoglobin (found in RBC) ® Cell mediated immunity 4. Antimicrobial proteins (AMPs) B cells ® Short peptides that have a broad spectrum of antimicrobial activity ® Descendants of B cells (plasma cells) produce Mode of action: antibodies 1. Inhibit cell wall synthesis 2. Forming pores to plasma membrane resulting to lysis TYPES OF WBC 3. Destroy DNA and RNA Examples: LEUKOCYTOSIS refers to the explosive increase of WBC Dermcidin are produced by sweat glands LEUKOPENIA is the decrease of WBC Defensins and cathelicidins are produced by 1. Neutrophils: 65-70% (phagocytosis) neutrophils, macrophages and epithelia 2. Lymphocytes: 20-25% (immunoglobulin synthesis; destroy foreign cells) Thrombocidin are produced by platelets 3. Monocytes: 4-8% (phagocytosis) 4. Eosinophils: 2-5% (allergic reaction and parasitic infection) B. NATURAL KILLER CELLS (NK) 5. Basophils: 0-0.5% (increase in person nearing death) ® About 5-10% of lymphocytes in the blood are natural killer cells; also present in spleen, lymph nodes, and red bone marrow PHAGOCYTES Granules of NK cells: Phagocytosis refers to the ingestion of microorganism or other substances by a Perforins cell. This is performed by phagocytes, certain type of leukocyte or WBC and its derivatives. ® Inserts into plasma membrane of target cells and creates channels in the membrane ACTIONS OF PHAGOCYTIC CELLS Granzymes 1. Migration of the infected area ® Protein-digesting enzymes that induce the target cell to undergo 2. Transformation of monocytes apoptosis or self-destruction Fixed macrophages ® This type of attack kills infected cells but not the microbes inside Free macrophages the cells, the released microbes will be destroyed by phagocytes Mononuclear phagocytic system Mechanisms of NK cells 3. Predomination of WBC (neutrophils and macrophages) 1. It attacks body cells that display abnormal or unusual plasma membrane proteins by binding releasing vesicles TYPES OF MACROPHAGES containing toxic substances 1. Fixed Macrophages or Histiocytes 2. Contains perforin, a protein inserted into the plasma ® Resident in certain tissues and organs of the body membrane of the target cells and creates perforations in the Examples: membrane leading to cytolysis (cell burst) a. Kupffer’s cells – liver 3. Release granzymes which are protein digesting enzymes b. Alveolar macrophages – lungs that induce target cell to undergo apoptosis c. Microglial cells – nervous system d. Splenic macrophages – spleen C. PHAGOCYTES e. Peritoneal macrophages – lymph nodes, red bone ® Specialized cells that perform phagocytosis marrow, peritoneal cavity and abdominal organs 2 major types: 2. Free macrophages a. Neutrophil ® Wandering, which roam the tissues and gather at sites of infection b. Macrophages of inflammation 3. Mononuclear phagocytic system FORMED ELEMENTS IN BLOOD ® Various macrophages of the body Blood Plasma MAIN PHASES OF PHAGOCYTOSIS Formed elements 1. CHEMOTAXIS Leukocytes (WBC) ® The process by which phagocytes are attracted to ® 5000-10,000 per µL or mm3 microorganisms 1. Granulocytes (stained) 2. ADHERENCE 1. Neutrophils (PMNs- Polymorphonuclear neutrophils) ® The attachment of phagocyte’s plasma membrane to the surface ® Contains 60-70% of leukocytes of the microorganism. Toll-Like Receptors (TLRs) on a phagocyte ® Functions for phagocytosis adhere to microbial cells’ pathogen associated molecular 2. Basophiles (0.5-1%) patterns (PAMPs). Adherence may be facilitated by opsonization-coating to the microbe with serum protein called ® Responsible for the production of histamine 3. Eosinophils (2-4%) opsonin 3. INGESTION ® Responsible for the production of toxic proteins against certain parasites; some phagocytosis ® Pseudopods meet and fuse surrounding the microorganism with 2. Agranulocytes (stained) a sac called phagosomes or phagocytic vessel 1. Monocytes (3-8%) 4. DIGESTION ® Functions for phagocytosis (when they mature into ® Formation of phagolysosome containing lysosomal enzymes, macrophages) Lysosomal enzymes attack microbial cells directly Lysozyme hydrolyzes peptidoglycan in bacterial cell walls 2. Dendritic cells Lipases, proteases, ribonucleases, deoxyribonuclease ® Derived from monocytes; phagocytosis and initiation hydrolyze other macromolecular components of microorganisms of adaptive immune responses Superoxide radicals, hydrogen peroxide, nitric oxide are 3. Lymphocytes (20-25%) enzymes that can produce toxic oxygen Natural killer (NK) cells ® Destroys target cells by cytolysis and apoptosis 2  MIDTERMS GENERAL MICROBIOLOGY 1ST AND PARASITOLOGY SEMESTER PROCESS OF INFLAMMATION 1. Tissue damage ® parenteral portal of entry 2. Vasodilation and increased permeability of blood vessels ® Vasodilation refers to the dilation of blood vessels that is responsible for the redness (erythema) and heat associated with inflammation MICROBIAL EVASION OF PHAGOCYTOSIS Evasion mechanisms: a. M protein ® Inhibits the attachment of phagocytes to their surface making adherence difficult § Streptococcus pyogenes b. Capsules § Streptococcus pneumoniae, Haemophilus influenza type B c. Leukocidins and Streptolysin ® Kill phagocytes by causing the release of phagocytes own lysosomal enzymes in its cytoplasm § Staphylococcus and Streptococcus d. Pore forming toxins 3. Phagocyte migration and phagocytosis ® Lyse phagocyte cell membranes once inside the phagocyte 4. Tissue repair § Trypanosoma cruzi, Listeria mocytogenes e. Live inside the cell § Coxiella burnetiid – Q fever, requiring the low pH inside a phagolysosome to replicate FUNCTIONS OF INFLAMMATION § Listeria monocytogenes, Shigella, Rickettsia (rocky 1. To destroy the injurious agents and remove its by-products from the body mountain spotted fever, typhus) – have the ability to 2. Limit the effects on the body by confining injurious agents and its by- products escape from phagosome before it fuses with lysosome 3. To repair or replace tissue damaged by the injurious agents or its by-products. § Mycobacterium tuberculosis, HIV, Chlamydia, Leishmania, Plasmodium – prevent both the fusion of DEFENSIVE SUBSTANCES THAT CAUSE VASODILATION AND INCREASE phagosome with lysosome and acidification of digestive PERMEABILITY OF BLOOD VESSELS enzymes Histamine present in mast cells, basophils and blood platelets f. Biofilm formation Kinins present in blood plasma; play a role in chemotaxis by ® EPS (Extracellular Polymeric Substances) attracting phagocytic neutrophils to the injured site Prostaglandins released by damage cells; intensify the effect of histamine and kinins; help phagocytes move thru capillary walls SECOND LINE OF DEFENSE – INTERNAL DEFENSES Leukotrienes produced by mast cells and basophils; cause increased D. INFLAMMATION permeability of blood vessels; help attach phagocytes to ® A bodily local defensive response to cell damage pathogens SIGNS AND SYMPTOMS Cytokines from activated fixed macrophages; bring about vasodilation PAIN due to the release of certain chemicals and increased permeability that help deliver clotting elements REDNESS due to more blood that goes to the affected area to the injured area that prevent microbe from spreading to other area IMMOBILITY results from local loss of function in severe inflammation Pus HEAT due to an increase in blood flow to the affected area ® a mixture of dead cells and body fluids in a cavity formed by breakdown of body tissues TYPES OF INFLAMMATION ® focus infection known as abscess ACUTE INFLAMMATION If the cause of infection is removed in a relatively ® common abscesses are pustules and boils short period of time but intense § Staphylococcus aureus for boil CHRONIC INFLAMMATION The cause of inflammation is difficult or impossible to remove but less intense § Mycobacterium tuberculosis for tuberculosis (a chronic infection) 3  MIDTERMS GENERAL MICROBIOLOGY 1ST AND PARASITOLOGY SEMESTER Toll-like receptors (TLR) STEPS IN THE INFLAMMATORY RESPONSE ® attach to PAMPs (pathogen associated molecular patterns) o induce defensive cells to release cytokines Cytokines ® Proteins that regulate the intensity and duration of responses ® Recruit macrophages, dendritic cells and other defensive cells to isolate and destroy the microbes as part of the inflammatory response ® Activate B and T cells involves in adaptive immunity TWO PROPERTIES DISTINGUISH ADAPTIVE IMMUNITY FROM INNATE: SPECIFICITY for particular foreign molecules (antigen) which involves distinguishing self from non-self MEMORY For previously encountered antigens. This involves lymphocytes called B cells and T cells (named based on where they mature) B cells – bursa equivalent; bone marrow T cells- thymus gland DIFFERENTIATION OF B AND T CELLS SECOND LINE OF DEFENSE – INTERNAL DEFENSES E. FEVER ® abnormally high body temperature that occurs because the hypothalamic thermostat is reset ® commonly occurs during infection and inflammation Functions 1. Intensifies the effect of antiviral interferons 2. Increases production of transferrins that decrease the iron available to microbes 3. Speeds up body reactions thus aid in repair NATURE OF ANTIGENS ® Called as immunogens FEVER AS A DEFENSE AGAINST PATHOGENS ® Either proteins or large polysaccharides 1. Interleukin 1 helps step up production of T cells ® Lipids and nucleic acids are antigenic only when combined with proteins 2. High body temperature intensifies the effect of antiviral interferons or polysaccharides 3. Increases the production of transferrin that decrease the iron available ® Antigenic compounds are often components of invading microbes such to microbes as capsule, cell wall, flagella, fimbriae and toxins of bacteria 4. High temperature speeds up the body’s reaction for tissue repair. ® Non- microbial antigens include pollen, egg white, blood cell surface Hypothalamus molecules, serum proteins from other individuals/species and surface ® Bacterial endotoxins, interleukin-1, and tumor necrosis factor alpha can molecules of transplanted tissues and organs induce fever ® Most antigens have a MW of 10,000 Daltons or higher o Prostaglandins reset the hypothalamic thermostat at Hapten refers to a foreign substance that has a low molecular weight. It is often not higher temperature antigenic unless they are attached to a carrier molecule 2. SPECIFIC RESISTANCE / IMMUNE DEFENSE / ADAPTIVE IMMUNITY ® involves specific response to a specific microbe ® the ability of the body to defend itself against specific invading agents such as bacteria, toxins, viruses, and foreign tissues ® adapts or adjust to handle a specific microbe ® slower response and have a memory component ® responses are activated by protein receptors in the plasma membrane of defensive cells 4  MIDTERMS GENERAL MICROBIOLOGY 1ST AND PARASITOLOGY SEMESTER 3. IgA ® 10-15% of Ab in serum ® Found in sweat, tears, saliva, mucus, milk and GIT secretions so most abundant AB in the body ® Prevent attachment of microbes to mucous membrane ® In mothers milk (colostrum) help prevent infants from GIT infection 4. IgD ® 0.2 % of Ab in serum ® Found in blood, lymph, and on the surfaces of B cells as antigen receptor ® Involved in activation of B cells ® No well-defined function Epitopes / antigenic determinants 5. IgE ® Specific region in antigen that is recognize by antibodies ® 0.0002% of Ab in serum Penicillin ® Located on mast cells and basophils ® A good example of hapten ® Involved in allergic and hypersensitivity reactions ® This drug is not antigenic by itself but some people develop an allergic ® Protection against parasitic worms reaction to it ® When penicillin combines with host proteins, the resulting combined molecule initiates and immune response Cell Mediated Immunity Antibody-Mediated Immunity Globulin Proteins (Humoral) ® relatively soluble 1. T cells directly attack invading 1. B cells transform into plasma cells ® Each antibody has at least two identical sites that bind to epitopes cells which synthesize and secrete known as antigen-binding sites. 2. Effective against: specific proteins called a. Intracellular pathogens antibodies which are inside the cell 2. Works mainly against b. Some cancer cells extracellular pathogens that are in c. Foreign tissue transplants body fluids outside the cells 3. Includes inflammation and 3. Includes antibodies and phagocytosis processes complement system SUBTYPES OF CELL MEDIATED IMMUNITY A. Cytotoxic T killer ® First line of defense for immunity, attacks cells with foreign antigen in their surface causing lysis B. Helper T lymphocytes ® Assist B and other T cells by producing factors or molecules such as lymphokines in response to the presence of antigen C. T Regulatory Cells (Suppressor T Lymphocytes) ® Release chemicals to suppress the activity of T and B cells TYPES OF ANTIBODIES OR IMMUNOGLOBULINS ® Stop the immune response to prevent uncontrolled activity Agglutinins Clump cells ® Combat autoimmunity by suppressing T cells that escape deletion in the thymus Precipitins Precipitate foreign substances Opsonins Paralyze and neutralize cells causing microbes to be clump for phagocytosis FUNCTIONS OF CELLS IN ADAPTIVE IMMUNE RESPONSES Antitoxins Neutralize or counter act bacterial toxins CELL FUNCTIONS Antigen- CLASSES OF IMMUNOGLOBULINS Presenting Cells Processing and presentation of foreign antigens to T cells; 1. IgG (APCs) secretion of interleukin-1, which stimulates secretion of ® Accounts for the 80% of all Ab in serum Macrophages interleukin-2 by helper T cells and induces proliferation of B ® Found in blood, lymph, and intestines cells; secretion of interferons that stimulate T cell growth ® Protect against circulating bacteria and viruses, enhance, Dendritic cell Processes and presents antigen to T cells and B cells; found phagocytosis, neutralize toxins, trigger complement system in mucous membranes, skin, lymph nodes 2. IgM B cell Processes and presents antigen to helper T cells ® Makes up 5-10% of Ab in serum ® Found in lymph and blood LYMPHOCYTES ® Predominant Ab involved in the response of ABO blood grouping Cytotoxic T cell Kills host target cells by releasing granzymes that induce antigens on the surface of RBC apoptosis, perforin that forms channels to cause cytolysis, granulysin that destroys microbes, lymphotoxin that destroys ® First Ab in response to primary infection target cell DNA, gamma-interferon that attracts macrophages ® Short-lived and increases their phagocytic activity, and macrophage ® Causes agglutination and lysis microbes migration inhibition factor that prevents macrophage migration ® Remain in blood vessels without entering tissues since they are from site of infection large 5  MIDTERMS GENERAL MICROBIOLOGY 1ST AND PARASITOLOGY SEMESTER Helper T cell Cooperates with B cells to amplify antibody production by plasma cells and secretes interleukin-2, which stimulates proliferation of T cells and B cells. May secret gamma-IFN and tumor necrosis factor (TNF), which stimulate inflammatory response Memory T cell Remains in lymphatic tissue and recognizes original invading antigens, even years after first encounter B cell Differentiates into antibody-producing plasma cell Plasma cell Descendant of B cells that produces and secretes antibodies Memory B cell Descendant of B cell that remains after immune response and is ready to respond rapidly and forcefully should the same antigen enter body in future 6  MIDTERMS GENERAL MICROBIOLOGY 1ST AND PARASITOLOGY SEMESTER 7