Exam I Flashcards
majority of Ab in circulation, unique ability to cross mammalian placenta (passive immunity)
IgG
expressed on surface of naive B cells, only Ab made when see infection for primary immune response
IgM
Ab in allergic reactions and parasitic infections
IgE
less common than IgM
IgD
found in mucosal areas, most produced per day in adult
IgA
antigen that elicits immune response
immunogen
Ag that induces immunological tolerance or immune non-responsiveness
tolerogen
Ag that causes immediate hypersensitivity reaction
allergen
cross-reactivity
between Ab and Ag generated against a diff but similar Ag
differences between gram negative and positive cell envelopes
\+ = thick PDG, teichoic acid, small periplasmic space, no outer membrane or LPS - = thin PDG, no teichoic acid, outer membrane, LPS
transporters that move iron across outer membrane
TonB recepter (gram - only)- transfers iron siderophore complex
transporters that move iron across plasma/inner membrane
ABC transporters
gram positive cell wall
thick, lots PDG and teichoic acids
gram negative cell wall
thin, little PDG, b/t PM and OM in periplasmic space
hair like filaments ached to PM, function to attach to surfaces
pili (fimbriae)
types of specialized pili
F-pilus = sex pilus, exchange DNA b/t G- via conjugation
Type IV pilus = produced by pathogenic bacteria, adhere to host cell and inject virulence effector molecules
categories of metabolic reactions
fueling - generate energy, reducing agents and precursor metabolites
biosynthetic - use precursor metabolites to form macromolecules
polymerization - macromolecule synthesis
assembly - localization of macromolecules into cellular compartments
3 fueling reaction pathways
glycolytic, pentose phosphate, krebs
terminal e- acceptors of anaerobic respiration
Fe3+, SO42-, NO3-
types of mobile genetic elements
transposons, IS elements, plasmids
extrachromosomal, circular, self replicating DNA fragments
plasmids
mediate own transfer from cell to cell or species to species
- responsible for spread of antibiotic resistance
conjugative plasmid
What do plasmids and conjugative plasmids always have in structure
O of R, antibiotic resistance gene, restriction enzyme recognition site
What do plasmids sometimes have in structure
origin of transfer, other genes
advantages of plasmid
selective advantage, pathogenic ability
What are transposable elements
excise themselves from chromosome or plasmid and insert into another chromosome or plasmid
IS element structure
transposes gene flanked by inverted repeats
Non composite transposon structure
transposes + accessory genes; flanked by in repeats
composite transposon structure
accessory genes, flanked by 2 IS elements
advantages of transposition
disadvantages
- selective advantage and pathogenic virulence
- can knockout imp/essential/virulence genes
one way transfer of genetic material between bacterial cells through sex pilus
conjugation
what does TRA genes encode?
sex pilus proteins, proteins that fuse to membrane and surface exclusion proteins to prevent mating
direct uptake of naked DNA from environment by competent cells
transformation
What makes cell competent?
ability of bacterium to take up DNA directly from environment (induced by DNA damaging stress)
advantages of transformation
disadvantages
- DNA damage repair, selective advantage, pathogenic virulence
- possible gene activation or loss
transfer of DNA between bacterial cells by phage
transduction
options for linear DNA once acquired by bacterium (homologous recombination)
naked DNA -> transformation
transduced DNA -> incorporated into chromosome or plasmid
requirement for homologous recombination
large area, Rec A protein
Fur regulation (negative repressible operon)
iron = co-repressor
fur = repressor
High iron -> iron binds fur -> fur binds fur-box -> blocks transcription
Low iron -> promotor site free -> transcription -> express siderophore
alternative sigma factors
allow bacteria to alter gene expression in response to extracellular stress signals
components of 2 component regulatory system
component 1 = sensory histidine kinase
- detects signal -> autophosphorylates in response to signal -> transfers phosphoryl group to component 2
component 2 = response regulator
- gets phosphorylated -> activates or represses transcription
roles of normal human microbiota
exclude pathogens, prime immune system, aid in nutrition
skin defenses
skin lipids and fatty acids, conjunctiva/eye mucous membrane secretes lysozyme, digest cell wall
where are the highest bacterial levels in skin
moist areas, staphylococci, propionibacterium all over skin
mouth bacteria
streptococci
throat bacteria, stomach, small intestine, colon
neisseria, H.pylori, streptococci E.coli and clostridium, E coli
nostrils bacteria, nasopharynx, lower respiratory tract
S aureus, S pneumo N meningitidis Haemophilus, transient bacteria due to cilia
vagina bacteria, puberty, menopause, bladder
staphylococci, lactobacilli, lactobacilli, sterile except lower 1 cm
Where are virulence genes found in a cell?
pathogenicity islands, plasmid encoded (virulence plasmids), transposon, prophage
quorum sensing
system of cell to cell communication where bacteria monitor density of population to synchronize behavior to accomplish task
signaling molecule in gram - QS
acyl homoserine lactone (produced by LuxI)
receptor/response regulator in gram - QS
Lux R -detects AHL -> turns on expression of virulence genes
signaling molecule in gram + QS
oligopeptide - transported out of cell
receptor and response regulator in gram + QS
receptor = on cell surface regulator = transcription activator
How do non phagocytic bacteria survive once invade host?
lyse and escape vacuole -> replicate and infect adj cells
how do phagocytic cells survive once invade host?
lyse phagosome -> escape into cytosol -> replicate OR
remain in phagosome -> replicate -> prevent lysosome binding and block oxidative bursts
Types of immune evasion by bacteria
hide, cell envelope modification, effector molecule, mimicry
What is a biofilm?
organized multicellular community of bacteria
biofilm formation
planktonic bacteria in fluid environment -> attach to living or inert surface -> multiply -> reach particular density and secrete exopolysaccharide -> grow to mushroom shape
Active dispersal of biofilm
enzymatic degradation of polysaccharide matrix
passive dispersal of biofilm
sloughing off or breaking off
Advantages of biofilm
resistant to antimicrobials, host defenses, and mechanical removal, pool nutritional resources and traps addition nutrients from fluid
How is intracellular iron bound?
by ferritin or Hemoglobin
how is extracellular iron bound?
by transferrin
What does iron bind after RBC lysis?
haptoglobin and hemopexin
What does iron bind during infection
lactoferrin extracellularly
Sources of iron for bacteria
receptors already mentioned, siderophores, and hemophores
How has host cell adapted to bacterial siderophores?
Bacterial response?
produce siderocalin (Sn) -> binds to siderophore receptors so iron can't bind - bacteria produce stealth siderophores that prevent Sn binding
Severe systemic response, interaction of bacterial components with macrophages, characterized by hemodynamic derangement and multiple organ failure
sepsis
Most often cause of sepsis
endogenous infections of peritoneum, urinary tract and upper respiratory tract
features of hemodynamic derangement
decrease BP, increased cardiac output, low organ movement
modes of inhibiting cell wall synthesis
ALL bactericidal
- inhibit PDG synthesis
- disrupt translocation of PDG to cell wall
- district PDG cross links
Modes of inhibiting nucleic acid synthesis
ALL bactericidal
- inhibit DNA gyrase or topoisomerase
- produce cytotoxic int to damage DNA
- bind RNAP, prevent transcription
Mode of inhibiting protein synthesis
- irreversibly bind 30S ribosomal unit (bactericidal)
- block tRNA binding to 30S (bacteriostatic)
- bind peptide transferase component of 50S, blocking peptide elongation (bacteriostatic)
- bind 50S preventing ribosome movement (bacteriostatic)
Modes of inhibiting essential folate synthesis
ALL bacteriostatic
- inhibit dihydrofolate reductase preventing folic acid synthesis
- compete for incorporations into folic acid synthesis reaction
Modes of damaging cell membrane
ALL bactericidal
- cationic detergent like activity, permeabilize cells, contents leak out
3 types of antibiotic resistance
modifications of antibiotic, preventing antibiotic from reaching target, modification of target
When does somatic recombination (VDJ) occur and where?
in bone marrow during maturation
When does central tolerance occur?
maturation - checks to see if B cells are recognizing self antigens
When does somatic hypermutation occur and where?
lymph in differentiation
When does affinity maturation, peripheral tolerance and isotope witching occur?
differentiation
3 signal model of Td B cell activation
recognize antigen -> internalize and present on MHC -> B-T conjugate, linked recognition and CD40 costimulatory molecule interaction -> cytokine stimulation -> B cell differentiation
linked recognition
reduces likelihood that autoreactive B cell will be activated
- B and T cell epitopes must be present on same macromolecular structure or in same pathogen
lymphoid follicle vs germinal center
follicles are present in context of lymph nodes -> follicular dendritic cells trap ag on cell surface to stimulate B cell differentiation -> 1˚ follicle converted to 2˚/ germinal center
somatic hypermutation
random point mutation that occur in V region of Ab
Function of plasma cells
secrete Ab, neutralization and opsonization, APC to T cells
Which Ab is active in the primary immune response? secondary?
IgM
IgG
4 effector functions of AB
neutralization
classical complement activation - Fc region exposed from binding C1q and MAC
opsonization - Ab enhance recognition by phagocytic cells
Ab-dependent cell mediated cytotoxicity - destroy large pathogens, release granulocytes to destroy (NK cells and esosinophils)
Which effector functions of Ab are FcR mediated and isotope dependent?
classical complement activation is isotope dependent
opsonization and Ab-dependent cell-mediated cytotoxicity are both FcR mediated and isotope dependent
components of BCR
non-covalent assoc between membrane bound Ig and transmembrane Iga/IgB heterodimer = BCR
Somatic recombination
gene rearrangement, NOT Ag driven, occurs during B cell development in bone marrow
- H chain = VDJ while L chain is only VJ
Junctional diversity
imprecise joining of gene segments
- deletion of nucleotides, add P/N nucleotides during VDJ rearrangement
What are CDRs?
located on V regions of H/L chains, shortenings stretched of 5-7 aa separated by “framework” regions
- provide diversity for Ig to recognize molecules
Linear vs conformation epitope
linear = recognized by linear sequence aa conformational = 3D shape (most Ab recognize)
strength of non covalent assoc b/t one Ag binding site and antigenic epitope
affinity
overall strength of binding b/t multivalent Ab and Ag
avidity
results when 1 epitope shared by 2 Ag or 2 epitopes on separate Ag are similar in structure
cross-reactivity
2 examines of extracellular bacteria
strep. pneumonia and aeruginose and staphylococcus aureus
Endotoxin vs Exotoxin
endotoxin = lipid portions of LPS molecules within gram - cell wall, release when bacterial cell damaged, activate macrophages and induce cytokine production exotoxin = toxic proteins secreted by gram + or -
types of phagocytosis
type I = use PRR to bind PAMPs
type II = use opsonic receptors, more efficient
2 types intracellular bacteria
mycobacterium tuberculosis and listeria monocytogenes
Which type of immune mechanism is predominant in extracellular killing of bacteria?
cell mediated rather than Ab
Good effects of inflammation
dilution of toxins, entry of Ab, fibrin formation, delivery of nutrients and O2, stimulation of immune response
Harmful effects of inflammation
persistant cytokne release, destruction of normal tissues, swelling, inappropriate inflammatory response
prostaglandins and nitric oxide
vasodilation
histamine, bradykinin, complement leukotrienes, prostaglandins, O2 free radicals
increase vascular permeability
IL, leukotriene, complement
chemotaxis
complement, IL, platelet activating factor
lysosomal granule release
complement
phagocytosis
IL, TNF-a, prostaglandins
fever
prostaglandins, bradykinin, histamine
pain
lysosomal enzymes, O2 free radical, nitric oxides
tissue damage
granulomatous inflammation
distinctive pattern of chronic inflammation with focal collection of macrophages
2 types of outcomes after inflammation
resolution and fibrosis
variables affecting repair after inflammation
infection, nutrition, anti-inflammatory drugs, mechanical variables, vascular disease, tissue type, degree of exudate removal, regulation of cell proliferation
4 steps of leukocyte migration
1) tethering rolling: slow LC down
2) integrin activation: chemokine act on rolling LC increasing integrin affinity
3) adherence: cytoskeleton rearrangement
4) migration through endothelium
2 types of adhesins
chemokine = expressed on LC integrin = expressed on endothelial cells
MALT type I mucosa
simple columnar or pseudo stratified columnar, organized lymphoid structures (lungs, gut, uterus, urethra)
MALT type II mucosa
stratified squamous epithelial cells , lack organization (mouth, vagina, nose, middle ear)
inductive vs effector sites
inductive = encounter Ag 1st effector = dispatch LC
2 major sections of GALT
epithelium and lamina propria (lymphoid follicles in LP)
What is the main IG present in mucosal sites?
SIgA
3 components of SALT
epidermis, dermis, hypodermis
dendritic cells of skin
langerhan’s cells (APC)
What do TLR recognize?
LPS, not found in host cell
- TLR tells nucleus to make Type I interferons
What do Type I interferons do? TNF a/b?
prevent infection from occurring, TNF a/b are two classes of type I interferons that inhibit viral replication and protein synthesis
Receptors on phagocytes?
N-foryml-methionyl, mannose and scavenger
What happens when have DAMPS
phagocytosis increases
What do all TLR result in the production of?
inflammatory cytokines
What do intracellular TLR produce?
Type I IFN
What do cytokines induce formation of?
reactive endothelium
What are the 3 parts of LPS?
lipid A: anchors substrate, toxic
O-antigen: Ab target, outermost region
core polysaccharide: short chain uncommon sugars, highly conserved
