(I) Lecture 2: Innate Immunity Part I Flashcards
Pathogens and Innate immunity
Most pathogens are effectively stopped by innate immunity at an early stage
Deficiencies in innate defenses are very RARE
Key Properties of Innate Immunity
- very fast (minutes/hours)
- low specificity (recognizes general molecular patterns)
- germline encoded (born with it) –> limited diversity (every progeny has the same receptors)
- no memory (non adaptive = same response w/ each exposure)
- very good at it. RARELY FAILS
- innate immunity has the same speed of rxn and same magnitude despite re-exposure WHILE adaptive starts earlier and has higher magnitude w/ re-exposure
The Skin
- epidermis (top layer) and dermis is below
epidermis is made up of
- corneal layer (a keratin “shield”)
- keratinocytes (specialized epithelial cells)
Epithelial cells protect us from the outside world (they line points of entry in digestive and respiratory tracts)
Respiratory Tract
lined with cilia and goblet cell
epithelia in respiratory tract is coated w/ mucus (barrier to keep things from coming in and vector for flow of substances
Goblet cells
specialized epithelial cells that secrete mucin (main component of mucus) to form the mucous barrier which keep resp. tract moist AND guards from pathogens
keep things away from the cell + keep things moving flushing through system
Cilia
sweep microbes and debris up and out of the airways
Lung of a person w/ CF
cilia is collapsed w/ thicker, granular mucus that is dried
allows for bacterial infection
Mucocilliary Clearance (MCC)
- CF patients are either missing the CFTR gene or have mutations to the gene = thicker mucus and cilia collapse = NO mucocilliary clearance
perfect for opportunistic pathogens
Gastro-Intestinal Tract
Goblet cells and Paneth cells
Paneth cells
cells that make antimicrobial peptides (defenses) that inhibit/kill microbes
Epithelial Tissue Types
Shapes: cuboidal, squamous, columnar
Simple: single layer
Stratified: multiple layers
Key Properties of Epithelial Cells
- tight junctions btwn cells (prevents pathogens from “squeezing” inside the tissue) – also keeps things from leaking out
- regeneration (rapidly divide to replace dying cells)
- desquamation (shedding helps remove attached pathogens)
- secretions (ex. mucins/mucus MCC, and chemical defenses) – Goblet cells make secretions
Leaky Gut Syndrome
Loss of barrier integrity/dysfunction of intestinal epithelial cell tight junctions – allow things to leak out and toxins to come in
Common in inflammatory bowel disease and ulcerative colitis
Increased permeability and triggers inflammation
Gram-positive and gram-negative bacteria
Gram-positive bacteria only have a cell membrane and a thick layer of exposed peptidoglycan
Gram-negative bacteria have a double membrane (cell + outer membranes) = encloses thinner layer of peptidoglycan
Chemical Defenses
- secreted by epithelial cells
- can be microbicidal (kill microbe) or microbiostatic (prevent its growth)
Lysozyme
In tears, breastmilk and sweat
Glycosidase that breaks peptidoglycan
More effective against gram-positive bacteria b/c peptidoglycan layer is exposed
Antimicrobial peptides
- chemical defenses
- produced by immune cells or by epithelial cells
- short cationic (+ charge) peptides are attracted to neg. charge phospholipid bilayer
- disrupt cell membrane integrity (bacteria, fungi, viruses)
- humans make up to 21 diff. defensins
- ex. defensins, cathelicidins, histatins
Microbiota vs microbiome
Microbiota: organisms
Microbiome: organisms + genes (specialized for each location)
Mechanical barriers
- expel, flush out
- sneeze, cough, cilia, peristalsis (vomit, diarrhea)
- secretions: saliva, tears, urine, sweat, ear wzx
- mucus (goblet cells)
Chemical barriers
- fatty acids (skin)
- enzymes: lysozyme (saliva, sweat, tears), pepsin (gut)
- low pH (stomach)
- antimicrobial peptides (not just from epithelial cells)
Biological barriers
- microbiota (bacteria, viruses, yeast, etc.)
- products
Microbiome
Every surface (potential entry point of pathogen) has a microbiome
- every microbiota is ADAPTED to its unique environment (different in different parts of the body)
- vary from person to person (but less than variation in anatomical locations)
- essential to our health (absence of bacteria = immune defects)
- shifts RAPIDLY during first months of life (changes based on delivery mode, diet (breastmilk vs formula), solids)
Crohn’s disease
- inflammatory bowel disease
- chronic inflammation of GI tract (indigestion)
- cause remains unknown
Characteristics
- dysregulated immune system
- altered microbiota
- genetic susceptibility
- environmental factors
Gut Microbiome
Helps w/ digestion but also keeps pathogens away
- gut has a lot of commensal bacteria (healthy) and antibiotics kill many of the healthy bacteria
- C. difficle is a common infection after antibiotics that produces toxins (good bacteria that keep pathogens out are wiped out)
- After Covid, ppl can have diarrhea after (COV-2 virus can cause microbial imbalance in the body, which allows opportunistic pathogens to colonize the gut)
Microbial dysbiosis
imbalance of the gut microbiota
Opportunistic Pathogens
- pathogens cause disease in healthy indivduals
- “opportunistic” pathogens cause disease only under SPECIAL CIRCUMSTANCES (ex. immunocompromised, injured, pregnancy)
- ex. E. Coli, C. diff, Staphylococcus, Listeria)
Skin barriers
Mechanical
- epithelial cells joined by tight junctions
- longitudinal flow of air/fluid
Chemical
- fatty acids
- beta-defensins
Gut barriers
Mechanical
- epithelial cells joined by tight junctions
- longitudinal flow of air/fluid
Chemical
- low pH
- enzymes (pepsin)
- alpha defensins
Lung barriers
Mechanical
- epithelial cells joined by tight junctions
- MCC (mucociliary clearance)
Chemical
- pulmonary surfactant
Eyes/nose/oral cavity barriers
Mechanical
- epithelial cells joined by tight junctions
- tears
- nasal cilia
Chemical
- enzymes in tears and saliva (lysozyme)
Mucus-binding membrane proteins
Make pathogens more resistant to being cleared out w/ mechanical forces to get closer to cells
UPEC
bacteria that adheres to surface of epithelial cells of urinary tract – cause UTI
produce pili that allow them to attach
Extracellular phase
ALL pathogens have an extracellular phase
sites of infection
- interstitial spaces, blood, lymph, epithelial surfaces
Intracellular phase
only SOME pathogens have an intracellular phase
sites of infection
- cytoplasmic, vesicular
Bacteria
- prokaryotic cells
- can REPLICATE on their own (binary fission)
- most bacteria live exclusively EXTRAcellularly
- some also survive intracellularly (have both extra and intracellular phase)
Viruses
- non cellular
- CANNOT replicate on their own
- need to infect a host to use their machinery for replication
- all viruses have BOTH an extra and intracellular phase
Types of immune system barriers
mechanical, chemical and biological
True or False
Innate immunity specificity is germline-encoded
True
Important features of epithelial cells
- form tight junctions
- shed to release pathogens
- secrete antimicrobial peptides
- secrete mucus
The microbiome protects us against pathogens by:
- competing w/ other bacteria for nutrients
- forming a protective layer over epithelial cells
True or False
All bacteria have an intracellular life cycle
False
Most only have an extracellular
