Unit 3 Innate Host Defenses Against Microbial Invasion Flashcards
Immunity can be split into two parts:
Do they work separately or together?
Innate and Adaptive
Together, each with different roles
The study of the components and processes of the immune esystem
Immunology
The immune system distinguishes foreign substances from _______
Self structures
Innate immune defenses are found in all ____ organisms
Multicellular (insects, tiny worms, etc count)
Which provides the first line of defense against microbes, the innate or adaptive immune system?
It provides what type of defense a lot of the time?
The innate
Barriers (doesn’t let microbe in cells)
How does the innate immune system recognize microbes vs. host cells
Biochemical differences
The innate immune defenses can recognize microbes as foreign, but it can’t do what?
So what is the response then?
Determine the precise identity of the microbe
It responds in the same manner for an entire group of similar microbes
This term is used to describe the innate immune defenses, in that they respond to entire groups of microbes in the same manner
Nonspecific Response
Does the innate immune response have memory?
No. It occurs at the same level every time (doesn’t get better over time towards same pathogen)
The innate immune system is always activated
!
This immune defense is only found in vertebrates
Adaptive Immune Defense
This immune defense works with innate responses to achieve a stronger level of defense to provide a much stronger protection than each individually
Is it specific?
Adaptive Immune Defense
Yes
The adaptive immune defense response is mediated by molecules that bind to specific ___
pathogens
After initial exposure, does the adaptive immune defense system retain memory of the response used towards a specific pathogen?
Yes. It can initiate more quickly! Hence, adaptive immunity
This is made by the human as part of the adaptive immune system
this is made by the microbe that is targeted by the adaptive immune system
Anitbody
Antigen
What is the drawback of the adaptive immune defenses?
It is slow to activate the first time.
Why is the skin a barrier to infection
It is inhospitable to foreign microbes
What about the skin makes it so inhospitable for so many microbes?
- Cool, dry, acidic (ph 5.0)
- Dead layer of cells
- provides armor
- A layer of oil on top of the armor
- Sweat provides antimicrobial barrier
- Normal flora can crowd out potential invaders (starve them)
What is the pH of the skin?
What is the oil on the skin called?
Why is sweat toxic?
5.0
Sebum
Salt (hypertonic environment)
Where might a microbe colonize in the skin?
Hair follice, sweat gland, sebaceous gland
This is an interior surface coated with wet mucous that is a barrier to infection
Mucosal Membrane
How does the mucosal membrane prevent microbe attachment?
Moving along the surface
What are the 3 antimicrobial molecules that are contained in the mucosal membrane?
What else contributes to the barrier?
Defensin Proteins
Lysozyme
Lactoferrin
Normal flora crowding out infection
What prevents microbes from moving to underlying tissue if they get passed the mucosal membrane?
Tight junctions between cells. Makes it leak proof
Can water slip in between the tight junctions of underlying tissues of mucous?
No.
What sweep back and forth on the mucosal membrane to cause movement?
Cilia
These antimicrobial substances are proteins that can form pores in bacteria found in mucous. They also have a developmental role by leading to differentiation of cell
Defensin proteins
These antimicrobial substances are found in the mucosal membrane targets cell walls
Lysozyme
This antimicrobial substance is found in mucosal membranes and binds to iron in bacteria
Lactoferrin
Ferrin is a key word
It’s safer to use saliva than tap water for bacteria because tap water sometimes has protozoans that can get in your eye
!
What 4 areas are associated with mucosal membranes
Eye
Digestive Tract
Respiratory Tract
Urogenital Tract
What are the 4 defenses of the eye?
- Filtering by eyelashes
- Lysozyme
- NaCl
- Flushing by tears
What else, not mentioned before. about the respiratory tract prevent microbes from going further into respiratory tract
Nostil Hairs
Loss of upper layers of tissue, occurs in the mouth and small intestine
Desquamanation
What does the urinary tract do to wash off pathogens and lower the count?? Explains why it’s important to be well hydrated
Flushing by urine
Microbes need ____ to grow, we need it for our own cells’ function, and several types of cells make molecules to keep it away from microbes
Iron
These two cells bind oxygen and have an iron component to keep it away from bacteria
Hemoglobin and myoglobin
These iron binding molecule transports iron around the body in plasma
A higher than normal level of it indicates
Transferrin
Infection
This iron bonding molecule is in milk tears and saliva, found in secretions and binds iron
Lactoferrin
This iron binding molecule of the body is in cells and has small amounts present in plasma. It stores iron
Ferritin
This is an important, early physiological response to microbial invasion and damage
Inflammation
Inflammation is triggered by release of proinflammatory molecules such ____ and ___ from local cells
Histamine and cytokines
What are the 4 signs of inflammation
Why is inflammation good?
Redness, heat, swelling, pain
It contains and eliminates pathogens
In the inflammatory response, the first step is
Damaged tissues release this molecule, which communicates to mast cell and basophil (both types of white blood cells)
Bacteria then enter the tissue through it. ___ molecules are released such as histamine, prostaglandins, and serotonin
Tissue damage
bradykinin
Vasodilator Molecules
Bradykinins cause which cells to migrate towards damaged tissue
This causes the release of what molecule via degranulation of these two cell types?
basophil and mast cells
Histamine
What occurs after the release of histadine?
Vasodilation
This term means making blood vessels bigger
This is associated with what symptoms of inflammation
What else occurs? This leads to…
Vasodilation
Redness and heat
Permeability of blood vessels (fluids, clotting factors, opsonization factors) , swelling aka pain
There are two types of phagocytic white blood cells present in inflammation, these occur first
The second wave of white blood cells are these,
Neutrophils
Macrophages
Macrophages are a differentiated phase of
Monocytes
When neutrophils dominate, what phase of inflammation is occurring?
More macrophages is the ___ phase
Acute Phase
Chronic Phase
The three consequences of local inflammation are…
Vasodilation
Extravasation
Increase in vessel permeability
When white blood cells squeeze out of blood cells into surrounding tissues, it is called
These bring in immune cells, like phagocytes, to fight the infection. What are often used to communicate the status of the infection?
Extravasation
Cytokines
What is the goal of inflammation?
Containing the infection
What are the three responses that cytokines can induce?
Fever
Inflammation (attracting more white blood cells.
Further Immune Responses (like the adaptive response)
If inflammation gets out of hand, it can be damaging. Especially when the microbes or their products get into the ____
What two things can they cause
Bloodstream
Septic Shock and Toxic Shock
This response of systemic inflammation is widespread presence of bacteria in the body that induces system wide inflammation
This response is overstimulation of immune responses by bacterial exotoxins (superantigens) in the bloodstream
Septic Shock
Toxic Shock
Death rates of 30-50% are not uncommon when septic or toxic shock set in!
____ and _____ cytokines are potent mediators of systemic inflammation induced by microbes or their products
IL-1 and TNF-α
These are defined as structures found on foreign microbes but NOT on self cells
Pathogen associated molecular patterns (PAMPs)
These are receptors on our cells that can bind PAMPs to begin the responses against them (like lipopolysaccharides or peptidoglycan)
Pattern Recognition receptors (PRRs)
Are PRRs new or old? Why?
They are evolutionarily ancient, found in invertebrates, vertebrates, and plants
Are PRRs specific to individual pathogens or do they associate with groups of pathogens?
They are non specific, recognize common molecules found on entire groups of pathogens
These receptors are a form of PRR found in vertebrates and invertebrates. They recognize PAMP ligands and trigger internal signaling reactions (a cascade) in self cells
They were originally described in what organism’s embryo?
Toll like receptors
Fruit fly embryos
Do toll like receptors bind the same site on a pathogen?
No, lipotechoic acids, Flagella, Lipopeptides, etc can be bound to trigger the cascade which leads to phagocyctosis
These are examples of opsonizing-secreted PRRs that are made by the body on white blood cells.
This one coats the mannose-rich surface of yeasts and bacteria (binds to mannose)
This one binds to phospholipids found in bacterial and fungal plasma membranes
Mannose binding lectin and C-reactive protein
Mannose binding lectin
C-reactive protein
As review, this is defined as the coating of a microbe to enhance destruction or uptake by other cells
Opsonization
What are the two things that can occur after MBL binds to mannose on a bacterial pathogen?
Shape change, receptor can be bind the bacteria and leads to phagocytosis
Activation of complements (cascade) that form pores in the bacterial membrane
C-reactive protein levels can be monitored to tell if there if infection in the body (opsonization factor!)
!
These are defined as a group of 30+ serum proteins that are involved in antimicrobial activities
How many particular complement proteins become activated in the presence of PAMPs?
Activation results in 3 things..
Complements
Nine
- Inflammation (attracting white blood cells)
- Opsonization (enhancing phagocytosis)
- Direct killing by MAC
Three separate methods of activating the complement cascade exist…
Classical
Alternative (evolutionarily older)
Lectin (similar to classical, MBLs are an example)
Antibodies bind what on the microbial cell to trigger the classical complement cascade?
Which two do this?
Antigens
IgG or p IgM
What is the first step of the classical complement system? How many antibodies must it bind?
C1 binds antibody surface complex
It must bind two adjacent antibodies, there must be enough bound antibodies for this to occur.
Once complement protein 1 binds two antibodies, it becomes a protease (cuts proteins), what interacts with it and is ultimately cleaved into two parts
This part is released and attracts white blood cells to the vicinity
This part is going to bind to the antigen
C4 (cleaved into C4a and b)
C4a
C4b
This complement protein is cleaved after C4 by C1
This part flows away to recruit white blood cells
This one binds and attaches to the antibody
C2
C2b
C2a
(opposite to C4a and b)
C4b and C2a work together to form _____ which cleaves C3
This part floats away to attract white blood cells
This part binds near C4b, and C2a
C3 convertase
C3a
C3b
C4b, C2a, and C3b form this white cuts C5
This part is released to attract white blood cells
This part inserts into the membrane
What come in next?
What do these form?
C5 convertase
C5a
C5b
C6, C7, C8, and C9
The membrane attack complex (MAC)
What do MACs do?
Form pores which disrupt osmotic regulation to lyse the bacteria
What alternative can occur with C3b, etc in the complement cascade?
Opsonization
This is another function of a complement, it coats the microbe with activated complement to increase chances for phagocytosis
What molecule in the classical cascade that is the opsonization factor?
If this doesn’t occur, what happens?
Opsonization
C3b
MAC forms
C4a, C2b, C3a, C5a, can also trigger this event
Chemotaxis (white blood cells gobble up pathogens), leave a breadcrumb trail
This can initiate a natural antiviral state, and can also increase activities of antiviral cells. More than 300 genes increase expresion when exposed to them. Even promotes antiviral responses in neighboring cells, or proliferation of natural killer cells.
Type I Interferons
Possible method of future treatment!
Are interferons specific or nonspecific?
Specific
These inteferons interfere with the ribosome binding, degrade RNA, and make changes in membrane components
IFN α/β
What are the three methods that IFN α and β have antiviral effects
Which method leads to apoptosis of the infected cell?
Which affects neighboring cells of the infected cell?
Inhibit ribosome binding (cell protein production) Degrade RNA (prevent viral protein production) Changes membrane components (Block viral attachment and entry)
Ribosome binding
Membrane changes, they are induced in neighboring cells
These are the immune system cells that engulf foreign invaders
What are the 4 types to know
What two ways are they activated?
Phagocytes
Neutrophils
Monocytes
Macrophages
Dendritic
PRRs and cytokine signaling
The monocyte can become two types of phagocytic cells
Macrophage and Dendritic Cell
Monocytes work for innate, adaptive, or both?
What about macrophages and dendritic cells?
Innate only
Both
What is the secondary role of macrophage and dendritic cells?
Antigen Present Cells
___ prior to ingestion enhances uptake
____ granule contents released extracellularly attack invaders without having to phagocyte them
Once the invader is ingested, a complex process takes place to destroy it, often this process involves fusion with ___ and the use of a controlled respiratory burst
Opsonization (not necessary tho!)
Neutrophil
Lysosomes
Once the opsonization factors of phagocytosis bind the receptors of the microbe, they change shape so the phagocyte receptor binds them
!
In phagocytosis, the opsonized microbe binds to phagocyte surface receptors. Cytoplasmic extensions surround and engulf the bound microbe. What forms?
A Phagosome (like an endsosome, its a food vacuole)
Once the phagosome has been formed in phagocytosis, what occurs next?
Next the phagosome fuses with ____ to form _____
_______ and lysosomal _____ kill the microbe
The debris are expelled by ____
Acidification
Lysosome to form phagolysosome
Oxidative Burst (toxic free radicals), lysosomal enzymes (breaks up microbe)
Exycytosis
What cells can do phagocytosis?
Neutrophils
Macrophage
Dendritic cells (only in innate)
Some cells are too big for phagocytosis, like extracellular parasitic worms and fungi. What cells help fight these pathogens by releasing toxic granule contents (degranulation process) near them?
Eosiniophils, basophils, mast cells
Note: basophils and mast cells increase inflammation by releasing histamines
This cell, in contrast to basophils and mast cells turns down inflammatory responses (via degranulation as well)
Eosinophils
This cell is useful for eliminating host cells infected with pathogens
Are they phagocytic?
Natural Killer Cells
No, but they make contact with target cells
What type of cell are NK cells?
Lymphocytes, unique for innate defenses, usually lymphocytes are adaptive
After contact is initiated with NK cells, what are released?
This granule produces a pore structure in target cell plasma membranes
These induce apoptosis
Also are useful for eliminating abnormal self cells aka
Granules
Perforin
Granzymes
Cancer
What initiates necrosis?
What initiates apoptosis?
What does the first step of apoptosis result in
Physical or chemical trauma that damages the cell membrane
Cell signaling occurs
Decreased cell volume
What does the damaged cell membrane in necrosis result in? Two things
Contents of the cell leak into the surrounding tissues
Nearby cells may be damaged by the released cell contents
In apoptosis, what occurs when the cell decreases in volume?
What then occurs?
What digests the apoptitic bodies
Cytosplasmic blebbing and chromatin condensation
DNA fragmentation and the cell is parceled into apoptitic bodies
A phagocytic cell
Which leads to inflammatory responses? Necrosis or Apoptosis?
Therefore which is safer? (used in destruction of webbed feet cell’s, or example)
Necrosis (damaged cell contents are released)
Apoptosis
Normal nucleated cells have a surface molecule that NK cells recognize known as ______, virally infected cells often turn off its expression and cancer cells tend to shut down expression as well
Class I major histocompatibility complex (MHC 1)
It’s the self marker. Explains why twins don’t need to suppress the immune system in organ transplants but others do
Does the NK cell have MCH 1?
Yes, all nucleated body cells have them (not red blood cells)
MHC II must be on the surface of a cell in order for it to be…
Antigen presenting (like macrophages and dendritic cells)
In the binding of a NK cell to a cell, it binds to the cell and it completes the activation signal
In healthy cells, there is a protein on NK cells that can bind to MHC 1 which has what type of effect?
Inhibitory Signaling effect
The cell is released.
In an abnormal cell, there is no ______ so the activation signal is not inhibited
MHC 1
The NK cell kills it.
