Lecture 13 - Innate Immunity Flashcards
what is innate immunity?
the first and second line of defenses against invaders
what are the two arms of the immune system that work together?
- Innate immunity: immediate defenses; 1st and 2nd line defenses.
- Adaptive immunity: delayed defense; 3rd line defenses. It is developed when you have an infection, and it is not innate.
how do the two arms of the immune system work together?
they work together against foregin invaders with the help of cytokines
what are cytokines?
they are chemical communication signals that promote immune functions
what are the hallmarks/characteristics of innate immunity?
-First and second-line defense
-Inborn immunity: present since birth.
-Initial, immediate defenses against foreign invaders.
-Same responses regardless of the invader: non-specific.
-Same responses regardless of the number of exposures: no memory.
if the barrier is breached in first-line defense, what happens next?
second line defenses are used and kicked in
how are second-line defenses used/kicked in?
-They are kicked in by recognizing pathogen-associated molecular patterns (PAMPs) or microbe-associated molecular patterns (MAMPs) on foreign invaders using pattern recognition receptors (PRRs) on sentinel cells; example: toll-like receptors (TLRs) on phagocytes.
are second-line defenses specific?
they are partially specific; which is about 20 PAMPs
what do PRR’s do?
PRRs detect PAMPs or MAMPs and make a response
what are the two components of innate immunity?
first-line defenses and second-line defenses
what are the components of first-line defenses?
Skin and mucous membranes
what are the 3 barriers at surfaces under first-line defenses?
- Physical
- Chemical
- Biological
what are the two physical barriers of first-line defenses?
-Skin
-Mucous membranes
what are the two layers of the skin?
-Dermis: tough and durable bottom layer
-Epidermis: multi-layers thick top layer
what does the epidermis consist of?
The topmost layer made of dead cells filled with keratin - a water-proof protein that keeps the skin dry
what are the skin’s flushing actions in first-line defenses?
Trying to wash away the invaders by:
-Dead cells flake off, taking away the attached invaders.
-Sweat falls off, carrying away invaders
in the physical barrier of mucous membranes within the first-line defense, what does it line and produce?
Mucous membranes line “tubes” and eyes. They produce sticky mucus that traps and flushes out the invaders.
what are the flushing actions of the mucous membranes?
- Eyes: tears
- Digestive tract:
- Saliva (washes away invaders from mouth/teeth).
- Peristalsis (rhythmic contraction and relaxation of muscles that pushes the invaders toward and out of the anus).
- Vomiting and diarrhea (ways to purge out invaders during infection). - Respiratory tract:
- Mucociliary escalator (cilia push the mucus up away from the lungs and towards the throat and finally the anus).
- Coughing and sneezing (ways to purge out invaders during infection). - Urogenital tract:
- Urination
- Genital secretions
what are the chemical barriers in first-line defense?
They are chemicals that inhibit or kill microbes by secreting antimicrobial chemicals.
what things do the chemical barriers secrete?
-Enzymes (ex: lysozyme in tears, saliva, mucus, sweat, and breastmilk. It breaks down PG wall).
-Salt (in sweat)
-Acids (in stomach and vagina)
-Antimicrobial peptides (ex: defensins)
-Iron-binding proteins (ex: lactoferrin in saliva, mucus, breastmilk, phagocytes, hide away iron from invaders. They bind to iron to keep it away from the invaders).
what are the biological barriers in first-line defense?
The normal microbiota (flora):
-It covers all binding sites with mucus, so the invaders cannot attach.
-Compete for nutrients
-It makes antimicrobial chemicals
-Alters pH, O2, and other parameters.
what are the outcomes of physical + chemical + biological surface barriers?
they are strategically placed to prevent the invasion of deeper tissues
which of the following is NOT a first-line defense in the innate immune system?
1. Mucociliary escalator
2. Skin microbiota
3. Stomach acid
4. Fever
- Fever
what are the components of second-line defenses?
Leukocytes (WBCs)
Protein substances
Inflammation
Fever
what are two kinds of leukocytes?
granulocytes and agranulocytes
what is hematopoiesis?
the formation of blood cells
what do all blood cells arise from?
all blood cells arise from stem cells in the bone marrow
what are the 3 types of granulocytes?
-Neutrophils
-Basophils (in blood) and Mast cells (in tissues)
-Eosinophils
what are the 2 types of agranulocytes?
-Lymphocytes
-Monocytes
what do granulocytes contain?
Cytoplasmic granules
what are neutrophils?
-The most numerous WBCs
what do neutrophils function as?
they function as phagocytes
how many nuclei are in neutrophils?
the nucleus is 3-5 lobed
how do the granules stain in neutrophils? what do they contain?
Granules stain light purple; they contain digestive enzymes and antimicrobials (defensins, etc.)
where are neutrophils located? where do they migrate to during infection?
they are in blood and migrate to tissues during infection
where are basophils and mast cells located? how common are they? what is their function?
-Basophils are in blood and Mast cells are in tissues.
-They are the least common in blood.
-Their function is in inflammatory responses including allergies
what are the granules stained like in basophils and mast cells? what does it contain?
The granules are dark-staining; they contain histamines and other pro-inflammatory mediators
how common are eosinophils? what is their function?
-They are not very common in blood
-They function in parasite control and allergies
what are the granules staining in eosinophils?
bright red staining
do agranulocytes contain granules?
no
what are lymphocytes?
they are the smallest WBC and have a big nucleus in moon-shaped cytoplasm
what are the two types of lymphocytes?
-B cells and T cells: involved in adaptive immunity.
-NK cells: (natural killer) kill abnormal body cells like cancer cells or virally-infected cells.
what are monocytes?
they are the largest WBC and have a kidney-bean-shaped nucleus
where do monocytes circulate in?
in blood
what do monocytes differentiate into when they enter tissues?
they differentiate into sentinel cells when they enter tissues
what are two types of sentinel cells that monocytes differentiate into when they enter tissues?
-Macrophages: phagocytes; slower acting than neutrophils but last longer
-Dendritic cells: phagocytes; scouts for adaptive immune system
what are resident macrophages in tissues?
Agranulocytes, they act as scouts for foreign invaders and detect them
what is the mnemonic device to help us remember the frequency of leukocytes in blood?
Never (neutrophils - most common)
Let (lymphocytes)
Monkeys (monocytes)
Eat (eosinophils)
Bananas (basophils - least common)
what is phagocytosis?
it is the outcome of leukocytes acting as a second-line defense.
It is the phagocytosis of bacteria, fungi, etc. (neutrophils, macrophages, and dendritic cells).
what are the steps of phagocytosis?
-Chemotaxis via cytokines
-Recognition and attachment via receptors
-Engulfment via pseudopods into phagosome
-Formation of phagolysosome via fusion of phagosome with lysosome
-Digestion and killing (lysosomal enzymes and acids & toxic oxygen free radicals)
-Removal of waste via exocytosis
what are the outcomes of leukocytes performing second-line defense?
-Extracellular destruction (neutrophils, macrophages): spray the infected area with digestive enzymes and antimicrobials
-Promotion of inflammation (basophils, mast cells)
-Destruction of virus-infected and cancer cells (NK cells)
-Destruction of parasites, modulation of inflammation (eosinophils)
what are the 3 protein substances that aid in second-line defense?
- AMPs
- IFNs
- Complement proteins
what are AMPs?
Antimicrobial peptides; they are proteins made by the skin, mucous membranes, and blood cells. Example: defensins are antimicrobial peptides that poke holes in the membranes of invaders.
do AMPs have a broad spectrum of activity? what does that mean?
Yes, AMPs have a broad spectrum of activity - meaning they can munch holes in all the membranes
is there resistance in AMPs?
no resistance observed
what are the outcomes of AMPs?
-Kills foreign invaders
-Stimulate/activate immune responses
what are IFNs?
Interferons; they are cytokines made by virus-infected cells
what are the outcomes of IFNs?
It prevents viral replication in infected neighboring cells
what are IFNs used for?
for treating viral infection
what are IFNs secreted from? what do they do?
they are secreted from infected cells, and they go to other cells to warn they about the pathogens
what is the IFNs role?
Inhibits Viral Replication
what are complement proteins?
they are a series of C proteins in blood and tissue fluids
are complement proteins active or inactive?
complement proteins are present in inactive form
when are complement proteins activated?
they are activated when they bind to pathogens or by the adaptive immune system
what are the 3 outcomes of the complement system?
- MACs (Membrane Attack Complexes)
- Opsonization
- Inflammation
what happens in MACs outcome in the complement system?
Lysis of foreign cells via Membrane Attack Complexes (MACs) - which punch holes in the cell membrane which causes lysis.
what happens during opsonization in the complement system?
It coats bacterial cells, tagging them for destruction by phagocytes.
is inflammation a local or systemic response?
local
what are the series of events during inflammation? what triggers it?
It is triggered by microbes and tissue damage.
1. Resident macrophages (sentinel cells - PRR) detect PAMPs on invaders.
2. Pro-inflammatory mediators are released by macrophages and damaged cells, including:
-Histamine
-Prostaglandins
-Leukotrienes
3. Vasodilation occurs - the widening of blood vessels causing more blood flow. (Causes redness, heat).
4. Increase in vascular permeability causing the influx of leukocytes, fluid containing complement proteins, abs, clotting factors, etc. (Causes swelling and pain).
5. Phagocyte diapedesis: the neutrophils enter, then monocytes enter and differentiate into macrophages. Both perform phagocytosis of invaders.
5. Phagocyte and microbial death cause pus (abscess; which is just clumps of dead cells, host cell, etc.)
6. Clearing of debris and waste is done by macrophages.
7. Blood clots are made to prevent the spread.
what are the outcomes of inflammation?
-Destroys the invader
-Localizes the response
-Restores function
which phagocyte is the first to get to the infection during inflammation?
Neutrophils
in the outcomes of inflammation, would the same responses be beneficial if they were chronic? or system-wide?
** septic shock?
is fever a local or systemic response?
systemic
what is a normal body temperature (BT)? what does this mean?
37 degrees celsius; this means the hypothalamus is regulated
during a fever, in an infection, cytokines called ____ are released by macrophages?
pyrogens; an examples is IL-4
what do pyrogens stimulate the release of?
pyrogens stimulate the release of prostaglandins in the brain which set the “thermostat” higher. Pyrogens go to out blood then to our brain.
what are the outcomes of a fever?
-Microbes inhibited
-Body defenses accelerated - production of more lymphocytes, etc.
should all fevers be treated?
-If its a low-grade fever, it is usually better to let it run its course.
-It is is an old person, a young child, or a high-grade fever it is usually better to treat it.
which second line of defense triggers vasodilation and diapedesis?
Inflammation
what is important about interferons?
cytokines secreted by virus-infected cells that diffuse to neighboring cells and prepare them so that the virus cannot replicate in them.
summarize the complement system.
series of C proteins in blood and tissue fluids that
come together to cause the following outcomes:
- Cell lysis - C proteins form MACs or membrane attack complexes, which insert into membranes of invaders poking big holes and causing cell lysis.
- Opsonization - C proteins coat invader surfaces and tag them for destruction by phagocytes.
- Promote inflammation
The mucociliary escalator is part of the body’s first line of defense against invasion. Its function is to:
1. Kill bacteria
2. Remove foreign invaders from body cavities
3. Phagocytize organisms and debris
4. Sweep microorganisms away from the lower respiratory tract
5. Provide a chemical barrier to infection
- Sweep microorganisms away from the lower respiratory tract
Which of the following cells represents a lymphocyte used in innate immunity?
1. T cell
2. Macrophage
3. Natural killer (NK) cell
4. Neutrophil
5. B cell
- Natural killer (NK) cell
Following digestion and killing of a microorganism by phagocytes, the debris is excreted by:
1. Exocytosis
2. Engulfment
3. Chemotaxis
4. Budding
5. Diapedesis
- Exocytosis
All of the following are true about the complement cascade except:
1. It may be activated via exposure to microbes
2. It comprises many different C proteins
3. It can result in the formation of the MAC (membrane attack complex)
4. It is part of the body’s innate defenses
5. It decreases inflammation at an injury site
- It decreases inflammation at an injury site
When pyrogens are released by leukocytes and bacteria, this specifically leads to:
1. Fever
2. Inflammation
3. Complement cascade
4. Release of defensins
5. Phagocyte recognition and attachment
- Fever
In medical labs, hematologists perform differential white blood cell counts on blood samples to see if the percentage of each leukocyte type is within the normal range. Different leukocytes can increase or decrease in various diseases. What information might a neutrophilia (increased neutrophils) provide about a patient? A monocytosis (increased monocytes)?
Answer: The results of a differential white blood cell count can be used to narrow the possible causes and even look at the course of the disease. Remember that neutrophils are the first cells to the area of infection/inflammation. Macrophages are formed when blood monocytes migrate out into the tissues and differentiate into macrophages. They come in after neutrophils and not only kill pathogens but also clean up cellular debris. Since neutrophils and macrophages are both phagocytes, they destroy foreign materials, especially bacteria. The patient likely has an inflammatory response caused by a bacterial infection (although other types of infection and inflammatory triggers cannot be ruled out).
Which is not a component of innate immunity?
1. Inflammation
2. Fever
3. Antibody
4. Mucous membrane
5. Skin
- Antibody
A group of interacting serum proteins that provide a nonspecific defense mechanism is …..
complement
Interferons function to make cells…
1. Lyse when exposed to a virus
2. Prevent viral replication
3. Resistant to phagocytosis
4. non-motile when infected with virus.
5. form endospores
- Prevent viral replication
The first kind of leukocyte lured to the site of inflammation is the….
neutrophil
Please select the correct sequence for the steps of phagocytosis:
- Conditions in the phagosome change, increasing its antimicrobial activities.
- The phagocytic cell binds microbial invaders and engulfs them, internalizing them in a phagosome.
- Phagocytic cells are recruited to the site of an injury by chemoattractants.
- Within the phagolysosome, various factors work together to destroy an engulfed invader.
- The phagosome fuses with enzyme-filled lysosomes, forming a phagolysosome.
3, 2, 1, 5, 4
