Innate Immune System Flashcards
Learn innate immune system
Sequence the events that occur when a circulating neutrophil enters tissue and phagocytizes a microorganism.
- increased adhesion molecules
- margination
- diapedesis
- chemotaxis
- recognition and attachment
- engulfment and attachment
- formation of phagolysosome
- destruction of the microorganism
What is the difference between a PAMP and a DAMP?
PAMP: molecular pattern associated with pathogenic microorganisms.
DAMP: molecular pattern associated with injured or stressed host cells.
Difference between Opsonins and Cytokines?
Opsonins: molecules that mark antigens for destruction by innate immune cells (MARKERS)
Cytokines: signaling molecules that influence behavior of immune and other types of cells. (SIGNALING)
What is Diapedesis?
passage of blood cells (esp WBC’s) through intact walls and into the surrounding tissue
What happens to the RBC’s (WBCs) that leave by diapedesis into the tissue?
They move by CHEMOTAXIS to the area (of inflammation/invasion) where the chemotactic CYTOKINES are signaling molecules that influence behavior of immune and other types of cells.
PMN means?
Polymorphonuclear Neutrophils
What is the first line of defense against microorganisms.
Anatomic barriers (skin, epithelial linings, etc)
What do NK (Natural Killer) cells do?
eliminate virus-infected cells
Mast Cells do?
Release chemicals (by degranulation) that initiate the inflammatory response
What do Neutrophils do?
Phagocytize microorganisms and cellular debris soon after injury; secrete chemicals (proteins in three types of granules) that call in longer-acting phagocytes. Neutrophils migrate along a chemical gradient (chemicals released by microorganism and site of infection) to get to inflamed area.
What is degranulation?
When a WBC, such as a neutrophil, releases granules from inside themselves that contain a toxic substance to kill an invading pathogen.
Toll-like receptor’s function?
A pattern recognition protein on innate immune cells
Macrophages’ function?
phagocytize pathogens and cellular debris; secrete chemicals that promote tissue healing; activate adaptive immunity
What defends against parasites and degrades vasoactive substances released by mast cells?
Eaosinophils
What substance is released by damaged cells that activates coagulation?
Plasmin
A pattern-recognition protein on innate immune cells.
Toll-like receptor
What is a signaling molecule that attracts WBC’s?
CHEMOKINE (a family of small cytokines)
What is an enzyme that degrades fibrin polymers in clots?
TISSUE FACTOR
What substance is released by damaged cells that activates coagulation.
Plasmin
what does a membrane attack complex cause
cell lysis
What is a membrane attack complex (MAC) formed by?
the activated complement cascade
What are antimicrobial peptides
defensins
proteins that become ACTIVATED in the inflammatory response
kinins
Our innate immune cell can recognize many different types of pathogenic bacteria because it has _____
pattern recognition receptors
Microorganisms that normally colonize the body surfaces are called the normal_______
microbiome
the mast cell is what type of immune cell
non-phagocytic innate
the lymphocyte is what type of immune cell
adaptive
the macrophage is what type of immune cell
phagocytic innate
the neutrophil is what type of immune cell
phagocytic innate
Sequence the steps that occur during acute inflammation.
- Tissue damage
- Vasodilation
- Increased Vascular Permeability
- Leakage of plasma into tissues
- Local edema
- WBC margination and entry into tissues
When fibroblasts migrate into the area of a healing wound, which phagocytic cells secrete chemicals to attract them?
Macrophages
What is the function of fibroblasts that migrate to the area of a healing wound?
secrete collagen that forms the scar
Does wound contraction occur before or after fibroblast migration and proliferation?
After
Natural immunity and native immunity are other terms for ________
Innate immunity
During chronic inflammation, the body may wall off an infectious agent by forming a __________.
granuloma
When each component of the system activates the next in immunity it is called a _________.
cascade, as in a complement cascade (plasma protein system)
A raised scar that extends beyond the original boundaries of the wound is called a ________.
keloid
The pulling apart at the suture line is called
dehiscence
Activated mast cells release ______ inflammatory mediators immediately, and release other inflammatory mediators more slowly after _______ them.
preformed; synthesizing
5 steps of phagocytosis
- recognition and adherence of the phagoctye to its target.
- engulfment (ingestion or endocytosis)
- formation of a phagosome
- fusion of the phagosome with lysosomal granules within the phagocyte.
- destruction of target
what is a member of a special family of cytokines that are chemotactic and primarily attract leukocytes to sites of inflammation?
chemokines, which are synthesized by many cell types, including macrophages, fibroblasts, and endothelial cells, in response to pro-inflammatory cytokines.
Are cytokines pro-inflammatory or anti-inflammatory?
Both, depending on whether they tend to induce or inhibit inflammatory response.
What types of cell is the predominant one needed to kill bacteria in the early stages of inflammation?
Neutrophil
What is the most important cellular ACTIVATOR of the inflammatory response?
Mast cells
What three products are released during degranulation (the release of mast cells’ contents)?
Histamines, chemotactic factors, cytokines
Where are mast cells found?
In loose connective tissue next to blood vessels
Where are basophils found?
in the blood, although they function much like mast cells
What are mast cells filled with?
granules
What does the release of histamine cause?
a. adherence of WBC’s to lining of vessels
b. increased vascular permeability
c. increased blood flow into microcirculation
What are PRR’s and what do they recognize?
Pattern-recognition receptors.
They recognize PAMPS and DAMPS.
Name the 3 Plasma Protein Systems
a. Complement system
b. Clotting System
c. Kinin System
Which plasma protein system eventually stimulates activation of the Membrane Attack Complex?
Complement System
Which plasma protein system eventually stimulates Thrombin and Fibrinogen to form Fibrin and a blood clot?
Clotting System
Which plasma protein system stimulates the production of Bradykinin, which has histamine-like effects?
Kinin System
Which very important cells help connect the innate and acquired immune responses?
Dendritic cells
Name the three major categories of WBC’s.
Granulocytes, Monocytes, Lymphocytes
Monocytes are precursors of what cells?
Macrophages, which they become when they leave the blood vessel for tissue.
Which leukocytes (WBC’s) are granulocytes?
Basophils, Eosinophils, Neutrophils
What cells are Lymphocytes?
Natural Killer cells (innate immune response), and T-cells, B-cells (acquired immune response)
Can inflammation happen in an avascular area?
No, only in blood and tissues near it.
What are the most biologically potent products of the complement system?
C3b or opsonin, and C3a or anaphylatoxin, and C5a (anaphylatoxin chemotactic factor)
What is the 2nd line of defense?
Inflammatory Response
What is in saliva, tears, mucous and perspiration that provides a chemical barrier to invaders?
anti-bacterial peptides
Name 4 antibacterial peptides
Defensins, cathelicidins, collectins, mannose-binding lectin
What do humans take to block the binding of histamines to its receptors, reducing inflammation?
anti-histamines
Name two types of receptors of histamine
H 1 and H 2
Is H 1 pro or anti-inflammatory?
it is pro-inflammatory, and present on bronchial smooth muscles causing them to contract (bronchoconstriction)
Is H 2 pro or anti-inflammatory?
it’s anti-inflammatory, suppressing WBC function, and can be antagonistic to H 1’s effects
Which leukocyte helps regulate the inflammatory response?
Eosinophil
What biologically active substances are released from mast cells?
Histamine, cytokines, chemotactic factors, phospholipase A2.
What biologically active substances result from degranulation of mast cells and the chemotactic factors that come of that?
Neutrophils and Eosinophils get released by Neutrophil chemotactic factors and eosinophil chemotactic factors
What substances are the end result of the synthesis reaction in a mast cell?
prostaglandins, which have vascular effects and induce pain, and leukotrienes, which also have vascular effects, and platelet activating factor which has vascular effect and activates platelets (clotting)
What do histamine and serotonin have in common?
They are vasoactive amines, which are molecules that cause temporary, rapid constriction of smooth muscle and dilation of the postcapillary venules, which results in increased blood flow into the microcirculation.
What other effect does histamine have?
Increased vascular permeability resulting from contraction of endothelial cells lining the capillaries and increased adherence of leukocytes to the endothelium.
Which histamine receptor is proinflammatory?
H1, when histamine binds to this receptor, it promotes inflammation, causing smooth muscles to contract when stimulated (as in bronchoconstriction).
H1 and H2 receptors can be on the same cell? T or F
True, and they can be on many different kinds of cells and act antagonistically.
How does the H2 receptor work in parietal cells of the stomach mucosa?
induces secretion of gastric acid as part of the normal physiology of the stomach
What’s an example of a cell that has both H1 and H2 receptors?
A neutrophil having both, and according to which one is being bound to, either augments neutrophil chemotaxis, or inhibits it.
Prostaglandins (that result of mast cell degranulation) cause increased vascular permeability, neutrophil chemotaxis, and ________________.
Pain by direct effect on nerves.
What cells regulate circulating components of the inflammatory system and maintain normal blood flow by preventing spontaneous activation of platelets and members of the clotting system?
endothelial cells
What other two substances maintain blood flow and pressure and inhibit platelet activation?
Nitric oxide (NO) which is made from arginine, and Prostacyclin, which is made from arachidonic acid.
What is the primary role of most granulocytes (BEN’s), and monocytes/macrophages?
Phagocytosis
Which phagocyte is predominant in the early stages of inflammation?
neutrophil or PMN (polymorphonuclear neutrophil), arriving within 6-12 hrs after initial injury
The primary roles of ______ is the removal of debris and dead cells in sterile lesions, such as burns, and destruction of bacteria in nonsterile lesions.
Neutrophils
What are the two primary roles of eosinophils?
- serve as the body’s primary defense against parasites (in conjunction with antibodies from acquired immune response)
- help regulate vascular mediators released from mast cells by degrading vasoactive molecules, thereby controlling vascular effects of inflammation (put the stop on it or else it would get out of hand)
NOTE: they are only mildly phagocytic
What granulocyte is a key regulator of the acquired immune system and is an important source of IL-4?
Basophils, also the least prevalent granulocytes
What are the largest normal blood cells?
Monocytes
Monoctyes are produced where?
Bone marrow, from where they enter circulation
What large pathogen eaters evolve from monocytes?
Macrophages, which monocytes evolve into when they enter tissue from the bloodstream.
How do neutrophils and macrophages mostly differ?
speed of arrival (neutrophils first), active lifespan (macrophages can divide), chemotactic factors (neutrophils release macrophage chemotactic factors to attract them), enzymatic content of their lysosomes or digestive vacuoles, role in immune response (macrophages activate the acquired immune system), role in wound repair: macrophages activate fibroblasts and promote collage synthesis, so do lots more in that area.
What is the most enigmatic of the granuloctyes?
the basophil, which also is known to act in asthma and allergies but still is being studied for its effects
Macrophage activation results in two subpopulations of cells. Which ones?
M1’s have great bacteria killing capacity while M2’s are primarily involved in healing and repair.
Name some bacteria that can survive granuloctyes AND macrophages, even living in the macrophage.
the bacteria for tuberculosis, leprosy, salmonella, brucellosis, listeriosis, typhoid fever can remain dormant and multiply inside the phagolysosomes of macrophages.
What phagocytic cells are the primary ones in the skin and peripheral organs?
Dendritic cells, which also link the innate and the acquired immune systems, by phagocytizing bacterium and then bringing them via lymph system to T-lymphocyte cells.
The process by which leukocytes and endothelial cells begin expressing molecules that increase adhesion, or stickiness, causing leukocytes to adhere to endothelial cell walls in the vessels is ________________.
Margination (or pavementing)
When leukocyte-endothelial interactions lead to emigration of the cells through the inter-endothelial junctions that have loosened in response to the inflammatory process this is called _________.
Diapedesis
What is directed migration of leukocytes once in the tissue?
Chemotaxis (lead by chemotactic factors)
What greatly enhances adherence by acting as a glue to tighten the affinity of adherence between the phagocyte and the target cell?
Opsonization
What are the most efficient opsonins?
Antibodies and C3b produced by the complement system.
Where are antigens made?
On the surface of bacteria
The surface of _______ contains a variety of specific receptors that will strongly bind to opsonins.
phagocytes
After engulfment (endocytosis) an intracellular phagosome is formed. When that converges with a lysosome, which discharges its contents, what does it create?
Phagolysosome, where destruction of the bacterium is accomplished
Microbe killing mechanisms are oxygen-dependent or oxygen independent?
Both
Oxygen-dependent uses what substance to kill the bacteria?
hydrogen peroxide
Oxygen-independent uses what mechanisms to kill bacteria?
a. acidic pH (3.5-4.0) of phagolysosome
b. cationic proteins that bind and damage cell membrane
c. enzymatic attack of the microorganism cell all by lysozyme and other enzymes
d. inhibition of bacterial growth by lactoferrin binding of iron
What is the main function of natural killer cells?
recognition and destruction of cells infected with viruses, but also abnormal cells and cancer cells, especially in the circulatory system, as opposed to within tissues
NK cells have inhibitory and activating receptors that allow differentiation between infect or tumor cells and _____.
normal cells
name three interrelated steps in process of phagocytosis
- adherence and diapedesis
- tissue invasion by chemotaxis
- phagocytosis
Fever is partially induced by specific cytokines–which ones?
IL-1, released from neutrophils and macrophages
What acts directly on the hypothalamus, in regards to fever?
Pyrogens, which can be endogenous, which are produced by IL-1, or exogenous, which are pathogen-produced
What is it called when there’s an increase in the number of circulating WBC’s?
Leukocytosis
What are plasma-proteins synthesized by the liver in response to inflammation?
Acute-phase reactants, which can be pro or anti-inflammatory
What does common lab tests for inflammation test for?
the number of acute-phase reactants
What is a good indicator of an acute inflammatory response?
Erythrocyte sedimentation (increased adhesion) rate in a tube.
How long does chronic inflammation last?
2 weeks or longer
What is chronic inflammation sometimes preceded by?
an UNSUCCESSFUL acute inflammatory response
What is suppuration?
purulent discharge (pus)
What densely infiltrates during chronic inflammation?
lymphocytes and macrophages
When the body tries to wall off an area of infection because macrophages can’t protect the body against some bacteria, fungi, or parasites, what is that called?
forming of a granuloma (as in TB)
What primarily drives granuloma formation?
TNF a
Some macrophages differentiate into epithelioid cells which specialize in taking up debris and other small particles. T or F
true
Which cells come from macrophages fused into eaters of very large particles?
multinucleated GIANT cells
What cells make up a granuloma?
Giant cells and epithelioid cells surrounded by a wall of lymphocytes.
T or F The granuloma can be encapsulated by collagen and may even become cartilaginous or calcified?
true
During TB infection, what is in the wall of epithelioid cells?
cheeselike proteinaceous center derived from dead and decaying tissue (caseous necrosis) and mycobacteria
What is the conclusion of successful inflammation?
healing and repair
In a good outcome after inflammation, destroyed tissues are capable of _______ .
regeneration, which is the replacement of damaged tissue with healthy tissue, such as occurs in the epithelia of the skin and intestines and in some organs such as the liver
Restoration of healthy tissue is called________.
Resolution and may take up to 2 years. IL-10 appears to play a critical role.
If resolution does not happen, what takes its place?
Repair, which means destroyed tissue is replaced with scar tissue.
What is scar tissue primarily made of?
Collagen, and it does not have the same physiological functions of the healthy tissue it replaced.
Wound healing involves what major processes?
- fill in
- sealing (epilthelialization)
- shrink the wound (contraction)
A clean wound (paper cut, surgical incision) heals mainly by what process?
collagen synthesis
Wound that heal under conditions of minimal tissue loss are said to heal by ________________.
primary intention
In wounds such as decubitus ulcers, which take longer and do not heal easily, how does the healing occur?
through secondary intention
What cells ARE capable of complete mitotic regeneration of the normal tissue (known as compensatory hyperplasia)?
epithelial, hepatic (liver) and bone marrow cells
Can some tissues heal without replacement of cells?
Yes, as in mycardial infarction: the cardiac muscle is replaced with fibrous tissue (scar).
What are the three overlapping phases of wound healing?
- Inflammation
- proliferation and new tissue formation
- remodeling and maturation
What is creation of a new blood supply?
angiogenesis
What is another word for coagulation?
hemostasis
What does one need for good wound healing?
Vitamin C, iron and molecular oxygen (O2).
What cells secrete collagen for wound healing?
fibroblasts
What is the most abundant protein in the body?
collagen
What specialized cells contribute to wound contraction?
myofibroblasts, which have features of both smooth muscle cells and fibroblasts
How long after injury is contraction noticeable?
6-12 days after
T or F Wound contraction is necessary for closure of all wounds, especially those that heal by secondary intention.
true
Ischemic tissue is deprived of ________?
oxygen
Ischemic tissue is prone to cellular death and _________.
infection
What three things does ischemia reduce?
- energy production
- collagen production
- tensile strength of regenerating connective tissue
What other things can delay wound healing?
- obesity
- excessive bleeding or not enough blood to the area
- excessive fibrin deposition (adhesions)
- wound infection
- poor nutrition (metabolic needs increase)
- medication
- dysfunctional collagen synthesis, excessive as in a keloid or hypertrophic scar
When the wound pulls apart at the suture line that is called?
Dehiscence
When does dehiscence occur?
Usually 5-12 days when collagen synthesis is at peak
What increases the risk for dehiscence occurring?
strain, often caused by obesity (adipose doesn’t suture well), and infection
What is performed to relieve internal contractures?
surgery
Can contracture happen in cirrhosis of the liver?
Yes, and it can contribute to the constriction of blood flow and to the development of portal hypertension and esophageal varices (which cause blood vomiting).
What can be used to overcome excessive skin contractures?
ROM exercises, proper positioning, and surgery
Can anti-inflammatory drugs reduce healing success in general?
yes
T or F Cesarean-born newborns have reduced gut microbial diversity.
true
