Lecture 2-Exam 2 Flashcards
(114 cards)
1
Q
What is a phagocyte and what type of cells are phagocytes?
A
Phagocyte = any cell that carriers out phagocytosis
* Dendritic cell
* Macrophage
* Neutrophil
2
Q
How does phagocytosis work?
A
3
Q
How does MHC 1 and Virses relate?
A
- Viruses are obligate intracellular parasites, which hijack the host cell’s biosynthetic machinery to enable the translation of viral proteins and the replication of the viral genome.
- The major histocompatibility (MHC) class I antigen presentation pathway plays an important role in alerting the immune system to virally infected cells.
- MHC class I molecules are expressed on the cell surface of all nucleated cells and present peptide fragments derived from intracellular proteins.
4
Q
- MHC class II molecules are found only on where?
- Where are the peptides derived from?
A
- MHC Class II molecules are found only on antigen presenting cells such as dendritic cells, monocytes, B cells, macrophages.
- The antigens presented by class II peptides are derived from extracellular proteins (not cytosolic as in MHC class I)
5
Q
How does the loading of the MHC class II molecules occur?
A
Loading of a MHC class II molecule occurs by phagocytosis; extracellular proteins are endocytosed, digested in lysosomes, and the resulting epitopic peptide fragments are loaded onto MHC class II molecules prior to their migration to the cell surface
6
Q
- Once a pathogen or antigen has been identified as foreign, it is marked for destruction in a permanent manner by what?
- Once it is activated it proceeds by what?
A
Once a pathogen or antigen has been identified as foreign, it is marked for destruction in a permanent manner by the complement system. Once activated it proceeds by a series of enzymatic reactions called the classical pathway of complement
Got its name for this system providing proteins to “complement” the antigen-binding function of antibodies
7
Q
Activation of the complement system initiates what?
A
initiates a series of enzymatic reactions in which proteolytic cleavage and activation of successive complement components leads to covalent bonding of complement fragments to pathogen surface
8
Q
Phagocytes have what? What do they recognize and do?
A
Phagocytes have surface receptors that recognize the complement fragments which facilitates the uptake and destruction of complement-coated microbes by neutrophils and macrophages
9
Q
Complements fixed on bacterial surfaces can also initiate what?
A
a complex of proteins that attack the pathogen by poking holes in their cell membranes
10
Q
What are the other two pathways of the complement system?
A
Lectin Pathway:
* mannose-binding lectin binds to pathogen surface, binding a plasma protein to mannose-containing peptidoglycans
Alternative Pathway:
* pathogen surface creates local environment conductive to complement activation, triggered by direct environmental influence of the microbial surface
11
Q
For the complement system, they are initiated by different molecules but what is activated?
A
They are initiated by different molecules but they all activate to generate the same set of effector molecules
12
Q
Complement activation results in three main consequences: Explain
A
- opsonization of pathogens
- the recruitment of inflammatory cells,
- direct killing of pathogens.
13
Q
A
14
Q
Complement components:
* Made where?
* Circulate in what?
* Compromised more than what?
* Many components are what?
* Where does activation take place?
* How can complement components can be grouped?
A
- Made in the liver
- Circulate in plasma
- Compromise more than 30 proteins with a variety of biochemical functions
- Many are enzymes, which are secreted and circulated in the inactive form know as a zymogen (only activated when they reach their destination)
- Activation takes place in the tissues
- Complement components can be grouped on the basis of their function
15
Q
The classical complement cascade is initiated when?
A
when an antibody is bound to multiple sites on a pathogen surface
* Only antibodies IgG and IgM can trigger complement.
16
Q
Which isotype that is the most efficient at activating complement?
A
IgM
17
Q
Why is IgM special?
A
IgM has multiple areas to bind for a stable interaction, which makes it easier to start the beginning reactions
18
Q
_ IgM may activate complement but _ IgG antibodies are needed
A
One and Two
19
Q
For all 3 pathways of complement activation, what is different and what is the same?
A
Differ in the way they are triggered, however all three pathways converge on the same reaction
20
Q
The cleavage of complement component C3 into what? What binds?
A
The cleavage of complement component C3 into C3a and C3b and the covalent bonding of C3b to the pathogens surface
21
Q
What is the most important function of the complement system?
A
Complement fixation
22
Q
- Cells and proteins in the damaged tissue sense the presence of the bacteria and the cells send out soluble proteins called what?
- What do they interact with and what do they cause?
A
Cells and proteins in the damaged tissue sense the presence of the bacteria and the cells send out soluble proteins called cytokines that interact with other cells to trigger the innate immune response of inflammation
23
Q
What is inflammation do to?
A
- Inflammation is not due to the infection itself but to the immunes response to it!
24
Q
What does cytokines induce?
A
- Cytokines induce local dilation of blood capillaries (increased blood flow causes the skin to be warm and red)
25
What does vasodilation introduce? What does it cause?
Cytokines invite what?
* Vasodilation introduces gaps between endothelial cells increasing the leak of blood plasma into the connective tissue (causes edema, swelling)
* Cytokines invite WBC’s to attach to the vascular endothelium and move from the blood to the tissue
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What are inflammatory cells?
WBC’s release substances that contribute to the inflammation
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What are the cons and pros of inflammation?
* **Con**: increased pain, swelling, warmth, ecchymosis.
* **Pro**: the right cells are brought rapidly and in large numbers into the infected tissue
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C3, C4, and C5 can be further cleaved into fragments. The larger fragments continue down what?
the pathway of complement activation to cause inflammation
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What happens to the smaller solube C3a, C4a and C5a fragmenrs?
physiologically active and increase inflammation at the site of complement activation through binding to receptors on several cell types.
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* Sometimes these fragments induce what? Which one is the most potent?
induce anaphylaxis (**C5a is the most potent**, then C3a and C4a) so they are called **anaphylatoxins**
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What happens in anaphylaxis with anaphylatoxins?
* Induce smooth muscle contraction and degranulation of mast cells and basophils, release of histamine, increased capillary permeability
* The increase blood flow and vascular permebility make it easier for antibody, complement proteins, phagocytic cells and lymphocytes to pass out of blood and into site of infection
* Also hastens the passage of pathogen containing antigen presenting cells to the draining lymph noes and initiation of B and T cell response
*** Phagocytes, endothelial cells and mast cells have receptors specific for C5a and C3a**
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What does C5a directly act on? What does it do?
* C5a acts directly on neutrophils and monocytes to increase their adherence to vessel walls and direct their migration towards sites of antigen deposition
* Increases capacity for phagocytosis
| CHEMOATTRACTANT
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The anaphylatoxins act in concert with other complement components to do what?
speed destruction of pathogens by phagocytes
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Prominent cytokines produced by activated macrophages include (what do they do?:
* IL-1
* IL-6
* IL-8
* IL-12
* Tumor necrosis factor-alpha (TNF-alpha)
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Transcription factor nuclear factor-κB (NF-κB):
* What is their role?
* What is the structure of NF-KB?
* plays a pivotal role in orchestrating the inflammatory response
* NF-κB is a heterodimer that normally exists in the cytoplasm of cells
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* Stimuli such as cytokines, viruses, and oxidants induce what?
* NF-κB moves where and does what?
* Stimuli such as cytokines, viruses, and oxidants induce signals that allow NF-κB to dissociate from **IκBα (inhibitor of nuclear factor kappa B),** which is then degraded
* NF-κB moves to the nucleus, where it binds to the DNA of genes for numerous inflammatory mediators, resulting in their increased production and secretion
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What inhibits the activation of NF-KB? How does that happen?
| ⭐️
Corticosteroids inhibit the activation of NF-κB by increasing the production of IκBα, and this is one of their anti-inflammatory action
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What is apart of local inflammation (overview)?
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# Local inflammation
* Cytokine IL-12 activates what?
* Cytokines IL-1 and TNF-alpha facilitates what?
* Cytokine IL-12 activated NK cells (innate immune system) that enter infected site soon after infection
* Cytokines IL-1 and TNF-alpha facilitate entry of neutrophils, NK cells, and other effectors by inducing change in endothelial cells of local blood vessels
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# Local inflammation
* What do macrophages release? What does it contribute to?
* In the course of complement activation, fragments C3a and C5a recruit what?
* Macrophage releases other effector cells such as plasmogin activator, prostaglandins, oxygen radicals, leukotrienes, and platelet activating factor which all contribute to inflammation and tissue damage
* In the course of complement activation, fragments C3a and C5a recruit neutrophils from the blood into the tissue and stimulate mast cells to degranulate, releasing histamine and TNF alpha
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What is apart of systemic inflammation? (overview)
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# systemic inflammation
* In response to TNF-alpha, vascular endothelial cells make what?
* What does this cause?
* make platelet activating factor which triggers blood clotting and blockage of local blood vessels
* This restricts the leakage of plasma from the blood and prevents pathogens from entering the blood and disseminating infection throughout the body
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What happens when alarge amount of bacteria gets into the blood?
macrophages in the liver, spleen and other sites are activated to release TNF-alpha which causes dilation of blood vessels and massive leakage of fluid into tissues throughout the body leading to **septic shock**
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What does septic shock lead to?
Leads to failure of vital organs such as the kidneys, liver, heart, and lungs by lack of normal blood supply/intravascular volume
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Most of the features of acute inflammation continue as the inflammation becomes chronic, including what?
the expansion of blood vessels (vasodilation), increase in blood flow, capillary permeability and migration of neutrophils into the infected tissue through the capillary wall.
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The features of acute inflammation that continue as inflammation becomes chronic which does what to WBCs?
the composition of the white blood cells changes and the macrophages and lymphocytes begin to replace short lived neutrophils
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Thus the hallmarks of chronic inflammation are what?
the infiltration of the primary inflammatory cells such as macrophages, lymphocytes, and plasma cells in the tissue site, producing inflammatory cytokines, growth factors, enzymes and hence contributing to the progression of tissue damage and secondary repair including fibrosis and granuloma formation
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What are is the morality of common chronic inflammation diseases? (5)
| LY
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In some circumstances, certain innocuous molecules stimulate what?
stimulate an adaptive immune response and the development of immunological memory in predisposed members of the population
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On next exposure to the antigen the immune memory produces what?
produces inflammation and tissue damage in varying degrees- simple irritation->life threatening
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What is Hypersensitivity reactions/allergic reactions
over reaction of the immune system to harmless environmental antigens
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What tissues are most commonly exposed to allergens?
mucosa of respiratory and GI tract (airborne inhaled, ingested), and blood and connective tissue (insect bites, skin wounds)
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Over reaction of the Immune system is most common where?
* Most commonly found in people who live in developed countries
* 10-40% of people in developed countries are allergic to one or more environmental antigens
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* What is atopy?
* As a group Atopic people have higher levels of what?
* Is there a genetic basis?
* Atopy- a predisposed state to develop allergies
* As a group Atopic people have higher levels of soluble IgE and circulating eosinophils than nonatopic people.
* Genetic studies have revealed a genetic basis for atopy with involvement of genes on chromosome 5 and 11
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How many hypersensitivty reactions are there? How are they grouped?
4 types of hypersensitivity reactions – grouped according to the effector mechanisms that produce the reaction
* Types I- III are mediated by **antibodies**, while type IV is mediated by **T cell lymphocytes**
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Type I hypersensitivity reaction:
* Results from what? What does the interaction cause?
* Commonly caused by what?
* Effects vary how?
* What is a mast cell?
* What does mast cell degranulation cause?
* results from binding of antigen to antigen specific IgE,
principally on mast cells
* This interaction causes the degranulation of mast cells and release of inflammatory mediators
* Commonly caused by inhaled particulate antigens, ex. Pollen, allergic rhinitis, asthma, anaphylaxis
* Have effects of varying degrees and severity: runny nose à SOB -> anaphylaxis
* **Mast cell – has storage of 50-200 granules – composed of histamine, tumor necrosis factor alpha, neutral proteases and other degradative enzymes and inflammatory mediators**
* Mast cell degranulation recruits eosinophils and basophils
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Mast cells have granules composed of what?
| ⭐️
Mast cell – has storage of 50-200 granules – composed of histamine, tumor necrosis factor alpha, neutral proteases and other degradative enzymes and inflammatory mediators
58
Type II hypersensitivity:
* What is this caused by?
* What are examples?
caused by small molecules that bond covalently to cell surface components of human cells, producing modified structures that are perceived as foreign by the immune system (IgG mediated)
* Example: penicillin, blood transfusion reaction
| Complex
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TypeIII hypersensitivity:
* What is it caused by?
* Where do the complexes go?
* What do the complexes activate?
* What are examples?
* The principle feature that separates type III reactions from other hypersensitivity reactions is what?
* Caused by a small solube immune complexes formed by protein antigens binding to the IgG made against them (igG complex mediated
* These complexes become deposited in the walls of small blood vessels or alveoli in the lungs
* The complexes activate complement and initate an inflammatory response that damages the tissue, impaiting its physiologic function
* Examples: serum sickness, post-streptococcal glomerulonephritis, systemic lupus erythematosus, farmers' lung (hypersensitivity pneumonitis) and RA
* feature that separates typeIII reactions from other hypersensitivity reactions is that in type III reactions, the antigen-antibody complexes are pre-formed in the circulation before their deposition in tissues
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Type IV hypersensitivity:
* What is it caused by?
* When does this reaction happen?
* Degradation of these chemically modified proteins yields what?
* What are examples?
* caused by the products of antigen specific effector T cells, specifically CD4 cells (only a small percentage is caused by CD8)
* This reaction happens when small, reactive lipid soluble molecules pass through cell membranes and bond covalently to intracellular human proteins
* Degradation of these chemically modified proteins yields abnormal peptides that stimulate a cytotoxic T cell response
* Examples: poison ivy, contact dermatitis, chronic asthma
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Eosinophil:
* What are eosinophil?
* Do we have a lot or a little?
* What happens once activated?
* What is their function?
* What is the eosinophil response to host?
* are granulocytes who granules contain arginine rich basic proteins
* Normally only a very small amount of eosinophils are circulating, most are residents in
tissue
* Once activated by external stimuli leads to release of toxic molecules and inflammatory mediators
* Function is to kill invading microorganisms and parasites directly
* The eosinophil response is highly toxic and potentially dangerous to the host (as well as parasites) – there is tight control of the amount of eosinophils, controlled by limiting production in the bone marrow
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What is hypereosinophilia?
elevated eosinophil levels, if higher levels become activated can suffer from heart failure and neuropathy (thought to be due to cytotoxic and neurotoxic proteins released by the eosinophil granules
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Basophils:
* What are they similar to in terms of granules and developmentally?
* High or low numbers in body?
* Recruited to sites of what?
* have granules that are similar to mast cells, but are developmentally more similar to eosinophils
* Normally present in very low numbers in the body
* Recruited into sites of allergic reactions, where it is degranulated by antigen cross linking the IgE bound to the receptor on the basophil surface
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When an allergen enters the bloodstream it can cause what? What can this be called?
can cause widespread activation of the connective tissue mast cells associated with blood vessels, which causes a dangerous hypersensitivity reaction called **systemic anaphylaxis**
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SYSTEMIC ANAPHYLAXIS
* What does disseminated mast cell activation cause?
* What usually causes death?
* What it treatment? How does it work?
* What is the most common cause of systemic anaphylaxis? Why?
* Disseminated mast cell activation causes both an increase in vascular permeability and a widespread constriction of smooth muscle.
* Death is usually caused by asphyxiation due to construction of airways and swelling of the epiglottis
* **Treatment with epinephrine**: stimulates the reformation of tight junctions between endothelial cells, reducing their permeability and prevents fluid loss from the blood, diminishing swelling. Can also relax constricted bronchial smooth muscle
* Most common cause of systemic anaphylaxis is **allergy to penicillin and related antibiotics**
* Beta lactam ring can be opened up to produce conjugates with proteins of the body, creating “foreign” epitopes. B cells ultimately create IgE antibodies which highly react when encountered again
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Allergic Rhinitis:
* When does this happen?
* What is activated?
* What is it characterized by?
* When allergens are inhaled and diffuse across the mucous membrane of the nasal passages
* Activates mucosal mast cells beneath the nasal epithelium
* **Allergic rhinitis** is characterized by local edema leading to obstruction of the nasal airways and nasal discharge, generalized irritation and itching of nose due to histamine release, and sneezing, runny eyes
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Allergic asthma:
* How does it happen?
* What does it cause?
* **Inhaled allergen activating submucosal mast cells in the lower airways of the respiratory tract**
* Causes an increase in mast cell degranulation which leads to **increase in the fluid and mucus being secreted into the respiratory tract and bronchial constriction due to contraction of the smooth muscle surrounding the airways**
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allergic asthma:
* What is it initally caused by?
* Casues what? (symptoms)
* It is initially caused by a response to a specific allergen, but then subsequently develops into chronic inflammation. At that point, **environmental factors other than re- exposure to the specific allergen can trigger asthmatic attacks**
* Causes chronic difficulties in breathing, SOB, wheezing
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Urticaria or hives are what?
allergens that activate mast cells in the skin to release histamine cause raised, red, itchy areas of edema
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A more prolonged allergic response in the skin is observed in what? ⭐️
* What is it characterized by?
* Associated with high levels of what? ⭐️
* Severity does not correlate with what?
atopic dermatitis or eczema
* Characterized by an inflammatory response that causes a chronic itchy skin rash with associated skin eruptions and fluid discharge
* Associated with **high IgE levels**
* Severity does not correlate with amount of exposure
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Where are parasitic helminth infections endemic?
In tropical countries, parasitic helminth infections are endemic, more than 1 billion people worldwide are heavily and persistently infected
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* parasitic helminth infections are mitigated by what?
* Despite the abundance of variety of IgE in their system, people with helminth infections are rarely afflicted by what?
* These infections are mitigated by **CD4 that produce raised levels of IgE**
* Despite the abundance of variety of IgE in their system, people with helminth infections are **rarely afflicted by allergic disease**
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For populations of western Europe and north America, helminth and other parasitic infections have largely been eradicated:
* However, what has increased?
* What is the hygiene hypothesis? ⭐️
* However, the **prevalence of IgE mediated allergy and asthma has steadily increased**
* **“Hygiene hypothesis”** – proposes that this increase has been caused by better hygiene, vaccination to prevent infection, and the increased use of antibiotics and other drugs
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Children are exposed to fewer and less heavy infections than their parents which results in what?
immune systems that are insufficiently used and become less successfully regulated
| Hygiene hypothesis
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* Most antibodies will create immunologic memory cells, but some pathogens can do what?
* What are examples?
Most antibodies will create immunologic memory cells,** but some pathogens can evade such protection by existing as numerous different strains which differ in the antigenic macromolecules on their outer surface**
* **Example**: Streptococcus pneumoniae – bacterium that causes pneumonia
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What is s. pneumoniae?
is a common cause of bacterial pneumonia because its genetic variation prevents individuals from developing an effective immunological memory against all strains
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* Different genetic strains differ in what?
* What are these different strains called?
* Different genetic strains differ in their structure of the capsular polysaccharides and compete with each other to infect humans
* The strains are called **serotypes** because antibody-based serological assays are used to define the differences between them – **there are 90 serotypes for S. pneumoniae**
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After resolution of infection with a particular serotype, what will a person have and not have?
will have antibodies that prevent reinfection with that type, but will not prevent primary infection with another type
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What is a virus that displays genetic variation?
Influenza
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Influenza :
* Infects what?
* Antibodies are made when?
* Pattern of infection with influenza causes what?
* This virus infects epithelia of the respiratory tract and passes easily from one person to another in the
aerosols generated by coughs and sneezes
* Antibodies are made during primary immune response over 1-2 weeks
* Pattern of infection with influenza causes an **epidemic – a situation where a virus spreads rapidly through the population and then quickly subsides**
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What an epidemic?
a situation where a virus spreads rapidly through the population and then quickly subsides
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Influenza:
* RNA virus with genome consisting of what? RNA replication is relatively what?
* An individuals protective immunity against influenza is determined by what?
* This type of evolution of influenza, which causes relatively mild and limited disease epidemics is called what?
* RNA virus with genome consisting of 8 RNA molecules. RNA replication is relatively error prone and generates many point mutations where new viral strains are produced which leads to a lack of protective immunity in the previous epidemic and cause an influenza epidemic the following winter
* An individuals protective immunity against influenza is determined by the strain of virus they were first exposed to- phenomenon called the **“original antigenic sin”**
* This type of evolution of influenza, which causes relatively mild and limited disease epidemics is called **antigenic drift**
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Influenza:
* Every 10-50 years an influenza virus emerges that is what?
* What is widespread spreading called?
* The virus can cause what?
* Every 10-50 years an influenza virus emerges that is structurally quite different from its predecessors and is able to infect almost everyone
* This widespread spreading is referred to as a pandemic
* The virus can cause more severe disease and a greater number of deaths than the viruses seen
with antigenic drift
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Influenza:
* The influenza viruses that cause pandemics are what?
* Usually arises where?
* **The influenza viruses that cause pandemics are recombinant viruses that have some of their RNA genome derived from an avian influenza virus and the remainder from a human influenza virus**
* Usually arises in parts of south-east Asia where farmers live in close proximity to their livestock such as pigs, chickens and ducks
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Herpes virus:
* How does it enter?
* What is the dormant state called?
* Later when the initial immune response has subsided, the virus will what?
* Some viruses are not able to be efficiently cleared with the usual CD8 cytotoxic cells, antibodies, and neutralizing particles
* Herpes virus enters a quiescent state within human cells, **one in which they neither replicate nor generate enough virus derived peptides to signal their presence to cytotoxic T cells.**
* This dormant state is called **latency** and does not cause disease
* Later when the initial immune response has subsided, the virus will reactivate and cause an
episode of disease
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Herpes simplex:
* First infects what?
* The immune response does what to the infection?
* What are various stressors that can reactive the virus?
* After reactivation, the virus travels how?
* first infects the epithelial cells and then spread to sensory neurons serving the area of infection, HSV-1 and HSV-II
* The immune response clears the virus from the epithelium, but the virus persists in a latent state in the sensory neurons.
* Various stressors can reactive the virus- sunlight, bacterial infections, hormonal changes
* After reactivation, the virus travels down the axons of the sensory neurons and re-infects the epithelial tissue
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What is the difference btw HSV 1 and 2
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What is Varicella-Zoster/Shingles
is a herpes virus that causes chickenpox and then stays latent in the dorsal root ganglia. Stress or immunosuppression will reaction the virus which moves down the nerve and infect the skin in that dermatome.
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Epstein-Barr virus:
* What is the difference btw first exposure in children and adults?
* What happens after clearing the infection?
* first exposure in childhood produces a mild cold, whereas adolescents or adults encountering EBV for the first time develop infectious mononucleosis.
* After clearing the infection, the virus remains latent, but is unusual for reactivation, unless patient is severely immunosuppressed
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IMMUNODEFICIENC Y DISEASES:
* Caused by what?
* When was it first described by?
* Most inherited immunodeficiency disease are caused by what?
* Caused by inherited defects in genes for components of the immune system
* Was first described in 1950’s because before then, many babies and young children died from infection
* Most inherited immunodeficiency disease are caused by **recessive mutations** in single genes
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If the recessive defect is located in a gene on the x chromosome, inheritance is what? For males and females?
If the recessive defect is located in a gene on the x chromosome, inheritance of one defective copy of an x-linked gene by a male child is sufficient to cause disease.
* Women have 2 x chromosomes and are able to have one defective and one normal
* X-linked immunodeficiencies are far more common in men than in women
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What is HIV?
an RNA virus within RNA nucleoprotein core surrounded by a lipid envelope derived from the host cell membrane and containing virally encoded envelope proteins
94
HIV:
* What is it an example of?
* Causes what?
* diseases is characterized by what?
* Its an example of a **retrovirus** because these viruses use an RNA genome to direct the synthesis of a DNA intermediate which is **backwards** from that used by most biological entities
* Causes **acquired immune deficiency syndrome (AIDS)** – first described by a physician in the early 1980’s
* Disease is characterized by a massive reduction in the number of **CD4 T cells**, accompanied by severe infections of pathogens that rarely trouble healthy people
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Early versions of that vaccine contained what?
Early versions of that vaccine contained the smallpox virus itself, but many people who received the vaccine were
developing small pox
96
The cowpox virus is called what? What does it cause?
vaccinia and only caused a mild infection in humans, but the immunity produced gave effective protection against smallpox as well as cowpox because the two viruses have some antigens in common
97
Most vaccines used today are composed of what?
preparations of the disease causing virus for which the ability to cause disease has been destroyed or weakened
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What are killed/inactivated virus vaccines? What are examples?
virus particles that have been chemically treated with formalin or physically treated with heat or irradiation so that they are no longer able to replicate
* Example:influenza vaccine,polio vaccine, rabies
99
* What is a live attenuated virus vaccine?
* What are examples?
* Better or worse than killed virus vaccines?
consists of live virus that has mutated so that it has a reduced ability to grow in human cells and is no longer pathogenic to humans
* Example: measles, mumps, polio
* Usually more potent at eliciting protective immunity than killed virus vaccines, most vaccines are of this type
100
* What are subunit vaccines?
* What is an example?
include only the components, or antigens, that best stimulate the immune system. Although this design can make vaccines safer and easier to produce, it often requires the incorporation of adjuvants to elicit a strong protective immune response because the antigens alone are not sufficient to induce adequate long-term immunity.
* Example: Hep B, Shingles, HPV
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Wound healing:
* What does it involve ?
* How is the initial cascade designed to stop bleeding?
* Involves a complex interplay between numerous cell types, cytokines, mediators, and the vascular system.
* The cascade of initial vasoconstriction of blood vessels and platelet aggregation is designed to stop bleeding.
106
Wound Healing:
* After the inital cascade of VC and platelet agg. what is it followed by? What does this cause?
This is followed by an influx of a variety of inflammatory cells, starting with the neutrophil.
* These inflammatory cells, in turn, release a variety of mediators and cytokines to promote angiogenesis, thrombosis, and re-epithelialization.
* The fibroblasts, in turn, lay down extracellular components which will serve as scaffolding
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# INITIAL PHASE OF WOUND HEALING
* The initial phase starts with what?
* What is activated? What do they play a role in?
* What follos the arterial VC?
* What is released and what does this cause?
initial phase starts with an outpouring of lymphatic fluid and blood. It is during this process that adequate hemostasis is achieved.
* Both the **extrinsic and intrinsic coagulation pathways** are activated and play a role in stopping blood loss.
* **Aggregation of platelets** follows the arterial vasoconstriction to the damaged endothelial lining.
* A **release of adenosine 5 ́ diphosphate (ADP) results in the clumping of platelets and initiates the process of thrombosis**. This vasoconstriction is a short-lived process that is soon followed by vasodilation, which allows the influx of white cells and more thrombocytes.
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# INFLAMMATORY PHASE
* The inflammatory phase begins with what?
* Multiple different factors promote what?
* The inflammatory phase begins with hemostasis and chemotaxis. Both the white cells and thrombocytes speed up the inflammatory process by releasing more mediators and cytokines.
* Multiple different factors promote collagen degradation, the transformation of fibroblasts, the growth of new vessels, and re-epithelialization. All of the processes occur at the same time but in a synchronized fashion.
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Inflammatory phase:
* What increases cellular permeability?
* The platelet-derived growth factor attracts what? What does this cause?
* Mediators like serotonin and histamine are released from platelets and increase cellular permeability.
* The platelet-derived growth factor attracts fibroblasts and, along with transforming growth factor, enhances the division and multiplication of fibroblasts. **The fibroblasts, in turn, synthesize collagen.**
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Inflammatory cells, such as neutrophils, monocytes, and endothelial cells, adhere to what? What does neutrophils do?
Inflammatory cells, such as neutrophils, monocytes, and endothelial cells, adhere to a fibrin scaffold formed by platelet activation. **The neutrophils enable phagocytosis of cellular debris and bacteria, allowing for decontamination of the wound**
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# PROLIFERATIVE/GRANULATION PHASE
* By days 5 through 7, the fibroblasts have started to do what?
* Re-epithelialization starts to occur with what?
* What happens initially? Then over time?
* By days 5 through 7, the **fibroblasts have started to lay down new collagen and glycosaminoglycans**. These proteoglycans form the core of the wound and help stabilize the wound.
* Then, **re-epithelialization starts to occur with the migration of cells from the wound periphery and adjacent edges.**
* Initially, only a thin superficial layer of epithelial cells is laid down, but a thicker and more durable layer of cells will bridge the wound over time
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neovascularization occurs through both what?
both **angiogenesis**, forming new blood vessels from existing vessels, and **vasculogenesis**, which is the formation of new vessels from endothelial progenitor cells (EPCs).
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* Once collagen fibers have been laid down on the fibrin framework, the wound starts to do what?
* The wound also begins to contract and is facilitated by what?
* Once collagen fibers have been laid down on the fibrin framework, the wound starts to mature.
* The wound also begins to contract and is facilitated by continued deposition of fibroblasts and myofibroblasts
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# MATURATION/REMODEL PHASE
* Starts when? How long does it last?
* What degrades? Peak when?
* Wound contraction occurs to a much greater extent when?
* The maximal tensile strength of the incision wound occurs when?
* The ultimate resulting scar will never have what?
* Starts around week 3 and can last up to 12 months.
* The excess collagen degrades, and wound contraction also begins to peak around week 3.
* **Wound contraction occurs to a much greater extent in secondary healing than in primary healing.**
* The maximal tensile strength of the incision wound occurs after about 11 to 14 weeks.
* **The ultimate resulting scar will never have 100% of the original strength of the wound and only about 80% of the tensile strength**
