Flashcards in Core Principles Deck (112):
What are the two major roles of the immune system?
1. Host defense against microbial invaders (bacteria, virus, fungi)
2. Defense against harmful assaults leading to trauma (tissue damage, environmental irritants, ionizing radiation)
When facing invasion by infection, what does the immune system recognize and differentiate between?
When there needs to be wound healing or regulation of body homeostasis, what does the immune system recognize?
1. Self and non-self
2. Danger signals which are self substances released from the tissue to signal damage or aberrant metabolism
What is by far the most important role of the immune system?
Defense against microbes
What is the first line of defense against immune threats?
What is the time frame?
What 2 actions does it usually involve?
When did this defense arise evolutionarily?
The innate immune system - immediate response
It usually involves:
1. inflammation to sterilize the body and block the assault by "walling off" the injury
2. Activates downstream host defenses including adaptive immunity
Innate immune system appeared early in evolution (amoeba)
What is the second line of defense in the immune system?
What is the time frame?
What is different between this systems sensing mechanisms from those of the first line of defense?
When did it develop evolutionarily?
1. Adaptive immune system
2. If microorganisms break through innate immune system, adaptive will respond but will be delayed
3. The sensing mechanisms are more focused and specific
4. Arose in jawed vertebrates (present in frogs and fish)
What system allows us to develop memory?
What is the benefit of memory?
The adaptive immune system allows for the development of memory and it allows us to respond more rapidly and effectively to a subsequent attack by the same invader
What genetic factor is the hallmark of the mammalian immune system?
How does it arise?
Polymorphism - variability of genes encoding immune components in different populations
It arises from selective pressures exerted by fast evolving pathogens in distinct geographical regions
What is the major consequence of of polymorphism in genes encoding immune response?
High variable pattern in how different species and different individuals within the same species respond to pathogens
What would be a negative feature of having too powerful of an immunity against foreign invaders?
There is a greater chance for "friendly fire" against "self" which can damage the host.
What percent of people in the world die of infectious disease?
1/4 or 25.9%
What were the three big infectious diseases of the past that caused global pandemics?
Smallpox, tuberculosis, plague
Even if the human immune system is healthy, what can cause it to fail?
The subversion of the microbe (adapting and mutating to enhance survival and dodge detection)
What are the top 6 infectious disease killers of 2002?
Which are caused by a single agent?
1. Lower respiratory
2. HIV/AIDS- single agent
4. TB- single agent
5. Malaria- single agent
6. Measles, pertussis, tetanus
What were the three most life threatening diseases of the us in 2008?
(influenza -8, sepsis-10)
What two major initiatives drastically reduced the prevalence of infectious disease related deaths?
1. Improved sanitation
2. Vaccination programs
How many cancers are caused by the failure of the body to eradicate a virus, bacteria or parasite?
What are the three most common pathogenic causes?
Helicobacter pylori- gastric
Hepatitis B and C- liver
HPV- mainly cervical but can affect other areas (female or male)
Healthy inflammation plays a role in what three things?
1. Wound healing
2. Tissue regeneration
3. Regulation of metabolic pathways (after pathogen induced or external trauma)
What is an immune privileged site?
Tissue that does not regenerate like the eye, brain, testes or maternal-fetal interface
So it is extra important for the immune system to work in these areas
What are the six main ways our immune system can fail?
2. Acute inflammation and sepsis
3. Chronic inflammation
4. Autoinflammatory Disease
6. Autoimmune disease
What is an immunodeficiency?
What age groups experience this and why?
What non-age related factors can cause it?
When one or more components of the immune system is absent or reduced.
Newborns/children- immaturity of the system
Diet, stress, radiation, cancer, genetics
What is the major example of pathogen acquired immunodeficiency?
What is the major example of inherited immunodeficiency?
SCID- bubble boy disease
What causes sepsis?
What can it lead to?
When an infectious organism escapes the infected tissue and spreads through blood circulation and lymphatics to overwhelm the host.
It can lead to organ dysfunction.
10th leading cause of death in the world
What causes inflammation to be chronic?
Why is chronic inflammation harmful to the host?
What two actions does it do simultaneously?
1. Persistence of the pathogen in the host
2. It leads to a shift in cell type at the site of inflammation and produces harmful mediators
3. It destroys tissue and regenerates/scars
What are the 5 non-immunological disorders listed that may be caused by chronic inflammation?
1. Atherosclerosis- immune inflammation leads to the initiation, progression and thrombotic complications
2. Obesity and type 2 diabetes- excess adipose triggers inflammation
3. Cancer- proliferation, survival and migration of neoplasms
4. Depression- stress and alcohol activate the innate immune system
5. Acute inflammation promotes muscle growth , but chronic inflammation promotes muscle loss
What is autoinflammatory disease?
What normally causes it?
How does it differ from autoimmune disease?
Autoinflammatory disease is where the innate immune system turns against self for unknown reasons (without an intruder).
It is caused by a strong genetic component and can be neonatal.
It differs from autoimmune disease because autoimmune disease is when the adaptive immune system attacks self.
What is autoimmune disease?
What are the most common in the US?
What is the cause?
Does it affect more men or women?
When the adaptive immune pathways recognize and damage self instead of "non-self".
Hypo and hyperthyroidism, rheumatoid arthritis, vitiligo, type 1 diabetes, mult. Sclerosis, lupus, myasthenia gravis
Strong genetic influence- affects more women than men
What is hypersensitivity?
Inappropriate response to foreign or self-derived antigens that can lead to self-damage independent of the antigen
What is type 1 hypersensitivity mediated by?
What are examples of reactions?
Respond to allergens like hay fever, asthma, food allergies
What is type 2 hypersensitivity mediated by?
What does it react to?
Responds to blood transfusions
What is type 3 hypersensitivity mediated by?
What does it respond to?
Immune complex mediated
Responds to serum sickness, SLE
What is type 4 hypersensitivity mediated by?
what can it also be called?
What does it respond to?
Delayed type hypersensitivity because it takes time to develop
Graft-rejection, dermatitis, most auto-immune disorders
Which hypersensitivity is associated with autoimmune disorders?
Type 4 although there can be aspects of other types
What are the three listed examples of immunomodulatory drugs?
3. Monoclonal antibodies
What are examples of anti-inflammatories?
Aspirin, ibuprofen, Tylenol, acetaminophen, roids
When would you use an immunosuppressant drug?
Transplants and grafts (anything where there would be implication of autoimmune, auto inflammatory, or hypersensitivity)
What are the 6 current challenges listed for immunology?
1. Vaccine development
2. Vaccine implementation
3. Treatment and prevention of rare diseases
4. Transplantations (organ and marrow) and stopping rejection of grafts
5. Personalized medicine to the patients specific polymorphic immune system
6. Monoclonal antibody reagents for diagnosis
How many Nobel prizes have been in immunology?
What was Dr. Beutler's prize for?
Activation of innate immunity regarding the dendritic cell
What bacteria caused the bubonic plague? How was it nearly eradicated?
Yersinia Pestis- essentially eradicated by improved sanitation
What type of pathogen caused smallpox?
What observation led to Edward Jenner's discoveries?
Milkmaids who had been infected by cowpox were not susceptible ("immune") to smallpox outbreaks
How did Jenner test his hypothesis about acquired immunity?
He inoculated a 12 year old boy with scrapings from a cowpox lesion and the boy developed one "cowpox" at the site of the lesion.
Next, he inoculated the boy with scrapings from a smallpox lesion and found the boy did not develop the disease = acquired immunity.
What was a negative consequence of Jenner's study?
Physicians started inoculating patients with mildly virulent smallpox with the hopes that the people would become resistant to more severe cases of the smallpox later.
Obviously, some of these patients got very severe cases.
What are the names of the smallpox and cowpox viruses?
Why is cowpox able to serve as an attenuated virus of smallpox?
The have similar antigens thus making them able to elicit an adaptive response from the immune system
Cowpox and Smallpox viruses are perceived by the immune system as a combination of ___________and produce ________ to structurally bind to them. This allows them to generate ______________.
antigens; antibodies;acquired immunity
What was Lois Pasteurs theory and what was he able to create vaccines for?
Germ theory (germs arise from other germs)
Anthrax and rabies
Who was responsible for developing a set of postulates for demonstrating that an organism causes infectious disease?
What pathogenic microorganisms did he work with?
Cholera, tuberculosis and anthrax
What were the three steps taken in von Behring, Kitasato and Ehrlichs discovery of passive immunization?
1. Attenuate strains of pathogen to make less toxic forms
2. Inject attenuated strain into healthy animal --> Still healthy; inject unattenuated strain--> animal dies
3. Do multiple injections of the attenuated strain into an animal, take that animals plasma (anti-serum) and inject into an animal that had been infected with the virulent strain--> stopped the second animal from getting sick
Why did Erlich decide to inject the animal multiple times with attenuated serum instead of just once?
To build up a lot of antibodies
What made von Behring and Erlichs study different from Jenners?
They found that if they injected the plasma from an immune animal, it was capable of protecting a naive animal from pathogenic Diphtheria.
jWhat pathogen did Jenner research?
What pathogen did Erlich and von Behring do research on?
What is the process of transfering plasma or serum from an animal injected with an attenuated pathogen to a naive animal to protect the second from virulent strains of the pathogen?
What were some of the side effects for serum therapy (passive immunization) discovered by von Behring?
1. not consistently protective
2. effective for a short period of time
3. high frequency of side effects (serum sickness)
What diseases processes are still treated by passive immunization (serum therapy) today?
3. snake bites (venom)
What was Landsteiner's major contribution to immunology?
Characterization of blood group antigens
He analyzed protein structure to define what parts of the antigen bound to the antibody.
Describe the steps in Landsteiner's experimentation for antibody-antigen specificity.
1. covalently attached synthesized chemical compounds to horse serum proteins
2. Immunized a rabbit with these protein derivatives multiple times to generate a strong antibody response
3. Took the antibodies and tested them in lab assays to check specificity
What were the results of Landsteiner's study regarding chicken and horse serum?
Antibodies develop in response to small structural components of the serum (epitope) and not in response to the overall protein structures in the serum.
Rabbit antibodies developed in response to horse meta sulfate epitopes were more likely to bind to chicken serum with meta sulfate epitopes than horse serum with different structural features.
What is an epitope?
the small chemical structure of an antigen that is specifically bound by an antibody molecule.
Antibodies bind to molecules based on what two criteria?
1. the epitope
2. the position of the antigen on the molecule
What is a "conjugate" vaccine and who developed the idea?
A conjugate vaccine uses derivatized proteins as the antigens to elicit and antibody response.
This is much safer and more efficient than using serum therapy.
What did Porter and Edelman discover?
The structure of antibodies
How did Porter and Edelman elucidate the structure of antibodies?
1. immunized rabbits multiple times to elicit production of large amounts of antibodies
2. assayed the antibodies to known antigens
3. Isolated fragments of antibody using chemical and enzymatic degradation (pepsin and papain)
How are the light and heavy chains bound in the antibody?
What are the two major regions of the antibody?
variable region (light and heavy)
constant region ( heavy)
Where are the antigen binding sites on the antibody?
the N-terminal region of one heavy and one light chain in the variable region
What body system is the source of immunity?
What cells produce antibodies?
What two facts needed to be accounted for about the production of antibodies?
1. there are antibodies against virtually any chemical structure the body could come into contact with
2. there are not antibodies against self antigens
What was Erlich's hypothesis about how the immune system produces different arrays of antibodies?
Is it the currently held belief?
1. Each immune cell could produce multiple antibodies and express them on the cell surface.
2. When a foreign antigen enters and binds to one antibody, the production of more of this specific antibody are made on the cell.
This is not the currently held belief.
What is the clonal hypothesis of antibody production?
1. The immune system makes many cells each with the capability of making ONE antibody.
2. There is ONE antibody on the cell surface that is unique and specific for ONE antigen
3. If an antigen binds the receptor, it will make clones of itself, which will produce a large amount of antibody
What is the currently held hypothesis for antibody generation and specificity?
the clonal hypothesis
How does the Burnet clonal hypothesis account for the elimination of self reactive antibodies?
1. Immune cells with unique antibodies differentiate from a common precursor.
2. Self-reactive immature lymphocytes are removed by clonal deletion
When do immune cells become mature and move to the periphery?
After removal of the self-reactive antibodies, the lymphocyte matures and moves to the periphery to be activated by a foreign antigen
How long does a primary adaptive immune response take to produce detectable levels of antibodies in the serum?
What occurs during the lag phase of the primary adaptive immune response?
1. The antigen is presented to the mature lymphocyte in the periphery
2. The lymphocyte activates and proliferates
3. Immune cells (esp. B) differentiate into antibody secreting cells and start releasing antibody
How long are antibodies able to persist in serum under normal circumstances?
weeks or months
What can lymphocytes differentiate into to proliferate for longer in serum?
Memory cells that remain for years after the primary exposure
During the primary adaptive immune response, what fights the pathogen while the antibodies are building?
Do memory cells allow our immune system to abort infection?
No, they just allow a faster and larger increase in antibodies after exposure to fight the infection better (accelerated and amplified)
What body surfaces are normally colonized by bacteria?
3. Nasopharynx/Lower Respiratory tract
4. GI tract
5. Urogenital tracts
Roughly how many bacteria do we have colonizing our bodies?
How many human cells do we have?
(ten times as much bacteria as human cells)
What are three roles performed by commensal bacteria?
1. Prevent inflammation
2. Help the immune system develop
3. Take up space so virulent bacteria can't fit
What are the three types of host-parasite interactions?
What are the two things a parasite uses a host for?
1. a source of nutrition
2. a means to reproduce
What is commensalism?
Where the parasite has no effect on the host (except maybe mild benefit because it prevents inflammation, helps the immune system develop and takes up space).
Do we make antibodies against the commensal bacteria colonizing our gut and skin?
What is mutualism?
The presence of a microbe directly benefits the host.
Ex. Some gut organisms synthesize vitamin K
What is parasitism?
When the microbe causes harm to the host.
What is a pathogen?
What is meant by virulence?
A pathogen is a microorganism that can cause harm to the host.
Virulence is a quantitative measure of how much harm the pathogen can cause.
What is colonization and how is it different from infection?
Colonization is when bacteria move into normally non-sterile surfaces and does not involve a breach in the chemical or mechanical barrier separating that surface from a normally sterile tissue.
Infection is the colonization of a sterile tissue.
How is infection different from disease?
Infection can be asymptomatic and may not cause illness, but disease is associated with illness.
What are the four major classes of pathogen?
1. Extracellular bacteria, parasite, fungi
2. Intracellular bacteria, parasite, fungi
3. Virus (always intracellular)
4. Parasitic worms (extracellular)
What are some examples of extracellular bacteria, parasites or fungi?
What are some examples of intracellular bacteria, parasite, fungi?`
mycobacterium leprae (leprosy)
Plasmodium falciparum (malaria)
What are examples of viruses?
What are examples of parasitic worms?
Where is the progenitor stem cell for all immune cells located?
What are the two major lineages from the precursor stem cell for the immune system?
What cells in the myeloid lineage are the primary effector cells that respond immediately at the site of infection of sterile tissue?
What do they do?
Granulocytes (neutrophils, eosinophils, basophils)
The are phagocytic so they remove and kill the pathogen
What lineage do monocytes arise from? What is their function?
They arise from myeloid lineage and they initiate inflammatory response.
They are the precursors for macrophages
What are the three major divisions of the lymphoid lineage?>
What are the 3 major roles of dendritic cells?
1. initiate inflammation
2. initiate adaptive immune response by delivering antigen to T cells
3. produce cytokines for lymphocyte activation
What does it mean that immune cell lineages are highly mobile?
They constantly migrate through the body surveying the tissues of the body.
What are the two cells in the periphery responsible for phagocytosing microbes and releasing cytokines to activate lymphoid cells?
1. Resident macrophages
2. Dendritic cells
Where do dendritic cells take material from the infecting pathogen?
into the regional lymph node to activate the adaptive immune response
The nature of the immune response is determined by the __________ and __________.
1. type of infectious agent
2. efficacy of the response (did the innate immunity clear it?)
What occurs in the first four hours after infection?
What cells are responsible for this?
1. The pathogen is recognized by non-specific and broadly specific effectors
2. The infectious agent is potentially removed
Resident cells and tissue fluid at the site of infection are responsible for this broad effector response.
What occurs 4-96 hours after the infection?
1. More effector cells are recruited
2. PAMPs are recognized and activate effectors
3. Inflammation occurs
4. The infectious agent is potentially removed
What happens after 96 hours (adaptive immune response)?
1. The antigen is transported to lymph node by dendritic cells
2. Naive B and T cells recognize the antigen
3. Lymphoid cells clonally expand and differentiate into effector cells and memory cells
4. The infectious agent is cleared
What are the three separate effector functions mediated by antibody binding to antigens?
3. Complement Activation
What is neutralization?
What is an example of a pathogen that can be neutralized?
Neutralization is when the antibody binds to the antigen and cancels its toxic properties and speeds up removal and degradation by the macrophage.
What is opsonization?
What is an example of a pathogen that must be opsinized?
When the bacteria has a polysaccharide capsule and can't be phagocytosed by the macrophage, antibodies make it easier to be engulfed.
Ex. Haemophilus or pneumonia