Week 8 material Flashcards
What is tolerance and what is the important form of tolerance
a immunological non-reactivity to an antigen resulting from a previous exposure to that same antigen
(No reaction to an antigen due to the immune system
having had been exposed to it before)
the most important form is non-reactivity to self-antigens
What classifies a properly functioning immune system
protects one from a foreign object but doesn’t provide a response to its own antigens (self-antigens)
What is the immune system a balance between
a normal response and a deficient response
- both types of responses can encompass harmful responses to specific antigens
What is hypersensitivity
An excessive, damaging, discomfort-producing, and sometimes fatal response created by the normal immune system to an antigen
Relies on 2 things: antigens + pre-sensitized state of the host (host has to be sensitive to the antigen)
Divided into 4 types based on the mechanisms involved + time taken for the rxn to occur
What is autoimmunity
immune system creates a strong response against a self-antigen due to the loss of self-tolerance
What are antigens
molecules the body finds foreign and gets attacked
Includes:
- things in our environment
- bacterial components
- proteins of virus, fungi, and protozoa
- food
- dust
What are the 4 types of hypersensitivity rxns
Type I: Immediate + IgE-mediated response
- Ex: allergic response
- Antibody: IgE
Type II: Cell-mediated (cytotoxic) response mediated by IgG and IgM binding to the antigens on the cell’s surface
- Antigens are also NOT soluble
Type III: Immune-complex mediated
- Antigens are soluble
- also used by IgG and IgM
Type IV: Delayed-type (T-cell mediated)
- The only response mediated by T cells
ACID: allergy, cytotoxic, immune-complex, delayed
What is Type I Hypersensitivity
Immediate + IgE-mediated response = Allergic Rxn
Antibody that gets released in response to antigen: IgE
Response Time: Rapid (15-30 minutes)
Mechanism: allergen causes the production of IgE antibodies. IgE binds to the mast cells and causes for the mast cells to release histamine and other mediators (degranulation) which causes allergy symptoms
Examples: anaphylaxis, hay fever, and asthma
What is anaphylaxis
Severe allergic reaction that comes on rapidly. It is mediated by an IgE-dependent immune response
Mediated by histamine + other chemical mediators
- stimulates mucus production
- interacts with nerve ending causing itchiness
- vasodilation (face and tongue swells and low blood pressure)
- bronchiole constriction (wheezing, shortness of breath)
Why does anaphylaxis occur to the 2nd exposure to an antigen
During the 1st exposure, the mast cells do NOT have the IgE antibodies
In order for this rxn to occur, mast cells need to be primed with the IgE antibodies
What is Type II Hypersensitivity
Cell-Mediated
Antibody that gets released in response to antigen: IgG + IgM which reacts to the cell-bound antigen
Response time: minutes - hours
Mechanism: IgG + IgM binds to the antigen on the cell. The binding of the antibody leads to complement activation, cell lysis, and possibly activating cytotoxic T cells, natural killer cells, macrophages, and neutrophils
Example: if the wrong blood type is donated (Type A blood is given to a person with Type B, anti-A antibodies will bind to the donated A RBC’s, activate the complement cascade, and cause for the A RBC’s to lyse (hemolysis)
What is Type III Hypersensitivity
Immune-Complex Mediated
Antibody that gets released in response to antigen: IgG + IgM - in response to the soluble antigen
Response Time: 3-8 hours
Mechanism: the antigen-antibody complexes get deposited in the tissues which brings on complement activation. This complement activation provides inflammatory mediators and recruits neutrophils
This response can cause kidney injury due to the immune complexes being able to block the glomerulus in the kidneys. The glomerulus is what filters the urine.
Example: lupus
What is Type IV Hypersensitivity
What gets released in response to antigen: T cells respond to soluble antigens or antigens bound to the cell
Response Time: 48 - 72 hours
Mechanism: Th1 cells secrete cytokines. Cytokines activate macrophages and cytotoxic T cells
Example: tuberculin test + contact dermatitis
How does the tuberculin skin test work
it gets used to see if someone has had exposure to TB before
1st exposure = NO rxn but stimulates memory helper T cell
exposures are the 1st one = memory T cells get activated + creates inflammatory cytokines and stimulates macrophages and cytotoxic T cells
- extract protein from TB
- protein gets injected into the forearm
- if the person has had TB before, their memory T cells will be activated and present
- when memory T cells get activated - it causes localized swelling + hardness at the injection site after 48-72 hours
What is a test used to test for hypersensitivity
Prick Puncture Skin Test
- allergens are introduced via superficial skin pricks on the arm
Wheel-Flare Reactions
- occurs within 15-20 minutes
- this shows a Type I hypersensitivity rxns
What are treatments for hypersensitivity, specifically anaphylaxis, mild type 1, and the other types of hypersensitivity
Anaphylaxis
= Use epinephrine to combat the vasodilation done by chemical mediators that occurs when you have this rxn.
Mild Type I
= antihistamines + anti-inflammatory drugs (targets histamines or chemical mediators)
Type I, II, III
= avoid exposure to the antigen + use anti-inflammatory drugs and +/- anti-histamines
Desensitization
= expose the person to dilute concentrations of the allergen to lessen the allergic response - this tricks the body to create a different type of antibody (IgG instead of IgE)
- IgG act as blocking antibodies - it neutralizes the allergen before the allergen binds to IgE mast cells
What is an autoimmune disease
The body loses tolerance which causes the adaptive immune system to attack itself/ the body
Mechanisms that cause this type of disease can be mediated by type II, III, IV hypersensitivity rxns
These diseases can range from being systemic to organ specific
Why does autoimmunity occur
We don’t know the exact reason
Genetics
Environmental factors
- Infections: molecular mimicry - the pathogens resemble self-antigens
- Vaccines
- Physical injury
- Drugs or Toxins
Imbalance of the regulatory T and B cells
What are some examples of organ-specific autoimmune diseases
Celiac Disease = antibodies that bind to gluten turn into autoantibodies that target small intestine cells
Type I Diabetes/Diabetes Mellitus = cytotoxic T cells destruct the pancreas’ insulin producing beta cells
Graves Disease = autoantibodies target thyroid-stimulating hormone receptors - this causes for the thyroid to be overstimulated
What are examples of systemic autoimmune diseases
Myasthenia Gravis = autoantibodies targets/blocs the acetylcholine receptors in the neuromuscular junction/on muscle cells
- acetylcholine is a neurotransmitter that gets released by nerve cells + binds to the receptors on the muscle cells
Rheumatoid Arthritis = autoantibodies, immune complexes, complement activation, phagocytes, and T cells damage the membrane and bone in joints
What are some treatments for autoimmune diseases and the goal of treatments
Goal: suppress the immune system and manage symptoms
Treatments:
- organ-specific targeted therapy
- immunosuppressants
- biologics targeting cytokines or immune checkpoints (TNF-alpha, interleukins, B-cell therapies, and complement inhibitors)
If someone is starting an immunosuppressive agent, what sort of infections would you want to screen for
HIV, TB, HSV, Hepatitis B and C
Infections that can exist in a latent or inactive form
What infections should you be cautious of when being on immunosuppressants
TB: screen with a skin test or interferon gamma release assay
Hep B + C: risk of reactivation + worsening with immunosuppressants
HIV: risk of accelerating the progression of HIV with immunosuppressants
Herpes viruses: vaccinate before taking immunosuppressants
Strongyloides (Parasitic Infection): risk of hyperinfection syndrome
What is variolation
Taking the pus or scab from a small pox patient and inserting it into a healthy individual
Inoculate healthy individuals with the infectious material
What did Edward Jenner do to create vaccination (creating the 1st vaccine for smallpox)r.
- Milkmaid (Sarah Nelmes) was infected with cowpox
- James Phipps gets inoculated with cowpox pus from the milkmaid
- James falls ill with a mild case of cowpox
- Scabs are taken from a cowpox patient and inoculates James with it
- James is unaffected and protection is complete
When is eradication of a disease possible
When the disease has a reservoir
Reservoir of Infection: person, animal, plant, soil, or substance where an infectious agent can live and multiples. The reservoir doesn’t get injured and can help other things get infected.
How has vaccines impacted…
- Measles
- Diphtheria
- Pertussis
- Tetanus
- Poliomyelitis
DECLINE in infectious disease rates
What is a vaccine
A biological agent (protein, glycoconjugate, nucleic acid, attenuated pathogen)
that gets inoculated or administered with or without adjuvant
triggers the production of antibodies and memory B + T cells specific to the pathogen or toxin being introduced
- do this by using a similar antigen to the actual disease causing antigen
the antibodies protects the body against the pathogen or toxin to suppress the replication or disease
What is the detailed immune response to a vaccine
Vaccine gets administered
Antigen comes in contact with antigen presenting cells/dendritic cells- binds to the MHC II
Dendritic cells present antigen to CD4+ and CD8+ T cells
CD8+ effector and memory T cells and B cells get activated
- B cells bind to the soluble vaccine antigen via its BCR
B cells proliferate and mature into memory B cells + plasma cells which create antibodies
What do vaccines do for the infection curve?
It tries to shift the immune response forward or occur earlier
Once exposed the first time to the antigen, the secondary immune response to the antigen will be stronger and faster
What are the different types of vaccines
- Live (weakened or inactivated)
- Killed
- Synthetic
- Toxoid
- Conjugate
- Recombinant Subunit
What is a live vaccine and what are the implications and contraindications of it
- Lower dose or the antigen (can be weakened or inactivated)
- Multiples in the host at LOW LEVELS
- Immunogenic (causes for body to have an immune response to the antigen) and creates a strong cellular response
Implications:
- Side effects
- Can lead to pathogenicity in very rare cases
Contraindication:
- Allergy to the manufactured component
- Can be dangerous for immunocompromised people
What is a killed vaccine and the implications and contraindications of it
- High dose of the antigen
- Can NOT multiply in the host
- Not as immunogenic so we will need a higher dose of it
Implications
- Side effects occurs in 24-48 hours
- No possibility for diseases or for it to turn pathogenic
- No transmission
Contraindications
- Allergy to the the manufactured component
What is a synthetic vaccine
A manmade vaccine that gets made through genetic engineering (created from DNA or RNA)
- Have to find what antigen is the most important and inject that specific antigen
- Only uses the antigen part (polysaccharide, protein, or the subunit of protein)
What is a toxoid vaccine
A bacterial toxin that gets treated with chemicals or heat to eliminate the toxic qualities but keeps the antigenic properties
What are conjugate vaccines and the problems and solutions to it
Targets the polysaccharide capsule
Proteins tend to be the most antigenic and can kill the T cell response - it gives a stronger immune response
Polysaccharide are specific to the pathogen
Problem:
Some bacterial polysaccharides can trigger the release (?) of protective antibodies
T-cells only respond to protein epitopes
Both T-cells and B-cells are required to create a strong B-cell memory response especially in children under the age of 2/young children
Solution:
- Conjugate the bacterial polysaccharide to a carrier protein and trigger the release of B cells that recognize the polysaccharide to produce antibodies + memory cells
What is recombinant subunit vaccine
A small portion of the virus is expressed (an important protein) using recombinant DNA technology
DNA then creates protein components in large quantities
What are other vaccine components
Preservations/antibodies
Stabilizers
Adjuvants: substances that enhances the immunogenicity of antigens
- tetanus toxoid requires this to trigger the antibody production
- some are licensed to be used in humans
- research adjuvants exist
What is herd immunity
When a certain amount of the population is immune (vaccine or natural infection) to the point where disease transmission is prevented and those who aren’t immune are protected
vaccine coverage ABOVE a certain threshold can create herd immunity
What is herd immunity dependent on
reproduction number
What is basic reproduction number
estimates how many people an infected person will infect in a community WITHOUT immunity
What is herd immunity threshold (HIT)
the minimum proportion of the population that must be immune to prevent continuous/sustained disease spread
What are determinants of herd immunity
If the vaccine has 100% efficacy - Herd immunity is reached when vaccination rate = HIT
If the vaccine is LESS than 100% efficacy - a higher proportion of the population has to be vaccinated
Herd immunity depends on..
- Disease transmission potential, Ro
- Vaccine performance, the efficacy and effectiveness
- Vaccine coverage
What is vaccine hesitancy
A delay in acceptance or the refusal of getting the vaccine despite them being available
What is dengvaxia, the challenges to developing the disease and its relation to vaccine hesitancy
Dengvaxia: 1st vaccine approved for prevention of dengue fever + targets all 4 serotypes
**Dengue Fever:* mosquito-borne viral infection
*Challenges for vaccine development:**
- virus occurs in 4 serotypes and there needs to be a vaccine for each
- antibody-dependent enhancement: being infected with 1 serotype and developing immunity towards it can cause a more severe infection when you get infected with another serotype
Which part of the epidemic triangle is social acceptance of vaccination a part of
the environment factor
