Week 8 material Flashcards
(46 cards)
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