Ch.9 - Hypersensitivity Flashcards
Define/differentiate between: A. Allergic B. Autoimmunity C. Alloimmunity
Allergic - Deleterious effects of hypersensitivity to environmental antigens
AGAINST ENVIRONMENT
ex) pollen, peanuts, Type I Hypersensitivity
Autoimmunity - disturbance in the immunological tolerance of self antigens to the point that the host own tissue are damaged
AGAINST SELF
ex) Type 1 Diabetes
Alloimmunity - an individual produces an immunological reaction against the tissues of another person (mother against fetus or transplant rejection)
AGAINST OTHERS
ex) Rh- mother with Rh+ fetus
Type I hypersensitivity reactions
IgE mediated through Mast Cells
Type II hypersensitivity reactions
Tissue specific reactions, IgM and IgG.
Type III hypersensitivity reactions
Immune complex reactions. IgG.
Type IV hypersensitivity reactions
Tissue specific, cell mediated reactions. Tc.
- note Hypersensitivity reactions can be immediate (anaphylaxis) or delayed (takes hours to reach max severity sever days post exposure to the antigen)
Describe objective 2 in terms of antibodies, target tissues, and cellular components involved in the immune response and be prepared to give examples of each type of hypersensitivity reaction.
Type 1 Hypersensitivity
IgE mediated
- Involved environmental antigens –> allergens
- Repeated exposure to high levels of antigen
- Triggers the production of IgE antibodies rather than IgG or IgM. (IgE is usually only for parasites)
- Fc portion of IgE binds to mast cells
- Antigen binds to FAB portion of 2 adjacent IgE antibodies bound to Mast cell
- Repeated allergen exposure causes massive MAST CELL DEGRANULATION
- Histamine binds to H1 and H2 receptors on target cells
ex)
GI - allergens are usually foods like milk, chocolate, citrus fruits, eggs, glutin, peanut butter, fish
–> vomiting, diarrhea, abdominal pain, mal absorption
Urticaria - Hives, white fluid- filled blisters
Lungs - ASTHMA, airway obstruction of large and small airways
Describe objective 2 in terms of antibodies, target tissues, and cellular components involved in the immune response and be prepared to give examples of each type of hypersensitivity reaction.
Type II Hypersensitivity
Tissue specific autoimmunity
(can be autoimmunity or allo-immunity)
–> activation of B lymphocytes to produce IgG or IgM against a SPECIFIC ANTIGEN
–> tissues or cells have MHC markers but also have specific antigens ex) platelets and RBC’s
4 tissue effects:
- Cell destruction mediated through complement activation
ex) Autoimmune Hemolytic Anemia
Alloimmune, ABP mismatch for transfusion
- Cell Destruction through Phagocytosis
ex) Rh+ baby with Rh- mother, mom’s IgG antibodies bind and cause opsonization, tag RBC’s for destruction in the spleen, slow anemia develops - Antigen-Antibody complex attracts Neutrophils
ex) if cells are endothelial cells phagocytosis can’t occur, neutrophils will release lysoenzymes into the blood
VERY SIMILAR TO TYPE III BUT ANTIGENS ARE FIXED
- Antigen Dependent Cell Mediated Cytotoxicity
ex) Activated Tc cells or NK cells once antibody is attached. Activated Fc portion of IgG.
*** Type II doesn’t destroy the target cell but causes cells to malfunction
ex) Graves Disease
Describe objective 2 in terms of antibodies, target tissues, and cellular components involved in the immune response and be prepared to give examples of each type of hypersensitivity reaction.
Type III Hypersensitivity
Formation of antigen-antibody complexes in circulation which deposit in organs and tissue —> THIS IS NOT SPECIFIC OR FIXED LIKE TYPE II
- Formation of antigen-antibody complexes formed in circulation
Antigen is soluble and released in blood - Deposition of complex in vessel wall or in any organ or tissue
- Activation of compliment, triggers chemotaxis
- Neutrophils to to phagocytize the complexes
- Neutrophils degranulate, releasing large quantities of lysozymes causing significant tissue or organ damage
ex) Lupus Erythematosus
Antibody targets: clotting proteins, platelets, RBC’s, Nucleic Acids in circulation released from damaged cells
Immune complexes reacting with Neutrophils damage: Renal Tubular Basement Membrane, Brain Choroid Plexus, Heart, Spleen, Lung, GI tract
Anaphylactic reactions to exogenous Gamma Globulin
Describe objective 2 in terms of antibodies, target tissues, and cellular components involved in the immune response and be prepared to give examples of each type of hypersensitivity reaction.
Type IV
Tc or lymphokine producing cells (Td), activate the macrophages
***Td cells induce macrophage function
DOESN’T INVOLVE ANTIBODIES
ex) Alloimmunity - Graft Rejection
Autoimmunity - tumor rejection, hashimotos disease, DMI
Contact dermatitis –> poison oak or ivy
*** note: rarely do hypersensitivity reactions just involve one
ex) DMI B cells are destroyed by Tc cells, but low levels of anti B cells antibodies are present in blood
Describe the role of Mast cells in the type I hypersensitivity response. Identify the locations where the majority of mast cells reside. Discuss the role of Histamine, Leukotrienes, and Prostaglandin E in type I hypersensitivity reactions
Mast cells degranulate by Fc portion of IgE antibodies binding to Mast cells.
Mast cells reside tissues found in GI tract, the skin, and respiratory tract
Histamine binds to the H1 and H2 receptors on target cells.
–> causes large vessel vasoconstriction, post capillary venule dilation, increased capillary permeability, and exudation.
Leukotrienes cause smooth mm. relaxation, increased capillary permeability, vasodilation and some chemotaxic properties
Prostaglandin E cause pain and increased capillary permeability only with some chemotaxic properties
What is the role of the two different types of histamine receptors. H1 and H2
H1 receptor:
a. contraction of bronchial smooth mm.
b. increased capillary permeability –> edema
c. vasodilation exacerbating edema in throat and lungs
d. chemotaxis for eosinophils, then deactivates diapedesis so they can’t leave the inflammatory site
H2 receptor:
a. increase gastric secretion
b. decreased mast cell and basophil release of histamine
c. negative feedback loop control
Discuss briefly the value of allergy testing and the use of the flare wheel in diagnosing allergies.
Some people genetically produce more IgE antibodies, making them more susceptible to allergic reactions. Could possibly be from a diminished ability to suppress IgE secreting B lymphocytes.
1 parent with allergies –> 40% chance of allergies in offspring
2 parents with allergies –> 80% chance of getting allergies
Intradermal skin tests with small amounts of allergens. Wheel flare reactions occur in a few minutes. Diameter of wheel indicates degree of sensitivity.
In true auto-immunity, the body’s immune system attacks a tissue that normally should be
recognized as self. Explain the type of hypersensitivity each of the following is and how the hypersensitivity damages the tissues.
Hashimoto’s Disease
Hashimoto’s disease is a Type IV Hypersensitivity
Hashimoto’s disease is a result of Tc cell destruction of the thyroid gland –> leading to hypothyroidism (unexplained weight gain and fatigue)
In true auto-immunity, the body’s immune system attacks a tissue that normally should be
recognized as self. Explain the type of hypersensitivity each of the following is and how the hypersensitivity damages the tissues.
Graves Disease
Graves Disease is a Type II Hypersensitivity
IgG antibody irreversibly bind to TSH receptor and causes increased levels of thyroxine
There is no negative feed back loop for antibodies so production doesn’t end.
Person develops Graves with weight loss, puffy eyes, and enlarged thyroid.
In true auto-immunity, the body’s immune system attacks a tissue that normally should be
recognized as self. Explain the type of hypersensitivity each of the following is and how the hypersensitivity damages the tissues.
Myasthenia Gravis - weakened and rapid fatigue of mm.
This is a Type II Hypersensitivity Reaction
IgG antibody binds to nicotinic receptors on skeletal mm. and breakdown communication between mm. and nerves.
–> leads to weakness in arm and leg mm., double vision, and difficulties with speech and chewing, droopy eyelid
In true auto-immunity, the body’s immune system attacks a tissue that normally should be
recognized as self. Explain the type of hypersensitivity each of the following is and how the hypersensitivity damages the tissues.
Diabetes Type I
Type IV Hypersensitivity
This is due to Tc destruction of B cells.
In true auto-immunity, the body’s immune system attacks a tissue that normally should be
recognized as self. Explain the type of hypersensitivity each of the following is and how the hypersensitivity damages the tissues.
Gluten related Celiac Disease
Type III Hypersensitivity
Gluten binds to protein on cell membrane of host cell forming a new antigen –> neoantigens!!!
(also known as hapten - small foreign molecule that binds to a protein)
Primary Difference between type II and III is that type II antibody binds to antigen on the cell surface whereas type III the antibody binds to soluble antigen released into blood and then deposited in tissues.
–> these are not organ specific
I guess Gluten is soluble antigen released into blood, bound by antigens and then deposited into tissue
In true auto-immunity, the body’s immune system attacks a tissue that normally should be
recognized as self. Explain the type of hypersensitivity each of the following is and how the hypersensitivity damages the tissues.
Poison Ivy contact dermatitis
Type IV hypersensitivity reaction
This is a hapten –> catechols bound to protein
Reacts with normal self proteins in the skin and causes a cell mediated response. Contact dermatitis results.
ONLY FOUND IN AREA OF CONTACT, DOESN’T SPREAD
In true auto-immunity, the body’s immune system attacks a tissue that normally should be
recognized as self. Explain the type of hypersensitivity each of the following is and how the hypersensitivity damages the tissues.
Lupus Erythematosus
Type III Hypersensitivity
This is a result of antigen antibody complexes that float through circulation and deposit on organs. Not tissue specific or fixed antigens.
This will cause complement activation
This then causes neutrophil chemotaxis
Neutrophils try to phagocytize the complexes
Neutrophils degranulate releasing large quantities of lysozymes causing significant tissue or organ damage
–> due to what the antigen-antibody complex deposits on, could develop antibodies against DNA, erythrocytes, coagulation proteins, phospholipids, and platelets
–> this causes damage to the brain choroid plexus, RENAL GLOMERULAR BASEMENT MEMBRANE DUE TO HIGH GFR, heart, spleen, lungs, skin, GI tract, peritoneum
–> manifest by facial rash, skin photosensitivity, oral and nasal ulcers, arthritic symptoms, pleurisy/pericarditis, renal disorders, neural disorders, hematologic disorders, immune disorders, ANTINUCLEAR ANTIBODY
In true auto-immunity, the body’s immune system attacks a tissue that normally should be
recognized as self. Explain the type of hypersensitivity each of the following is and how the hypersensitivity damages the tissues.
Rheumatoid Arthritis
Type I Hypersensitivity
IgE mediated
–>causes massive Mast cell release
Activates the H1 receptors
- -> bronchiole constriction
- -> increased capillary permeability
- -> peripheral vasodilation which only exaserbates edema
- -> eosinophil chemotaxis
Be prepare to discuss the role of each of the following in the erroneous auto-immune responses. Define and differentiate the following:
Neoantigens
Autoimmunity - the tolerated antigens must be present before birth; autoreactive lymphocytes should have been suppressed or eliminated before birth
How we get autoimmunity –> Neoantigens is 1 way!
New antigens on cell surface produced by:
- Mutations of DNA producing membrane bound proteins
- Viral infected cells producing membrane bound viral proteins
- Fetal or embryonic antigens produced by cancer cells undergoing reverse differentiation
Body doesn’t recognize as self and reacts against
Be prepare to discuss the role of each of the following in the erroneous auto-immune responses. Define and differentiate the following:
Viral Infections
Virally infected cells can produce virally induced antigens on plasma membrane
ex) Rubella induced encephalitis
Produces autoimmune disease
Be prepare to discuss the role of each of the following in the erroneous auto-immune responses. Define and differentiate the following:
Spontaneous Mutations
Spontaneous mutations will cause neoantigens to be produced on cell surface
Body will no longer recognize as self and cause auto-immune response
Be prepare to discuss the role of each of the following in the erroneous auto-immune responses. Define and differentiate the following:
Haptens
Haptens are proteins bound to a small foreign molecule on cell membrane of host cell –> forms new antigen or neoantigen!!!
ex) PCN, Gluten, Contact dermatitis
Be prepare to discuss the role of each of the following in the erroneous auto-immune responses. Define and differentiate the following:
Infectious Disease
Infectious Diseases
- Formation of immune complexes with endotoxins which deposit in organs or tissues (Kidney failure results from deposition of immune complexes)
- Introduction of antigen so closely resembling self antigen that activated antibodies will bind to both foreign and self antigens
ex) Rhematic fever from Strep A
- IgM and IgG bind to endocardium
- immune system attacks your heart valves
- antigens on endocardial cells are similar enough to strep A so our antibodies bind
Be prepare to discuss the role of each of the following in the erroneous auto-immune responses. Define and differentiate the following:
Failure of T reg cells
Loss or dysfunction of T reg cells which have been providing peripheral tolerance suppressing a forbidden B or T lymphocyte made against a self antigen
Be prepare to discuss the role of each of the following in the erroneous auto-immune responses. Define and differentiate the following:
Sequestered Antigens
These are self antigens located in Immuno-priviledged sites
Ex) sperm in the testes and cornea and lens of eye
Since embryonic exposure didn’t occur, truamtic injury to the area will expose immune system to sequestered antigens and develop antibodies against self because tolerance was never developed
This is why you want boys to wear cup in sports
How cataracts form
- if Type II Hypersensitivity occurs because of damage to one eye, with consequent exposure to immune response, other cornea is also at risk because you have now developed antibodies against both!
Be prepare to discuss the role of each of the following in the erroneous auto-immune responses. Define and differentiate the following:
forbidden clones
Embryonic clones that were developed but then suppressed, but some of the cloned B lymphocytes survived and proliferate later in life
Be prepare to discuss the role of each of the following in the erroneous auto-immune responses. Define and differentiate the following:
T reg lymphocytes
these are responsible for peripheral tolerance and preventing the formation of antibodies against self
We need these to function to continue to mask or suppress forbidden clones
Explain possible causes of immunno-deficiencies and differentiate between:
a. Congenital
b. Acquired
Congenital = chief cause is disruption of B and T lymphocyte function
a) Stem cell defect for B or T lymphocytes or both
b) Lymphoid tissue function disorder, abnormal development of lymphocytes
c) Hyperactive t’s (suppressor lymphocytes)
Acquired =
a) Infections - rubella, measels, leprosy, TB
b) Malignancies - hodgkins and leukemia
c) chemotherapy or radiation therapy
d) stress
e) malnutrition
f) aging
g) diabetes –> glycosylation
h) alcoholism
I) corticosteroids
j) pregnancy and infancy
K) surgery and anethesia
List at least 10 contributing factors that might lead to acquired immuno-deficiencies.
a) Infections ex) rubella, measels, leprosy, TB
b) Malignancies - hogkins and leukemia
c) chemotherapy or radiation therapy
d) stress
e) malnutrition
f) aging
g) diabetes –> glycosylation
h) alcoholism
i) corticosteroids
j) pregnancy and infancy
k) surgery and anesthesia
Specifically explain how HIV infection causes Acquired Immunodeficiency Disease, (AIDS)
Infects the CD4 receptors on Th cells –> other T cells seem unaffected
Retrovirus carries RNA, reverse transcriptase and produces double stranded DNA
Has profound effect on function of immune system!
Affects CNS leading to DEMENTIA
Person may become infectious within 2 weeks!
Vaccine possibility is poor –> it’s an RNA virus which means it is constantly mutating
