Lecture 16 - Immunologic Disorders Flashcards
(97 cards)
1
Q
To produce an allergic reaction in Type I hypersensitivity, the antigen must…
A
must bind to two neighboring IgE molecules on mast cells, crosslinking them.
2
Q
The redness and swelling found after a tuberculin skin test involve the action of…
A
sensitized T cells
3
Q
Delayed-type cell-mediated hypersensitivity is also known as ________ hypersensitivity.
A
Type IV
4
Q
Please select the correct sequence of events that occur during an immune-complex hypersensitivity reaction.
- Ag-Ab immune complexes form.
- Immune-complexes activate complement, resulting in increased vascular permeability.
- Neutrophils are attracted, and release enzymes that cause tissue damage.
- Circulating immune complexes are trapped in the blood vessels.
A
1, 4, 2, 3
5
Q
A secondary immunodeficiency disease is not the result of which of the following:
1. Genetic defects
2. Malnutrition
3. Advanced age
4. Certain virus infections
5. Malignancies
A
- Genetic defects
6
Q
what are immunological disorders/what do they cause?
A
they cause abnormal immune responses (it is when the immune system does not properly respond)
7
Q
what are the 3 categories of immunological disorders?
A
- Hypersensitivities
- Autoimmune diseases
- Immune deficiency disorders
8
Q
define hypersensitivities
A
An exaggerated immune response to non-pathogenic foreign Ag’s (that are not harmful) that damage the host tissues.
9
Q
what are the 4 types of hypersensitivities?
A
Types 1 through 4 (I, II, III, IV)
10
Q
what are allergens?
A
harmless foreign antigens causing allergies (non-pathogenic foreign Ags)
11
Q
what are autoimmune diseases?
A
misdirected immune responses that attack normal host tissues (the immune system attacks our own cells)
12
Q
what are immune deficiency disorders?
A
an inadequate immune responses (something is lacking)
13
Q
what is type I hypersensitivity mediated by?
A
IgE mediated (antibody-mediated)
14
Q
is type 1 hypersensitivity immediate or delayed?
A
immediate response - within minutes of exposure to an allergen (ex. pollen)
15
Q
is sensitization required for type 1?
A
yes - initial exposure to the Ag is required for sensitization
16
Q
what is sensitization?
A
the administration of an antigen to produce a primary immune response
17
Q
in type 1, what do subsequent exposures to the Ag lead to?
A
it leads to the release of inflammatory mediators, which cause an allergic reaction, including blood vessel dilation, fluid leakage, constriction of smooth vessels (in airways causes bronchoconstriction), and increased mucus production
18
Q
what happens during first exposure to the allergen in type 1 hypersensitivity?
subsequent exposure to the allergen?
A
First exposure to the allergen:
- B cell activation (the whole process).
- Plasma cells and memory cells are produced.
- IgE antibodies are produced specific for the allergen.
- Sensitization occurs: the Fc portions of IgE antibodies bind to the mast cell receptors.
- No allergic reaction occurs.
Subsequent exposure to the allergen:
- B cell activation occurs (the whole process)
- Plasma cells and memory cells are produced.
- IgE antibodies
- Cross-linking of cell-bound IgE occurs. The allergen binds to two different IgE antibodies - causing the mast cell to degranulate.
- Degranulation and release of mediators occur.
- HIstamines and other mediators are released.
- Allergic reactions ensues
19
Q
in type 1 hypersensitivity, what happens during the 1st exposure? what are the two signals of the B cell activation?
A
- Activation of B cells:
- Signal 1: Ag binds to BCR of a specific B cell
- Signal 2: TH cell binds to MHC 2-Ag and secretes cytokines. - Clonal expansion and differentiation of B cells to form plasma cells and memory B cells.
- Plasma cells secrete IgE Ab’s that bind to receptors on mast cells and basophils using their Fc regions.
20
Q
in type 1 hypersensitivity, what happens during 2nd exposure?
A
- The Ag binds to the variable region of IgE antibodies that are stuck to sensitized mast cells and basophils.
- Crosslinking of Ige Abs trigger degranulation and release of pro-inflammatory mediators.
- Allergic reaction: blood vessel dilation, fluid leakage, etc.
21
Q
during type 1 hypersensitivity, is there an allergic reaction in the first exposure?
A
no, since sensitization is required
22
Q
what two categories of examples can type 1 hypersensitivity cause?
A
Localized anaphylaxis and systemic (generalized) anaphylaxis
23
Q
what is anaphylaxis?
A
an allergic reaction caused by IgE, localized or systemic
24
Q
what are the three examples of localized anaphylaxis?
A
-Hives (urticaria)
-Hayfever (allergic rhinitis)
-Asthma
25
what are hives (urticaria)?
it is on the skin due to allergens like food
26
what is hayfever (allergic rhinitis)?
-In the upper respiratory system due to allergens like pollen or dust mites.
-It causes sneezing and congestion
27
what is asthma?
-In the lower respiratory tract in the bronchioles.
-It leads to the accumulation of mucus and constriction of airways
28
when does systemic anaphylaxis occur?
It occurs when the Ag enters the bloodstream and spreads throughout the body (Ex: bee stings, peanuts, and penicillin)
29
what does systemic anaphylaxis cause?
generalized inflammation:
-blood vessels dilate
-fluid loss from blood
-low BP causes insufficient blood flow to vital organs, which causes organ failure
-bronchoconstriction can lead to respiratory failure
-can lead to death
30
what is anaphylactic shock? is this caused by systemic or local anaphylaxis?
it is caused by systemic anaphylaxis and is when you have a low BP, which causes insufficient blood flow to vital organs, which then causes organ failure
31
what are five types of treatments for type 1 hypersensitivity (local and systemic anaphylaxis)?
-antihistamines
-bronchodilators
-epinephrine
-steroids
-avoid triggers
-immunotherapy to stimulate IgG
32
how do antihistamines treat anaphylaxis caused by type 1 hypersensitivity?
-They suppress histamines (Ex: claritin or Benedryl)
-It reduces the intensity of the response
33
how do bronchodilators treat anaphylaxis caused by type 1 hypersensitivity?
they open up airways (ex: Albuterol)
34
how does epinephrine treat anaphylaxis caused by type 1 hypersensitivity?
-It reverses inflammation (Ex: EpiPen)
-Taken during systemic anaphylaxis
-Constricts blood vessels to maintain normal BP and dilates airways to allow normal breathing
35
how do steroids treat anaphylaxis caused by type 1 hypersensitivity?
-Suppresses immune system (Ex: prednisone/cortisone)
-Preventative measure: can be taken during allergy season (Ex: flo-vent)
36
how is immunotherapy used to stimulate IgG to treat anaphylaxis caused by type 1 hypersensitivity?
-Small doses may prompt the production of IgG instead of IgE.
IgG can neutralize the antigen
37
what is type 2 hypersensitivity mediated by?
IgG and IgM mediated
38
how long is the response for type 2 hypersensitivity?
the response is hours to days later after the first exposure to the Ag
39
what is the cytotoxic reaction in type 2 hypersensitivity?
Cytotoxic reaction via complement cascade and ADCC:
-Abs are produced against an Ag on the surface of a cell (self Ag on our own cell or non-pathogenic Ag on a foreign cell).
-Abs go and bind to the Ag on the cell surface.
-Ag-Ab binding activates complement proteins causing lysis of the cell via MACs.
-Abs recruit other leukocytes to the cell causing its destruction via ADCC.
40
what can happen in blood transfusions in type 2 hypersensitivity?
Blood transfusion reactions: when Abs bind to foreign RBCs causing their destruction
41
what is an example of a disease caused by type 2 hypersensitivity?
Rheumatic fever:
-It is developed a few weeks after untreated Streptococcus infections (Strep throat, scarlet fever).
-Abs against strep cross-react with and damage host cells, especially of hearts, joints, brain, and skin causing inflammation.
-In severe cases, it can cause damage to the heart valves that can eventually lead to heart failure.
-Prompt treatment with antibiotics is recommended
42
what is type 3 hypersensitivity mediated by?
Ag-Ab complex mediated
43
what is the response like in type 3 hypersensitivity?
The response is from hours to days later
44
what forms during type 3 hypersensitivity?
antigen-antibody complexes form that are not engulfed by phagocytes
45
where do the Ag-Ab complex deposits in type 3 hypersensitivity?
they deposit in small blood vessels especially in skin, joints, and kidneys
46
what do Ag-Ab complexes stimulate in type 3 hypersensitivity?
They stimulate clotting, inflammation, and tissue damage (some Ag-Ab complexes are not cleared out after infection and it causes damage)
47
what is an example of a disease caused by type 3 hypersensitivity?
Glomerulonephritis:
-It is inflammation of the tiny filters in kidneys called glomeruli that filter the blood to make urine.
-It develops after untreated Streptococcus infections (since we have so many Ag-Ab complexes left over)
-Ag-Ab complexes deposit within walls of blood vessels causing inflammation (recruited leukocytes).
-May lead to kidney failure
48
what is type 4 hypersensitivity mediated by?
T cell mediated
49
what is the response like for type 4 hypersensitivity?
it has a delayed response - peaks at 2-3 days later
50
which type of hypersensitivity is the only one that is T-cell mediated?
type 4
51
does type 4 require sensitization?
yes
52
what happens during the initial exposure to the Ag in type 4 hypersensitivity?
Sensitization:
-Helper T cells activated to create memory helper T cells.
-Cytotoxic T cells are activated to create memory cytotoxic T cells.
53
what happens to subsequent exposure to the Ag in type 4 hypersensitivity?
-Memory helper T cells are activated to form effector TH cells that activate macrophages, which promote inflammation.
-Memory cytotoxic T cells are activated to form effector killer T cells (Tc cells) that kill cells.
54
what is the result of subsequent exposure in type 4 hypersensitivity?
tissue damage
55
study chart of type 4 hypersensitivity on slide 23
56
what are 3 examples of reactions/diseases caused by type 4 hypersensitivity?
-Contact dermatitis
-Tuberculin skin test
-Part of tissue transplant rejection
57
what causes contact dermatitis? what is the treatment?
-It can be caused by poison oak, metal jewelry, latex products, etc.
-Treatment can be local application of an anti-inflammatory steroid (Cortsone) cream
58
what happens in the tuberculin skin test?
-M. tuberculosis protein is injected in the arm to detect previous exposure of tuberculosis.
-Causes inflammation and cell death that is seen as a red bump
59
what is the prevention of tissue transplantation rejection?
prevention using immunosuppressive drugs
60
which hypersensitivity type involves a sensitization step where IgE molecules attach to mast cells, but there is no reaction?
type 1
61
what do autoimmune diseases do?
attack "self" cells
62
during autoimmune diseases, the body sees itself as foreign. what are two factors that causes this?
1. Genetic factors:
-B and T cells with self Ags that are not completely destroyed.
2. Environmental factors:
-Molecular mimicry
-Hygiene hypothesis
63
what is molecular mimicry?
microbes have molecules that look like host molecules. Immune cells against these microbes cross-react with and damage host cells that causes the body to see itself as foreign.
64
what is the hygiene hypothesis?
an untrained immune system that can cause the body to see itself as foreign
65
what do autoimmune diseases use to attack tissues?
it uses antibodies and/or immune cells to attack tissues
66
are autoimmune diseases localized or systemic?
both
67
how can autoimmune diseases be localized and what is an example?
Diabetes is an example; T cells destroy pancreatic B cells that secrete insulin - the lack of insulin causes an increase in blood sugar leading to disease
68
how can autoimmune diseases be systemic and what is an example?
SLE is an example; Antibodies, DNA, and other nuclear components attack cells throughout the body
69
what are two examples of autoimmune diseases?
Rheumatoid arthritis and multiple sclerosis
70
is rheumatoid arthritis systemic or localized?
systemic
71
what things attack cells in rheumatoid arthritis?
T cells and Abs attack cells in the synovial membrane that protects and lubricates joints
72
what does rheumatoid arthritis cause?
it causes pain and swelling followed by erosion of joints, they become knobby and non-functional. (bone erosion, inflammation, non-functional genes)
73
what happens in multiple sclerosis/what attacks the cells?
immune cells attack the myelin sheath (which is the protective sheath covering nerves) leading to communication problems between the brain and body
74
what are the symptoms of multiple sclerosis?
symptoms vary depending on which nerve gets destroyed/which nerve is affected
75
what is the treatment of multiple sclerosis?
-immunosuppressive drugs like steroids
-monoclonal Abs against pro-inflammatory mediators
76
what happens in immune deficiency disorders?
when there is an inadequate immune response - a loss of immune function
77
what are the two types of immune deficiency disorders?
Primary and Secondary
78
what is primary immune deficiency disorder?
it is present from birth due to genetic defect or developmental abnormality (don't have a functional immune system)
79
what is secondary immune deficiency disorder?
it is acquired via immunosuppressive drugs or radiation, cancer, loss of spleen (a secondary lymphoid organ), pregnancy, infections (ex: HIV - infects T-helper cells), chronic stress, age (young and old), or malnutrition
80
what is an example of a primary immune deficiency disorder?
Severe combined immunodeficiency (SCID)
81
what happens with SCID?
-You have no functional lymphocytes (so you can't be protected from infections).
-Die within the first year of life due to infections.
82
who is the famous boy who had SCID?
David Vetter - the bubble boy from 1970s
83
what is the treatment for SCID?
Early detection by newborn screening and bone marrow transplant or gene therapy
84
what is an example of a secondary immune deficiency disorder?
Human immunodeficiency virus (HIV)
85
what happens with HIV?
-Attacks and destroys helper T cells.
-Spreads by contact with infected blood and bodily fluids
-Prone to secondary infections that may lead to death
86
can cancer be facilitated by immunodeficiency?
Yes, because if you don't have NK cells in innate immunity or cytotoxic T killer cells in adaptive immunity (which all kill cancer cells).
87
An example of an immune deficiency disorder is:
1. Rheumatoid arthritis
2. Poison oak allergy
3. SCID
4. Rheumatic fever
3. SCID
88
Which of the following results from generalized anaphylaxis?
1. Hayfever
2. Asthma
3. Urticaria
4. Rheumatoid arthritis
5. Shock
5. Shock
89
Rheumatic fever after untreated Strep infections is a(n) ________ hypersensitivity.
antibody-mediated, cytotoxic, type 2
90
Which of the following is not true about Type III hypersensitivity?
1. Antigens form complexes with antibodies
2. An example is glomerulonephritis after untreated Strep throat
3. Immune complexes can settle into small blood vessels
4. It is mediated by T cells
5. Resulting inflammation damages tissues
4. It is mediated by T cells
91
Allergic contact dermatitis is due to:
1. Macrophages and killer T cells
2. IgG antibodies
3. IgE antibodies
4. IgM antibodies
5. Memory B cells
1. Macrophages and killer T cells
92
Secondary immunodeficiency is not caused by:
1. SCID
2. HIV/AIDS
3. Cancer
4. Immunosuppressive drugs taken for autoimmune conditions
5. Advanced age
1. SCID
93
A mother comes to your office with her son, Maximillian. “Max” is a bright, well-adjusted first grader who moved to Brentwood about a year ago. He has been healthy all of his life until now. Recently, according to his mom, he has had episodes of wheezing and shortness of breath. The problem began in the spring when the fruit trees were blooming. Today, he also got some “puffy blisters” on his skin after running around in the grass. What is going on with Max?? What can you suggest to treat these symptoms? What might you try to help prevent these symptoms??
Answer: Max has become sensitized to some local allergens, most likely fruit tree pollen and grasses. Upon initial exposure to these allergens, he made IgE antibodies that attached to mast cells in his body. With subsequent exposures, allergens caused cross-linking of the IgE antibodies, allowing mast cell degranulation. The granules released inflammatory mediators, such as histamine, which promoted inflammatory responses. This reaction represents a Type I or “immediate” hypersensitivity reaction which occurs within minutes of the subsequent exposure. Max’s shortness of breath and wheezing indicate asthma, an abnormal bronchoconstriction and increased mucus production. His “puffy blisters” represent hives or urticaria, each of which is composed of a wheal (blister) and surrounding flare (redness). Both of these conditions are examples of localized anaphylaxis. However, Max should always be monitored in case the symptoms progress into a more life-threatening systemic anaphylaxis.
To treat Max’s symptoms, Max may be advised to use antihistamines and bronchodilators. To help prevent these symptoms, Max should avoid his triggers as best as he can. He can use certain medications in a preventative manner, including antihistamines and steroids (pills, inhaler). He can also begin a series of injections called immunotherapy. These involve injecting small amounts of the allergens that he is sensitive to, stimulating a buildup of IgG antibodies. The IgG antibodies will bind newly acquired allergens and prevent them from cross-linking IgE antibodies on mast cells.
94
Why do people get C. diff infections after taking a course of antibiotics?
Our gut is full of good bacteria (healthy microbiome) that keep bad bacteria causing diseases in check by not giving them enough food & space, by making antimicrobials, and by modifying the environment. When we take broad spectrum antibiotics to treat an infection, they not only kill bad bacteria causing that infection, but also kill all the good bacteria in our guts. In absence of these good bacteria, bad bacteria like C. diff that manage to escape antibiotics (due to formation of endospores or antibiotic resistance genes) can take over our gut causing a diarrheal infection.
95
What component in feces helps treat the C. diff infection?
The good bacteria or the healthy microbiome.
96
Who can donate feces?
Any healthy person who is free of pathogens, not on medications and hasn't travelled overseas.
97
Can FMT be used to treat other diseases?
Clinical trials are ongoing to treat other diseases using FMT like IBS, Crohn's disease etc.
