Lecture 15: Hypersensitivity Type II, III, and IV Reactions Flashcards
Do Type II hypersensitivity reactions involves soluble or insoluble antigens?
Insoluble
True or False: Type II hypersensitivity reactions only occur with involvement of complement activation
False
- Type II hypersensitivity reactions occur WITH or WITHOUT complement activation
If a Type II hypersensitivity reaction occurs WITH involvement of complement activation, what is the final outcome?
Lysis of cell
If a Type II hypersensitivity reaction occurs WITHOUT involvement of complement activation, what is the final outcome?
Antibody opsonization occurs, cell is coated with IgG, IgM, or C3b =>
1) phagocytosis/destruction of cell via: neutrophils/macrophages OR
2) lysis via: ADCC/NK cells
____ system: alloantigens and naturally occuring antibodies
A. Rh System
B. ABO System
B. ABO System
What three alleles control the blood groups?
A, B, and O
Human serum contains naturally ocurring IgM antibodies called ______ (e.g anti-A, anti-B)
isohemaglutinins
True or False: Isohemaglutinins are natural antibodies, in that they occur without deliberate sensitization/immunization against them
True
True or False: Newborns lack anti-A and anti-B
True
- but acquire with time
Isohemaglutinins are of the ___ isotype
A. IgE
B. IgG
C. IgM
D. IgA
C. IgM
AA/AO genotype corresponds to A phenotype.
Which antibodies are present in the sera?
A. Anti-A
B. Anti-B
C. None
D. Anti-A and Anti-B
B. Anti-B
BB/BO genotype corresponds to B phenotype.
Which antibodies are present in the sera?
A. Anti-A
B. Anti-B
C. None
D. Anti-A and Anti-B
A. Anti-A
AB genotype corresponds to AB phenotype.
Which antibodies are present in the sera?
A. Anti-A
B. Anti-B
C. None
D. Anti-A and Anti-B
C. None
OO genotype corresponds to O phenotype. Which antibodies are present in the sera?
A. Anti-A
B. Anti-B
C. None
D. Anti-A and Anti-B
D. Anti-A and Anti-B
True or False: Humans have naturally occurring anti-bodies to Rh antigens
False - humans do NOT have naturally occurring anti-bodies to Rh antigens
What are two ways in which Rh antibodies can be induced?
1) Transfusion
2) Pregnancy
True or False: Rh antigens appear on cell bodies other than the RBC surface
False - Rh antigens do not appear on other cell bodies
The presence of a big __ confers Rh+ phenotype
D
Under what condition does erythroblastosis fetalis (hemolytic disease of the newborn) typically occur?
Rh+ child and Rh- mother
At or about the time of ___, there is a high degree of mixing of maternal and fetal circulation
parturition (birth)
Rh+ RBC’s of the infant induce ___ anti-Rh antibodies in the mother
A. IgM
B. IgG
C. IgA
B. IgG
True or False: During a mother’s first pregnancy with Rh incompatibility, IgG anti-Rh antibodies cross the placenta, enter fetal circulation, bind to RBC, leading to opsonization
False - this occurs during second or subsequent pregnancies
True or False: Rh incompatibility can cause hepato/splenomegaly in infant, as well as anemia, leukopenia, and thrombocytopenia
True
True or False: The second and subsequent pregnancies result in an ever-increasing risk of HDN
True
Typically, during postpartum, plasma cells make ___. Therefore, in subsequent pregnancy, ____IgG crosses the placenta
anti-RhD+; anti-RhD+ IgG
____: IgG anti-Rh from human donors, given to mother within 72 hrs of birth, helps to prevent HDN
RhoGam
How does RhoGam work?
Binds and removal fetal RBC’s from mother’s immune system prior to initiating immune response against Rh antigen
If Rh sensitization occurs, affected fetus may be treated by ____ or ____
intrauterine transfusion; exchange transfusion with O-
Contaminated blood is an example of which type of transfusion traction?
A. Immune (Hemolytic)
B. Immune (Non-Hemolytic)
C. Non-Immune Reactions
C. Non-Immune Reactions
If Type B blood is transfused into a patient with Type A blood, this is an example of which type of transfusion reaction?
A. Major Incompatibility
B. Minor Incompatibility
C. Delayed Reaction
A. Major Incompatibility
- Recipient has antibodies against donor
If Type B plasma (contains anti-A isohemagglutinin antibody) is transfused into a patient with Type A blood, this is an example of which type of transfusion reaction?
A. Major Incompatibility
B. Minor Incompatibility
C. Delayed Reaction
B. Minor Incompatibility
In which case does the donor have antibodies against recipient RBC?
A. Major Incompatibility
B. Minor Incompatibility
C. Delayed Reaction
B. Minor Incompatibility
____ Reaction: occurs when antibodies to donor’s cells form after transfusion
Delayed
- Primary immune response (7-10 days)
A patient who has received multiple transfusions has antibodies to white blood cells (anti-HLA). Which type of reaction is this?
A. Immune (Non-Hemolytic Transfusion Rx)
B. Immune (Hemolytic)
C. None of the Above
D. Major Incompatibility
A. Immune (Non-Hemolytic Transfusion Rx)
True or False: Anti-IgA of the IgE class is an example of Immune (Hemolytic) Reaction
False - Immune (non-hemolytic transfusion reaction)
True or False: The antigens seen in Type 3 hypersensitivity reactions must be insoluble
False - antigens in type 3 hypersensitivity reactions must be soluble
____: A localized reaction caused by aggregates of antigen and antibody, also known as immune complexes. Soluble antigen becomes insoluble when bound to antibody.
Arthus Reaction
When does sensitization occur in an Arthus reaction?
A. Immediately
B. 7-10 days
C. Following several consecutive injections
C. Following several consecutive injections
- High serum IgG levels must be achieved
In Arthus reactions, eliciting dose of antigen is inject ___ or ___
SC; ID
-remains localized
In sensitized people, the earliest stages of Arthus reactions are visible within ___ hrs after injection
1-2 hrs
Clinical symptoms of Arthus reaction?
1) Swelling at site of injection
2) Redness
3) Hemorrhage at center of lesion (blockage of cap/vessels)
4) Possibly necrotic
In Arthus reactions, what immune cell accumulates in capillary and venule walls?
Neutrophils
True or False: In Arthus reactions, blood flow through small vessels is increased and accompanied by formation of thrombi rich in platelets and leukocytes
False - while arthus reactions are often accompanied by formation of thrombi that is rich in platelets and leukocytes, blood flow through small vessels is SLOWED!
True or False: In Arthus reactions, there is eventually infiltration by ___ and mononuclear cells
eosinophils
What are the five steps of Arthus reaction?
1) Anti-Ab complex forms at site of antigen localization, in tissue - precipitates out of solution
2) Fc regions of IgG bind C1 = initiates classical complement pathway
3) C5a and C3a is made => increases permeability of blood vessels => edema
4) C5a attracts neutrophils to site
5) Frustrated Phagocytosis
6) Slowed blood flow and thrombi formation
What is the role of C5a in Arthus reactions?
attracts neutrophils to site
In an Arthus reaction, activated ___ may attempt to phagocytose immune complexes that have been deposited along with adjacent tissue, but are unable to due to size.
neutrophils
In Arthus Reactions, Frusturated Phagocytosis can occur.
In this process, which two cell types release proteases, collagenases, ROS, etc?
Platelets and Neutrophils
In an Arthus Reaction, thrombi formation + destructive enzyme activity can lead to rupture of vessel wall. As a result of this ___ and ___ can occur.
hemorrhage and necrosis of local tissue
What is the most common example of an Arthus reaction?
Deltoid muscle soreness one gets s/p IM booster immunization
Fever, enlarged lymph nodes, rash, painful joints, edema, are all symptoms of:
A. Arthus Rection
B. Serum Sickness
C. Rh Incompatibility
B. Serum Sickness
____: systemic reaction to antigen, usually antigens administered IV
Serum Sickness
In a sensitized person, serum sickness syndrome can take hours to ____ days (anamnestic response)
In a non-sensitized person, the primary response can take ___ days
3-4 days
7-14 days
True or False: Serum Sickness Syndrome cannot occur unless there has been prior sensitization
False - Serum Sickness Syndrome can occur WITHOUT prior sensitization in cases when LARGE amounts of antigens are given, which persist in circulation for a long period of time
In Serum Sickness Syndrome, where do immune complexes form?
1) Blood vessels
2) Glomeruli
3) Joint fluid
True or False: Serum Sickness Syndrome has localized responses in ways that are similar to Arthus Reaction
True
In Serum Sickness Syndrome, immune complexes that are formed may be carried directly to the phagocytic cells of the ___ and ____ (reticuloendothelial system)
liver; spleen
Serum levels, as measured via CH50 in Serum Sickness Syndrome, will reach lowest levels at what point in the disease?
A. Initial onset
B. Height of disease
C. Re-infection phase
D. Recovery phase
B. Height of disease
- This occurs because complement is being fixed and byproducts are released faster than they can be replaced
When do symptoms of Serum Sickness Syndrome subside?
When free antibody in serum appears
True or False: Systemic lupus and RA are also immune complex disorders
True
Which hypersensitivity reaction is cell mediated?
Type 4
In Type 4 hypersensitivity reactions, immune responses are primarily initiated by which cells?
Antigen specific T cells
In Type 4 hypersensitivity reactions, memory T cells become effector T cells on the ___ exposure to antigen, releasing mediators and cytokines that attract and activate other mononuclear cells and macrophages
second
Why are Type 4 hypersensitivity reactions considered to be delayed?
Because it takes 24-48 hrs for reactions to occur in sensitized people
What is the key manifestation of Type 4 Hypersensitivity Reaction?
Induration (cutaneous or subcutaneous hardening caused by cellular infiltrate)
What occurs in Sensitization Stage of Type 4 Hypersensitivity Reaction?
- subcutaneous antigen is processed by APC (Langerhans cell)
- Th cell recognizes HLA-peptide on APC and differentiates into Th1 cell
What occurs in the Elicitation Stage of Type 4 Hypersensitivity Reactions?
- antigen challenge activates specific Th1 cells, which make cytokines (IFN-gamma; MCP-1; TNF-a), leading to activation of macrophages
- Macrophages accumulate, resulting in local tissue damage