6. Type II Hypersensitivity

Question 1

Type II Hypersensitivity—antibody mediated cytotoxic

• Cytotoxic reactions:
reactions
– Antibody-dependent cell mediated cytotoxicity (ADCC)
– Antigen associated with circulating cells: antibody/complement mediated _____ and/or _____
– Antigen associated with tissue: _____ and complement mediated _____ and _____
• Examples:
– _____ antigen: Erythroblastosis fetalis
– Mis-matched _____ reaction
– _____ graft rejection
– See autoimmune lectures
• _____ antibodies against extracellular matrix antigens

• Type I is mediated by IgE, Type II is mediated by 2 classes: \_\_\_\_\_ and \_\_\_\_\_
• Reaction is to an antigen that is always \_\_\_\_\_-associated or \_\_\_\_\_-associated (with the BM, for example) > not a free soluble antigen
• Interaction of IgG and IgM with the cell > destruction/elimination of cell
• Bottom panel: ab binds antigen (membrane of cell, BM, etc.) > activates complement > attract neutro's, and will try to phago the cell, if antigen on tissue it will release lysosomal enzymes and cause damage to \_\_\_\_\_; or, the action of complement on surface of cell will cause \_\_\_\_\_; will also lead to opsoninzation and phagocytosis
• The antigen is not an autoantigen, it is foreign (can be drug, etc.) that is adsorbed on the surface - this is not AID
• ADCC - \_\_\_\_\_; target cell coated with antigen, ab to that antigen - instead of phagocytosis; the Fc region of IgG is recognized by another cell type - \_\_\_\_\_ cell, or macrophage - the killer cell cannot phago, the macrophage can; but here, instead of phago, the NK cell will release substance \_\_\_\_\_ - not enzymes, they are moieties that are produced locally, binds to target cell > induces apoptosis
	○ If target cell is red cell, \_\_\_\_\_cannot occur there

Answer 1

lysis
phagocytosis
damage
inflammation

Rh
transfusion
hyperacute
IgM/IgG

IgM
IgG
cell
tissue
BM
lysis
IgG
NK
EC

ADCC

Question 2

Mismatched blood transfusion
• Mechanism:
– Antibody mediated agglutination and lysis of RBC

* A and B antigens - carbs on cell surface
* Red cells work fine whether or not the antigens are there
* You don't make antibody to the antigen you have > you're tolerant to the antigen that you express
* Antibodies - iso-hemagglutanin antibodies
* If type A never been exposed to type B - these antibodies are \_\_\_\_\_-specific - occurs when you have antigen that's not processed by T cells
* Antigens that are similar to bacterial antigens - create \_\_\_\_\_ antibodies; similar to antigens that bacteria (not necessarily disease-causing) carries, when exposed, we are exposed to that antigen > we then produce the antibody, and we only produce the ab if we're lacking tolerance
* A from A or O
* B from B or O
* AB can only get AB

Answer 2

IgM

cross-reacting

Question 3

Mis-matched blood transfusion

* Type B individual > infuse blood from type A donor > \_\_\_\_\_ antibodies in recipient bind to the transfused RBC and destroy them
* As a result, IgM (\_\_\_\_\_ antigen combining sites) > agglutinates the RBC > circulatory blockage > complement activation, there will be severe \_\_\_\_\_ > obstruction of BV will lead to \_\_\_\_\_ (micro thrombi)

Answer 3

IgM
10
hemolysis
clotting

Question 4

Mismatched blood transfusion

• Pathogenesis:
– Antibody mediated agglutination and lysis of RBC

– Functional/morphologic changes:
• Diminished _____-carrying capacity, clumped RBC impede _____, lysed RBC release Hemoglobin—_____ failure; depletion of _____ factors

• Clinical manifestations:
– Mild: _____ and chills
– Severe: acute _____ failure or complete vascular _____ and death
– Disseminated intravascular coagulation (DIC): _____/spontaneous bleeding

* Given the transfusion for anemia initially; this mismatch exasperates
* Pee out \_\_\_\_\_, a breakdown product of RBC
* Because of complement activation > chills, fever; but as BF through kidney is impeded > renal failure > vascular collapse
* A lot of \_\_\_\_\_ formation > consuming clotting factors > deficiency In factors and patient is susceptible to infarction and go into phase where they undergo spontaneous bleeding > DIC

Answer 4

oxygen
blood flow
kidney
clotting

fever
kidney
collapse
infarction
bilirubin
microthrombi

Question 5

Hemolytic Disease of the Newborn (Erythroblastosis fetalis)

• Pathogenesis: antibody (anti D) and complement mediated damage to RBC
• Functional/morphological changes: _____

• Clinical symptoms:
– Mild hemolysis:
• \_\_\_\_\_, mild anemia
– Profound hemolysis:
• Increased \_\_\_\_\_
• Jaundice
• Kernicturus
• Severe anemia:
• Heart failure
• Enlarged \_\_\_\_\_ and/or spleen
• Generalized swelling and respiratory distress
• \_\_\_\_\_

• Rh antigen (\_\_\_\_\_ antigen) - glycoprotein on surface of RBC
	○ Either Rh+ or Rh-; 85% is \_\_\_\_\_
• Not a disease due to clerical error, but of nature
• Parent is Rh+ (father is), and mother is Rh-
	○ Both don't make antibody, but she can make it if she's challenged if \_\_\_\_\_ to it
• During first pregnancy, if fetus is Rh+; at birth - mixing of blood supply of mother and fetus - exposure to fetal Rh BC > now develop and carry \_\_\_\_\_
• Following second pregnancy > the antibodies will attack the Rh+ fetus; the antibody must be \_\_\_\_\_
	○ Due to a normal immune response involving T cells, class-switching and cause an array of symptoms (dependent on titer of ab's)
• Bilirubin in brain > \_\_\_\_\_ - toxic
• Fetus tries to respond via extramedullary hematopoiesis within liver to compensate
• Whenever complement is activated > C3a, C5a > act on mast cells and induce histamine release (anaphlytoxins) > can mimic \_\_\_\_\_; but here they're being triggered by \_\_\_\_\_

Answer 5

hemolysis
jaundice
bilirubin
liver
hydrops fetalis

D
Rh+
exposed
antibodies
IgG
kernicturus

anaphylaxis
IgG

Question 6

• Rh+ recognized by maternal immune system > _____ antibodies
  
  • Subsequent delivery where express _____ fetus

Answer 6

Rh+

Rh+

Question 7

Tx hemolytic disease of the newborn
• During pregnancy:
– Intrauterine _____
– Maternal _____ exchange to decrease IgG levels

• After birth:
– Blood \_\_\_\_\_ for severe anemia
– IV fluids for low \_\_\_\_\_
– Phototherapy
– \_\_\_\_\_ therapy
– Exchange transfusion
• Prevention: \_\_\_\_\_ to Rh- mother at birth

• If father is Rh+ and mother is Rh- > at birth, when mother's immune system is exposed to RBC > given an injection > Rhogam, immune serum containing \_\_\_\_\_ to the Rh antigen, cover and removed by spleen > binds to and destroys \_\_\_\_\_ before the mother's immune system can see it
• Example of \_\_\_\_\_ immunization, only lasts as long as the passively injected antibodies are expressed (usually a few \_\_\_\_\_); upon injection to Rhogam
• During prgenancy, if determine a reaction is occurring > give the fetus IU transfusions to \_\_\_\_\_ maternal antibody that is crossing
	○ Also give the mother plasma exchange, draw blood and lower \_\_\_\_\_ levels so there's less that crosses the placenta
• Phototherapy - remove \_\_\_\_\_

Answer 7

transfusions
plasma
transfusions
bp
respiratory
rhogam

IgG
fetal RBC
passive
weeks

dilute
IgG
bilirubin