Immune Complex Disease

Question 1

What does it mean to be sensitized to an immunogen?

Answer 1

Sensitized = you have been exposed to the antigen and mounted an adaptive immune response to it

Question 2

What does it mean when an the immune system is hypersensitized to an antigen?

Answer 2

When the immune system cannot or should not get rid of an antigen but is trying to anyways

This leads to an acute or chronic response that causes too much collateral damage

Question 3

Describe Type 1 hypersensitivity

Answer 3

Mediated by IgE and Th2

Injury is caused by mast cells, eosinophils and their mediators –> anaphylaxis, lip swelling, hives etc

Question 4

Discuss type II hypersensitivity

Answer 4

Antibody against thing (IgM or IgG)–> opsonization and phagocytosis of cells + compliment activation

Example: Graves disease- one antibody against the TSH receptor stimulates thyroid to overactivate

Question 5

Discuss type III hypersensitivity

Answer 5

Immune complex disease: circulating or local antigens that are poly/multi valent and several antigens attach, form a ring and make a large deposited complex –> inflammation

Question 6

Discuss type IV hypersensitivity

Answer 6

Mediated by Th cells and CD8+ –> cell mediated inflammation

Eg. PPD reaction or poison ivy

Question 7

What does valency refer to?

Answer 7

How many epitopes there are on an antigen

Polyvalent antigens are better immunogens and activators of immune effector functions

Question 8

Differentiate affinity vs avidity

Answer 8

Affinity= strength of antigen/epitope binding (increases with somatic hypermutation)

Avidity = affinity + valency

Question 9

How do immune complexes form?

Answer 9

Soluble immunoglobulins bind polyvalent antigens and form complexes

Question 10

What determines the relative size of immune complexes formed?

Answer 10

The more equivalent the antibody/antigen ratio, the more likely large complexes will form

–This is only bad if the body cannot clear the complexes fast enough

Question 11

Which is the most powerful anaphylatoxin in the innate immune system?

Answer 11

C5a

Question 12

How are immune complexes usually cleared from the system?

Answer 12

C1R on RBCs circulate, pick up antibody/immune system and dumps them out in the liver (by kupffer cells) and spleen

Question 13

What is ITAM?

Answer 13

Immunoreceptor tyrosine-based activation motif

In b-cells + co-receptor: stimulated by Ag binding
In innate cells and their FcRs: stimulated by immune complexes

Question 14

What is ITIM:

Answer 14

Immunoreceptor tyrosine-based inhibitory motif

Found on B cells and other cells

Can be stimulated by immune complexes via inhibitory FcR

Question 15

How does activation of ITAM lead to a cellular response?

Answer 15

ITAM is activated via receptor cross-linking, which leads to phosphorylation of ITAM

Phosphorylated ITAM –> translocation of molecules –> transcription of inflammatory molecules

Question 16

Name one important inhibitory Fc receptor

Answer 16

FcRgamma R2B- binds to Fc portion of antibody and dephosphorylates proteins important for spitting out inflammatory molecules

Causes repression of inflammatory responses

Question 17

Describe the binding affinity of FcRI for immune complexes

Answer 17

FcRI has high affinity binding: low amounts of immune complexes are enough to activate them

Easy activation of ITAM

Question 18

Describe the binding affinity of Fc gamma RIIB (the major inhibitory receptor) for immune complexes

Answer 18

Fc gamma RIIB has a lower binding affinity and therefore requires high amounts of IC in order to sustain its response

More difficult activation of ITIM

Question 19

What is the issue with an Rh- mother giving birth to an Rh+ fetus?

Answer 19

If the mother is Rh-, it will develop antibodies against Rh ( the mother is sensitized against Rh)

If the mother has a second baby, the antibodies will attack the Rh+ of the fetus causing lysis of the RBCs (hydrops fetalis- severe anemia)

Question 20

How does Rhogam work?

Answer 20

Passive Rh immunization

Teaches the mother’s immune system not to react against Rh

B cells are inhibited via FcRIIB –> ITIM signaling

Question 21

What type of hypersensitivity reaction is an Arthus reaction?

Answer 21

Type III hypersensitivity –> immune complex disease

Question 22

What is the Arthus reaction?

Answer 22

Antibody-antigen immune complexes form –> compliment activation –> local inflammation and phagocytosis of the complexes

Question 23

Do immune complexes form in both primary and secondary immune responses?

Answer 23

Yes- generally it happens with the primary response if the infection lasts awhile.