Mimm 314: Distribution And Fct Of Ig Isotypes

Front 1

What is the primary role of B lymphocytes during an immune response?

Back 1

Production of Ab

Front 2

What are the roles of Ab (2)?

Back 2

Destruction of extracellular microorganisms
Prevention of the spreading of intracellular pathogens

Front 3

What are the 3 ways Abs can help protect the host?

Back 3

Neutralization: Binding pathogen and stopping it from entering the host cell
Opsonization: Coat pathogens, Ab facilitate the uptake and the destruction of the pathogen by phagocytic cells that express receptors that rec'z the Fc portion of the Abs
Complement activation: activation of complement enhances opsonization and some complement ptns can directly destroy some pathogens by pore formation

Front 4

Describe IgM

Back 4

FirstAb produced in an immune response
Low affinity but forms pentamers with 10Ag-binding sites (high overall avidity)
Large-size => blood and lymph
Efficient activation of the complement cascade

Front 5

Describe IgE, IgG and IgA

Back 5

Smaller than IgM so they can easily diffuse from blood--> tissues
IgG and IgE: Monomeric
IgA: can form dimers
High affinity (selected from germinal centers)

Front 6

What is IgG for?

Back 6

Principle isotype in the blood and extracellular fluid
Opsonization and activation of the complement cascade

Front 7

What is IgA for?

Back 7

Found in Secretions (mucus of the intestinal and respiratory tracts)
Less potent in opsonization and activation of the complement cascade
Neutralization

Front 8

What is IgE for?

Back 8

Very low levels in the blood and extracellular fluid
Bind to receptors on mast cells that are found beneath the skin and mucosa and along blood vessels in connective tissue
->mediators -> coughing, sneezing and vomitting (mechanical expulsion of the pathogen)

Front 9

Which Ig has the lowedt mean serum level?

Back 9

IgE

Front 10

Where are IgA found?

Back 10

Lamina propria (connective tissue which lies immediately below the basement mb of many surface epithelia)

Front 11

What does IgA bind to?

Back 11

Secreted as a dimer with one J chain and binds through its Fc portion to the poly-Ig receptor present on the basolateral surfaces of epithelial cells

Front 12

What is transcytosis?

Back 12

Internalization and transport of vesicles to the luminal face of epithelial cell

Front 13

What happens at the luminal face?

Back 13

The poly-Ig receptor is cleaved and its extracellular portion (secretory component) remains attached to the Fc portion of the IgA

Front 14

What are the principle sites of IgAsecretion?

Back 14

Gut, respiratory epithelium, lactating breast, exocrine glands: salivary and tear glands

Front 15

What is the primary fctnal role of IgA?

Back 15

Protection of epithelial surfaces from infectious agents through neutralization (prevention of attachment of bacteria, virus or toxins to epithelial cells)

Front 16

How can IgA protect infants?

Back 16

Secreted in breast milk, transfered to the gut of infant where they provide protection from newly encountered bacteria

Front 17

How is maternal IgG is transported across the placenta?

Back 17

Directly into the bloodstream of the fetus (during intrauterine life)

Front 18

Which IgG transport protein is involved in transplacental transport? Where is it found?

Back 18

FcRn
In the placenta

Front 19

How many FcRn molec bind 1 IgG? Where do they bind?

Back 19

2 FcRn bind 1 IgG
Bind Fc portion of IgG

Front 20

Where is FcRn found in adults?

Back 20

Gut
Liver
Endothelial cells

Front 21

What is the role of FcRn?

Back 21

Regulate the level of IgG in serum and other body fluids

Front 22

What is the distrivution of Igs in the body?

Back 22

IgM and IgG: blood
IgG and monomeric IgA: extreacellular fluid
Dimeric IgA: secretions across the epithelia
IgE: ass't with mast cells just beneath epithelial surfaces
(especially of the respt tract, GI tract and skin)

Front 23

page 6: examples neutralization of bacterial toxins by Ab

Back 23

Look at old exams to se if you need to know this

Front 24

What do toxins bind?

Back 24

Cellular receptors
->In many toxins, the receptor binding domain is on one polypeptide chain and the toxin fct is carried by a second polypeptide chain

Front 25

What happens when Ab bind the receptor binding domain?

Back 25

Can prevent the toxin from entering the cell and thus protect the cell from the attack by the toxin portion
-> Neutralizing Ab

Front 26

What are the principal neutralizing Ab?

Back 26

IgG

Front 27

Where do IgA neutralize toxins?

Back 27

Mucosal surfaces of the body

Front 28

Can Ig's block viruses?

Back 28

Yes, high affinity IgG and IgA can neutralize viruses by blocking the binding of a virus to host cell surface receptors
(Ab can block viral entry or fusion of cell membranes)

Front 29

What are adhesins?

Back 29

Bacterial cell surface molec that help them bind to the surface of host cells

Front 30

What is the cell surface protein of gonorrhea?

Back 30

Pilin
=>Lets the bacteria adhere to epithelial clls of the urinary and reproductive tract and is essential for its infectivity
->Abs vs pilin can prevent infection

Front 31

Can Abs activate complement?

Back 31

Yes

Front 32

How is complement activated?

Back 32

Series of proteolytic cleavages
->Inactive plasma components are cleaved to form proteolytic enzymes that attach covalently to the pathogen surface
-Covalently attached complement fragemnts (mostly C3b) act as opsonins: promote uptake and removal by phagocytes
->Complement fragments with inflammatory and chemotactic activity are released and recruit phagocytes to the point of infection
-Teminal complement components can make a mb-attack complex that damages some bacteria

Front 33

By which path do Abs initiate complement?

Back 33

Classical path

Front 34

What is the first part of the classical complement path?

Back 34

C1 (made of C1q, C1r, C1s)
Activated when Abs, attached to surface of a pathogen , bind C1q

Front 35

Which Ig's can bind C1q?

Back 35

IgM, IgG

Front 36

Describe C1q.

Back 36

6 globular heads joined to a common stem by long filamentous domains
Each globular head can bind 1 Fc domain

Front 37

How many globular heads of C1q need to be bound for it to be activated?

Back 37

2 or more

Front 38

Why doesn't IgM bind C1q in the plasma?

Back 38

IgM has a planar conformation in the plasma

Front 39

How can IgM bind C1q?

Back 39

When it binds a pathogen, IgM changes conformation (staple) and this exposes binding sites for C1q heads

Front 40

What initiates the classical path?

Back 40

Activation of C1q

Front 41

What forms immune (Ab:Ag) complexes?

Back 41

Small soluble Ags

Front 42

How are immune complexes removed from circulation?

Back 42

Action of complement through binding of C1q

Front 43

What happens whenimmune complexes bind C1q?

Back 43

Leads to binding of C4b and C3b to the complex
C3b then binds CR1 on the surface of erythrocytes
Erythrocytes transport the complexes formed by the Ag, Ab and complement fragments to the liver and the spleen
Macrophages bearing receptors for bound complemen components and the Fc portion of Abs remove the complec from the erythrocytes and degrade the immune complexes

Front 44

Where do immune complexes deposit?

Back 44

Basement mbsof small blood vessels, espoecially the ones in the renal glomeruls where the blood is filtered to fomr urine (must be removed)

Front 45

What happens to the immune complexes thatpass through the basement mb of the glomerulus?

Back 45

Bind to CR1 on renal podocytes (cells beneath basement mb)

Front 46

What happens in systemic lupus erythematous (kidney autoimmune disease)?

Back 46

Excessive lvls of immune complexes accumulate on the renal podocytes and this leads to damage of the glomerulus
->can get kidney failure

Front 47

What are Fc receptors?

Back 47

Link between Ab-coated pathogen and accessory cells

Front 48

What are accessory cells?

Back 48

Macrophages and neutrophils
NK, eosinophils, basophils and mast cells (secrete stored mediators when thei Fc receptors are engaged)

Front 49

What do Fc receptors bind?

Back 49

Fc portionof Abs
(Fc-gamma-R's bind IgG)
(Fc-alpha-R's bind IgA)
(Fc-epsilon-R's bind IgE)

Front 50

What on Fc mediates specific recognition?

Back 50

Alpha chain

Front 51

What mediates signal transduction on Fc?

Back 51

Gamma chain (closely related to the zeta chain of TCR)

Front 52

Describe FcγTII-A.

Back 52

α and γ chains fused into a single chain receptor

Front 53

Describe FcγRII-B1 and B2.

Back 53

Single chain receptor that contains an ITIM motif (inhibitory
->Important for B cells

Front 54

Whe do Fc receptors generate intracellular signalling?

Back 54

When they're cross-linked

Front 55

Can free Ig bind Fc receptors?

Back 55

Yes, most of them, with low affinity, but they can't cross-link Fc receptors

Front 56

Where do Ag-bound Abs bind to multiple Fc receptors?

Back 56

Surface of accessory cell

Front 57

What can the intracellular signal made from the cross-linking do?

Back 57

Activate or inhibit accessory cells

Front 58

What helps uptake of pathogens by phagocytic cells?

Back 58

Binding of complement

Front 59

When is phagocytosis by complement receptor important?

Back 59

Early in immune response, before isotype switching of Ab

Front 60

Does IgM have an Fc receptor?

Back 60

No, but can still activate complement

Front 61

This time I want to go to Jeju Island together.

Back 61

이번엔 제주도 여행에 같이 가고 싶었어요.

Front 62

What do NK cells do?

Back 62

Kill virally infected host cells that are bound by Abs
-> Ab-dependent cell-mediated cytotoxicity (ADCC)

Front 63

What Fc do NK cells express?

Back 63

FcγRIII which recognizes IgG1 and IgG3 and when cross-linked triggers ther release of cytoplasmic granules contianng perforin and granzymes by the NK cell

.:ADCC is another mechanism, by which, through engaging an Fc receptor; Abs can direct an Ag specific attack by an effector cell that itself lacks specififcity for Ag**

Front 64

What are mast cells?

Back 64

Vascularized connective tissue just beneath body and epithelial surfaces (GI and resp tracts, dermis)
Granules that contain histamine that make local blood vessels more permeable
->influx of PMNs, macrophages, eosinophils and lymphocytes

Front 65

What Fc's do mast cells express?

Back 65

FCγRIII and FcεRI

Front 66

What else expressed FcεRI?
What activates it?

Back 66

Basophils also express it
Eosinophils activate it

Front 67

How does free IgE contrast IgG?

Back 67

Free IgE has very high affinity for FcεRi and mast cells are usually stably ass't with IgE

Front 68

How are mast cells activated?

Back 68

Binding of IgE and FcεRI and when the bound IgE is cross-linked by multivalent Ag

Front 69

What are the 3 important fcts?

Back 69

-Recruitment of effector elements to the site of infection
-They increase the flow of lymph from sites of infection to the regional LN where lymphocytres are activated
-Trigger muscular contraction that can contribute tothe physical expulsion of pathogens