Immunology Block: Imm # 5 - Antibodies/antigens/ Effector Mechanisms

Front 1

describe the difference between antigens and immunogens:

Back 1

immunogens illicit an immune response. All immunogens are antigens.


Antigens are things that bind to antibodies. Not all antigens are immunogens! Some can be allergins and tolerogens.

Front 2

describe the basic structure of an Ig:

Back 2

Y shaped.

Heavy chains are connected by disfulfide bonds. Thye're identical.

Light chains connected to heavy chains by disfulfide bonds. they're identical to each other too.

The N terms of the H and L chains are together the Antigen-Binding Site. This is the variable (V) region - each Ig has 2 of these.

The C region, or constant region, is at the C terminal of each and L chain and is involved in the effector action.

the AA sequence of the C (heavy) region is what determines if it's IgG, A, E, D, or M...and so this determines its biological action.

Note that light chains can be Lambda or Kappa.

Front 3

What gets across the placenta?

Back 3

IgG

Front 4

What's the first antibody made? What does somatic hypermutation do? What does converstion to IgG allow?

Back 4

First antibody made is IgM.

Somatic hypermutation in secondary sites allows for the selection of those antibodies which bind more tightly.

Converstion to IgG allows for presentation of the pathogen to phagocytes.

Front 5

difference between plasma and serum?

Back 5

plasma is the fluid portion of blood.

serum comes from coagulated blood - so it is absent of fibrinogen.

Front 6

Talk about the globulins again when you run serum out on a gel:

Back 6

first peak is the albumen peak, it's huge. Then there's alpha 1, alpha 2, beta, and gamma.

note that most immunoglobulins are in the gamma section.

Front 7

what drives the proliferation and clonal selection of B cells?

Back 7

antigen in the germinal centers of secondary follicles.

Front 8

talk about the 3 zones of germinal centers:

Back 8

dark zone - proliferation of B cells and somatic hypermutation.

Basal light zone: selection of those cells which bind the dendridic cells best.

Apical zone: class switching and generation of plasma/memory cells.

Front 9

What's unique about IgM and IgA secreted? while you're at it, describe the appearance of all the Ig's.

Back 9

Both are polymers - require a J chain for polymerization!

NOTE = IgA has a SECRETORY COMPONENT, because it's getting kicked out in mucous secretions and needs to survive outside the blood/lymph system.

IgM is a pentamer.

IgA is a dimer.

IgG and IgD look identical.

IgE is like IgG/D, but a little longer.

Front 10

prevalence of these? subclasses?

Back 10

IgG has 4 subclasses. Ig1 is the most common.

IgM is so big it's found only in the vasculature.

Most live about a week. IgG can last 3

Front 11

talk about the nifty little facts about each different class:

Back 11

IgE is all about allergic reaction and binds to mast cells.. Hemlith fighting.

IgA is in breast milk. It's also super important for activating the ALTERNATIVE COMPLEMENT PATHWAY (A = Alt) - there's basal activity here all the time.

IgD - no idea, stays bound.

IgG - crosses the placenta.

Front 12

WIthin an individual Ig, what are the regions?

Back 12

The Fab is the outer most region, which consists of the entire light chain (constant and variable).

It also includes the heavy chain variable sequence and one of the heavy chain constant regions (C1).

The Fc is the region that assigns biological activity. It consists of the heavy chain C2 and C3 regions.

Front 13

compare and contrast affinity and avidity:

Back 13

affinity is the strength with which a variable region binds an antigen. This is identical at all the antigen binding sites on the Ig.

Avidity - this is an additive effect of all the Ab regions on an individual Ig. So, IgM, with its pentamer and 10 possible antbody binding sites, tends to have really high avidity.

Front 14

what's a hapten?

Back 14

something too small to be immunogenic on its own.

typically, want to be greater than 10 kDa to illicit immune response (and shape, rigidity, location of epitodes, and tertiary structure matters too).

if too small, sometimes it'll complex with a carrier molecule to become immmunogenic.

Front 15

what epitopes are recognized preferentially by T cells or B cells?

Back 15

T cells can be amphipathic. interested in primary amino acid sequence.

B cells - hydrophilic! also, more interested in surface exposed, with special confirmations.

Front 16

If an Fc can bind to a cell's receptor, what do you call that antibody?

Back 16

cytophilic. this is seen when you coat with antibodies then present to phagocyte.

Front 17

function of IgG:

Back 17

most important in secondary Ab response.

ALSO: IgG 1 and 3 are cytophilic.

IgG 1, 2, and 3 can all activate the classical complement pathway!

Front 18

Function of IgM:

Back 18

Main player in the primary antibody response.

Good for blood borne pathogens.

Also can activate the classical complement pathway.

Front 19

IgA:

Back 19

secreted in secretions. Activates ALTERNATIVE COMPLEMENT PATHWAY.

Front 20

talk about 2 classes of pathogens and the kinds of immunity mounted:

Back 20

if it's extracellular, get antibody-mediated immunity (humoral).

if it's intracellular, get cellular-mediated immunity.

Front 21

if it's an extracellular pathogen and you make antibodies, what are possible outcomes?

Back 21

activate the complement pathway (either alternative or classical).

can opsonize with cytophilic

can neutralize

can ADCC (antibody dependent cellular cytotoxcisity).note that this is like opsonisation, but NK cells and eosinophils shoot out poisons into the offending invader

Front 22

talk about the complement pathway:

Back 22

there's classical, alternative, and lechtin.

classical is an adaptive response, medited by IgG 1 through 3 (and also IgM). takes a few days to kick in.

alternative is an innate response, as it's always on a little from basal IgA actiivty. begns at C3.

C3 is the main step. Cleavage makes lots of products.

Complement can cause invader lysis (MAC = membrane attack complex).

also, complement + antibody binding = SUPER OPSONISATION. See this with C3b.

Also, serves for chemotaxis. C5a.

C3a can degranulate mast cells to express histamine and stuff.

Front 23

Now, to talk about complement. What are the main pathways and which antibodies might be involved?

Back 23

there's classical, alternative, and lechtin. all we need to know about the lechtin pathway is that it's related to the alternative.

alternative is always on a little bit, involves IgA, and immediately starts at C3, which can be good if you have mutations in C1 and C2.

The classical pathway can involve IgG1, IgG2, and IgG3. It needs at least 2 IgG's to get going, or 1 IgM.

Note that there are 4 IgG's, but IgG4 doesn't help with complement.

Front 24

The complement pathway is divded into 3 phases. what are they?

Back 24

recognition and initiation by our Ig's, then amplification and opsonization by all of C3's cleavage products, then the MAC (membrane attack complex).

Front 25

Which complement proteins should we know?

Back 25

C3a, C4a, C5a = anaphalotoxins (all start with A, so does anaphalaxis). NOte that C5a is also involved in CHEMOTAXIS OF NEUTROPHILS.

C3b = buttering the biscuit for opsonisation.

C5b, C6, C7, C8, Poly C9 = cell lysis/MAC complex.

Front 26

talk about the kinds of things that tend to activate the various complement pathways?

Back 26

the classical complement pathway is more adaptive - in that it's activated by things like antibody complexes, IgG (which requires T-cell activation and isotpype switching).

The atlernative pathway is more constitutive, undergoes stronger activation by things like LPS and other bacterial toxins, and can also be related to IgA.

Front 27

What interleuken might be involved in allergies?

Back 27

At least Ig4, because you know that allergies are all about IgE, which requires isotype switching.