(5) Antigens & Immunogens, Complement Activation

molecule that initiates an immune response

immunogen

molecule that binds to the product/mediators of an immune response, such as antibodies or T cell receptors

**can be a protein, carbohydrate, lipid, or other similar macromolecule

antigen

Are all immunogens antigens?

yes

Are all antigens immunogens?

no

What are 4 examples of molecules that make good immunogens?

large proteins, large glycoproteins, large polysaccharides, large nucleic acids

Do phospholipids, glycolipids, lipids in general, small carbohydrates, small polypeptides, and amino acids make good or bad immunogens?

bad

True or false: The charge on a protein has an influence on that protein's immunogenicity.

false

True or false: The shape of a protein has an influence on that protein's immunogenicity.

false

True or false: The size of a protein has an influence on that protein's immunogenicity.

true

(size is directly proportional to immunogenicity)

The bigger the protein, the better (stronger) or worse (weaker) it is as an immunogen?

better

The smaller the protein, the better (stronger) or worse (weaker) it is as an immunogen?

worse

antigens that are too small to provoke an immune responses; attach to carrier molecules to become conjugated so that they can elicit a response

haptens

How can small, non-immunogenic molecules elicit an immune response?

conjugate with a large immunogenic molecule

antigenic determinant; certain region of an antigen molecule that binds to an antibody or TCR and stimulates an immune response

epitope

Epitopes are regions on the antigen that can bind to what two things?

antibody, TCR (via MHC)

True or false: An antigen can have multiple epitopes.

true

True or false: Epitopes are unique.

true

(think about it: antibodies have specificity for a certain epitope on an antigen - a certain epitope can't be recognized by all antibodies, only specific ones)

True or false: Most microorganisms have several antigens, which each can have multiple epitopes.

true

Immunogens are seen differently by B and T cells. What quality of an epitope do B cells recognize?

structure

(antibodies can't interact with it enough to recognize its full sequence - just binds to general structure)

Immunogens are seen differently by B and T cells. What quality of an epitope do T cells recognize?

linear sequence

(since antigen is chopped up by APCs and presented to T cells)

True or false: The complexity of a protein has an influence on that protein's immunogenicity.

true

(complexity is directly proportional to immunogenicity)

The more complex the protein, the better (stronger) or worse (weaker) it is as an immunogen?

better

The less complex the protein, the better (stronger) or worse (weaker) it is as an immunogen?

worse

In regards to epitopes, what classifies a molecule as a hapten? Why?

only one epitope, not complex enough to be immunogenic

(complexity is directly proportional to immunogenicity, and if an antigen only has one epitope, that's not very complex, so it is non-immunogenic, which is a hapten)

example of an immunogenic antigen with many identical epitopes

carbohydrate polymers

example of an immunogenic antigen with many different epitopes

(large) protein

Which 3 of the following are the strongest immunogens based on complexity?

A. amino acids

B. carbohydrates

C. lipids

D. complex proteins

E. haptens

F. simple peptides

G. steroids

B, D, F

Which 2 of the following are the weakest immunogens based on complexity?

A. amino acids

B. carbohydrates

C. lipids

D. complex proteins

E. haptens

F. simple peptides

G. steroids

A, E

Which has higher immunogenicity: lipids or steroids?

steroids

(more complex structure)

How does genetics play a role in determining immunogenicity?

some people are more responsive to an antigen than others

How is foreignness an important determinant of immunogenicity?

stronger immunogen is something that the body doesn't encounter regularly

How does persistence of an antigen determine immunogenicity?

if it is present for an abnormally long time, this gets the attention of the immune system

How does age determine immunogenicity?

immune system weakens with age, so older = less immunogenicity

How does nutritional status determine immunogenicity?

malnutrition weakens immune system = less immunogenicity

How does stress determine immunogenicity?

weakens immune system = less immunogenicity

How does overall health determine immunogenicity?

different health factors decrease immune response

Which of the following factors is most important in determining the immunogenicity of an antigen?

A. charge

B. shape

C. size

C

binding of an antibody to an epitope corresponding to an antigen that is different from the one the antibody was raised against

cross reactivity

close resemblance between foreign antigen and self antigen; exhibits immunological cross reactivity that may lead to autoimmune disorders

molecular mimicry

Many of the serum proteins that are a part of the complement cascade (10% of all serum proteins) are in what form? How are they activated?

inactive zymogens, cleaved into smaller molecules

Where are inactive complement proteins found?

blood

Where are complement proteins made?

liver

(also monocytes/macrophages)

refers to smaller subunits cleaved from unstable complement proteins that have biological activity (acts as a chemokine)

a

refers to larger subunits cleaved from unstable complement proteins that bind to membranes

b

Are opsonins examples of a or b subunits?

**prepare molecule for phagocytosis

b

Are cytokines examples of a or b subunits?

**lure in other leukocytes for the immune response

a

antibody or other substance that binds to foreign microorganisms or cells, making them more susceptible to phagocytosis

opsonin

enhancement of phagocytosis by coating an antigen with antibodies

tagging of particles and microorganisms for removal by immune system cells that have complement receptors

opsonization

What does the complement cascade do to immune complexes? (Ag-Ab linked complexes)

removes from blood by tagging with complement b fragments

In the complement cascade, what is the protein C3 cleaved into?

C3a, C3b

When C3 is cleaved into C3a and C3b, which subunit binds microbes and antibody/antigen complexes? (acts as a strong opsonin)

C3b

When C3 is cleaved into C3a and C3b, which subunit acts as a chemoattractant?

C3a

Both C3b and C4b bind microbes and antibody/antigen complexes. Which one is stronger?

C3b

C3b receptor present on antibodies to bind to C3b (which has attached to microbes)

CR1

In addition to opsonization and phagocytosis, the complement cascade recruits and activates phagocytic and inflammatory cells to the site of complement activation. For example, it plays a role in the activation of what cells in order to promote inflammation?

mast cells

(promotes inflammation by releasing histamine)

complement subunits that directly stimulate mast cell release of histamine (general name + specific proteins)

anaphylatoxins; C5a, C3a, C4a

What is the strongest anaphylatoxin out of C3a, C5a, and C4a?

C5a

(C5a > C3a > C4a)

Which of the complement subunits functions as the strongest chemoattractant and activator of leukocytes?

C5a

(strongest anaphylatoxin; also C3a and C4a)

Which three complement subunits play a role in mast cell activation, chemoattraction, and general activation of leukocytes? (in order from strongest to weakest)

C5a, C3a, C4a

complex of terminal complement components that forms a pore in the membrane of the target cell, damaging the membrane and leading to cell lysis

membrane attack complex (MAC)

What is the ultimate goal of the complement system?

form MAC to lyse microbes

Which two complement subunits are responsible for regulation of vascular tone via vasodilation & edema?

C2a, C5a

The complement cascade functions to remove immune complexes. Specifically, what cells clear antigen-antibody complexes from plasma, especially if they are opsonized by C3b?

erythrocytes

The complement cascade functions to remove immune complexes. Specifically, what cells destroy them in the liver and spleen? (after erythrocytes have brought them there)

phagocytes

Which of the following is involved in opsonization?

A. C3b

B. MAC

C. C3a

D. C4a

A

Which of the following is NOT attributable to complement activity?

A. acting as opsonins

B. walling-off the inflamed area

C. serving as chemotaxins

D. stimulating the release of histamine

E. forming a membrane attack complex

B

A large, complex molecule that triggers a specific immune response against itself when it gains entry into the body is known as a(n)...

A. interferon

B. antigen

C. antibody

D. complement

E. opsonin

B

Opsonins...

A. enhance phagocytosis by linking the foreign cell to a phagocytic cell

B. include antibodies

C. include a certain complement protein

D. include antibodies and a certain complement protein

E. have all of the above characteristics

E