Lec. 3 Antigens & Histocompatibility Complex

Exam 1

What factors influence our immune system to respond to immunogens?

Age, Overall health, Route of inoculation, Dose (too little → doesn’t create lasting immunity, too much → ignores antigen), genetics

Why does our body not cause an immune response to antigens entering the oral cavity?

Believed that we don’t create an immune response orally because then we could be very responsive to foods.

Define immunogenicity. What are the 4 things it depends on?

Ability of an antigen to stimulate a host response

• Macromolecular size: has to be 10,000 daltons

• Foreignness: super unrelated, heightened response chance

• Chemical composition & molecular complexity: The more irregular/complex the immunogen is, the more efficient it is at triggering a response

• Ability to present on MHC

What is an epitope/antigenic determinant?

Part of protein (on MHC) that is shown to T or B cells

What is the size of a linear epitope and what WBC’s recognize it?

short, single chain

• Seen by T & B cells

What is the size of a conformational epitope and what WBC(s) recognize it?

folded chain & can be brought together

• B cells (can recognize the folding)

What could make an antigen more immunogenic?

when an antigen consists of many different sequences (complex)

Define nonimmunogenic. What are haptens? Give an example.

Nonimmunogenic: small substances that can’t cause response

Haptens: small particles that don’t cause a response (a.k.a nonimmunogenic) until bound to a carrier molecule.

• ex. catechols from poison ivy bind to tissue carrier protein and then cause a reaction

Define Adjuvant. How does this help with creating immunity? What’s an example?

Adjuvant: substance used to enhance immune response by acting as an irritant and stimulating PRRs.

• Irritant reaction caused by it attracts more immune cells and increases immunity.

ex. Aluminum salts in Hep B shot

What is an autoantigen?

• Host antigens that do not create an immune response → if a response does occur then it is likely an autoimmune disease

What is an Alloantigen? What do we do with this information medically?

Antigen from other members of the host’s species (other people’s antigens)

• Blood & transplants has to be checked for close matches to prevent rejection due to different antigens

Define heteroantigens

Antigens that aren’t from the same species. Ex. animal antigens vs. human antigens

Define heterophile antigens. Give an example of how this can help show an infection of a disease (real-life disease)

Heterophile antigen: antigens from unrelated species (ex. plants vs. animals) but have very similar structure to each other that it can cause a reaction.

Real-life disease: EBV which causes mono was once tested for by exposing the patient’s (potentially infected) blood to sheep, horse, or cow blood. The animal blood had antigens that would get bound by the infection and clump, showing a positive test for EBV.

What two tests were used to check for EBV? What was the difference between them?

Paul-Bunnell Test: used sheep

Monospot test: cow & horse blood

What are some facts about MHC (HLA)?

• On all nucleated cells (NOT RBCs)

• Linked to genetics

• Serve as peptide antigen carriers for recognition by T cells

• Determines compatibility of transplanted tissue

• Crucial for development of humoral & cellular immunity

MHC is encoded in DNA and all on the same chromosome. What chromosome are all MHC encoded from and how many classes are there? How is it inherited (what’s the word for this)?

Chromosome 6

• Class 1: 3 Loci (A-C)

• Class 2: D region (DP-DR)

• Class 3: found between class 1 & 2. Codes for C4a&b, C2 & B

Haplotype: inherited as a group

What are the three classes of MHC in charge of doing? What cells are classes 1 & 2 present on?

Class 1: Antigen recognition (cell surface) - All nucleated cells

Class 2: Antigen recognition (cell surface) - APCs

Class 3: secrete proteins (cytokines)

MHC in humans are polymorphic and codominant. What does this mean?

Polymorphic: Variable due to thousands of alleles.

Codominant: Mom and dad allele are expressed on all cells

What cells/organ has the lowest amount of MHC in/on it? How does this help medically?

Liver, allows chances of transplant rejection to be very low.

Other cells: neural cells, muscle cells, sperm cells

What 2 things does MHC 1 structurally have?

alpha chain w/ 3 domains & beta-2 microglobulin

What does MHC 1 specifically present to cytotoxic T cells (CD8+)?

endogenous antigens: they come from within the cell (ex. reg. cell peptides, viral peptides, tumor peptides)

What happens when a cytotoxic T cell (CD8+) interact with MHC 1 showing a foreign/bad peptide?

If the Tc cells marks it as foreign it releases enzymes (perforins & granzymes) to kill the cell.

Because MHC I binds stuff already found in the cell, what kind of binding cleft can you expect for it to have? (open or closed?)

Closed b/c it binds short peptides

What cells express MHC II? What are the structures of MHC II?

• APCs: B cells, monocytes, macrophages, Dendritic cells, thymic epithelial cells

Heterodimer: 2 non-covalently linked polypeptides encoded by separate MHC genes, also has 1 alpha and beta chain

What does MHC II specifically present to T helper cells (CD4+)?

Exogenous antigens: antigens that aren’t found/made in the cell. (ex. bacterial peptides, fungal, parasitic - phagocytosed)

What does the helper T cell do when it interacts with foreign antigen?

Releases cytokines that cause B cells to divide and become plasma cells to produce antibodies

Because MHC II binds stuff that came from outside the cell, what kind of binding cleft can you expect for it to have? (open or closed?)

open b/c it binds larger peptides from phagocytosed particles

Because MHCs are inherited as a haplotype from each parent, it can be used to check what two things about a person?

• Paternity & ancestry

What alleles are associated with the following diseases?

1. Ankylosing spondylitis

2. Celiac disease

3. Rheumatoid arthritis

4. Type 1 diabetes

5. Psoriasis

1. Ankylosing spondylitis → B27

2. Celiac disease → DQB-1

3. Rheumatoid arthritis → DRB-1

4. Type 1 diabetes → DQB-1

5. Psoriasis → C-w6