Immunogenetics

Question 1

What are the essential functions of the immune system? (3)

Answer 1

1. Detect infection
2. Eliminate or contain the infection
3. Tolerate oneself

Question 2

What are the major components of the innate Immune system?

Answer 2

Two Major divisions:

Cell-mediated (cellular):

• Natural Killer (Nk) Cells: Responds to viral infections & some tumors
• Antigen Presenting Cells (APC’s): Phagocytize bacteria and present foreign peptides on cell membrane to activate secondary pathways. Includes Neutrophils, macrophages, & Dendritic Cells.

Complement-mediated:

• Capable of destroying microbes directly by perforating their membrane
• Can also mark cells for phagocytes by coating their microbial surface

Question 3

What is the major challenge of the Innate IS?

Answer 3

Recognition:

• Receptors are germ line-encoded (non-rearranging) & relatively few in number
• Repertoire of selection reflects evolutionary processes
• No single physiological system; Diverse defense mechanisms

Needs to overcome:

• Enormous molecular variability of MO’s
  
  • Due to High mutation rate of MO’s
• Discrimination of self & non-self

Question 4

How does the innate immune system recognize foreign pathogens?

Answer 4

Pathogen-Associated Molecular Patterns (PAMP) of the MO’s are recognized by Pattern Recognition Receptors (PRR) expressed on immune response cells.

PRRs:

• Germ-line encoded membrane receptors which respond to PAMPs (& DAMPs)
  
  • Belong to the Toll-Like Receptor (TLR) family
• They mediate the:
  
  • Initiation of Agn-specific adaptive immune response
  • Release of Cytokines

PAMPs:

• Patterns present on/in bacteria that is distinct from self

Question 5

What are the example PAMPs?

Answer 5

1. Bacterial Carbohydrates Lipopolysaccharide (LPS), Mannose
2. Nucleic Acids: Bacterial or viral DNA or RNA
3. Bacterial Peptides: Flagellin, microtubule elongation factors
4. Peptidoglycans & lipoteichoic acids (from Gram+ bacteria)
5. N-FormylMethionine (N-fMet)
6. Lipoproteins
7. Fungal Glucans & Chitin

Question 6

How do Neutrophils accomplish protecting the host?

Answer 6

Neutrophils “Chase” bacteria via chemotaxis:

1. Pathogens secrete a foreign substance (PAMP) which the neutrophils recognize via PRRs.
2. Neutrophils leave the bloodstream to reach the site of infection via Diapedesis (Requiring CD18 on the neutrophils)

Question 7

Describe Leukocyte Adhesion Deficiency (LAD-1)

Answer 7

LAD is the failure of leukocyte migration to the sites of infection

Inheritance: Autosomal Recessive

LAD-1:

Cause: Defect in CD18 (B-chain of B2 integrins)

Result: recurrent bacterial & fungal infections, & Impaired wound healing

Question 8

Describe Chronic Granulomatous Disease

Answer 8

Chronic Granulomatous Disease:

Inheritance: X-linked; Rare (1 in 200,000 to 1 in 1,000,000)

Cause: Mutation in Phagocyte Oxidase (Cytochrome B558)

Result: Defective production of Reactive Oxygen Species (ROS), & thus recurrent infections & granuloma formation.

Question 9

Describe the components of the Adaptive immunity

Answer 9

Two major divisions:

1. Cell-mediated (Cellular)
   
   1. Primarily T-cells
2. Ab-mediated (Humoral)
   
   1. Primarily B-cells