Innate Immunity Learning Questions Flashcards
What are 5 genetic deficiencies of the innate immune system?
- Congenital neutropenia
- Chronic granulomatous disease
- Leukocyte adhesion deficiency (LAD)
- Complement defects (various)
- Chediak-Higashi Syndrome
What is congenital neutropenia?
(still have some protection due to NK cells)
- Lack of GM-CSF
- Frequent bacterial infections
What is chronic granulomatous disease?
- Inability to produce hydrogen peroxide and hypochlorous acid
- Inability to kill phagocytosed bacteria
What is leukocyte adhesion deficiency (LAD)?
- Lack of integrin subunit, the common beta chain
- Inability to recruit innate immune cells to site of inflammation
- Increased susceptibility to bacterial, fungal and viral infections
What are complement defects (various)?
- Increased susceptibility to bacterial infections
- Reduced ability to remove immunocomplexes
What is Chediak-Higashi syndrome?
- Defect in gene LYST (CHS1), a lysosomal trafficking gene that affects lysosomes and melanosomes
- Increased susceptibility to bacterial infections
What are defensins and cathelicidins?
- Major families of antimicrobial peptides
- Widely expressed in a variety of epithelial cells & sometimes leukocytes
What are defensins and cathelicidins?
- Major families of antimicrobial peptides
- Widely expressed in a variety of epithelial cells & sometimes leukocytes
- Most are short peptides (
What are defensins&cathelicidins role in the innate immune system?
Antimicrobial, chemotactic and regulatory activities
- Protect against bacteria, fungi, viruses and parasites
- Ancient arm of innate immune system that evolved to directly neutralize invading microbes
- 100s of defensin proteins have been identified from amoeba, plants, birds, mammals, etc.
How are defensins and cathelicidins classified?
Based on their secondary structural features
- Cathelicidins (CAtionic HELical, bacteriCIDal proteIN) are alpha-helical peptides
- -Human cathelicidin LL37 is highly expressed by PMNs and numerous mucosal and epithelial cell types
- Defensins are beta-strand peptides connected by disulfide bonds
What do Defensins and cathelicidins do to the cell membrane? What other function do they have?
- Interact with microbial cell wall membrane components to increase cellular permeability leading to cell death.
- They also act to modulate the inflammatory response
What are the two main classes of defensins?
Alpha and beta (based on linking pattern of the cysteines)
What is Alpha defensin?
- 29-35 AA long
- Highly concentrated in granules of PMNs and Paneth cells of the small intestine
- Production is regulated by pro-inflammatory cytokines
- 6 types of human alpha-defensins
Two types of alpha defensinL
- Human neutrophil peptide (HNP) 1-4 are primarily expressed with PMNs, monocytes, and lymphocytes
- Human defensins (HD) 5-6 are mainly expressed in Paneth cells
What is Alpha defensin?
- 29-35 AA long
- Highly concentrated in granules of PMNs and Paneth cells of the small intestine
- Production is regulated by pro-inflammatory cytokines
