Innate Immunity Flashcards
Basic properties Of Innate Immune Defense
Provide physical and chemical barriers (epithelia and associated commensals)
Rely on phagocytosis
Produce inhospitable environment (granulocytes)
Which type of immunity evolved first?
Innate Immunity before Adaptive Immunity
Two Animal Classes with only Innate immunity
Echinodermata
Urochordata
What do all innate immune defenses have in common
They rel on mechanisms that exist before the infection, are capable of responding rapidly to microbes, and react in the same way to repeat infections
Hematopoietic Antigen Presenting Cells
Neutrophils
Monocytes
Macrophage
Dendritic Cell
Hematopoietic Granulocytes
Eosinophil
Basophil
Mast Cell
Non-hematopoietic Epithelia
Simple Squamous Simple Cuboidal Simple Columnar Psuedostratified Columnar Stratified Squamous Stratified Columnar Transitional
Antimicrobial peptides (AMPs)
Antibiotic proteins secreted by epithelial cells - Targeted toward microbe-containing environment via secretory pathway
Activity of AMPs
Small peptides that form pores through the membranes of multiple microbes including Gram (neg and pos) bacteria, fungi, protozoa and some viruses
Defensins
AMPs produced by polymorphonuclear leukocytes
Commensals (Associated with Epithelial Tissues)
1) Compete for resources with more virulent organisms
2) Produce their own AMPs
3) Keep innate immune cells in an “attentive” state
4) Lower vaginal pH
Phagocyte Subsets (Circulating or Tissue Resident)
Neutrophil - Circulating
Macrophage - Tissue resident, but originally derive from circulating monocytes
Dendritic Cells - Tissue resident, but also monocyte derived (Langerhans cells - skin)
PMNs (4 things)
First phagocyte to emigrate into an infected tissue
Short lived, dying within a few hours after reaching an infected site
Phagocytose microbes
Produce cytokines that attract other PMNs
PMN actions to kill microbes (4)
1) Fusion with lysosomes which contain lysozyme, defensins, lactoferrin, hydrolases, and myeloperoxidase (MPO)
2) MPO catalyzes the production of HOCl from H2O and Cl-
3) NADPH oxidase dependent production of superoxide
4) Inducible nitric oxide synthase (iNOS) catalyzes formation of NO from arginine
Macrophages
Tissue resident phagocytes that differentiate from circulating monocytes
“Activate” upon encountering a microbe
PAMP
Pathogen associated molecular pattern (Macrophages)
PRR
Pattern Recognition Receptors (Macrophages)
Activity of Activated Macrophages (4)
1) Have recognized a PAMP through one or more PRRs
2) Have enhanced phagocytosis
3) Secrete pro-inflammatory cytokines
4) Couple phagocytosis to “antigen presentation” on MHC Class II molecules (Critical to adaptive immune response)
The Coupling of phagocytosis to the Class II MHC Pathway
1) Peptides of varying length and sequence result from phago-lysosome digestion of microbes
2) These peptides accumulate in endocytic vesicles that fuse with Class II MHC containing vesicles
3) If Class II MHC binds one of the peptides, this complex moves to the cell surface where it can activate T-Cells
Dendrites are similar to Macrophages
1) They are more efficient at processing phagocytosed microbes into antigens (Ag) for Ag-presentation
2) Dendrites extend from their cell body to increase the surface area available for MHCII: T-cell interactions
3) They are more efficient at migrating to the draining lymph nodes for Ag-presentation to adaptive immune cells
DCs are referred to as immune sentinels for the following reasons (4)
1) Like macrophages, they constantly sample their environment
2) Unlike macrophages, DC’s migrate via the lymphatics to the draining lymph node
3) Once in the lymph node, DC’s come into greater contact with T and B cells, initiating the adaptive immune response
4) In addition to expressing high levels of MHCII, DCs increase their expression of co-stimulatory proteins
Co-Stimulatory proteins associated with Dendritic cells
CD80, CD86, CD40
Why don’t phagocytes defend against pathogenic helminths?
They are too big to be phagocytosed
Three types of Granulocytes
Eosinophils
Basophils
Mast Cells
Granulocyte Qualities
1) Non-phagocytic
2) 3 types of Granulocytes are more similar to one another than the 3 types of phagocytes
3) Defend their host by releasing granule contents into the extracellular space (Degranulation)
4) Activated by Ag-bound IgE binding cell surface FceRI
Granule Secretions
Cytokines
Leukotrienes
Prostoglandins
Granule Exocytosis
Proteases - Disrupt parasite tegument (link to host) Vasoactive amines (Histamine) - promote parasite expulsion from gut
