2. Innate Immunity Flashcards
Barriers of the innate immunity
- Mechanical: skin
- Chemical: pH of skin 5.5, stomach pH 1.2-3, vagina pH 4.5
- Biological: eg. lactoperoxidase in saliva and colostrums
What are soluble antimicrobial molecules?
Amphipathic molecules: positively charged aa’s on one side and negative on the other side -> makes “wormholes” in the membrane
(Defensins)
Function of immature dendritic cells
Antigen uptake and processing
Function: Mature dendritic cells
Antigen presentation, costimulation, T cell activation
Where do we find dendritic cells?
Immature dendritic cells found in peripheral tissues, migrate via afforestation lymphatic to regional lymph nodes -> mature dendritic cells found deep in the cortex
Development of macrophages
Myeloid progenitor (bone marrow) -> monocytes (blood) -> tissues: tissue resident macrophages, recruited macrophage (-> classically/alternatively activated)
Function: M1 (classically activates)
- Proinflammatory cells
- Promote Th1-Th17 immunity
- Host defense
- Antitumor immunity
Function: M2 (alternatively activated)
- Regulates wound healing
- Suppresses T cell responses
- Suppresses host defense and antitumor immunity
Apoptosis cells sends … signals
Find me, eat me, tolerate me
Three major types of I nnate lymphoid cells
Type I: IFN gamma producers (NK cell)
Type II: IL17 or IL22 producers
Type III: Producers of Th2 cytokines
Where can we find innate lymphoid cells?
Mucosa (gut, lungs), skin, adipose and lymphoid tissues
What kind of receptor does NK cells have?
Neither B or T receptor. Inhibitory and activating receptors.
One inhibitory and one activating NK cell receptor
Activating: NKG2D
Inhibitory: NKG2A
Explain frustrated phagocytosis
Eg. a parasite is too large to be taken up in the phagocyte -> phagocyte releases lysosomes to ECS instead
Process of endocytosis and phagocytosis
- Endocytosis: receptor binding -> clarhrin coated pit -> endosomes
- Phagocytosis: receptor binding -> actin polymerization -> phagosome
- Golgi sending out lysosomes with hydrologic enzymes
- > endosome, lysosome and phagosome join to form phagolysosome
What is opsonization?
Facilitation if phagocytosis by binding of antibody or complement protein to antigen
What can we use to cleave the Fc region of the antibody?
Papain
Fc gamma receptor
- Bind IgG
- Facilitate phagocytosis
- May suppress the function of B cells
Fc epsilon receptor
- Bind IgE
- high affinity form is on mast cells and basophils -> plays a role in allergy
PolyIg receptor (Fc receptor)
- Bind polymeric antibodies (IgA)
- Play a role in the transcytosis through the epithelium of the mucous membrane
Neutrophil effector functions
Phagocytosis, degranulation, NETs
Intravesical killing- oxygen dependent
NADPH oxidase in the mem. of the phagosome -> formation of ROS -> direct killing of microbe inside the phagosome
What is pus?
Live and dead neutrophils and tissue debris
What disease is caused by phagocyte oxidase deficiency?
Chronic granulomatosus disease (CGD)
Three major types of PPRs
Pattern recognition receptors in the membrane, secreted, or intracellular
Types of membrane PRRs
Lectin binding receptors, NK cell R, complement Rs, toll like Rs, scavenger Rs
Shape, morphology of toll like receptors
Horse shoe shape, leucine rich repeats, well known for PAMP recognition
Intracellular PRRs
Nod like receptors (NLR)-> recognition of bacteria, RIG like receptors-> recognition of virus
What is an inflammasome and what is it composed of?
Detecting PAMPs and DAMPs. Cytoplasmic multiprotein composed of NOD PRR and proteins like Caspase 1
How is the inflammasome activated by DAMPs?
Signal from outside will cause eg. K+ efflux -> activation of NLRP3, ASC and pro-caspase-1 -> release of interleukins (IL- 1beta, IL-18)
What are inflammasompathies?
Autoinflammatory diseases with a common feature; release of IL-1beta
Where are TLRs located in the gut?
Intracellularly and on the basolateral side of the gut epithelial cells
Examples of tissue resident macrophages
Kupffer cells, histiocytes, microglia, osteoclasts
Recruited macrophages
Classically activated and alternatively activated
Involved in the production of M1
IFNgamma
Involved in the production of M2
IL-4, IL-13
Innate-like cells
B1 B-cell, marginal zone B cells, iNKT cells, MAIT cells
