IHO Week 1 Diebel Flashcards
Major Functions of Innate Immunity
- Complement activation 2. Inflammation 3. Cell activation (cytokine and chemokine production, phagocytosis and other killing microbes) 4. priming of the adaptive immune response
3 Things Recognized by the Innate Immune System
- Foreign molecular structures called PAMPs 2. stress or damage indicators aka DAMPs 3. absence of certain ‘self’ MHC1marker molecules by NK cells
PRRs
pattern recognition receptors; 13 TLRs are included in this
PRRs that recognize PAMPs do not activate phagocytosis and do trigger cell signaling leading to gene transcription events to foreign material
TLRs
C-Type Lectin Receptors
Mannose, Dectin 1, DC-SIGN
Scavenger Receptors
SR-A and SR-B
Steps Phagocytosis
- bacterium attaches to membrane and evaginations called pseudopodia 2. ingested to form phagosome 3. fuses with lysosome 4. bacterium is killed and digested by lysosomal enzymes 5. digestion products released from cell
Phagocytosis Oxidative Attack from:
Reactive Oxygen Species (O2, OH, H2O2, HClO) and Reactive Nitrogen Species (NO, NO2, ONOO-)
Alternative Pathway to activate the complement system
innate immune defense strategy which results in opsonization and facilitated uptake of the coated microorganism by phagocytosis
Classical Pathway to Activated by
Antibodies or mannose binding lectin
Complement activation is a cascade reaction leads to:
opsonization, chemotaxis of phagocytes, increased blood flow, increased permeability, damage to plasma membranes on cells, G(-) bacteria, enveloped viruses, and other organisms, release of inflammatory mediators from mast cells
Classical Pathway (Adaptive Immunity) direct destruction
- C1q binds to antigen: antibody complex; cleaves and activates downstream complement components 2. C5b binds to the membrane associated with the antigen:antibody complex which leads to the formation of the membrane attack complex
Lectin Pathway (Innate Immunity) direct destruction
- Mannose binding protein bound to bacterial carbohydrates mimics C1q -> cleavage and activation of downstream complement components 2. C5b binds to the membrane to form attack complex
Alternative Pathway (Innate Immunity)
C3 is spontaneously cleaved or cleaved by C3b by serum proteases activated by bacteria; C3b binds to bacterial and yeast cell walls and viral envelopes; bound C3b leads to the downstream activation of the complement components
A Components-C3a, C4a and C5a action
-chemotactic factors that direct migration of/degranulation of PMNs and macrophages and degranulate mast cells and basophils to large amounts of histamine
Potency of A Complement Components
C5a»C3a»C4a
What complement deposits on any surface with an exposed amine or hydroxyl ie bacteria cell
C3b and C4b
What complement acts as opsonins and further cleaves C3 to ramp up signaling at the surface
C3b and C4b
What are inactivated when bound to host cells by decay accelerating factor
C3b and C4b
What complement binds to microorganisms or host body cells
C5b
What complement acts as a focal point for the deposition of the membrane attack complex?
C5b
What complement associated with CD59 protectin and homologous restriction factor to prevent formation of membrane attack complex
C5b
Phagocytosis-Opsonin Receptors: Collagen-domain receptor examples and ligands
examples: CD91/calreticulin
ligands: collectins SP-A, SP-D, MBL; L-ficolin; C1q
Phagocytosis-Opsonin Receptors: Complement Receptors examples and ligands
ex: CR1, CR3, CR4, CRig, C1qRp
ligands: complement components and fragments
Phagocytosis-Opsonin Receptors: immunoglobulin Fc receptors
ex: FcalphaR and FcgammaRs
ligands: specific IgA or IgG antibodies bound to antigen and CRP
Hallmarks of Inflammation
-edema, hyperthermia, local hypoxia, extravasation (influx of WBC via IL-8)
What increases vascular permeability besides Leukotriene D4
histamine-complement C5a stimulation of basophil and mast cell degranulation
What causes vasodilation and increased vascular permeability
prostaglandin E2-complement C5a stimulation of basophil and mast cell degranulation
What causes neutrophil chemotaxis, increased vascular permability
Leukotriene-complement C5a stimulation of basophil and mast cell degranulation
What besides histamine increased vascular permeabillity
Leukotriene D4-complement C5a stimulation of basophil and mast cell degranulation
Macrophages Triggers of Inflammation: 3
TNF, IL-1 and IL-8
can cause a fever, stimulates expression of E-selectin
TNF
induction of local inflammation; activates endothelial cells to express adhesion molecules; induces the production of chemokines to recruit leukocytes and role in fever
IL-1
chemotaxis
IL-8
activation of phagocytic cells and NK cells in trigger of inflammation
IFNgamma
Name 3 changes in tissue during acute inflammation
- increased blood supply 2. increased capillary permeability 3. increased leukocyte migration
Cells in acute inflammation
more neutrophils and activated helper T cells
Cells in chronic inflammation
more macrophages, cytotoxic T cells and B cells
Important Inflammatory Cytokines (3)
TNFalpha, IL-1 and IFNgamma
More migration in high shear or low shear
low shear
3 Step Model of Leukocyte Adhesion
- Tethering with CD15 and E-selectin 2. Triggering with direct signal and chemokines 3. Adhesion-activation of integrins and CR3/LFA-1, ICAM-1
histamine main source and action
mast/basophils: increased permeability, smooth muscle contraction, chemokinesis
5HT
platelets/mast cells: increased permeability, smooth muscle contraction
platelet activating factor main source and action
basophils/neutrophils/macrophages: mediator release from platelets, increased perm., smooth muscle contraction, neutrophil activation
IL-8 main source and action
mast/endothelium/monocytes and lymphocytes: polymorph and monocyte localization
C3a main source and action
C3: mast cell degranulation, smooth muscle contraction