Innate Immunity Flashcards
What are the four main functions of the innate immune response?
- complement activation
- inflammation
- cell activation
- priming of the adaptive immune response
What is the basis for the innate imune response? What is the body trying to do?
The basis is the recognition by TLRs of PAMPs and DAMPS (or host cells that don’t have the appropriate markers) and signal phagocytosis of those cells
What are defensins and cathelicidins?
THey are small antimicrobial peptides that are produced in cells of the physical barrier - mostly epithelial cells but some leukocytes as well
How do defensins and cathelicidins differ structurally?
cathelicidins are alpha helical peptides while defensins are beta strand peptides connected by disulfide bonds
How do defensins and cathelicidins promote bacterial dcell death?
They carry positive charges that interact with the cell membrane components, then once they integrate in the membrane they dimerize and pull the membrane apart to increase cellular permeability, resulting in cell death
Stimulation of the TLRs by PAMPS or DAMPS results in activation of the “mother of all immune system tranxcription factors” which is…
NF-KB
the MyD88 depentent pathway is common to all TLRs except for…
TLR3
What are the three distinct pathways that are common to TLR signalling?
- MyD88 dependent production of inflammatory cytokines
- MyD88 dependent production ofINF-alpha
- MyD88 INdependent produciton of INF beta and maturation of dendritic cells
While C3b, C4b and C5b of complement bind to the membrane of invaders, what do the “a” components do?
They act as chemotactic factors and activate PMN and macrophage degranulation
If C3b and C4b bind to host cells, what inactivates them?
decay-accelerating factor (DAF)
WHat are the hallmarks of inflammation?
influx of fluid (edema), increased temp, local hypoxia, influx of white blood cells
When C5a triggers basophils and mast cells to degranulate and activate, what inflammatory mediators are released?
histamine (increase permeability), PGE2 (vasodilation and permeability), leukotriene D2 (neutrophil chemotaxis), Leukotriend D4 (permeability)
What cytokines are released from macrophages and what do they do?
- TNF - cause fever, stimulate E selectin expression
- IL-2 - pyrogen, stimulate expression of E selectin
- IL-8 - chemotaxis
How do the cell populations differ in acute vs chronic infection
acute: more neutrphils and activated T helpers
chronic: more macrophages, cytotoxic T cells and B cells
What three cytokines are the most important inflammatory cytokines?
IL-1, TNFalpha and IFNgamma
What cells are the primary producers of TNF alpha?
macrophages an dother mononuclear phagocytes
THrough what transcription factor does TNF alpha induce further inflammation and through what molecule does it induce apoptosis?
NF-KB and caspase 8
Does diapedesis usually occur at the arterial or venule end? Why?
venule - because there you have a slighly lower charge and shear of the blood stream so that leukocytes can actually recognize adhesion molecules.
Signals from inflammation allows for the production of what molecule that binds to proteins on the surface of leukocytes to start the initial interaction for diapedesis?
E-selectin
What CD marker on macrophages in particular binds to E-selectin?
CD15
When the leukocyte is attached thorugh E-selecting and it receives cytokine signaling telling it there’s inflammation, what additional adhesion molecule is upregulated? What will it bind to on the cell?
ICAM1
It will bind to CR3/LFA-1 on the leukocyte
What about chemokines’ binding sites allows them to attach nonspecifically to the luminal side of the epithelium?
They have a binding site for carbohydrate groups on proteoglycans - which are everywhere.
Eosinophils carry what molecule in its granules as a potent toxin against helminth worms?
major basic protein
What are some ways to differentiate basophils from mast cells?
mast cells are mononuclear cells, they are present in tissues and not in the circulation and they are mediators of the immediate allergic response
What are the two precursors that dendritic cells can be derived from?
- myeloid progenitor leads to myeloid (or bone marrow) DCs
2. lymphoid progenitor develps plasmacytoid DCs
How do the myeloird and plasmacytoid CDs differ in terms of localizaitons?
myeloid - diffuse
plasmacytoid - rsestricted to T cell areas of secondary lymphoid organs and tissues
What are the steps of phagocytosis?
- bindings (bia FcR, Cr or MR)
- engulfement
- phagosome formation (acidification, cytotoxic molecules, proteolysis)
- lysosome fusion (digestioon)
- membrane disruption/fusion - present the antigen on MHC
What two CD markers are imporant for the NK cells?
CD16 and CD56
What do NK cells recognize?
cells that are deficiency in MHC antigens
Exposure to what type of cytokines is highly activating for the NK cells?
interferons
What’s the cause of congenital neutropenia and what happens?
lack of GM-CSF
you get frequent bacterial infections
What happens in chronic granulomatou disease?
you can’t product hydrogen peroxide or hypochlorous aid so you are unable to kill phagocytosed bacteria
What happens in leukocyte adhesion deficiency?
You don’t have a beta chain necessary for integran, so you can’t get leukocytes to the site of inflammation
What happens on chediak-higashi syndrome?
You have a defect in the LYST gene, which is a lysosomal trafficking gene - affects lysosomal degradation so you have increased susceptibility to bacterial infections
