Lecture 4 & 5: Innate and Adaptive Immunity Flashcards
Describe the uniques characteristics of the innate immune system
The innate immune system is an imediate, but nonspecific response to pathogens mounted by phagocytic cells and natural killer cells
Epithelial barriers protect as a barrier and certain cells can secrete antimicrobial peptides called defensins
The small and large intestine also have defensins, lysozymes, mucus secreting goblet cells, and paneth cellls
There is no memory of the innate immune system - if the same pathogen infects the host months in the future, the innate response and time of response will be the same
Cells of the innate immune system
- Phagocytic Cells
- NK Cells
- Mediator Releasers
Phagocytic Cells
Cells containing azurophilic and specific granules with anti-pathogen molecule and enzymes to lower cytoplasmic pH and generate oxidizing agents that are leathal to pathogens and surrounding tissues
Includes neutrophils, monocytes, dendritic cells, and eosinophils
Neutrophils
FIRST RESPONDER
60% of all circulating white blood cells
Short lived - die once they release granules to kill the invading molecule (6-24hrs)
Rapid exit from circulation to tissue sites of injury or infection
Inductive process draws the neutrophils out of circulation into the tissue where the neutrophils phagocytize the invadding microbe and DIE
NEUTROPHILS DIE
NEUTROPHILS DIE - after release of granules
Monocytes
Monocytes become long lived macrophages in many tissues and organs
5% of all circulating leukocytes
Among the first cells to encounter a pathogen, comming in after the neutrophils
Digest a pathogen and display the peptide fragment on the cell surface in the context of a MHC receptor
Has an indented nucleus
Dendritic Cells
Most dendritic cells are probabbly derived from monocytes
Reside within or just below the epithilial
Major gaurds against invading pathogens
After phagocytosis of pathogen the dendritic cell migrates to the regional lymph node where itpresents a peptide fragment in the context of a MHC receptor to activate a T cell - IMPORTANT INDUCERS OF T CELL IMMUNITY
Most efficent antigen presenting cell in the body (100x more efficent)
Eosinophils
Granues stain red with most blood stains
Granules are antiparasitic
Prominent meddiators of allergic reactions - levels in peripherial blood can increase with an allergic response
2-4% of circulating leukocytes
Phagocytosis of an antigen-antibody complex
NK Cells
Large mononuclear cells with azurophillic granules
1-2% of all circulating leukocytes
Sample the surface of virally infected cells or tumor cells for evidence of abnomality (lack of MHC receptor) and if an abnomality is dected, the NK cell kills the infected cell
NK cells secretes molecules which activates members of the adaptive immune system (INFy)
Mediator Releasers
Include basophils and mast cells
Function in immediate hypersensitivity release of histamine, heparin, and peroxidase from granules - Allergic reactions
Basophils are found circulating in peripheral blood and represent .5% of white blood cells
Mast cells are only found in tissue
Have receptors for IgE on the surface
PAMPs
Pathogen associated Mononuclear Paterns
Phagocytic cells must recognize PAMPs
Very chemoatractive to neutrophils
PAMPS include:
- Terminal mannose residues
- Double stranded RNA in viruses
- Short sequence unmethylated CPG motif in bacteria
- LPS - lipids in lipopolysacharide of microbes
TLR
Toll Like Receptor
When a TLR is bound to a PAMP on a pathogen, it activates a signaling pathway so that phagocytic cells can release infamitory mediators to further activate the immune system
TLR activation leads to translocation of NFkB to the nucleus, where NFkB activates the transcription of genes that produce cytokines that activate the immune response
Humans have at least 10 TLRs which lead to the translocation of NFkB into the nucleus
Activation of TLR4
- LPS (a PAMP) binds to TLR4
- Activated TLR4 releases the activated form of MyD88
- MyD88 activates NFkB translocation to the nucleus
- NFkB transcibes INF (interferon) inducible genes
- Accute inflamation occurs and adaptive immunity is stimulated
TLR4 activation can also promote the transcription of proinflamatory genes through IRF5 and Jun/Fos creating an antiviral like state
There are also TLRs that can be activated within the cell located in endosomes
Activation of IL1
- After NFkB is activated and induces the transcription of the inactive form of IL1 (ProIL1) it is cleaved and eleased into circulation, which can cause accute inflamation
- The NLRP3 inflamasome is activated through ion concentration, and does not require a TLR. The inflamasome cleaves Pro-IL1 by releasing casoase and activating IL1 to be released into circulation
Secreted IL1 cause Accute Inflamation
Phagocytic Cells Engulf and Destroy Pathogens
- A microbe identified by an antibody or complement binds to the Fc receptor or complement receptor of the macrophage
- The microbe is endocytosed
- Cytoplasmic NADPH oxidase on the phagosomal membrane catalyzes the production of O2 and HOCl - resulting in a respiratory burst killing the microbe
- Neutrophils die, while macrophages process the peptide of the microbe and ppresent it in the context of a MHC class 2 molecule
Respiratory Burst
After the engulfment of a foreing particle NADPH oxidase is released from the phagosomal membrane and the production the following compounds is catalize resulting in the destruction of the forgien particle:
O2
HOCl
Hydroxyl Radicals
NO
*Mammals defficent in NADPH oxidase are very suceptible to bacterial infection