Question

In: Biology

How can DAMPs and PAMPs both lead to a similar immune response? Explain in detail at...

How can DAMPs and PAMPs both lead to a similar immune response? Explain in detail at the molecular level.

Solutions

Expert Solution

PAMP and DAMP stands for, Pathogen-associated molecular pattern and Damage/danger Associated Molecular Pattern respectivey. Inflammation results from stimuli signaling damage or infection. The inflammatory response can be beneficial or harmful depending on the type and duration of stimuli. The source, structure, and abundance of these stimuli vary quite a bit. Both PAMP and DAMP comes in the catogory of signal 0s.

PAMPs are derived from microorganisms and thus drive inflammation in response to infections, One well-known PAMP is lipopolysaccharide (LPS), which is found on the outer cell wall of gram-negative bacteria.
DAMPs are derived from host cells including tumor cells, dead or dying cells, or products released from cells in response to signals such as hypoxia. Because they are derived from host materials, DAMPs induce what’s known as sterile inflammatory responses. DAMPs are often created or exposed in environments of trauma, ischemia, or tissue damage and do not require pathogenic infection.
PAMPs and DAMPs bind to pattern recognition receptors, which include Toll-like receptors (TLRs), cytoplasmic NOD-like receptors (NLRs), intracellular retinoic acid-inducible gene-I)-like receptors (RLR), transmembrane C-type lectin receptors, and absent in melanoma 2-like receptors (AIM2).Cell types expressing pattern recognition receptors include innate immune cells such as macrophages, monocytes, dendritic cells, and mast cells but also non-immune cells such as epithelial cells and fibroblasts.Pattern recognition receptor-ligand binding and their concomitant conformational changes prompt a cascade of downstream signaling that result in transcriptional changes as well as post-translational modifications.Broadly, pattern recognition receptor engagement results in signals that prompt leukocyte recruitment.
Pattern recognition receptors are capable of recognizing a variety of molecular patterns, which in turn induce a receptor-dependent response. A single pattern recognition receptor can recognize multiple PAMPs and DAMPs.


The role of TLR s, RLR s, and NLR s in PAMP and DAMP recognition.
Signaling pathways triggered by pathogen‐associated molecular pattern (PAMPs) and damage‐associated molecular pattern molecules (DAMPs). Lipopolysaccharide (LPS) activates both the myeloid differentiation factor 88 (MyD88)‐dependent and TIR‐domain‐containing adapter‐inducing interferon‐β (TRIF)‐dependent Toll‐like receptor 4 (TLR4) pathways. The MyD88‐dependent pathway is responsible for NF‐κB and mitogen‐activated protein kinase (MAPK) activation, which controls induction of proinflammatory cytokines. The TRIF‐dependent pathway activates IRF3 by TANK‐binding kinase 1 (TBK1)/IKKε, which is required for the induction of IFN‐inducible genes. TLR1‐TLR2 and TLR2‐TLR6 recognize bacterial triacylated lipopeptide or diacyl lipopeptide, respectively, and recruit TIR adapter protein (TIRAP) and MyD88 at the plasma membrane to activate the MyD88‐dependent pathway. TLR5 recognizes flagellin and activates the MyD88‐dependent pathway. TLR3, TLR7, TLR8, and TLR9 reside in the endosome and recognize dsRNA, ssRNA, CpG DNA, or mitochondrial DNA (Mit DNA), respectively. They recruit TRIF or MyD88 to activate the IRF3 or IRF7 pathway. All immunogenic nucleic acids bind indicated cytosolic DNA sensors or RNA sensors, including retinoid acid‐inducible gene I (RIG‐I)‐like receptors (RLRs), which are required for subsequent recognition by specific pattern recognition receptors to activate innate immune responses. DAMPs such as HMGB1, S100 proteins (S100s), and heat shock proteins (HSPs) recognize the receptor for advanced glycation end products (RAGE), TLR4, or triggering receptor expressed on myeloid cells‐1 (TREM‐1) and activate the MyD88‐MAPK‐NF‐κB pathway. HMGB1 and RAGE activate the TLR9‐MyD88 dependent pathway, which contributes to autoimmune pathogenesis. CD24 is a negative receptor to inhibit the DAMP‐induced TLR4 pathway. ATP binding of the P2X7 receptor and uric acid, as well as asbestos and alum, increase activation of caspase‐1 by the NALP3 inflammasome and other nucleotide‐binding oligomerization domain (NOD)‐like receptors (NLRs) to promote secretion of IL‐1β and IL‐18. PAMP and DAMP‐mediated signaling and induction of an innate immune response usually results in resolution of infection, but may also cause chronic inflammation or autoimmunity by altering various cell death and survival mechanisms.

Related Solutions

How innate immune reactions stimulate adaptive immune responses What are examples of PAMPs and DAMPs recognized...
How innate immune reactions stimulate adaptive immune responses What are examples of PAMPs and DAMPs recognized by the innate immune system? What is the outcome of recognition?
Explain in detail how contractarianism may lead to different results from both utilitarianism and egalitarianism in...
Explain in detail how contractarianism may lead to different results from both utilitarianism and egalitarianism in deciding the distribution of medical resourses.
_____ 25) How is a secondary immune response different from a primary immune response? A) it...
_____ 25) How is a secondary immune response different from a primary immune response? A) it is faster and more effective B) it is slower, but more effective C) it is faster, but less effective D) it is slower, and less effective E) there is no difference _____ 19) Which of the following is not a function of antibodies? A) opsonization                                 B) activating complement proteins C) activating T-helper cells            D) enhancing phagocytosis          E) neutralization _____ 13) The complement system involves...
The immune response to any virus is similar to the one you've mapped out in your...
The immune response to any virus is similar to the one you've mapped out in your flow chart. HIV is an infection that targets and kills helper T cells. Explain why HIV leads to AIDS, or acquired immunodeficiency syndrome, where the immune system is non-functional. Be sure you discuss APCs, helper T cells, cytotoxic T cells and B cells in your answer.
In innate immune response, a) How is the virus recognized by the host? Explain and name...
In innate immune response, a) How is the virus recognized by the host? Explain and name the cells/receptors involved b) What signaling pathways are triggered? Name and explain the major pathways needed to mount an antiviral response.
how breakdown in immune cells' functions can lead to disease/disorders, etc.).
how breakdown in immune cells' functions can lead to disease/disorders, etc.).
How does immune system reacts to alpha- gal syndrome? explain in detail
How does immune system reacts to alpha- gal syndrome? explain in detail
Why is deflation dangerous? Explain how both unanticipated and anticipated inflation can lead to lower real...
Why is deflation dangerous? Explain how both unanticipated and anticipated inflation can lead to lower real GDP and higher unemployment. Why was there deflation during the Great Depression, from 1929 to 1933?
Provide two examples of how the immune response to bacterial antigens or toxins can cause severe...
Provide two examples of how the immune response to bacterial antigens or toxins can cause severe disease and pathology. For each example, name the disease, the bacterial species, the corresponding bacterial toxin or antigen associated with the disease, and the immune response driving the pathology.
Can the use of -on-investment (ROI) lead to bad business decisions? Explain your response.
Can the use of -on-investment (ROI) lead to bad business decisions? Explain your response.
ADVERTISEMENT
ADVERTISEMENT
ADVERTISEMENT