1 - Innate immunity Flashcards
What is immunology?
The study of all aspects of host defense against infection and of adverse consequences of immune responses
What are some examples of immunodeficiency?
Genetic immunodeficiency and AIDS
What is the central role of the immune system?
Protection against microbial infection - evolutionary pressure has shaped the immune system so that it can best function against the microbial world
What does the immune system fight off?
Fight off the following:
- Viruses (must be intracellular)
- Bacteria (extracellular and intracellular)
- Parasites (unicellular and multicellular, intracellular and extracellular)
- Note that you need different mechanisms to fight off the three different types of infections listed above
What does the immune system target?
The immune system…
- Destroys a diversity of pathogens
- Attacks cancer cells
- Eliminates toxins
There are two types or “arms” of immunity. What are they?
Which type of immunity is an immediate response? Which type will take days or weeks to occur?
Innate
- Immediate response
- Hours to 1-2 days
Specific
- Later
- 7-10 days to weeks
Which type of immunity utilizes T and B lymphocytes? Which type utilizes phagocytes, neutrophils and natural killer cells? Are they always differentiated?
Specific
- T and B lymphocytes
- These cells are further differentiated by activation and selected amplification
Innate
- Phagocytes (macrophages), neutrophils and natural killer cells
- These cells are terminally differentiated
Which type of immunity involves non-polymorphic complement as the circulating molecule? Which type involves a diverse population of immunoglobulins as the circulating molecule?
Innate
- Complement (non-polymorphic)
Specific
- Immunoglobulins (diverse)
Which type of immunity involves lymphocyte-derived factors as the soluble mediators? Which type involves macrophage-derived cytokines?
Specific - soluble mediators
- Lymphocyte-derived factors (local growth and regulation)
Innate - soluble mediators
- Macrophage-derived cytokines
- Other acute phase reactants
- Systemic effects
- Inflammation
How is inate immunity amplified? How is specific immunity amplified?
Innate
- Recruitment
Specific
- Clonal expansion
Which type of immunity involves a memory?
ONLY specific (aquired) immunity, NOT innate (natural) immunity
__________ immunity is the initial response to mcrobes that prevents, controls or eliminates infection of the host by many pathogens.
Innate
There are three types of components of the innate immune system. What are they?
- Cell associated components
- Cellular components
- Soluble components
What types of cell associated components will you find in the innate immune system?
Cell associated components
- There are pattern recogntition receptors and sensors
- Toll-like receptors
- Cytosolic receptors
What types of cellular components are part of the innate immune system?
Cellular components of the innate immune system
- Epithelial barriers
- Phagocytes
- NK cells
What type of soluble components are part of the innate immune system?
Soluble recognition molecules and soluble effector molecules
- Complement
- Cytokines
What are the two types of pattern recognition receptors (PRRs)?
PAMPs = pathogen-associated molecular patterns
DAMPs = damage associated molecular patterns
What are the molecular structures that are produced by microbial pathogens and recognized by the innate immune system?
PAMPs
- Pathogen-associated molecular patterns
- These microbial products are often essential for the survival of microbes and include:
- ssRNA (virus)
- dsRNA (virus)
- Flagellin (bacteria)
- Libopolysaccharide (LPS, endotoxin) (gram-negative bacteria)
- Lipoteichoic acid (gram-positive bacteria)
What is lipopolysaccharide?
What are DAMPs?
Damage associate molecular patterns
- Not as important to know
- Endogenous molecules that are produced by or released from damaged and dying cells
- HMGB1 and HSPs are examples
What does toll-like receptor 4 (TLR4) bind to?
Lipopolysaccharides
- TLR4 is a PRR or pattern recognition receptor
- It binds to LPS, which, as you recall, is a PAMP that is common in almost all gram-negative bacteria
- TLR4 will therefore be active in gram-negative bacteria
***
What does TLR4 result in?
The production of proinflammatory cytokines from monocytes and macrophages
Are toll like receptors expressed on the surface of cells or as endosomes?
Can be either
Are TLRs found in the homodimer or heterodimer state?
Can be either
When a toll-like receptor (TLR) recognizes a microbial ligand, what results?
The activation of several signaling pathways
- Ultimately transcription factors will induce the transcription of certain factors which will then induce the expression of genes that are important for the inflammatory and antiviral responses
What is the role of the transcription factors NFkB and IRF?
NFκB and IRFs…
- Both are activated in response to PRR ligation
- NFκB results in induction of an inflammatory state
- IRF results in induction of an antiviral state
What drives inflammation?
Inflammation is driven by cytokines such as TNF, IL-1 and IL-6
So, what is the innate immune response that is triggered by TLR (toll-linked receptors)?
PAMP/TLR → NFkB and IRFs → Inflammation and Antiviral state
What do toll-linked receptors (TLRs) detect when they are located on the cell surface?
Extracellular pathogens - they recognize the pathogen associated molecular pattern (PAMP)
What do toll-linked receptors (TLRs) recognize when they are found on the endosomal membrane?
Well, we know that they can’t detect PAMPs of extracullular pathogens because they are found within the cell and not on the surface.
Instead, they recognize nucleic acids of microbes that have already been phagocytosed by the cell
What are cytosolic sensors of microbial infection?
These receptors are found within the cytosol and detect microbial infections. Examples include…
- NOD-like receptors family (NLR)
- RIG-like receptor family (RLRs)
- Cytosolic DNA sensors (CDS)
What are inflammasomes?
Inflammasomes are the cells that are responsible for inducing the inflammatory response
What do inflammasomes activate?
IL-1 and IL-18
What happens when there is a dysregulated activation of the inflammasome?
Autoinflammatory syndromes
- Caused by a gain-of-function maturation in inflammasome components
- Leads to excess IL-1
What happens when excess IL-1 is present?
Response
- Recurrent attacks of fever
- Localized inflammation (joints and intestines)
How do you treat a autoinflammatory syndrome?
IL-1 antagonists