Immune System II

How does the complement system interact with both innate and acquired immunity?

There's a lot of interaction from innate and adaptive immunity Components of innate are needed to trigger adaptive immune responses Cells of our adaptive immunity use components of innate immunity to fight infections with specificity Components of adaptive and borrow components of adaptive - fight infections Use of antigen recognition

Which cells possess class I MHCs?

All cells except for Red blood cells

Which cells possess class II MHCs?

Antigen-presenting cells 1. Macrophages 2. Dendritic cells 3. B cells

What events can initiate a local inflammatory response?

These can elicit an inflammatory response: 1. Tissue injury (hypoxia/undue stress/fatigue) 2. Presence of a pathogen They can occur together or independently of each other.

What roles do class I MHCs play in immunity?

They are recognized by cytotoxic T cells and NK cells Indicates virus infected, non-self OR abnormal self cells

What role do Mast Cells play in inflammation?

They are the cellular initiator of inflammation Mast cells release pro-inflammatory mediators that activate Macrophages Undergo degranulation (dump out all of the mediators - also release leukotrienes and prostaglandins

What is TNF-alpha?

Cytokine that is rapidly mobilized in response to stressors such as injury and infection It is a potent vasodilator and increases vascular permeability It is a trigger for inflammation

What triggers the "Acute phase response"?

Cytokines: get released systemically: travel and act on tissue.

What is the role of neutrophils?

Induces inflammation by oxidation of cells, release lysosomal enzymes, damage bacteria that damage healthy cells, start eating up the mess and then they die

How does the complement system interact with both innate?

Innate immunity occurs without activation of adaptive immunity. Plasma Proteins are groups of proteins that contribute to RNA immunity. The most important of them being the complement system which can destroy pathogens regardless of whether we've had previous experience with them or not.

What is the role of IL-1?

It is a trigger for mast cell activation. Once macrophages release IL-1, they release mast cells. Once those mast cells become activated: inflammatory response increases.

What are the two acute phase response proteins that we spoke about in class and are their respective functions?

Liver produces these protein 1. C-reactive protein: Endothelial cells are critical: responsible for controlling blood flow 2. Manos binding leficin (MBL): Binds to walls/complement proteins bind to MBL and CRP when found on pathogen surface. (Helps trigger complement attack)

What are the Major Histocompatibility Complex molecules?

MHC is group of genes that code for proteins found on the surfaces of cells that help the immune system recognize foreign substances

By what mechanism is the inflammatory response triggered?

Macrophage is a cell that triggers inflammation as a result of a pathogen Macrophages that live in tissue; highly sensitive to the presence of any pathogenic organism. When the macrophages sense pathogen, cytokines will activate and be released. Those cytokines help start the inflammatory reaction.

What is the respective functions of the metabolites of cyclooxygenase?

Prostacyclin: causes vasodilation & inhibits platelet aggregation Thromboxane: causes vasoconstriction & promotes platelet aggregation PGD/PGE/PGF: causes vasodilation and edema

What roles do class II MHCs play in immunity?

Recognized by helper by T cells Involved in antigen presentation and activation of an adaptive immune response

What has the ability to block the production of arachidonic acid?

The prostaglandins create pain as a result of inflammation. They block the production of any arachidonic acid itself. This will prevent the production of leukotrienes and prostaglandins.

What are the relevant metabolites of Arachidonic Acid in relation to acute inflammation?

1. 5-Lipoxygenase 2. Cyclooxygenase

The process of inflammation tends to bring about some degree of damage to otherwise healthy local tissue. What cells are responsible for this "collateral damage"?

1. Cytokines released 2. WBC signals phagocytic cells to come to the area 3. First wave - neutrophils 4. Second phase - macrophages 5. When they arrive on scene, they sniff out cytokines and get to the area of inflammation 6. They undergo transmigration - go through pores to get to interstitial space 7. Spill out lysozomes and make a mess Collateral damage as a result

What are the steps of inflammatory response?

1. Damaged tissues release histamines, increasing blood flow to the area 2. Histamines cause capillaries to leak, releasing phagocytes and clotting factors into the wound 3. Phagocytes engulf bacteria, dead cells, and cellular debris 4. Platelets move out of the capillary to seal the wounded area

What are the vascular and cellular events of acute inflammation and in what sequence do they occur?

1. Injury of tissue to area release cytokines that activate macrophages 2. Mast cells release pro-inflammatory mediators 3. Macrophages detect/ingest pathogen then release pro-inflammatory mediators 4. Vasodilation 5. Increased permeability 6. Cell migration 7. Attack of pathogens

What are the causes of chronic inflammation?

1. Persistent infections by certain microorganisms 2. Prolonged exposure to potentially toxic agents 3. Autoimmunity (rheumatoid arthritis)

What are the three ways to activate the complement system?

1. Presence of a pathogen 2. As part of a systemic inflammatory response 3. Can be activated by adaptive immunity (antibody-mediated)

What are the three main outcomes of the complement system?

1. Promotes inflammation 2. Opsonization (tagging a pathogen for later killing by a macrophage or neutrophil) 3. Membrane attack complex-- directly killing pathogen

What are the mediators of collateral damage?

1. lysosomal enzymes 2. reactive O2 species.

What is the respective functions of the metabolites of 5-Lipoxygenase?

5-HETE 1. Chemotaxis Leukotriene: 2. Vasoconstriction 3. Bronchospasm 4. Increased permeability

What is the complement system?

A powerful plasma protein system in innate immunity A group of circulating plasma proteins that act in a cascade to destroy invading microbes; these function to keep blood pathogen-free It is activated by a pathogen in bloodstream, triggers inflammation, and can directly kill the pathogen.

What lymphocytes are involved in acquired immunity?

B lymphocytes are a group of immune cells that carry out what we call antibody mediated immunity and the release of antibodies into the bloodstream that can actually fight infections. T lymphocytes carry out what's called a cell mediated immunity.

What is the "Acute phase response"?

Body's systemic inflammatory response (increase WBCs, fever, malaise)

If a pathogen manages to slip past an epithelial border without damage to tissue, what are the first cells that recognize it and initiate an inflammatory response?

Cells that live in the tissue: live where the pathogen is going to enter. Cellular initiator: mast cell and macrophage

What is a membrane attack complex?

Complement proteins assemble and form what is called a membrane attack complex where a big hole is formed as proteins insert themselves into the bacteria. Bunch of water rushes in and the cell dies

How does the complement system interact with acquired immunity?

Composed of a few cell types and they will adapt and learn from experience With experience of a particular organism - our adaptive immune system will be faster and more effective at clearing the infection Allows us to have immunologic memory