Lecture 2-Exam 2 Flashcards
What is a phagocyte and what type of cells are phagocytes?
Phagocyte = any cell that carriers out phagocytosis
* Dendritic cell
* Macrophage
* Neutrophil
How does phagocytosis work?
How does MHC 1 and Virses relate?
- Viruses are obligate intracellular parasites, which hijack the host cell’s biosynthetic machinery to enable the translation of viral proteins and the replication of the viral genome.
- The major histocompatibility (MHC) class I antigen presentation pathway plays an important role in alerting the immune system to virally infected cells.
- MHC class I molecules are expressed on the cell surface of all nucleated cells and present peptide fragments derived from intracellular proteins.
- MHC class II molecules are found only on where?
- Where are the peptides derived from?
- MHC Class II molecules are found only on antigen presenting cells such as dendritic cells, monocytes, B cells, macrophages.
- The antigens presented by class II peptides are derived from extracellular proteins (not cytosolic as in MHC class I)
How does the loading of the MHC class II molecules occur?
Loading of a MHC class II molecule occurs by phagocytosis; extracellular proteins are endocytosed, digested in lysosomes, and the resulting epitopic peptide fragments are loaded onto MHC class II molecules prior to their migration to the cell surface
- Once a pathogen or antigen has been identified as foreign, it is marked for destruction in a permanent manner by what?
- Once it is activated it proceeds by what?
Once a pathogen or antigen has been identified as foreign, it is marked for destruction in a permanent manner by the complement system. Once activated it proceeds by a series of enzymatic reactions called the classical pathway of complement
Got its name for this system providing proteins to “complement” the antigen-binding function of antibodies
Activation of the complement system initiates what?
initiates a series of enzymatic reactions in which proteolytic cleavage and activation of successive complement components leads to covalent bonding of complement fragments to pathogen surface
Phagocytes have what? What do they recognize and do?
Phagocytes have surface receptors that recognize the complement fragments which facilitates the uptake and destruction of complement-coated microbes by neutrophils and macrophages
Complements fixed on bacterial surfaces can also initiate what?
a complex of proteins that attack the pathogen by poking holes in their cell membranes
What are the other two pathways of the complement system?
Lectin Pathway:
* mannose-binding lectin binds to pathogen surface, binding a plasma protein to mannose-containing peptidoglycans
Alternative Pathway:
* pathogen surface creates local environment conductive to complement activation, triggered by direct environmental influence of the microbial surface
For the complement system, they are initiated by different molecules but what is activated?
They are initiated by different molecules but they all activate to generate the same set of effector molecules
Complement activation results in three main consequences: Explain
- opsonization of pathogens
- the recruitment of inflammatory cells,
- direct killing of pathogens.
Complement components:
* Made where?
* Circulate in what?
* Compromised more than what?
* Many components are what?
* Where does activation take place?
* How can complement components can be grouped?
- Made in the liver
- Circulate in plasma
- Compromise more than 30 proteins with a variety of biochemical functions
- Many are enzymes, which are secreted and circulated in the inactive form know as a zymogen (only activated when they reach their destination)
- Activation takes place in the tissues
- Complement components can be grouped on the basis of their function
The classical complement cascade is initiated when?
when an antibody is bound to multiple sites on a pathogen surface
* Only antibodies IgG and IgM can trigger complement.
Which isotype that is the most efficient at activating complement?
IgM
Why is IgM special?
IgM has multiple areas to bind for a stable interaction, which makes it easier to start the beginning reactions
_ IgM may activate complement but _ IgG antibodies are needed
One and Two
For all 3 pathways of complement activation, what is different and what is the same?
Differ in the way they are triggered, however all three pathways converge on the same reaction
The cleavage of complement component C3 into what? What binds?
The cleavage of complement component C3 into C3a and C3b and the covalent bonding of C3b to the pathogens surface
What is the most important function of the complement system?
Complement fixation
- Cells and proteins in the damaged tissue sense the presence of the bacteria and the cells send out soluble proteins called what?
- What do they interact with and what do they cause?
Cells and proteins in the damaged tissue sense the presence of the bacteria and the cells send out soluble proteins called cytokines that interact with other cells to trigger the innate immune response of inflammation
What is inflammation do to?
- Inflammation is not due to the infection itself but to the immunes response to it!
What does cytokines induce?
- Cytokines induce local dilation of blood capillaries (increased blood flow causes the skin to be warm and red)
What does vasodilation introduce? What does it cause?
Cytokines invite what?
- Vasodilation introduces gaps between endothelial cells increasing the leak of blood plasma into the connective tissue (causes edema, swelling)
- Cytokines invite WBC’s to attach to the vascular endothelium and move from the blood to the tissue
What are inflammatory cells?
WBC’s release substances that contribute to the inflammation
What are the cons and pros of inflammation?
- Con: increased pain, swelling, warmth, ecchymosis.
- Pro: the right cells are brought rapidly and in large numbers into the infected tissue
C3, C4, and C5 can be further cleaved into fragments. The larger fragments continue down what?
the pathway of complement activation to cause inflammation
What happens to the smaller solube C3a, C4a and C5a fragmenrs?
physiologically active and increase inflammation at the site of complement activation through binding to receptors on several cell types.
- Sometimes these fragments induce what? Which one is the most potent?
induce anaphylaxis (C5a is the most potent, then C3a and C4a) so they are called anaphylatoxins
What happens in anaphylaxis with anaphylatoxins?
- Induce smooth muscle contraction and degranulation of mast cells and basophils, release of histamine, increased capillary permeability
- The increase blood flow and vascular permebility make it easier for antibody, complement proteins, phagocytic cells and lymphocytes to pass out of blood and into site of infection
- Also hastens the passage of pathogen containing antigen presenting cells to the draining lymph noes and initiation of B and T cell response
* Phagocytes, endothelial cells and mast cells have receptors specific for C5a and C3a
What does C5a directly act on? What does it do?
- C5a acts directly on neutrophils and monocytes to increase their adherence to vessel walls and direct their migration towards sites of antigen deposition
- Increases capacity for phagocytosis
CHEMOATTRACTANT
The anaphylatoxins act in concert with other complement components to do what?
speed destruction of pathogens by phagocytes
Prominent cytokines produced by activated macrophages include (what do they do?:
* IL-1
* IL-6
* IL-8
* IL-12
* Tumor necrosis factor-alpha (TNF-alpha)
Transcription factor nuclear factor-κB (NF-κB):
* What is their role?
* What is the structure of NF-KB?
- plays a pivotal role in orchestrating the inflammatory response
- NF-κB is a heterodimer that normally exists in the cytoplasm of cells
- Stimuli such as cytokines, viruses, and oxidants induce what?
- NF-κB moves where and does what?
- Stimuli such as cytokines, viruses, and oxidants induce signals that allow NF-κB to dissociate from IκBα (inhibitor of nuclear factor kappa B), which is then degraded
- NF-κB moves to the nucleus, where it binds to the DNA of genes for numerous inflammatory mediators, resulting in their increased production and secretion
What inhibits the activation of NF-KB? How does that happen?
⭐️
Corticosteroids inhibit the activation of NF-κB by increasing the production of IκBα, and this is one of their anti-inflammatory action
What is apart of local inflammation (overview)?
Local inflammation
- Cytokine IL-12 activates what?
- Cytokines IL-1 and TNF-alpha facilitates what?
- Cytokine IL-12 activated NK cells (innate immune system) that enter infected site soon after infection
- Cytokines IL-1 and TNF-alpha facilitate entry of neutrophils, NK cells, and other effectors by inducing change in endothelial cells of local blood vessels
Local inflammation
- What do macrophages release? What does it contribute to?
- In the course of complement activation, fragments C3a and C5a recruit what?
- Macrophage releases other effector cells such as plasmogin activator, prostaglandins, oxygen radicals, leukotrienes, and platelet activating factor which all contribute to inflammation and tissue damage
- In the course of complement activation, fragments C3a and C5a recruit neutrophils from the blood into the tissue and stimulate mast cells to degranulate, releasing histamine and TNF alpha
What is apart of systemic inflammation? (overview)
systemic inflammation
- In response to TNF-alpha, vascular endothelial cells make what?
- What does this cause?
- make platelet activating factor which triggers blood clotting and blockage of local blood vessels
- This restricts the leakage of plasma from the blood and prevents pathogens from entering the blood and disseminating infection throughout the body
What happens when alarge amount of bacteria gets into the blood?
macrophages in the liver, spleen and other sites are activated to release TNF-alpha which causes dilation of blood vessels and massive leakage of fluid into tissues throughout the body leading to septic shock
What does septic shock lead to?
Leads to failure of vital organs such as the kidneys, liver, heart, and lungs by lack of normal blood supply/intravascular volume
Most of the features of acute inflammation continue as the inflammation becomes chronic, including what?
the expansion of blood vessels (vasodilation), increase in blood flow, capillary permeability and migration of neutrophils into the infected tissue through the capillary wall.
What are is the morality of common chronic inflammation diseases? (5)
LY
Allergic Rhinitis:
* When does this happen?
* What is activated?
* What is it characterized by?
- When allergens are inhaled and diffuse across the mucous membrane of the nasal passages
- Activates mucosal mast cells beneath the nasal epithelium
- Allergic rhinitis is characterized by local edema leading to obstruction of the nasal airways and nasal discharge, generalized irritation and itching of nose due to histamine release, and sneezing, runny eyes
What is the difference btw HSV 1 and 2
What is Varicella-Zoster/Shingles
is a herpes virus that causes chickenpox and then stays latent in the dorsal root ganglia. Stress or immunosuppression will reaction the virus which moves down the nerve and infect the skin in that dermatome.
Epstein-Barr virus:
* What is the difference btw first exposure in children and adults?
* What happens after clearing the infection?
- first exposure in childhood produces a mild cold, whereas adolescents or adults encountering EBV for the first time develop infectious mononucleosis.
- After clearing the infection, the virus remains latent, but is unusual for reactivation, unless patient is severely immunosuppressed
