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Flashcards in Immunology-Response to Infection Deck (30):

How does the immune system view the vast amount of pathogens we are info

Extracellular (interstitial space, blood or lymph and epithelium) and Intracellular (restricted to vesicles or cytoplasmic)


Where do viruses finally reside on infection of the host?

They are obligate intracellular pathogens that reside in the cytoplasm because they need host macromolecular machinery for replication.


How does the immune system control viral infections?

Prevent infection of cells by type I interferons and elimination  of infected cells by using NK cells.


What are the type I interferons? When are they produced? How do they help prevent viral infection?

IFN-alpha: produced by mononuclear phagocytes. IFN-beta: produced by most cells in the body. They are produced when double-stranded RNA (PAMP) binds to a pattern recognition receptor (TLR3) in a virus-infected cell. These are then released from the infected cell and cause healthy cells to produce enzymes that block viral replication. They also induce expression of MHC I receptors on healthy cells, so that if they do get infected there will be high response of CTLs.


How do viruses shoot themselves in the foot when it comes to avoiding NK cells?

In the normal cells, a ligand binds to the NK cell activating receptor and MHC I binds to the NK cell inhibiting receptor. Both of these signals prevent killing of the healthy cell by the NK cells. In infected cells, the virus reduces expression of MHC I and induces killing of virus-infected cells by NK cells.


What molecules are released from NK cells to initiate cell apoptosis?

Perforin (polymerize to form pores in lipid bilayer of target cell) and granzymes (diffuse into target cell and activate caspases which induce apoptosis)


How does a virus initiate a CD8+ T-cell response?

Viral proteins are synthesized in the cytosol -> Peptide fragments are bound by MHC I in ER -> Bound peptides are transported to cell surface -> MHC I binds CD8+ TCR -> IL-2 release stimulates its own IL-2 receptor and T-cells proliferate and are activated to CTLs that kill virus-infected cells


How do CTLs kill virus infected cells?

1) Perforin opens cell membranes and granzymes activate apoptosis via caspases. 2) Fas ligand (FasL) engages Fas on target cells and induces apoptosis.


How do all of our vaccines use the immune system to prevent viral infection?

They induce production of antibodies that bind to cell surface receptors on the virus to prevent viral attachment to host cells.


What antibody isotypes are most effective for neutralization of viruses and toxins? How are they produced?

IgG and IgA. B-cells present viral peptide on MHC II to CD4+ TCR -> CD4+ T-cell produces CD40 ligand and cytokines -> CD40L binds to CD40 on B-cell and cytokines stimulate B-cell proliferation, differentiation, isotope switching (IgG, IgA, IgE), somatic hypermutation/affinity maturation (refines antibody specificity) and induces B-cell memory.


Innate immune factors against viruses

NK cells and type I interferons


Adaptive immune factors against viruses

CD8+ CTLs and antibodies.


When in a viral infection do the innate and adaptive immune response happen?

1) Innate interferons 2) Innate NK cells 3) Adaptive T-cell response


Where in the cell do Tb, listeria and leishmania typically live and thrive?

Within the phagosome and phagolysosomes. Note that by living in intracellular vesicles they are immune to antibody and most host damage is caused by the immune response.


If intracellular vesicular pathogens enjoy living in phagocytes and phagocytes are the only way we can get rid of them, how does our body deal with this conundrum?

Pattern-recognition receptor binds microbe and releases IL-12 as phagocytosis occurs -> IL-12 activates NK cells and they release IFN-gamma -> Increased phagocytosis and up regulation of phagocyte oxidase to produce more ROS. Additionally, IL-12 causes CD4+ T-cells to differentiate into Th1 helper cells that eventually take over the role of NK cells and produce even more IFN-gamma. These Th1 cells also express CD40L for the phagocyte’s CD40 receptor that further stimulates phagocytosis and production of ROS.


What players are involved in mediating defense against intracellular bacteria, fungi and protozoa?

Phagocytes (PMNs and macrophages), NK cells and cytokines (IL-12 and IF-gamma)


How does phagocytosis normally occur when a phagocyte encounters a pathogen?

Microbe is recognized by pattern recognition receptors (alpha-helical transmembrane receptors, TLRs, mannose receptors) -> Cytoskeletal movement of phagosome, cytokine production induces ROS production and phagocytosis of microbe -> phagosome fuses with lysosome -> phagocyte oxidase activated and produces ROS


2 things that NK cells do

1) Kill virus-infected cells 2) Act as a source of IF-gamma for macrophage activation


What is the difference between the types of cells that differentiated from an activated naive CD4+ T-cell?

Clonal expansion and differentiation yields Th1 cells that produce IFN-gamma and Th2 cells that produce IL-4 and IL-5.


What is the positive feedback loop that exists between activated macrophages and NK/Th1 cells?

Activated macrophages produce more IL-12 -> NK cells and Th1 cells produce more IFN-gamma in response to IL-12 which further activates the macrophages.


What type of immune response determines if you’ll get the worst kind of leprosy?

An effective Th1 response potentiates phagocyte control of mycobacterium and localization to extremities resulting in tuberculoid leprosy. A Th2 response results in production of IL-4 and IL-5 that do not potentiate phagocytes (IL-5 actually suppresses macrophage activation) and you get the systemic lepromatous leprosy where the disease is poorly controlled.


What is the main distinguishing feature in the immune response to extracellular pathogens vs. intracellular pathogens?

Since the pathogens are extracellular they are susceptible to complement.


How can complement become innately activated (not involving antibody)

Alternative pathway and mannose-binding lectin pathway (note that the classical pathway is activated by antibody).


3 main actions of complement

1) Opsinization of microbe by C3b to enhance phagocytosis 2) Soluble C3a and C5a stimulate inflammation and recruitment of phagocytes to sites of infection 3) Formation of membrane attack complexes


In addition to phagocytosis and stimulation of phagocyte oxidase, how else to macrophages help to fight infection?

They produce cytokines IL-1, IL-6 and TNF-alpha. These mediate systemic reactions shown below.


Although antibodies activate the classical pathway to induce microbial opsinization by C3b, how do they opsinize microbes in the absence of complement?

IgG antibodies opsinize microbe -> Antibody Fc region binds phagocyte Fc receptors -> Phagocyte activation -> Ingestion and killing of microbe


What type of antibodies are best at activating the classical pathway of complement?



What differentiated CD4+ T-cells are important in recruitment of PMNs to site of infection?

Th17 cells produce IL-17 which is chemotactic for neutrophils


What are the innate immune defenses and adaptive immune defenses our body uses against viruses? Intracellular bacteria/fungi/protozoa? Extracellular bacteria/fungi/protozoa?



What T-cells are key in fighting helminth infection? 

Th2 cells produce IL-4 and IL-5 -> IL-4 stimulates IgG and IgE production and IL-5 activates eosinophils -> IgE degranulates mast cells and binds eosinophils -> Eosinophils degranulate to kill helminth