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279 Cards in this Set

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  • Back
What are the four outcomes of viral infection?
1. Productive infection (release of progeny)
2. Persistent infection (virus doesn't kill cell, low level of progeny shed from cell)
3. Abortive infection (viral multiplication arrested, no progeny)
4. Latent infection w/reactivation (virus goes through cycles of latency and reactivation)
In general, what are the six stages in the (productive) viral life cycle?
1. Attachment
2. Penetration
3. Uncoating
4. Replication
5. Assembly
6. Egress
What is a one-step growth curve and how is it obtained for a particular virus?
one step growth curve is a curve showing the rate of viral replication at different stages in time after the infection. The infection must be synchronized: therefore all viruses must be at the same point of the life cycle.
Why is there a latent period shortly after infection onset?
The latent period is due to the virus uncoating. During this time it is inactive.
Where would you find the viral attachment proteins?
on the capsid (naked virus) or on the envelope (enveloped virus)
In treating viral infections, why can't we just knock out the viral receptors on the host cells?
these receptors often perform important cell functions. to knock them out would mean death of the host.
1. tropism
2. host range
1. tropism is specificity for a certain tissue (ie. hepatotoxic viruses)
3. host range is the range of different types of hosts that the virus can infect. (ie. rabies in both humans and other mammals)
How do enveloped viruses penetrate the host cell membrane?
via membrane fusion
How do naked viruses penetrate the host cell membrane? (2)
1. creating a pore-like structure in the membrane
2. receptor mediated endocytosis, then lysing the internal cellular membrane (ie. endosomal membrane)
What is viropexis?
viropexis is another word for receptor mediated endocytosis
What happens to the viral envelope during membrane fusion and why is this an important drawback?
The viral envelope is incorporated into the host cell membrane. This leaves an external marker that is easily recognizable by the immune system.
How does a naked virus penetrate via pore formation?
The capsid proteins of the virus insert into the cell membrane creating a pore, then RNA is released through the pore into the cytoplasm.
What occurs in uncoating?
Uncoating releases the viral genome into the host cell cytoplasm
What are the 3 mechanisms of uncoating?

What is the main mechanism?
1. conformational changes in capsid subunit
2. host or viral protease
3. acidification of endosome

acidification of endosome
How does acidification of the endosome occur?
there are proton pumps in membrane of the endosome - they pump H+ out of the cytoplasm into the endosome (plasma membrane H+ pumps also pump out of the cytoplasm). The endosome becomes very acidic due to the increased [H+].
1. Where do most RNA viruses replicate?
2. Where do all DNA viruses replicate?
1. in the cytoplasm
2. in the nucleus
1. How are DNA viruses targeted to the nucleus?
2. How are DNA viruses transported to the nucleus?
1. DNA viruses are targeted to the nucleus via "nuclear localization signals" found on viral protiens.
2. the DNA viruses are transported using cytoskeleton and cellular motor protiens (dynein).
What are the 3 ways a DNA virus enters the nucleus?
1. passage of virus through nuclear pores (small viruses)
2. release of DNA through nuclear pores (virus is too big to fit through pore)
3. Transient Rupture of the nuclear membrane
mRNA production during viral gene expression is mediated by what general type of protien?
RNA polymerase
Which type of RNA polymerase do:
1. DNA Viruses use?
2. RNA Viruses use?
1. DNA viruses use DNA-dependent RNA polymerase that is usually of host origin.
2. RNA viruses use RNA-dependent RNA polymerase, it is always of viral origin
In regards to RNA viruses: what determines if the RNA transcriptase is virion associated?
the polarity of the RNA determines whether there will be virion association or not.(+)ssRNA is the only RNA virus that is not virion associated.

**+ssRNA can be read by the host directly as mRNA, the other RNA virus types can't and therefore need their own "virion associated" RNA transcriptase**
What does virion associated mean?
The RNA transcriptase enters the cell with the virion to allow expression of the uncoated viral genome.
Which RNA polarities are virion associated? (2)
1. (-)ssRNA
2. dsRNA
What are the three mechanisms in which RNA viruses can undergo gene expression?
1. Expression of segmented genomes
2. Start-Stop expression
3. Polyprotein expression
What is the mechanism behind polyprotien expession of RNA viruses?
translation of mRNA produces a polyprotien. The polyprotien is cleaved by proteases into the proper separate protiens.
How does a dsDNA virus replicate?
dsDNA--> dsDNA (DNA polymerase is used)
How does a (+)ssRNA Virus replicate?
(+)ssRNA->(-)ssRNA->(+)ssRNA (ssRNA viruses have their antigenome as an intermediate in replication)
How does a (-)ssRNA Virus replicate?
(-)ssRNA -> (+)ssRNA -> (-)ssRNA
The antigenome intermediate once again...
Assembly of progeny virions: where is the site of assembly for:
1. DNA viruses
2. RNA viruses
1. nucleus
2. cytoplasm
What is the mechanism for capsid assembly?
capsids self assemble
When is nucleic acid incorporated into the virus?
it is incorporated during assembly or after empty capsid is complete
What type of capsid processing is sometimes required for infectivity?
proteolytic processing
Where is the site of envelope acquisition for enveloped viruses (the progeny)?
envelope acquisition usually occurs at the outer cell membrane.
1. How do naked capsules usually escape the cell?
2. How do enveloped viruses usually escape the cell?
1. lysis
2. budding
what is a major difference between lysing and budding that allows a virus to be more virulent?
lysing kills the cell. A host cell can survive budding; this results in the release of thousands of progeny before it dies.
1. What is the significance behind viruses that have a high mutation rate?
2. Which class of virus has the highest mutation rate?
1. a high mutation rate leads to rapid adaptations (ie. drug resistance).
2. RNA viruses are known for their "sloppiness," they lack a proofreading function
1. Viruses can undergo genetic reassortment. What could this lead to?
2. Which type of virus undergoes genetic reassortment?
1. genetic reassortment could lead to an antigenic shift
2. viruses with segmented genomes undergo genetic reassortment. (ie. influenza A)
Viral transformation that is associated with continued expression is known to induce?
Which class of viruses are most often seen in viral induced oncogenicity?
DNA viruses (oncogenicity induced by RNA viruses is not so common)
How is size related to viral dependancy on their host?
The smaller the virus the more dependent they are on their host.
What are the 3 major functions of the viral capsid?
1. Protect nucleic acid from degradation
2. Provide attachment site for host cell (naked viruses)
3. provide antigens that are recognized by the host immune system (naked and enveloped)
What are the two major capsid types?
1. Helical
2. Icosahedral
Define monopartite in regards to the viral RNA genome.
monopartite refers to a single RNA molecule as the genome (vs. segmented which refers to multiple RNA molecules)
what difference do the (+) and (-) ssRNA genomes have in regards to translation?
the (+)ssRNA can be directly translated because it is the same polarity (sense) as mRNA. (-)ssRNA is antisense to mRNA and must be converted to (+)ssRNA before translation can occur.
in dsDNA or (+)ssRNA: What happens if the viral genome is separated from the capsid and injected into a host cell?
the genome alone can initiate a complete replication cycle and produce progeny viruses.

**dsDNA and (+)ssRNA are considered infectious, whereas (-)ssRNA is not.
Which enzyme is required for conversion of (-)ssRNA to (+)ssRNA?
Virion-associated RNA polymerase
the viral envelope is acquired via budding through which type of membrane?
the membrane can be cytoplasmic, nuclear, rough ER or Golgi membranes
in regards to the viral envelope: where are glycoprotiens found and what is their function?
glycoprotiens are visualized as spikes on the viral surface. They function in receptor binding and membrane fusion.
In some viruses a matrix protien lines the inner side of the envelope. Function?
the matrix protien plays an important role in viral maturation
compare naked and enveloped virions in the following aspects:
1. stability in the environment
1. naked - environmentally stable (can pass thru GI tract)
Enveloped - environmentally labile (succumb to acids, detergents, heat)
compare naked and enveloped virions in the following aspects:
infectivity in regards to drying
naked - retain infectivity after drying
enveloped - lose infectivity after drying
compare naked and enveloped virions in the following aspects:
route of egress
naked - escape via lysis
enveloped - escape via budding or lysis
compare naked and enveloped virions in the following aspects:
how easily they are spread
naked: spread easily by dust, small droplets, fomites
enveloped: spread in droplets, secretions, blood
which class of virus is resistant to detergents?
naked viruses
Which class of virus...
1. causes host pathogenesis due to hypersensitivity and inflammation?
2. What causes the hypersensitivity and inflammation?
1. enveloped viruses
2. cell mediated immunity is responsible for the pathogenesis
Do naked virions elicit cell mediated immunity?
NO, they only elicit a protective antibody response
What are the chemical criteria used for viral classification (3)?
1. nucleic acid composition and sequence
2. genome polarity
3. structure
What are the morphological criteria used for viral classification (2)?
1. capsoid shape
2. presence or absence of an envelope
after a wound occurs a thrombus is formed. What is it formed by and what is its function?
plasma fibrin and fibronectin form the thrombus. The thrombus is a two-way barrier: it stops things from entering and exiting the wound.
1. what is the name of the molecule that crosslinks fibronectin?
2. benefit of crosslinked fibronectin?
1. transglutaminases crosslink fibronectin
2. crosslinked fibronectin provides tensile strength and maintains closure.
what is the source of early growth factors at the wound site?
what happens to the thrombus late in wound healing?
the thrombus undergoes proteolysis, then it is penetrated by regenerating epithelium.
in what sequence does repair and regeneration occur in regards to wound healing?
repair and regeneration occurs after the inflammatory response
1. which type of acute inflammation will leave a scar?
2. what is the molecule that lays down the scar?
1. progressive acute inflammation (macrophage predominant inflammation)
2. collagen
what is the main function of neutrophils in a wound?
neutrophils liquefy and remove necrotic tissue
fibronectin and cellular debris release chemotactic factors to attract which two cell types?
what officially begins when macrophages appear at the site of injury?
the repair process
what types of things do macrophages secrete?
1. collagenase (assists with further liquefaction)
2. growth factors for:
- fibroblast proliferation
- collagen secretion
- neovascularization
what is the provisional matrix eventually replaced by?
granulation tissue replaces the provisional matrix
which cell type actively coordinates the development of granulation tissue? How does it do this?
they release cytokines and growth factors
in the formation of granulation tissue, what cells are myofibroblasts and fibroblasts derived from?
mesenchymal stem cells
in the formation of granulation tissue, what cells do capillaries form from?
capillaries form from the division of existing vessel endothelial cells
what are some reasons as to why granulation tissue is so highly resistant to bacterial infection?
granulation tissue is fluid-laden. It is highly vascularized and can therefore supply antibacterial antibodies.
what are the three main ingredients found in the early matrix of granulation tissue?
1. proteoglycans
2. glycoproteins
3. type III collagen
what change do fibroblasts undergo once activated and what do they do?
fibroblasts change from round to bipolar upon activation.
Fibroblasts form collagen and other matrix proteins (such as fibronectin).
what is the difference between type I and type III collagen in relation to wound healing?
Type III collagen is formed first and is weaker.
Type I collagen is formed later and has greater tensile strength.
what is the difference between angiogenesis and vasculogenesis?
angiogenesis - sprouting of endothelial cells from pre-existing capillary venules.
vasculogenesis - blood vessels form de novo from angioblasts.
What are BFGF (B for Beta) and VFGF and what do they do?
BFGF and VFGF are potent angiogenic growth factors. They associate with heparan sulfate - this is a crucial feature of angiogenesis.
how (and in which layer) does the epidermis renew itself?
how - mitosis
where - at the basal layer
what is the primary source of regenerating epithelium?
the hair follicle
in repair and regeneration, what is the main way that the cell surface is reepithelialized?
cellular migration is the predominant means of reepithelialization
which specialized cell is wound contraction dependant on and where is this cell found?
wound contraction is dependant on the myofibroblast - it is found in granulation tissue
what is the timeframe for myofibroblast appearance at the wound site?
myofibroblasts are first seen around day 3 of wound healing. they dissappear as repair progresses and wound has contracted.
how do myofibroblasts exert their contractile effects?
by forming tight junctions between myofibroblasts, this binds the cells together in a unit.
what is the difference between the structure of myofibroblasts and fibroblasts?
myofibroblasts bind together in a unit, fibroblasts are solitary cells
what cell types can myofibroblasts be derived from? (3)
1. pericyte
2. fibroblast
3. stem cell
what is the decrease in the size of a wound dependant on?
the presence of myofibroblasts
healed wounds have what percentage of the strength of the original unwounded site?
takes about 1 yr to gain this much function.
approximately what percentage of the original strength is present in a 2 week old wound?
what do platelets release when they are activated and what does this molecule facilitate?
platelets release PDGF, which facilitates adhesion, coagulation, vasoconstriction, repair and clot reabsorption.
What is the cell?
arrives at wound site early and migrates rapidly using small focal adhesions...
What is the cell?
is rapidly recruited from the bone marrow and invades the wound site within the 1st day...
What is the cell?
invades wound site within 1st day, releases granule contents resulting in degradation and destruction of non-viable tissue
arrive shortly after neutrophils but persist longer.
What are the two main macrophage actions:
1. phagocytose debris
2. orchestrate developing granulation tissue by release of cytokines and chemoattractants
when do the fibroblasts, myofibroblasts, pericytes and smooth muscle cells arrive on the scene?
what recruits these cells?
day 3 to 4.
recruited by growth factors and matrix degradation products.
what is:
1. lamellipodia
2. where are these seen
3. function?
1. broad, wavelike membrane extensions
2. leukocytes
3. locomotion for migrating leukocytes
what are:
1. filopodia
2. where seen
1. narrower and slower than lamellipodia, fingerlike extensions.
2. fibroblasts, smooth muscle cells
during cell movement the leading edge of the cell interacts with what molecule?
what are the 4 components of the ECM?
1. collagen fibers
2. elastin fibers
3. ground substance
4. fibronectin
what is important about fibronectin?
it can associate with the integrin receptor on the surface of the cell.
define: basement membrane
thin, well-defined layers of specialized ECM that separate the cells that synthesize it from the connective tissue.
what cell types produce basement membranes?
1. epithelium
2. endothelium
3. adipocytes
4. muscle cells
5. Schwann cells
which type of collagen is found in the basement membrane?
collagen type IV
besides collagen, what is the other predominant ECM molecule that is found in the basement membrane?
what happens when:
1. the equilibrium between collagen deposition and degradation has been restored
2. capillary formation is complete
3. inflammatory cells are diminished
remodeling begins
what is the class of main digestive enzymes during remodeling?
metalloproteinases (MMP)- function in matrix degradation during remodeling
what is the reason for digesting matrix proteins during remodeling?
degradation allows cellular migration through the stroma
MMPs are synthesized as zymogens. what activates them?
already activated MMPs or serine proteases
what regulates MMP activity?
MMP activity is regulated by TIMPs. (a series of endogenous tissue inhibitors of metalloproteinases)
the reaction of vascularized living tissue to local injury is known as________?
why is inflammation considered a protective process?
neutralizes the cause of injury
rids the body of necrotic tissue
acute inflammation is characterized by ______________ and lasts how long?
neutrophils, lasts minutes to a few days
chronic inflammation is characterized by which cell types and lasts how long?
characterized by macrophages and lymphocytes, lasts days to years
Regarding morphology of inflammation: One type of inflammation is generally more variable and the other is generally more uniform. Which is which?
acute - uniform
chronic - varied
what are the four cardinal signs of inflammation as described by Celcus?
1. Rubor (redness)
2. Tumor (swelling)
3. Calor (heat)
4. Dolor (pain)
what is the additional cardinal sign of inflammation that was added later by Virchow?
Functio laesa (loss of function)
in inflammation what does the following effect have:
1. vasodilation
2. structural changes in microvasculature
1. increased blood flow
2. allows plasma cells and leukocytes to leave the capillary.
when inflammation first begins, what do the blood vessels do (only for a short while)
Why is there slowing and stasis in the microvasculature during inflammation?
because of the increased vascular permeability
1. what is exudate?
2. what does it commonly cause?
1. protein rich fluid that leaks out of vascular system during inflammation
2. swelling is often due to exudate
1. what is transudate?
2. what are the normal components of transudate?
1. fluid with low protein content (this fluid leaks out of vascular system on a regular basis). it is non-inflammatory.
2. transudate consists of mainly H2O and albumin
1. define edema
2. define pus
1. excess fluid in interstitial tissue or serous cavity (can be transudate or exudate)
2. exudate rich in neutrophils
what forms the gaps in the microvasculature?
contraction of endothelial cells
where do these gaps in microvasculature most commonly occur?
(which type of vessel)
1. describe leukocyte dependent injury of the vasculature.
2. what is the timeframe for this injury in regards to inflammation?
1. leukocytes have a toxic effect when they adhere to the vascular wall, this damages the vessel.
2. it is a late inflammatory response
what are the three main cytokines that leak via gaps in the vasculature?
which cell type can intervene in allergic reactions and can kill parasites?
a macrophage precursor is called a ___________.
what are the two main functions of macrophages?
1. phagocytosis
2. synthesis of chemical mediators
which cell types (2) produce histamine and play a key role in anaphylaxis?
mast cells
what three things make up the sequence a leukocyte goes through before it can undergo diapedesis?
1. margination
2. rolling
3. adhesion (pavementing)
what two things does the leukocyte do in order to increase the avidity of binding in adhesion?
1. redistributes adhesion molecules to cell surface
2. induces adhesion molecules on endothelium
what is chemotaxis?
migration along a chemical gradient
what type of chemotactic agent would bacterial products be?
exogenous agent
give an example of 3 endogenous chemotactic agents
leukocytes move via which structure?
pseudopods (lamellapodia)
IgG Fc, C3b and collectins are all examples of?
what happens to the newly engulfed toxic agent?
killing or degradation via fusion of the phagosome with the lysosome
what most commonly mediates oxygen dependant degradation?
how do lysozymes mediate oxygen independent microbial killing?
by hydrolyzing the coating of bacteria
where is MBP found and what does it do?
MBP is found in eosinophils, it is cytotoxic to parasites
what are the three functions a leukocyte can have a defect in?
1. defect in adhesion
2. defect in phagocytosis
3. defect in microbiocidal activity
what would be observed in a defect of leukocyte adhesion? (2)
1. recurrent bacterial infections
2. impaired wound healing
Chediak-Higashi syndrome is a defect in which leukocyte function?
defect in phagocytosis (degranulation and killing)
chronic granulomous disease (CGD) is a result of a defect in which leukocyte function?
defect in microbiocidal activity
1. what is "frustrated" or "surface" phagocytosis?
2. why is this important?
1. when a leukocyte cannot phagocytose a microbe (most often due to its large size).
2. This can cause additional damage because lysozyme is released into the tissue.
give an example of chronic inflammation caused by:
1. organisms producing delayed hypersensitivity
2. prolonged exposure to toxic agents
3. autoimmunity
1. TB
2. silica, asbestos
3. SLE, RA
what are the three types of mononuclear cells?
1. macrophages
2. lymphocytes
3. plasma cells
what is characteristically seen in chronic inflammation that is attempting to heal?
damaged tissue (from acute inflammation) is replaced by connective tissue
chronic granulomatous inflammation is caused by a granuloma. What is a granuloma and what surrounds it?
a granuloma is a nodular collection of epitheliod cells (specialized macrophages). These epithelial cells are surrounded by lymphocytes.
what are the two major causes of chronic granulomatous inflammation (general)
1. T-cell mediated immunity (TB-a delayed hypersensitivity rxn)
2. poorly digestible irritants, foreign body rxn (sutures, sliver)
There are six morphologic patterns of inflammation. Describe serous inflammation
effusion, an outpouring of thin fluid derived from serum
There are six morphologic patterns of inflammation.
Describe fibrinous inflammation
exudate rich in fibrin
organization is seen
There are six morphologic patterns of inflammation.
Describe Suppurative (purulent) inflammation
mainly neutrophils present
lots of necrotic cells
There are six morphologic patterns of inflammation.
Describe an ulcer and what produces it.
a local defect or excavation of the surface of an organ, produced by sloughing of inflammatory necrotic tissue
There are six morphologic patterns of inflammation.
Describe an abscess
a localized collection of neutrophils with liquified necrotic tissue in the center
There are six morphologic patterns of inflammation.
Describe membranous inflammation
exudate seen on the surface
describe non-oxygen dependent bacterial killing by defensins

(what releases them, what do they kill)
defensins are released by PMNs and some lysozomes - they kill tons of things (gram + and - bacteria, fungi, some enveloped viruses)
describe non-oxygen dependent bacterial killing by lactoferrin
lactoferrin competes with bacteria for iron (lactoferrin is an iron chelator)
what is responsible for the Rubor seen in inflammation?
Rubor=redness: caused by dilation of blood vessels
what is responsible for the Calor seen in inflammation?
Calor=heat: caused by increased blood flow to area of injury
what is responsible for the Dolor seen in inflammation?
Dolor=pain: caused by:
1. increased pressure (accumulated interstitial fluid)
2. mediators such as bradykinin
what is responsible for the Tumor seen in inflammation?
Tumor=swelling: caused by an extravascular accumulation of fluid
1. lymphokine
2. monokines
1. soluble factors released from lymphocytes, are involved in the immune system
2. soluble factors released by monocytes and macrophages, are involved in the immune system
lymphokines and monokines are collectively known as?
what are chemokines?
chemokines are a subset of cytokines involved in chemotaxis
besides regulating the immune response what are the other functions of chemokines? (2)
1. cell growth and differentiation
2. tissue repair and remodeling
what do I mean when I say that cytokines are pleiotropic?
they act upon many different cell types
What are the three families of cytokines/receptors?
1. TNF related
2. Chemokines
3. Hematopoietins (Type I)
What are two examples of TNF related cytokines?
what are the two main functions of TNF receptors?
1. activation of gene expression
2. influence cell death via death domain
What is the difference between a Type I and a Type II TNF receptor?
TNF Type I receptor - functions in activation of gene expression
TNF Type II Receptor - contains death domain
What are 5 examples of Hematopoietins (Type I) cytokines?
describe the structure of the hematopoietin receptors
1. made up of 2 or more subunits
2. lots of redundancy because sub-units are shared by several members
Which cytokine receptors share a common beta chain?
IL 3,4,5,13
Which cytokine receptors share a common gamma chain?
IL 2,4,7,9,15
In general, describe the Jak-Stat paradigm
IL-R associates with Jak
Jak binds to Stat
results in modulation of gene expression
describe the structure of chemokine receptors
7 transmembrane helices
interacts with G proteins
what are 3 examples of chemokines?
in regards to chemokines:
1. what does its function of chemokinesis mean?
2. what does its function of chemotaxis mean?
1. stimulation of leukocyte motility
2. direction of leukocyte movement
what are the two classes of cytokines?
What is the difference between CXC and CC?
(which cell types does each attract)
CXC - predominately atract neutrophils
CC - predominately attract macrophages and monocytes
what are 3 early pro-inflammatory cytokines?
which cytokine is known as the bridge cytokine because it bridges innate and acquired immunity
in relation to a viral infection, put the following in chronological order:
NK cell mediated killing of infected cells
T-cell mediated killing of infected cells
production of IFN-alpha and beta, TNF-alpha, IL-12
1. production of IFN-alpha and beta, TNF-alpha, IL-12
2. NK mediated killing
3. T cell mediated killing
what are the pro-inflammatory cytokines we need to know? (5)
1. IFN-alpha and beta
2. IL-1
3. IL-6
4. IL-12
5. TNF-alpha
what are the four effects of IFN-alpha and beta?
1. inhibit viral replication
2. increase NK cells lytic ability
3. increase MHC class I expression
4. decrease MHC class II expression
what is the source of IFN-alpha vs. the source of IFN-beta?
IFN-alpha: macrophages
IFN-beta: fibroblasts
what is the stimulus for both IFN-alpha and beta?
viral infection
1. what is the source of TNF-alpha?
2. what two cells are the target of TNF-a?
3. what is the stimulus for TNF-a?
1. early - macrophages
later - TH1 cells
2. macrophages and neutrophils
3. LPS
what does TNF-alpha accomplish by targeting and stimulating macrophages?
production of TNF-a, IL-1, IL-6, NO.
what does TNF-alpha accomplish by targeting and stimulating neutrophils?
bacterial lysis
functionally, which two cytokines is TNF-alpha equivalent to?
IL-1 and IL-6 (IL-6 has a lesser effect on neutrophils)
1. what molecule triggers most of the cytokine production?
2. what other molecule can induce cytokine production?
2. LPS
regarding IL-12:
1. what is the source?
2. what is the target?
3. what effect does it have on NK cells?
4. what effect does it have on T cells?
1. macrophages and dendritic cells
2. NK cells and T cells
3. production of IFN-gamma and cytolysis
4. CD4+ T cell differentiation
Regarding TNF-alpha:
1. cell of origin?
2. target cell?
3. effector function?
1. macrophages (early) and T cells (later)
2. macrophages and neutrophils
3. induce adhesion molecule expression, facilitate chemotaxis, cell lysis via neutrophils
Regarding IL-2:
1. cell of origin?
2. target cell?
3. effector function?
1. activated T cells only (TH0, TH1, CTL)
2. principle T cell growth factor
3. mainly T cell proliferation (also B cell growth, NK cell growth)
Is the manner in which IL-2 activates T cells autocrine or paracrine?
both autocrine and paracrine
In an activated T cell:
1. what is the result of adding an alpha chain to the IL-2 receptor (making it IL-2R.alpha.beta.gamma)
2. what is the result of having only an IL-2R alpha chain?
1. upregulation of IL-2 (receptor has increased affinity)
2. IL-2 downregulation (receptor has decreased affinity)
what would a deficiency in IL-2 result in?
decreased T cell function
what is unique about the interferon (IFN) gamma receptor?
it must be a dimer to be biologically active
regarding IFN-gamma:
1. cell of origin?
2. target cells?
1. TH1, CTL and NK cells
2. T cells, B cells, macrophages, other leukocytes
what effect does IFN-gamma have on T cells? (2)
1. correlates with IL-12 to induce a TH1 response
2. Inhibits IL-4 induced TH2 responses
what effect does IFN-gamma have on B cells?
stimulates differentiation
what effect does IFN-gamma have on macrophages?
1. activation
2. upregulation of MHC class I and II responses
what would a deficiency in IFN-gamma result in?
an increased susceptibility to mycobacterial infections
Regarding IL-4:
1. cell of origin?
2. target cell?
3. effector function?
1. activated T cells
2. B and T cells
3. primary growth factor for B cells.
Enhances synthesis of IgE.
Responsible for TH2 response, Inhibits IL-2, IL-12, IFN-gamma TH1 type responses
what effect does IL-4 have on B cells? (3)
1. activation and growth
2. upregulation of MHC class II
3. Stimulation of IgG and IgE synthesis
what effect does IL-4 have on macrophages and mast cells?
inhibits activation of macrophages, stimulates mast cell growth
what would a deficiency of IL-4 result in?
and absent TH2 type response
regarding IL-10:
1. cell of origin?
2. target cell?
3. effector function?
1. TH2, B cells, macrophages, keratinocytes
2. TH1 cytokines (IL-2,3,12, IFN-gamma, TNF-alpha)
3. Indirectly favor TH2 functions (via suppressing IL-12 and IFN-gamma).
IL-10 is STRUCTURALLY similar to which cytokine?
IFN-gamma (function is opposite: IFN-gamma favors TH1 response, IL-10 favors TH2 response)
What effect does IL-10 have on:
1. B cells
2. macrophages
3. mast cells
1. upregulation of MHC class II
2. inhibits cytokine release
3. stimulates mast cell growth
What would a deficiency in IL-10 result in?
an alteration of the TH1:TH2 balance (in favor of the TH1 response)
regarding TGF-beta:
1. produced by?
2. general function?
1. virtually all cells of the immune system
2. general suppressive function
why are TGF-beta levels elevated late in an immune response?
TFG-beta downregulates the immune response
TH1 cells produce which cytokines (2)?
1. INF-gamma
2. IL-2
TH2 cells produce which cytokines (2)?
1. IL-4
2. IL-5
What happens in a TH1 response?
macrophages are activated
CD8 cells are formed
What happens in a TH2 response?
B cells make antibody (B is 2nd letter of the alphabet)
1. when a TH1 cell produces IFN-gamma the result is...
2. when a TH1 cell produces IL-2 the result is...
1. an activated macrophage
2. CD8 (cytotoxic) cell
a TH-o (naive helper T cell)would have to be exposed to which cytokines in order to become a TH1 cell?
a TH-o (naive helper T cell) would have to be exposed to which cytokine in order to become a TH2 cell?
Which type of infection would induce a TH1 response?
intracellular viral or bacterial (these induce dendritic cells to be the APCs)
Which type of infection would induce a TH2 response?
pathogens not inducing dendritic cells (ie. parasites)
what is the role of the Ag binding affinity in the TH1/TH2 decision?
Binds strongly --> TH1
Binds weakly --> TH2
TH1 cytokines have what role on TH2 activation and growth?
they inhibit
likewise, TH2 cytokines inhibit TH1 activation and growth
which type of response is this?
graft and tumor rejection
host defense against bacterial, viral or fungal infection?
TH1 (T cell mediated/ cell mediated immunity)
which type of response is this?
host defense against infection by opsonization
TH2 (B cell mediated/ Antibody mediated immunity)
which immune response mediates chronic inflammation of the airways (as in asthma or hayfever)
which immune response mediates an acute allergy?
define SCID

molecular cause?
(severe combined immunodeficiency disease)

mutation in IL-2 and Jak receptors,
result=can't make T cells.
define 5q minus syndrome
deletion in long arm of chromosome 5: result is error in development of hematopoietic stem cells,
lack of IL development
a patient that presents with increased susceptibility to mycobacterium infections and is also more prone to allergic reactions may have what kind of deficiency?
IL-12 deficiency
(could also be an IFN-gamma receptor deficiency but less likely)
which disorder is a virtually complete immunodeficiency?
Elevated levels of IL-4 are commonly seen in which disorders?
Hodgkin's lymphoma
chronic lymphocytic leukemia
after a parasitic infection a patient would have high levels of which cytokines?
IL-10, IL-3, IL-4 (mastocytosis)
in general what happens to cytokine levels in autoimmune diseases?
they increase significantly
what are the 5 portals of entry for viral infection?
1. skin
2. conjunctiva
3. respiratory tract
4. alimentary tract
5. urogenital tract
what is the innate defense present in the skin? (3)
outer layer is dead cells
constant shedding
what is the innate defense present in the conjunctiva? (2)
tear flow
lid wiping
what is the innate defense present in the respiratory tract? (4)
mucoid proteins
turibinate baffles cause virus to get trapped in mucus
mucociliary cells
alveolar macrophages
what is the innate defense present in the alimentary tract? (4)
mucoid proteins
what is the innate defense present in the urogenital tract? (4)
phagocytic cells
mechanical flushing by urine
acid environment (vagina)
how is virulence of a virus measured?
LD50 (the number of viruses required to kill 50% of the animals following viral infection)
what is changes in viral virulence usually associated with?
alterations/mutations in viral proteins (ie. 1918 flu pandemic)
How do viruses inhibit cell function? (3)
1. protein synthesis
2. DNA synthesis
3. RNA synthesis
how do viruses destroy cellular integrity? (5)
1. syncitia (giant cells)
2. inclusion bodies (viral factories)
3. vacuolation
4. chromosome condensation
5. apoptosis
what is the difference between a local infection and a disseminated infection?
local - confined, short incubation period
disseminated - spread, prolonged incubation period
give an example of a local infection
influenza, rhinoviruses
give an example of a disseminated infection
measles, rabies
what are the three routes of viral spread?
1. neural
2. lymphatic
3. hematogenous
describe the mechanism behind neural viral dissemination.
viral entry at nerve endings
transported up axons to soma
moves from peripheral nerves to CNS (or vice versa)
describe the mechanism behind lymphatic viral dissemination.
entry via lymphatic capillaries, transported to nodes. some viruses replicate in lymph nodes.
spread by lymph to blood
infected macrophages or lymphocytes disseminate infection
describe the mechanism behind hematogenous dissemination
virus entry via lymphatics or direct injury (needle, bite).
can move to secondary sites of replication
can establish primary/secondary/persistent viremia
in hematogenous dissemination how is the virus distributed?
free particles or cell associated
anatomical, physical and chemical barriers are considered which type of immunity?
give some examples of molecules that mediate innate immunity (5)
TLR, interferon, cytokines
macrophages, NK cells
in general, how do TLRs function in innate immunity?
they bind to pathogen associated molecules (PAMPs) and thereby induce expression of effector molecules (such as cytokines and IFN)
why is IFN-alpha and beta known as the "Paul Revere" of the immune system?
viral infected cells release IFN-alpha and beta: these bind to uninfected cells to "warn" them of the virus: this blocks viral replication
why is IFN-alpha and beta very effective?
they act early and limit the infection to the original cell
molecularly: how does IFN-alpha and beta block viral replication in uninfected cells?
they bind to cell and:
degrade mRNA
inhibit protein synthesis
what part of viruses can serve as antigens? (2)
1. surface proteins (capsid or envelope proteins)
2. Internal proteins
where in a virus would you look to distinguish between different viral groups (ie. to find group specific antigens)?
look at the internal proteins (not the surface ones)
what is the earliest antibody to show up in the immune response?
When does IgM peak?
2-3 weeks post infection
which antibody peaks a little later than IgM and correlates with resistance to a future infection?
Which antibody is a secretory antibody and correlates with local resistance at portals of entry?
antibodies are most important against viruses characterized by _________?
viremia (ie. yellow fever, polio)
how do macrophages participate in cell mediated immunity? (3)
1. produce TNF-alpha and compliment factors
2. phagocytose viral aggregates
3. process and present antigens to CD4+ T cells
how do CD4+ cytokines participate in cell mediated immunity?
1. recognize antigens bound to APCs
2. secrete cytokines
3. activate macrophages, NK cells, B cells and CTLs
what does the immune system resort to when a virus suppresses MHC I expression?
NK cells take care of it (CD8+ cells are MHC dependent)
what is an immune complex and what is it responsible for?
an aggregate of antibodies and antigens deposited in blood vessels. Activates compliment and induces vasoactive cytokine release -this causes increased vascular permeability and hemorrhage (ie. dengue fever)
what is a live vaccine composed of?
an attenuated strain of the virus (has reduced virulence)
what are the advantages of live vaccines? (3)
1. viral multiplication occurs which increases viral load
2. local response is usually caused
3. enhanced Ab and cell-mediated immune response
what are the disadvantages of live vaccines? (3)
1. possible reversion to virulent strain
2. possibility of dissemination
3. live preparation - has stricter care requirements (ie. must keep cold etc.)
what are the advantages of a killed vaccine? (2)
1. stable
2. no potential for reversion
what are the disadvantages of a killed vaccine? (3)
1. requires high concentrations of Antigen
2. injection only
3. lower cell mediated immunity