virology: rest of the final

what are the types of host defenses

\-physical barriers (intrinsic)

\-innate immune response

\-adaptive immune response

describe physical barriers

physical barriers that keep foreign objects out

\-innate = barriers and 2nd line

\-skin, mucous, cilia, tears

\-acid pH

describe innate immune response

\-very fast (takes minutes to hours)

\-always ready

\-non specific

\-we all have this naturally

\-constantly on

\-will respond to anything foreign

\-BUT does not have memory

\-relies on recognition of foreign molecular patterns

describe adaptive immune responses

\-takes about 1-2 weeks

\-needs to be activated

\-antigen specific

\-has memory

\-system will adapt over time

\-can be turned on and off

\-will act against what it is seeing specifically

\-separate cells deal with separate agents

where do all cells in the blood arise from

the same stem cells in the bone marrow through differentiation

\-hematopoetic stem cells (HSC)

what are hematopoetic stem cells (HSC)

\-can differentiate into different types of cells

\-referred to as “self removal”

\-system keeps replenishing this for you

what general categories does the blood stem cell in bone marrow give rise to

erythroid stem cell, myeloid stem cell, and lymphoid stem cell

what categories does the erythrocyte stem cell give rise to

erythrocyte → involved with gas transportation

what categories does the myeloid stem cell give rise to

\-platelets → involved with clotting and inflammation

\-basophils → involved with inflammation/innate

\-neutrophils → involved with phagocytosis/innate

\-eosinophils → involved with phagocytosis/innate

\-monocyte → involved with phagocytosis/innate

what categories does the lymphoid stem cell give rise to

lymphocytes → involved with adaptive immunity

describe granulocytes

\-consist of the types: neutrophils, eosinophils, basophils

\-has granules

describe neutrophils

\-if levels are high, indicates infection

\-will be the first to be sent out during infection

describe eosinophils

has granules

\-releases cytochemical stuff to degrade parasitic worms

describe basophils

has granules

\-if not stopped, results in an allergic reaction

\-associated with allergic reaciton

how do innate immune responses “sense” infection with a pathogen

has pattern recognition receptors

\-sends intracellular signal to the cell to alter its gene

\-cell may then respond by produces cytokines, secreting interferons, or producing chemicals called chemokines that attract additional phagocytes to the area of infection

\-detects virus via immune cells or by cells infected with the virus (then releases cytokines)

what are the sensors of the innate immune response and what is the overall function

toll like receptors (TLRs)

\-recognizes almost every pathogen likely to cause infection

\-there are different combinations

\-unique for viruses and bacteria

what is the process of the innate immune system recognizing a pathogen

1. influenza viral proteins interact with binding receptor → conformation change is induced
2. toll like receptors senses the viral particle and sees whether its okey to admit the object into a cell (looks for a pattern in a foreign entity, such as the repetitive pattern of the NC)
3. signal transduction occurs
4. phosphorylation cascade occurs, transmitting the signal down proteins
5. information is taken to the host’s nucleus where mRNA is made and transferred to the ribosomes to make necessary proteins (cytokines)


1. cytokines are released out of the cell for protection

what is the function of intracellular sensors in cells

trigger gene expression and the production and release of cytokines

describe pro inflammatory cytokines

\-forces body to become inflamed

\-all macrophages and neutrophils come to one spot

\-temperature increases

\-certain processes are shut down

\-effective since each virus has an optimal temperature to function

\-although our cells won’t be able to make its necessary proteins, it can withstand

what are cytokines and what do they do

the main produce of innate defense

\-chemicals involved in cell to cell communication

\-act at short range (locally)

\-released by cells and affect the behavior of other cells, and sometimes the releasing cell itself

what are some types of cytokines

chemokines

interferons

interleukins

what are some types of interleukins

IL 1, TNF, IL6, IL12

function of interluekins

involved in the communication between leukocytes

\-TNF is the major inducer of apoptosis

function of chemokines

attack more leukocytes to site

function of interferons

released in response to viral infections

what are cytokines the cause of

viral symptoms of fever, aches, loss of appetite, fatigue, etc

how are cytokines stopped

must stop binding at receptor that causes signal transduction

what are interferons produced from

virus infected fibroblasts/epithelium, sentinel cells

\-rapid within hours but declines after 10 hrs

what is the overall mechanism of interferons

1. virus infect cells
2. viral replication in cell triggers transcription and translation of alpha or beta interferon depending on type of host cell
3. interferon is released, diffuses to neighboring uninfected cells, and binds to receptors
4. binding triggers transcription and translation of inactive antiviral proteins (AVPs)
5. infected cell dies and releases its virus
6. when the second cell becomes infected with released viruses, ds RNA of the virus activates AVP
7. active AVPs degrade mRNA and bind to ribosomes, which stops protein synthesis and viral replication

what does interferon binding of neighboring cells do

turns on genes following signal transduction (Janus kinases and STAT

function of janus kinases

a signal transducer

\-is the start protein of signal transduction

function of STAT protein

an activator of transcription

\-is the response protein

what is the overall function of janus kinases and STAT protein

make the cell inhospitable for virus replication, should it become infect (antiviral state)

how do foreign agents interact with the JAK and STAT entry upon entry

these proteins are destroyed

\-no cytokines are made

\-no antiviral proteins made

\-cell communication is destroyed

what genes are expressed by interferons to maintain an antiviral state

\-Pkr (dsRNA activated protein kinase)

\-RNase L and 2’5’ oligo(A) synthetase

\-nitric oxidde synthase

\-tetherin

function of Pkr

phosphorylates eIF2- alpha

\-inhibits translation of viral proteins

function of RNase L and 2’5’ oligo(A) synthetase

activated by dsRNA

\-leads to cleavage of mRNA

function of nitric oxide synthase

NO rapidly reacts with proteins and inactivates them (forms ONOO-, peroxynitrite, which is highly toxic)

\-our cells make the environment toxic to destroy these foreign agents)

\-interferes with viral protein synthesis

function of tetherin

impairs the release of many enveloped viruses, sensor of viral infections, and activates NF kappaB to induce an inflammatory response

\-prevents the exit of the cell

why is apoptosis important

keeps damaged or bad cells from replciating

how may a cell respond to pattern recognition receptors sending intracellular signal to the nucleus to alter gene expression

\-produces cytokines

\-secretes interferons

\-produces chemokines that attract additional phagocytes to the area of infection

\-forces cells to undergo apoptosis

what are the cells of the innate immune response called

sentinel cells or professional phagocytes

where are sentinel cells usually found

strategically planted in the lymphoid

\-secondary lymphoid points include the neck (prevents URI sx), gut, and under armpit

describe sentinel cells

\-dendritic cells patrol mucous membranes

\-macrophages patrol tissues

\-neutrophils circulate blood

what are the cells that engulf particles called

professional antigen presenting cells

what are the types of APCs

dendritic cells

macrophages

B cells

describe APCs

\-usually the first to encounter the foreign entity

\-shows antigen on a platter to the rest of the cells

\-degrade the foreign particles and display them on their surface

describe MHC 1

peptides from inside the cell (so virus infected cell)

describe MHC II

peptides brought in from outside (so phagocytized particles)

what happens upon sensing and phagocytizing foreign particles

APCs mature and produce cytokines

\-amplify the response (interleukins and chemokines are released)

what is associated with inflammation

\-influx of phagocytes

\-increased blood flow (vasodilation)

\-increased capillary permeability

\-tissue repair

\-redness (rubor), pain (dolor), heat (calor), and swelling (tumor)

function of histamines

released from basophiles/mast cells

\-results in the dilation of capillaries

\-causes increased blood flow (redness, heat)

\-causes increased permeability/movement of cells and fluid into tissues, resulting in swelling and pain

what causes a fever

phagocytes release chemicals that act on the hypothalamus

\-prostaglandins are released which then resets temperature

what happens if an infection continues and is not controlled

larger quantities enter blood and have global effect

\-results in sx of sleepiness, lethargy, muscle pain, no appetite, nausea

describe natural killer cells

\-part of innate immune system

\-acts early (1-3 days after infection)

kills host cells that lack self molecules (cells infected with virus or cancer cells)

\-release perforin and protease granules and induce apoptosis

how does mature dendritic cells function

become mobile and presents antigens to T cells

\-this action produces more cytokines to activate the T cell

what makes the adaptive immune response effecive

as long as there is no change in the antigen, the secondary response will be faster and more robust

what are non-cytopathic viruses

viruses that do not stimulate the inflammatory response and do not activate the adaptive response very well

\-often cause a persistent infection since they are inefficiently cleared

\-usually occurs with enveloped viruses as they have a lipid bilayer that is ours and binds to our cells

what is the adaptive immune response activated by? what are its components

activated by antigen presenting cells and cytokines (from the innate immune response)

\-composed of humoral and cellular components

what is an antigen

a substance capable of eliciting an immune response and can react specifically with an immune recognition molecule

what is an epitope

site on an antigen that is recognized by an immune molecule

what may a virus have to combat our adaptive immune response

may have antigen generators (have generates antibodies)

\-our body develops antibodies against the region of an antigen called an epitope

what is the humeral immune response

B cells are involved

\-produces antibodies against an antigen (particularly the epitope of antigens)

\-then the antibody binds to the antigen, changes conformation, and prevents virus from getting into the host

what are the cells involved in cellular immune respose

CD4 T helper cells and CD8 T cytotoxic cells

how many antigen bindings sites does an antibody have

2

what are the parts of an antibody

an F constant region (Fc)

2 variable regions

describe the Fc region of an antibody

could be IgG, AgA, or IgM

\-stays constant

describe the variable regions

region that binds to the epitope

\-changes

describe IgM

1st to be produced in infection

describe IgG

highest amount

\-longest lived

\-crosses the placenta

describe IgA

mucosa

\-has a secreted peptide

describe IgE

produced in response to allergic reactoins

function of neutralizing antibodies

can render the virus noninfectious in a number of ways

\-blocks attachment to receptor and/or endocytosis

\-blocks uncoating (antibodies prevent conformational change)

\-tag the virus inside cell triggers proteosome degrading

\-tagging them for degradation by the proteosome

describe the humoral adaptive response

BCR on B cells bind extracellular antigen (virus)

\-plasma B cells produce antibodies that can act far away and bind virus

describe the cell mediated adaptive response

TCR on T cells recognize viral antigens displayed on surface of a cell

\-must be presented in the context of “self” MHC

\-effector cells act only at a short range

what do all cells have

MHC 1 (peptides being made from inside the cell)

what do only APC cells have

MHC II (peptides being brought into the cell from outside)

what is the function of B cells

\-produces antibodies (neutralizing pathogens and undergoes phagocytosis)

\-will bump into antigens and then recognize

what do T cells need in order to function

must have an antigen presented to them by an APC

overall function of CD4 T helper cells

calls more immune cells

overall function of CD8 cytotoxic cells

kills infected cells

\-encourages apoptosis (programmed cell death)

what are the molecules that induce apoptosis

perforin and granzymes

what does cytotoxic T lymphocytes recognize

specific viral peptide bound by MHC I on the surface of infected cells

how do cytotoxic T lymphocytes function

kills virus infected cells by inducing apoptosis

\-effector cells act only at a short range

\-cells themselves do the “action” and therefore must make contact

how have viruses evolved to evade the host immune response

\-bypass it by entering through inoculation

\-hide from it

\-disarm host defenses (interfere with or destroy)

\-encode genes that can module this communication, altering our immune response

what are some specific mechanisms that viruses use to evade the host immune resopnse

\-infection of immune cells

\-TLR interference

\-signal transduction pathway interference

\-interference with interferon signaling pathway

\-downregulation of MHC1 production in a cell

\-antigenic variation

\-ADCC

describe infection of immune cells

ex: HIV (T cells are infection), EBV

viruses are given the advantage as they can quickly disseminate since dendritic cells, T cells, and B cells move around a lot

\-can spread, hide, and kill

\-infects dendritic, T, and B cells

describe TLR interference

if inhibited, cytokines will not be produced

\-viral protease cleaves TLR signaling molecules and so signal never transferred → no signal transduction → no cytokine production → interferes with innate immune response to contain viral infection

ex: influenza

describe signal transduction pathway interference

\-multiple proteins are involved

\-tells the cell usually to produce cytokines

\-however, viruses makes it that cytokines are not released (it blocks communication between cells)

\
if intracellular pattern recognition receptors and pathways are interfered with

\-inhibition of interferon production

\-immunosuppression

\-viral infection cannot be contained

ex: ebola VP 24 binds STAT and inhibits signal transduction

describe interference with interferon signaling pathway

interferons usually tell neighboring cells to prepare for virus (tells them to make antiviral proteins

\-virus makes it that there is no preparation for onslaught

\
\-action of interferon on neighboring cells is inhibited → gene expression is inhibited → antiviral state produced → cell never goes into protection mode

\
ex: SARS CoV, Hep C

describe downregulation of MHCI production in a cell

never makes MHCI and will never travel to the surface

\-CD8 T cells never arrives

\
TAP protein is destroyed and we will never present the antigen

\-CD8 T cells never arrives

\
TAP is inhibited → downregulation of MHC1 presentation on surface of infected cell

ex: adeno, HIV, COVID19, HCMV

describe antigenic variation

\-changes surface proteins

ex: influenza, COVID-19, HIV

\-RNA poly lacks proofreading capabilities (allows for more mistakes)

\-creates quasi species or escape mutants

\-due to selective pressure by adaptive immune response (cytotoxic T lymphocytes or antibody

\
affects recognition and binding of CTL to Ag+ MGH1 (cell killing)

or

recognition and binding of antibody to the virus (neutralization)

describe ADCC

antibody must get rid of pathogens

\-if antibody cannot neutralize

\-ex: HIV, ebola

what do all nucleated cells in response to foreign proteins

process foreign protein and load it onto MHC 1 using TAP protein

\-TAP protein that helps to load antigen on MHCI to present

what are some viral strategies for interfering with the human immune response

\-infection of immune cells

\-stealth (latency)

\-interference with pattern recognition receptors (outside TLR or inside RIG-I)

\-inhibit interferon production or effect

\-blockage of antigen presentation (MHCI and MCHII)

\-mutation of antigenic epitopes

\-antibody enhancement

once an antibody is produced, what must we do to get rid of the foreign entity

1. virus must be neutralized (ensure that the virus can never enter the host)
2. complement lysis (lysis of pathogenic cells; mediates system of complement)
3. phagocytosis (of macrophages; has receptor on its surface; antigen attaches to variable region of antibody; antibody and virus are engulfed by macrophages via opsonization)

what does neutralization do

1. wants to block binding
2. wants to block uncoating

describe MHCI

will always present peptides from inside a cell

\-will call CD8 T cell (aka cytotoxic C cell) to function to kill infected cells

what receptors do APCs have

MHCI and MHCII

describe MHCII

\-peptides brought in and then presents

\-will call CD4 (aka helper T cell; functions to release cytokines to talk to B cells, which then makes antibodies, and will call other immune cells)