Microbio Exam 3

Final Exam!!

What is the MAIN task of the immune system?

to distinguish self from non-self

what must the immune system eliminate?

1. whole organisms (bacteria and fungi)
2. intracellular pathogens (viruses and bacteria)

What is the definition of immunology?

the study of the molecular and cellular interactions between a host and introduced __foreign__ molecules

What is immunity?

the ability to resist future infections caused by previously encountered pathogens

What is the first line of defense for immunology?

second line?

third line?

first: nonspecific tactics (physical and chemical)

second: innate cellular responses

third: adaptive cellular responses

In the analogy of the immune system as castle defense, what would the alligators/moat be? the boiling oil? the archers and arrows?

alligators: first line → innate, nonspecific protections

boiling oil: second line → innate chemical defense

arrows/archers: third line → antibodies and B cells

what is the difference between innate and adaptive immunity when it comes to response time? specificity?

response to repeat infections? what are the major components of each?

response time: innate= hours; adaptive= days

specificity: innate= limited and fixed; adaptive= highly diverse/improves during the course of immune response

response to repeat infections: innate= identical to primary response; adaptive= much more rapid than primary response

major components: innate= barriers, phagocytes, pattern recognition molecules; adaptive= lymphocytes, antigen-specific receptors, antibodies

between adaptive and innate immune response, which has the greater magnitude of immune response over the longer amount of time?

adaptive has a greater and longer response in comparison to innate for both the first and second responses

What is innate immunity?

nonspecific, immediate action that prevents infection without conferring immunity

what physical barriers are there in innate immunity? chemical barriers?

physical → intact skin, mucus

chemical → lysozyme, salt secretion

fevers

How are normal microbiota related to innate immunity?

they allow for the competitive exclusion of pathogens and their metabolic byproducts are toxic to other organisms

what are 3 examples of nonspecific cellular attacks in innate immunity?

1. phagocytes → pathogen-ingesting cells
2. complement → pathogen-destroying proteins
3. cytokines → signaling proteins secreted by WBCs

How is skin a defense for immunity?

it is a natural barrier:

* has closely packed cells
* continuous layering
* presence of keratin
* dryness and shedding of skin

How are mucous membranes a protection for immunity?

they have goblet cells that produce and secrete mucus which covers and protects fragile cells underneath and traps debris and particulates (including microbes)

* they line the entire GI, respiratory, and urogenital tracts

what is mechanical removal? How does it help with immunity?

* mucociliary escalator
* coughing, sneezing
* intestinal peristalsis
* defecation, vomiting, diarrhea
* urine, tears, vaginal secretions

What are the chemical defenses in immunity?

* sebum → secreted fatty acids (low skin pH)
* Lysozymes → cleaves peptidoglycan
* found in saliva, mucus, intestines, tears, sweat
* low pH of stomach

What are 3 ways normal microbiota provides resistance to disease?

1. competitive exclusion (example the microbia use up the nutrients in teh GI tract so bacteria have none)
2. inhibiting or killing pathogens
3. facilitating development of immune system

what can inhibiting or killing pathogens produce?

antimicrobial peptides (AMPs)

what are antimicrobial peptides?

* short peptides (10-100aa) that exert broad-spectrum antimicrobial activity
* most are cationic (+2→ +9 net charge) and amphiphilic
* AMPs can directly inhibit microbes, coordinate immune response, disrupt biofilmes, etc.

What are **defensins** and **cathelicidin**?

they destroy cytoplasmic membranes of microbiata

* expressed by many epithelial cells and stored in neutrophil granules

How does the positive charge of AMPs help them target bacterial membranes?

bacteria is negatively charged (acids have negative charge, lipopolysaccaride, etc)

What does IFN, IFNAR, and ISG stand for?

IFN = interferon

IFNAR= IFN alpha receptor

ISG= IFN-stimulated gene

______ cells can both produce and respond to type I IFN

ALL

What are Type I Interferons?

IFN-alpha and IFN-beta


1. when a virus enters a cell, the sensors start a cascade of events
2. sensors trigger the IRF’s
3. IRF’s trigger IFN in the nucleus and then travels out out of nucleus into cytoplasm and then all the way outside the cell
4. IFN triggers IFNAR which triggers JAK/STAT which ultimately triggers ISGs

what is an ISG’s purpose?

* it is an antiviral effector
* it can degrade viral RNA, inhibit protein synthesis
* It can increase MHC I expression and Ag presentation
* it can activate NK cells to kill virally infected cells

signaling of Type I Interferons is both _______ __and__ _________

autocrine and paracrine (signals itself and neighboring cells)

What is our blood composed of?

* plasma
* formed elements
* erythrocytes
* leukocytes
* platelets

what are formed elements? what is the process of forming them called?

elements created in the red bone marrow via hematopoiesis

what connects the immune system?

blood and lymph

what are the primary lymphoid organs?

where immature lymphocytes mature into Ag-sensitive B cells and T cells

* Thymus
* Bone Marrow

what are the secondary lymphoid organs?

where mature lymphocytes encounter antigens

* adenosoids
* tonsil
* thoracic duct
* right lymphatic duct
* lymph nodes
* spleen
* peyer’s patches
* tissue lymphatics

what does the lymphatic system do?

it returns fluids and screens for pathogens

* fluid in blood leaks out of capillaries, and the lymphatic system recovers the fluid.
* drains every part of the body → passes through lymph nodes, ultimately returns to your veins

Lymph carries microbes to __________ and ______+________destroy the pathogen

lymph nodes

lymphocytes and antigen-presenting cells (APCs)

nodes are packed with _____________

leukocytes

what are the gut-associated lymphoid tissues?

tonsils, adenoids, and Peyer's patches

__________ cells sample intestinal microbes

microfold (M)

what are pathogen-associated molecular patterns? (PAMPs)

structures unique to pathogens

* LPS, flagellin, PDG

what are pathogen recognition receptors? (PRRs)

cellular receptors that bind to PAMPs

* embedded on the plasma membrane and inside endosomes
* PAMP-PRR binding activates phagocytes

What cells are REALLY important in innate immunity? (not exclusive list of all cells)

* mast cell
* neutrophil
* monocyte
* dendritic cell
* macrophage
* natural killer cell
* (others are eosinophil and basophil)

what cells function in adaptive immunity?

* monocyte
* dendritic cell
* macrophage
* T cell
* B cell
* plasma cell
* natural killer cell

where are macrophages in the body? what is their function?

present in most tissues of the body and perform tissue-specific immune protection

both macrophages and dendritic cells destroy microbes by phagocytosis and are able to present antigens to T cells

where are dendritic cells present in the body? what is their function?

present in spleen, lymph nodes, skin, and mucous membrane

function: can take up small soluble ags from environment and is the primary initiator of the adaptive immune response

what first encounters pathogens? what directly kills invaders?

macrophages

invaders are directly killed by phaocytosis

in phagocytosis antigens are presented to adaptive immune cells

is phagocytosis part of the innate or adaptive immune system?

it is part of the innate immune system but activates adaptive immunity

what are phagocytic granulocytes?

neutrophils

what are polymorphonuclear neutrophils? (PMNs)

they have distinctive multilobed nuclei

highly active in initial stages of an infection

phagocytic, motile

60-70% of all leukocytes

which granulocytes release granules?

eosinophils, basophils, and mast cells

what do granulocytes do?

release products that are toxic to microbes

important in inflammation and allergy

which granulocyte acts agains parasites?

eosinophils

which granulocytes release histamine? which ones travel where?

basophils and mast cells

basophils stay in blood

mast cells migrate into tissues, mucosa

what are the agranulocytes?

natural killer cells

what do natural killer cells do?

they can kill a wide variety of infected body cells and tumor cells

what happens when a NK cell is bound to its target?

it releases toxic substances from lytic granules (perforin → forms a pore, granzymes → induce apoptosis)

what is the first mechanism for NK activation?

1. there must be an absence of the “self” protein, MHC I
2. there must be the presence of “altered self” or “nonself” proteins

what are the phagocyte cells?

neutrophils and macrophages

what is inflammation?

a host response to tissue damage characterized by

* heat
* edema
* redness
* pain
* altered function or movement

(HERPA acronym)

what is the difference between acute and chronic?

acute: mild and self-limiting (days to weeks)

chronic: severe and progressive; months to years

how does inflammation fight infection?

1. it delivers additional effector molecules and cells to site of infection
2. provides a physical barrier to prevent spread of infection
3. promotes repair of injured tissues

how are effector molecules delivered to the site of infection?

1. increase in vascular diameter (increase in blood volume)
2. decreased blood flow (heat & redness)
3. increase in vascular permeability

what are the vasoactive mediators?

histamine, kinins, prostaglandins, leukotrienes, cytokines

why is decreased blood flow important for inflammation?

allows leukocytes to better interact with the vascular endothelium → facilitates extravasation

* neutrophils and macrophages are recruitd from the blood to the site of infection

what is diapedesis?

when macrophages squeeze through endothelial cells

when you have an increase in vascular permeability how does that help in inflammation?

* it leads to swelling (edema) and pain
* also leads to the accumulation of Abs, complement, and other blood proteins

What controls trafficking of innate immune system cells?

appearance/disappearance of (1) adhesion molecules on endothelial cells and (2) their ligands on lymphocytes

What are selectins and how do they relate to inflammation? What are the rest of the steps of diapedesis?

they are pro-adhesion molecules that are induced on endothelial cells by cytokines (which were secreted by macrophages) at the site of inflammation.

\
the next step was that the ligands on the WBCs bind and cells slowed down and roll.

\
this induces the expression of true adhesion molecules (integrins) on white blood cells

\
cell extravasates (diapedesis)

\
chemokines then induce cells to move towards site of inflammation

What is the first responder of the inflammatory response? what do they do?

neutrophils

* destroy invading microbes via phaocytosis
* predominate but die off quickly via apoptosis

what follows neutrophils in inflammation?

monocytes

after WBCs die, what happens to end inflammation?

tissue repair -- new cells are produced by stroma and parenchyma

what happens if there is a lack of integrin in the blood?

it will cause a ton of neutrophils to build up in the blood.

T/F: fever is a systemic response to infection

True

how does a higher temperature (fever) fight infection?

reduces infectious potential of pathogens

stimulates innate and adaptive immunity

what substance causes fever?

pyrogen

internal pyrogens act on _____________ which releases what?

hypothalamus

prostaglandins

what composes the proteins in the complement system?

liver and macrophages

how does the complement system destroy microbes?

by cytolysis, opsonization, and inflammation

what is the process called when one reaction triggers the next and more product is formed with each reaction?

amplification

happens in the complement system

what are the three pathways of the complement system?

alternative pathway

classical pathway

lectin pathway

what step do all complement pathways converge on?

the cleavage and activation C3. Spits into C3a and C3b

what steps do the classical and lectin pathways differ on?

the initial pathogen recognition/activation step

what are three possible consequences of the complement cascade?

inflammation, lysis, and opsonization

what can one C3 convertase generate?

200 + C3b molecules

what is anaphylatoxin?

small peptides that cause smooth muscle contraction, increased vascular permeability, increased phagocytosis, degranulation of granulocytes and mast cells

anaphylatoxin triggers histamine release which →

increases vascular permeability

what does chemotactic factor do? →

attracts phagocytes to site of complement activation

what is opsonization?

immune adherence

* promotes attachment of phagocyte to a microbe

which complement product is used in cell lysis?

C5b-C9 and the membrane attack complex (MAC)

which complement product is used in the inflammatory response?

C3a and C5a

Which complement product is used in opsonization?

C3b

how does the innate immune system recognize foreign pathogens?

through pattern recognition receptors and opsonin receptors

triggering these receptors stimulates phagocytosis and activates phagocytes

what are pattern recognition receptors?

they trigger an imediate response in teh innate immune system and recognize a broad class of pathogens and __recognize microbes directly__

what are opsonin receptors?

they __recognize microbes indirectly__ and they have FcgammaR and complement receptors and their binding is mediated by Abs

what initiates the acute-phase response?

inflammatory cytokines

* C-reactive protein (CRP): opsonin and classical pathways
* Mannose-binding lectin (MBL): opsonin and lectin

what cytokines are communicators between leukocytes?

interleukins

* stimulate cell proliferation, maturation, migration, and activation

what cytokines induce leukocytes to migrate to areas of infection/tissue damage?

chemokines

what happens if cytokines get caught in a positive feedback loop?

they create a cytokine storm which damages tissues

What is different about adaptive immunity than innate?

* it’s a specific response that detects self from non-self
* and has memory; faster and stronger the second time

what is an antigen?

any molecule that binds specifically to an Ab or a T-cell receptor

what is an epitope?

specific region of Ab that actually binds to the Ag receptor

what is a hapten?

a “free” epitope that require a carrier molecule to elicit an immune response