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55 Cards in this Set

  • Front
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ORDER IN WHICH THE IMMUNE DEFENCES DEAL WITH A PATHOGEN
PHYSICAL BARRIERS

SOLUBLE FACTORS

INNATE ARM OF IMMUNE SYSTEM

ADAPTIVE ARM OF IMMUNE SYSTEM
IMMUNE SYSTEM PROVIDES PROTECTION FROM WHAT
FROM BEING COLONISED BY A VAST ARRAY OF MICROBES THAT LIVE ON AND IN US

SUCH AS PATHOGENS (BACTERIA, VIRUS, FUNGI)

AND PARASITES (PROTOZA AND HELMINTHS)
THERE ARE .... MAIN LEVELS OF DEFENCE

DESCRIBE EACH ONE
.first line of defence, have characteristics to make them less permeable, also competition from resident microflora


.second line of defence, can stop infection spreading in wait for adaptive immune system, also it activates the adaptive

.adaptive response more potent, comes in and clears the infection
EPITHELIAL LAYERS OF SKIN ARE MORE..

AND ACT AS
.epithelial layers of skin are more resistant to penetration by bacteria


STRONG EXTERNAL BARRIERS TO INFECTION
WHAT IS MORE VULNERABLE
airways, digestive tract, reproductive tract covered with mucosa are much more vulnerable
MECHANICAL AND CHEMICAL BARRIERS OF THE SKIN AND GUT
EPITHELIAL CELLS JOINED BY TIGHT JUNCTIONS
LONGITUDINAL FLOW OF AIR AND FLUID



CHEMICAL BARRIERS

FATTY ACIDS IN SKIN, B DEFENSINS, LAMELLAR BODIES,CATHELICIDIN


LOW PH AND AND ENZYMES SUCH AS PEPSIN FOR THE GUT, ALPHA DEFENSINS, AND LECTICIDINS
CHEMICAL AND MECHANICAL BARRIERS FOR LUNGS AND EYES NOSE ORAL CAVITY
BOTH HAVE EPITHELIAL CELLS JOINED BY TIGHT JUNCTIONS

IN LUNGS MOVEMENT OF STICKY MUCUS BY CILLIA, PULMONARY SURFACTANT (?)
ALPHA DEFENSINS AND CATHELICIDIN



NOSE, EYES, AIRWAYS
TEARS AND NASAL CILLIA ACT AS MECHANICAL

ENZYMES IN TEARS AND SALIVA E.G. LYSOZYME ASWELL

OTHER BARRIERS INCLUDE B DEFENSINS, HISTATINS
JOB OF MUCOUS
Mucous present in mucosa, they contain muccin glyco protiens and they prevent bacterial adhesion to epithelia.
JOB OF LYSOZYME ENZYME
Lysozymes, is a glycosidase enzymes, attacks peptiidglycan layer.
IMPORTANCE OF SALICA AS A DEFENCE FACTOR AS IN THE FORM OF 2 AGENTS
Saliva an inportant flushing agent, washes bacteria out of the mouth into acidic ph environment of the gut, saliva is also an important delivering agenet delivering enzymes such as lysozyme and also antimicrobial peptides (histatins, b defensins)to control bacteria in the mouth
WHERE ARE ANTIMICROBIAL PEPTIDES PRESENT
Present throughout saliva and all our tissues
WHAT IS ZYMOGEN
Zymogen = inactive form of an enzyme, usually needs proteolytic cleavage to become active.

Meaning it needs to be cut by a specific protease enzymeto become active
WHAT DO DEFENSINS DO AND HOW
Defensins are amphipathic.
Have +ve and –ve’ly charged domains to the molecules, and so they have both hydrophilic and hydrophobic domains allowing them to...
allowing Insertion into membranes generates pores, membranes become leaky

Multiple defensins into bacterial cell membrane, creaet pore, contents leak out, bacterial killed
HOW DO DEFENSINS GET TO THE LIPID BILAYER
ELECTROSTATIC ATTRACTION AND TRANSMEMBRANE ELECTRIC FIELD BRING THE DEFENSIN TO THE LIPID BILAYER
HISTATINS PRODUCED WHERE

ACTIVE AGAINST
Histatins produced by parotid, sublingual, submandibular glands. Because Histadine rich, are active against fungal pathogens.
ALL OF THESE

HISTATINS

DEFENSINS ETC ARE EXAMPLES OF
ANTIMICROBIAL PEPTIDES
COMPARE AND CONTRAST THE RESPONSE SPEED OF THE INNATE AND ADAPTIVE ARM
Innate arm
mins, hrs.
Always present


Adaptive arm
days, weeks
Usually silent, response needs to be activated and induced
COMPARE AND CONTRAST THE SELF/ NON SELF RECOGNITION OF THE INNATE AND ADAPTIVE ARM
INNATE
Limited range
Unchanged during response
Genome encoded receptors (DNA in inherited form


ADAPTIVE
Vast range
Receptor recognition improves
Receptors not genome encoded (DNA changes from inherited form)
COMMENT ON THE LASTING PROTECTION OF BOTH
INNATE NON

ADAPTIVE YEARS
COMPARE RESPONSE SPEED OF BOTH ARMS
Innate.
Provides initial defences, limiting pathogen proliferation and spread.
Can control less virulent pathogens.
Important role in inducing the adaptive immune response.


Adaptive response.
More potent activity to control more virulent pathogens
Takes more time to raise population of cells specific for pathogen
ABSCENE OF INNATE IMMUNE RESPONSE CAUSES WHAT
Abscence of innate immune response, rapid increase in level of micro organisms, eventually host overwhelmed
BENEFIT OF IMMUNOLOGICAL MEMORY
Immunological memory gives more efficient and effective immune response to previously seen pathogens.


Innate arm gives no lasting protection, whereas adaptive arm provides us with long lasting protection

If re exposed to the same pathogen the same response is much more eficient and much more potent, faster, stronger.


Immunological memory gives us a more efficient response to pathogens we’ve seen previously dealt with without even noticing. All our vaccination programmes are based on immunological memory
Found that something in serum complemented or enhanced the rate at which white white blood cells could engulf or ingest bacteria

WHAT IS THIS KNOWN AS
THE COMPLEMENT SYSTEM
WHAT DOES THE COMPLEMENT SYSTEM CONSIST OF

AND WHAT ARE ITS 2 FUNCTION
30+ plasma proteins
Zymogen activation cascade
Functions are

1) facilitates recognition of bacteria by phagocytes (wbc)

2) can directly lyse bacteria, without any blood cells

Detection of few pathogens leads to rapid, amplified response.because the molecules are already preformed and it amplifies quiclky because of the different layers of the cascade
how many complement activation pathways are there and

what are these pathways

name the 3 pathways
Three complement activation pathways

Different activatation mechanisms that converge on a key player, and then diverge again into different effector functions.

lectin pathway
classical pathway
alternative pathway
what does the lectin pathway consist of
MBL mannose binding lectin and ficolins , recognise and bind carbohydrates on the pathogen surface
what does the classical pathway do
in the classical pathway c1q interacts with pathogen surface or with antibodies bound to surface
what does the alternative pathway do
in the alternative pathway c3 undergoes spontaneous hydrolysis to to c3(h20) to intiate eventual deposition of c3 convertase on microbial surfaces
what do all pathways do
all pathways generate a c3 covertase, which cleaves c3, leaving c3b bound to the microbial surface and releasing c3a
what does c3 convertase do
C3 convertase releases C3a and generates C3b which in turn mediates release of C5a.
what does c3a and c5a do
what do phagocytes with the receptor for c3b do
completion of complement cascade leads to what
this is what happens 
C5b inserts into the membrane of bacteria and drws to it a complex of other compononets, once a complex is formed, c9 helps form a pore which inserts into the membrane causing cell lysis
this is what happens
C5b inserts into the membrane of bacteria and drws to it a complex of other compononets, once a complex is formed, c9 helps form a pore which inserts into the membrane causing cell lysis
explain how a phagolysosome is formed
These lyszomes fuse and deliver toxic chemicals and degrading enzymes to the site to degrade the bacteria
These lyszomes fuse and deliver toxic chemicals and degrading enzymes to the site to degrade the bacteria
all cells are derived from what....?

foollowing stem celll division what can happen

what does this mean for the cell
all cells Derived from common, pluripotent progenitor cell type in bone marrow.A cell that gives rise to all other types of cell

Following stem cell division daughter stem cells can differentiate or divide.

Differentiation and commitment to lineages restricts their potential and they lose the ability to self renew.
Cells become commited and become either one of these 3 and then their potential becomes resitricted?
myeloid
lymphoid
dendiritic cells
Monocyte (precursor) / Macrophage (mature effector)?


location

function
Immature formis monocyte, when they fuse into tissue and mature they become called macrophages

Immature monocytes circulate in blood Mature macrophages found in most tissues in sub mucosal layers


First (early)responders have a Relatively long lifespan potential to be Phagocytic and Engulf and kill pathogens and infected cells also theyClear dead cells and debris have Bactericidal activity Present antigen to T cells (adaptive im) Activate other immune cells Induce inflammatio bn
3 types of granulocytes

what is the main role of the last 2
Neutrophils
Eosinophils
Basophils

main role of last 2 is antiparasitic
Neutrophils

location

function
Location. Blood, then migrate to infection sites



Function. Phagocytic
Bactericidal
very Numerous
Short lifespan
Deployed in huge numbers main role is to just engulf or kill bacteria



Pus = mainly dead neutrophils
Dendritic cells

location

function
Location. Immature DC foudn under surface epithelial and in solid organs. Following uptake of antigen and migrate via lymphatic to lymph nodes and mature.


Function. Phagocytic function /Macropinocytosis Take up antigen to present to adaptive arm. (not just to kill them) Activate cells of the adaptive arm
Natural Killer cells
Location. Blood, migrates to infected tissue, and infiltrate tumours

Function.
Are lymphocytes BUT considered within innate arm
Extracellular release of cytotoxic granules into extra cellular space of target cell

Anti viral function

Anti tumour function
what is phagocytosis

Phagocytic receptors
phagocytosis is An ancient immune mechanism in both invertebrates and vertebrates.



Fc receptors bind antibody coated pathogens.

Pattern recognition receptors that recognise

PAMPS (pathogen associated molecular patterns)
Lectin like. Dectin 1

Scavenger receptors.

Toll like receptors

Broad range, distinguish self from non-self but without exquisite specificity.



Complement receptors
TLRs
how many human tlr genes

not just expressed on...


what do they do
TLRs
10 human TLR genes, each recognises a distinct set of PAMP not found in vertebrates.

E.g. One recognises LPS of gram negative bacterial outer membrane, one recognises lipoteichoic acids of gram positive cells walls, recognises double stranded RNA, another that recognises glucans such as zymosan (fungi).

Not just expressed on innate immune cells.

Dont just trigger phagocytosis but also,Trigger expression of antimicrobial peptides (saliva) and inflammatory cytokines.
example of tlr deficient
TLR deficient Drosophila melanogaster fly.
More susceptible and overwhelmed by fungal growth.
state the different antimicrobial mechanisms of phagocytes
acidfication- where phagocytes acidify vessels

toxic oxygen derived products - radicals, superoxide anion etc..


toxic nitrogen oxides
(Englufment of bacteria and binding of bacteria triggers a respiratory burst, involving generation of reactive oxygen and nitrogen species , that are toxic to the engulfed bacteria)


phagocytic cells also secrete antimicrobial peptides into the lysozome which then fuses with the phagosome

enzymes


also phagocytic cells secrete competitor molecules
what do macrophages do

what do cytokines, chemokines and complement components do
Macrophages and complement initiate inflammation.
Cytokines, chemokines and complement components attract additional phagocytes and cause local vascular changes
what does an increased permeability allow
Increased permeability, increased flow of plasma proteins to site

Macrophage role is not just to enguldf bacteria, they also initiate inflammatory responses
what is a chemokine
Chemokine is a small protien but its chemoattractant, it stimulates the migration and activation of cells so it draws cells towards a site of infection, and usually active againts immue cell types.
what is a cytokine
Cytokine is a small protien that effects the behaviour of other protiens, those made by lymphocytes are called leukins, so they act via specific cytokine receptor which is expressed on the type of cell they effect
complement binds and does what
Complement bind and also flag bacteria, highlighting it, complement system also generates c3a and c5a which are chemotactic which attract whtite blood cells to site of infection, macrophages engluf bacteria, following this they release cytokines and chemokines
what do macrophages do
Macrophages enguld bacteria and release chemokinES. and cytokines (tnf and IL-1, which have an effect on the endothelial cells. Increase diamete, slow down blood flow, which gives the whiteblood cells more time to migrate from blood to site of infection
what happens to the surface of the inside of the blood vessel and why
SURFACE OF INSIDE OF BLOOD VESSEL CHANGES ALLOWING WHITE BLOOD CELLS TO ADHERE AND STOP ROLLING AND RUSHING ALONG, AND ACTUALLY EXTRAVASE INTO THE TISSUE, BY THE ACTION OF THE CHEMOKINES
Clotting of some local micro vessels occurs to.....
inhibit infection spread
what does the endothelium now do
Endothelium now promotes leukocyte binding, increasing extravasion.
summary
Summary
The protection given by the immune system.

The roles of the innate and adaptive immune responses and how they differ,
speed of response
diversity of recognition
how the recognition receptors are encoded
memory

The molecular and cellular components of the innate immune response.
The processes used by the innate immune response.