Cells of the innate immune system L5 Flashcards by Yasmin Yau

what are the two types of immune responses

innate immunity

adaptive immunity

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what is innate immunity

fast response, but is fixed, wont adapt overtime not always enough to clear it – so have adaptive

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what is adaptive immunity

adapt to pathogen – takes longer about 3 days to adapt

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what cells are involved in innate immunity

macrophage
dendritic 
neutrophil
eosinophil
basophil
natural killer
mast

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what are general characteristics of macrophages and dendritic cells

High endocytic and phagocytic capacity
Sense and respond to environment
Wide range of killing mechanisms
Link between innate and adaptive immune systems§

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what is enodcytosis

method of taking up soluble compounds, or particulate matter

Engulf in the outside material – soluble components

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when is phagocytosis initiated

when certain receptors on the surface of the cell (usually macrophage, neutrophil or dendritic cell) interacts with the microbial surface

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other than phagocytosis how else can pathogens be taken up

macropinocytosis, in which large amounts of extracellular fluid and its contents are ingested

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how does a phagolysosome from

As endosome matures becomes more acidic to form lysosome

Lysosome joins with phagosome to form phagolysosome

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what can phagolysosomes cause

degradation of bacteria (some can survive this)

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how can macrophages recognise material

through:

opsonic (indirect recognition)
non-opsonic (direct recognition) receptors

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examples of indirect receptors

antibody-Fc receptor (FcR)

complement-complement receptor

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what is the Fc portion

constant region of the antibody

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what are PRRs

pattern recognition receptors

on receptor surface of all cell types

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what are PAMPs

pathogen associated molecular patterns

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what is the specificity receptors in adaptive immunity

one cell only have one specificity of receptor

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how do phagocytes bind to macrophages

macrophages have phagocytic receptors that bind microbes and their components

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how can phagocytes bind to many different things

they have many receptors on their surface

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where are PRRs present

cell surface as well as in endosomes and cytosol

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what is germ-line

receptors are in our DNA so don’t change

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how do PAMPs detect pathogens

PAMPs detecting patterns that are more associated with pathogens than commensals
Immediate response – immune response within hours to detect and kill pathogens

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how do the pattern recognition receptors attach to the pathogens

Coated in LPS lipid polysaccharide
receptors can bind to LPS interacts and macrophage can detect the pathogen
So much microbiome - need to know bacteria is good for you (commensal or pathogenic)

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how does the gram negative bacteria interact with the plasma membrane

Gram negative coated in LPS bind to LPS binding protein binds to the CD14 which then reacts to the TLR4, these can form complexes that can be recognised by the pathogen

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how does the gram positive bacteria interact with the plasma membrane

Gram positive don’t have LPS so look for different glycoproteins on surface e.g.fungi
Use TLR1 and TLR2 or TL2 and TLR6

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how can bacteria with flagellum use this for innate immunity

TLR5 bind to flagellum and helps phagocytosis – innate immunity to detect different things

where are toll like receptors

plasma membrane and endosomes

what happens when macrophages and dendritic cells encounter PRRs

Macrophages and dendritic cells respond to PRR engagement by producing cytokines

what size are cytokines

Cytokines are small (~25 kDa)

what are cytokines involved in

Involved in cell-cell communication

what does tumour necrosis factor alpha so

activates vascular endothelium and increases vascular permeability

what does interleukin - 1 beta do

Activates vascular endothelium and activates lymphocytes

what does interleukin - 6 do

Lymphocyte activation, increased antibody production

what does interleukin - 12 do

Activates NK cells, induces differentiation of CD4 T cells into TH1 cells

what are killing mechanism examples

``` acidification toxic oxygen-derived products toxic nitrogen oxides antimicrobial peptides enzymes competitors ```

what does acidification mechanism produce

pH `3.5-4 | bacteriostatic/bactericidal

what does toxic oxygen-derived products mechanisms produce

``` super oxide O2- hydrogen peroxide H2O2 singlet oxygen 1O2* hydroxyl radical OH* hypohalite OCl- ```

what does toxic nitrogen oxides mechanisms produce

nitric oxide

what does antimicrobial peptides mechanisms produce

defensins | cationic proteins

what does enzymes mechanisms produce

lysozyme - dissolves cell walls of walls of Gram-positive bacteria acid hydrolases - further digest bacteria

what does competitors mechanisms produce

lactoferrin (binds Fe) | vitamin B12-binding protein

what are the microbicidal activity of phagocytes

Toxic species damage bacterial proteins and DNA Iron pump to remove iron from phagosome Antimicrobial peptides Make phagosomes as inhospitable as possible

what happen to dendritic cells are infected

mature

what are the characteristics of immature dendritic cells

``` High endocytic activity Intracellular MHC class II Constantly sampling the environment ```

what are the characteristics of mature dendritic cells

``` Low endocytic activity High surface expression of MHC class II Once activated produce cytokines Migrate to lymph nodes Stop sampling and display MHC class II on surface ```

what do dendritic cells do

Present fragments on surface for antigen presentation for T cell

what is phagocytosis enhanced by

engagement of receptors

how is a phagolysosome formed

``` endosome early (less acidic) goes to late (more acidic) lysosome (very acidic) joins with the phagosome form phagolysosome ```

what is dendritic communication

Dendritic cells can “talk” to lymphocytes

when can T cells recognise peptides

T cells can only recognise peptides when presented by Major Histocompatability Complex

what are the two types of Major Histocompatability Complex

``` class I class II ```

what do all nucleated cells have

Major Histocompatability Complex I

what Major Histocompatability Complex do antigens have

class II

how do MHC class I interact with T cells

CD8 T cells (killer T cells) Present endogenous peptides

how do MHC class II interact with T cells

CD4 T cells (helper T cells) | Present peptides formed from exogenous peptides

where are mast cells predominantly

Mainly reside near small blood vessels in a wide variety of tissues

what do mast cells do

Release substances that alter vascular permeability such as histamine

what happens when mast cells binds to C3a and C5a

Binding to C3a and C5a induces degranulation and release of granule contents

what do mast cells release

histamine

what are the products of mast cell - preformed mediators

histamine heparin proteases chondroitin sulphate

what do mast cells do

``` recruitment and activation of immune cells phagocytosis and antimicrobial activity tissue repair vascular permeability toxin degradation ```

what are the products of the mast cells after histamine is released

blood clots frequent heartbeat adrenaline released ``` blood vessels to dilate bronchoconstriction increases capillary permeability swelling and inflammation gastric acid secretion ```

what are natural killer cells

large lymphocytes that circulate in blood

what do natural killer cells do

Provide innate immunity against intracellular pathogens and migrate from the blood into infected tissues in response to inflammatory cytokines

what happens to patients that lack natural killer cells

suffer from persistent viral infection which they can not clear without the help of antiviral drugs

what are the two types of effector function for natural killer cella

cell killing | secretion of cytokines

how do natural cells recognise their targets

NK cells express combinations of receptors specific for surface molecules

what do natural killers do when they bind to ligands

some of these receptors inhibit killing activity while others stimulate killer function

how are natural killer cells balanced

balance between inhibitory and stimulatory signals that determines whether a potential target is killed

what happens when the normal cell has +ve and -ve receptor - natural killer cells response

no killing

what happens when the abnormal cell has one +ve receptor - natural killer cells response

killing | clear infection

what happens when the abnormal cell has two +ve and -ve receptor - natural killer cells response

too much activation so not enough inhibition = killing | clear viral infection

what happens in the absence of MHC class 1 in cells

it activates killing as there is no longer a suppression of the receptor

how do natural killer cells kill

release lytic granules that kill some virus-infected cells

Cells of the innate immune system L5 Flashcards

(73 cards)