innate immuntiy Flashcards
innate immune responds — to microbe or damage and they broadly distinguish from —- to —
eliminates pathogens by inducing process as — and —-
acts as an — system by releasing — and —-
communicates directly with the —- of immunity to inform it of type threat using —- presentation
involves soluble components such as —
- rapidly
- self from non self
- phagocytosis and inflammation
- alarm
-cytokines and chemokines - adaptive arm
- antigen
- complement
what triggers the innate immune response?
- barrier breaches and they can be :
1- – injury regardless of type can cause inflammation as:
2- — when breach the barrier cause inflammation
- tissue as: splinter , cut +/- infection , insect bite , trauma
- microbes
Microbes have regular patterns of molecular structure that are recognised by innate immune cells called —-
cells when damaged release —-
—- , — , and —- cells express a number of receptors that allow them to recognise different pathogens collectively called —
-pathogen associated molecular patterns ( PAMPS)
- self molecules –
Damage-associated molecular patterns (DAMPs)
- neutrophils macrophages and dendritic cells
- pathogen recognition receptors ( PRR)
the 3 fundamental cellular processes of innate immune cell activation are
1- phagocytosis —> destroys pathogens
2- cytokine production —> inflammation
3- antigen presentation —> activate T cells
- phagocytosis englufs and kills microorganisms:
1- — and —- express receptors that bind to microbes
2- microbes are englufed into —
3- — fuses w the phagosome - the microbes are killed in the phagolysome by toxic substances as:
1- —- is made by iNOS ( nitric oxide synthase )
2- —- is made by phagocyte oxidase ( also known as NADPH oxidase ) causes respiratory burst
3- — break down micorbial proteins - —- are short lived (1-2 days)
- —- are long lived ( weeks )
- neutrophils and macrophages
- phagosomes
- lysosomes
- NO( nitric acid )
- ROS ( reactive oxygen species )
- lysosomal protease
- neutrophils
- macrophages
chronic graulomatous disease is a defect in the —- system
by which the – -doesnt function properly –> recruitment of — -> collection of — around the microbe –> —
65-70% of the cases are – so more frequenet in —
first it appears in childhood and leads to frequent and severe —- and — infections
most common infections occur in —-
diagnostic test for this is —-
- NADPH oxidase system ( nadph oxidase defect )
- neutrophils
- macrophages
- macrophages
- granuloma
- x linked
- males
- fungal and bacterial infections
- lungs skin liver and lymph nodes
- DHR ( dihydrorhodamine ) : Whole blood is taken and neutrophils tested for the conversion
of DHR to fluorescent rhodamine which only occurs in the
presence of ROS.
signs of inflammation include:
-redness ( rubor) –> increased blood flow
-loss of function
-pain( donor) –> stretching of pain receptors and nerves by inflammatory exudates, chemical mediators
-heat ( calor) —> increased blood flow , erudition of fluid and release of inflammatory mediators
-swelling —> exduction of fluids
the role of inflammation:
- respond to —-
- bring — cells to the site so they can fight it
- — the infection and – the body from further infection/injury
- increase production of —-
- promotes — and —- of the infection
- infection/insult/injury
- immune
- localise
- protects
- protective proteins
- tissue repair
- resolution of infection
the 3 main stages of inflammation are:
tissue injury ( regonition via PRR and release inflammatory mediators )
breech in barrier
microbe intry
in summary :
first step –> releases pro-inflammtory mediators
2nd step —> cell adhesion , rolling then tight )
3rd step —> extraversion
- the first step of inflammtion is:
1- recognition by tissue resident innate immune cells as:
2- induction of —- : - it — and — microbe by —
- — presentation by —
3- release — mediators as — and — : - — and —
- macrophages and dendritic cells
- phagocytosis
- engulfs and destroy by macrophages
- antigen presentation by dendritic cell
- inflammatory mediators as macrophages and mast cells
- cytokines (IL-1, TNF) ad chemotkines (IL-8)
- lipids ( prostaglandin , leucotreins and PAF)
the 2d step of inflammation is:
1- —- by —– which cause:
- increase in —- of blood vessels
- increase in —-
- decrease in —
2- —- by —-
- endothelial cells lining blood vessels become —
- enables influx of —- as
- influx of fluids enables —-
3- — by —-
- — are activated
- increased —-
- promotes binding of —-
- vasodilation by prostaglandin and PAF ( platelet activating factor)
- diameter
- blood flow
- velocity
- permeability by lekotrines and PAF
- leaky
- soluble proteins ( c5a)
- migration
- cell adhesion by IL-1 and TNF ( tumor necrosis factor )
- endothelial cells
- cell adhesion molecules
- circulating immune cells ( rolling and then tight adhesion )
the 3rd step of inflammation is :
1- — which occurs after adhesion
- — first and then —
2- activation of — through : — and —
3- activation of —- :
- differentiation into —
- relese more —–
- maintains —-
3- activation of — which releases —
-extravasion
- neutrophils then monocytes
- neutrophils
- phagocytosis and destruction of microbes
- monocytes
- macrophages
- more inflammatory mediators ( cytokines chemokine lipids and proteins )
- maintains inflammation
- mast cells
- histamines
check slide 20 PLSSSSSSSS
- chemokine are released by —- and —
- — is a key chemokine important in inflammatory response
- the functions of chemokine are:
- released locally in — concentrations
- cells w — respond and move – the concentration gradient
- damaged and immune cells
-IL-8 - functions:
*bring more cells (particularly neutrophils) to infected region -
‘Chemoattractants’ - Increase expression of adhesion molecules on immune
cells - high
- receptors
- up
— inflammtion resolution Must actively terminate inflammation to prevent bystander destruction of tissue
mechanism of resolution:
- — half life of neutrophils and inflammatory mediators
- macrophages will change character and promote — releasing —- to limit inflammtion
- —- releases growth factors ( FGF) which acts on fibroblasts to promote repair
- lipid mediators will switch to production of —– mediators as
- acute inflammation
- short half life
- repair
- inhibitory cytokines ( IL-10 and TGF-b)
- macrophages
- production of anti-inflammatory lipids mediators as lipoxins
the complement system consists of
several plasma proteins that work
together to: ( innate immune mechanism not specific )
- promote —
- — and —
- in some cases — the microbes
* info about the complement system:
- collection of — and associated proteins ( 20+)
- completment system is initiated by – different pathways
- they are — which works in an enzymatic cascade
- the products perform the — of the complement
- inflammation
- opsonisation and phagocytosis
- kills
- circulating and membrane associated protein
- 3
- proteolytic enzymes
- effector fucntion
1- promotes inflammtion :
- — and — fragments are important inflammatory activators which :
- acts as — for neutrophils and monocytes
- stimulates the release of — various immune cells
- enhances — and —
- C3a C5a ( they basically destructs microbes by leukoccytes )
- chemoattractants
- inflammatory mediators
- vasodilation and vascular permeability
2- opposition and phagocytosis :
- — is deposited on surface of microbe
-acts as an — to tag bacteria for recognition by phagocyte
- c3b is recognised by — of the phagocyte
- — is triggered
3- membrane attack complex :
- last steps of complement system occurs when – binds to —
- this causes – to polymerise and from a – aka membrane attack complex
- loss of cell — where — and – can enter
- causes — of certain microbes (Neisseria particularly susceptible)
- c3b
- opsonin
- complement receptor ( CR)
- phagocytosis
- c5b
- c6-c9
- c9
- pore
- integrity
- water and ions
- death
complement deficinecies : ( rare 1-2% immunodeficines )
1- —- is linked with frequent pyogenic (pus-forming) infection in infants and young children and severe pyogenic bacterial infections in adults.
2- —- (eg C2 and C4) are associated with an increase of immune complex-mediated autoimmune disease (eg systemic lupus erythematosus)
3- —- (C5-C9): The lack of MAC formation results in severe
recurrent infections by Neisseria gonorrhoeae or Neisseria meningitidis.
4- —- causes a disease called hereditary angioedema
- c3 deficiency
- difecinxy in some early component
- deficiency in terminal pathway
- deficiency in c1 INH
antigen presentation
1- — : natural and non specific
Born with it
Non-specific/broad
specificity
Fast
No memory
2- — : specific and acquired
Acquired after birth
Very specific
Lag phase
Memory
innate
adaptive
in antigen presentation :
1- microbes enter through —- barrier as
2- microbes are captured by — such as — and —- patrolling the tissue of enter —-
3- microbes ( and their antigens ) are transported to the —–
4- peptide fragmented of protein antigens are displayed by —- on their — for recognition by —- on the surface of t lymphocyte
- epithelial ( contact ingestion and inhalation )
- antigen presenting cells APC
- dendritic and macrophages
- lymphatic/blood vessels
- peripheral lymphoid organs
- APC
- major histocompatibility complex MHC
- T cell receptor TCR
MHC class — presentation is performed by all nucleated cells as epithelium endothelium fibroblast , they have cytotoxic T cell and cd8 T cell
MHC class — presentation performed by professional APC ( dendritic cell macrophages and b cells ) have t helper cell and CD4 T cell
- class 1
- class 2
MHC class 1 :
- constantly presenting — , — antigens or antigens derived from — or —–
- proteins re digested into peptdides by —
- peptides transported into —-
- landed onto MHC class 1 in – and tranported to —
- self peptide , cancer antigen , antigen from viruses or intracellular bacteria
- proteasome
- endoplasmic redituculm
- ER
- cell surface
MHC class ii:
- —- ,— ,—- that have been endocytose/phagosytosed
- proteins ingested to peptide in —
- MHC class ii transported from – to —
- peptids are loaded onto — and transported to —
- pathogen toxins and fragments
- endosome/lysosome
- er
- late endosome/lysosome
- MHC class II molecule
- cell surface
there are 2 types of antigen presentation;
1- the antigen is internal as —-
- antigens are presented on —-
- Mhc class I antigen presentation activates —–
- all nucleated cells axpress —- and all cells can be targets of virus
- it requires —
2- antigen is external as:
- antigen are presented on —-
- MHC class ii antigen presentation activates —-
- only —- presented cells ( mainly —- cels) can do this as they are the only ones expressing MHC class ii
- it requires ——
- viral proteins in the
cytoplasm of infected cells - Mhc class I
- cytotoxic T cells as ( CD8 T CELL )
- MHC class I
- proteasome and er
- extracellular
microbes or microbial protein - MHC class ii
- t helper cells ( CD4 T cells )
- antigen
- dendritic cells
- requires endosome/lysosome and er
summary of innate immune system:
1- occurs at the portal entry for microbes as :
2- In tissue resident:
-initiates— and ——
3- in blood:
- plasma proteins as —-
- — and recited from blood to site of infection
3- in lymph nodes:
- —- travel from site of infection to lymph nodes
- —- to T cells
- Epithelia barriers of skin, gastro and respiratory tracts
- resident macrophages , dendritic cells and mast cells
- phagocytosis and inflammation
- complement
- neutrophils
- dendritic cells
- antigen presentation
