Haematology Theory Flashcards
What is inflammation?
It is an important and normal part of the body defense mechanism that aims to restore the immune homeostasis
What happens within 30-60 min of inflammation?
Polymorphonuclear leukocytes are recruited to the site of injury for phagocytozin pathogen/damaged tissue
What happens within 4-6 hrs of inflammation?
Macrophages and lymphocytes recruited to site of injury ti enhance phagocytoces and present antigens for T cells to initiate specific response through antibody production
What will happen if the cause of inflammation persists?
What if polymorphonuclear fail to clear the cause of inflammation?
Macrophages and lymphocytes recruited to site of injury ti enhance phagocytoces and present antigens for T cells to initiate specific response through antibody production
What is the role of macrophages and lymphocyte during inflammation?
If the cause of inflamation persist Macrophages and lymphocytes recruited to site of injury ti enhance phagocytoces and present antigens for T cells to initiate specific response through antibody production
What happens within 5-7 days of inflammation/injury?
Antibodys are detected in the serum
When does inflammation initiated?
Once immune cells express PRR(pattern recognition receptors) binding to PAMPs ( pathogen associated molecular pattern)
What happens Once immune cells express PRR(pattern recognition receptors) binding to PAMPs ( pathogen associated molecular pattern)?
1-Inflammation initiated
2- release of proinflammatory cytokines ( IL-1. IL-6. TNF-alpha)
What is the result of releasing proinflammatory cytokines?
Liver is triggered to release C- reactive protiens , activation complement
What are the major symptoms of inflammation?
Pain, heat, redness
What is chronic inflammation?
When immune system is unable to clear the cause of inflammation and return normal
What are the proinflammatory cytokines released after binding PRR to PAMPs?
IL-1 , IL-6 , TNF-alpha
What is complement?
Group of more than 30 protiens , produced in the liver , soluble , kills pathogens,have 3 activation pathways.
Where does complement produced?
Liver
What are the steps of complement system ?
1- stimulation and initiation
2- Amplification cascade
3- biological activities
What are the three pathways of complement activation?
1- lectin pathway
2- classical pathway
3- alternative pathway
When does the complement cascade starts?
By the formation of C3 convertase
The Lectin pathway is apart of …………..system
a- innate
b- adaptive
c- both of them
innate
The classical pathway is apart of …………..system
a- innate
b- adaptive
c- both of them
c- both of them
The alternative pathway is apart of …………..system
a- innate
b- adaptive
c- both of them
a-innate
What are receptors involved in lectin pathway?
Mannose binding lectin (MBL)
Ficolins
MBL is homologous to ………..
C1q
What is the role of MBL in lectin pathway?
Binds to the sugars or carbohydrates on the surface of the pathogen
Why classical intitation pathway is considered as innate and adaptive immune system?
Because C1 complex can either bind directly to the surface of the pathogen or to antibodies on the surfae (IgG, IgM)
What is C1complex composed of ?
6 identical subunits of C1q , 2 of C1s, 2of C1r
What cleaves C4,C2
The enzymatic form of C1s
When does alternative pathway initiate?
By the cleavege if C3 by hydrolysis
What is the result from C3 cleavage that is used in alternative pathway?
C3b
C3b binds to ………….,.
Proteins and carbohydrates on the surface of the cell
What happens once C3b binds to Proteins and carbohydrates on the surface of the cell?
Factor B bind to it forming C3bB
How does factor B cleaved?
By factor D producing C3bBb
What is the C3 convertase of the alternative pathway?
C3bBb
What is the enzymatic pathway of lectin and classical pathway?
C4 is cleaved into C4a, C4b
The C4b binds to the surface of the antigen
C2 is cleaved , C2a binds to C4b formin the C3 convertase(C4bC2a)
What is the most abundant complement protien?
C3
Describe the enzymatic cascade of alternative pathway.
C3b is attached to the surface of the pathogen, factor B attached to C3b , factor D cleaves factor B ——> C3bBb “C3 convertase”
Describe the enzymatic cascade step 2 for lectin and classical pathway.
C3 is cleaved by C3 convertase( C4b2a) ——-> C4b2a3b “C5 convertase” then C5 is added and cleaved ——-> C5a C5b C3a
Describe the enzymatic cascade step 2 of the alternative pathway.
C3 is cleaved by C3 convertase( C3bBb) ——-> C3(b2)Bb “C5 convertase” then C5 is added and cleaved ——-> C5a C5b C3a
What are the biological effector activities result from complement cascade ?
Inflammation
Phagocytosis
Membrane attack
What are protiens resulted from complement cascade ?
C3a C5a C5b
What is the role of C3a and C5a in inflammatory?
They produce local inflammatory responce and bind to mast cells and endothelial cells
What cells do C3a and C5a bind to?
Mast and endothelial cells
What are complement protiens involved in inflammation?
C3a ,C5a
What is the function of releaes local inflammatory response produced by C3a ,C5a during inflammation?
They increase vascular permability
They induce phagocytosis
The induce releasing histamen and TNF- alpha leads to recruiting phagocytic cells , complement antibody
What does phagocytosis denpend on?
It depends on the recognition of complement components by complement receptors
What is the main opsonization protien?
C3b
What are complement receptors involved in phagocytosis?
CR1 CR3
What is the primary complement protien involved in forming membrane attack complex( MAC)?
C5b
What happens during MAC?
C5b bind to C6 C7 and the complex C5b67 binds to the cell surface through C7 then C8 ,C9 bind to the complex
10-15 molecules bind to the complex forming a pore in the pathogen membrane
Why regulating complement is important?
To avoid uncontrolled inflammation
To avoid vilneraibilty to infectious diseses
What are the types of regulation of complement?
Positive
Negative
What are positive regulation factors?
Factor P it Stabilise C3 convertase during alternative pathway
What is the role of factor P?
Stabilise C3 convertase during alternative pathway
List some negative regulation factors
FactorI Factor H C1 inhibitor C4binding protein “C4BP” Decay accelerating factor “DAF”