IMMUNO
Abbreviations
TMEC : Thymine medullary epithelial cells
MALT : mucosal associated lymphoid tissue
PAMPs : pathogen associated molecular patterns
DAMPs : damage associated molecular patterns
CD : cluster of differentiation
HSP : heat shock protein
HMGB 1 : high mobility group box
PRR : pattern recognition receptor
TLR : toll like receptor
MD2 : myeloid differentiation protein 2
CD 14 : co stimulatory protein 14
MyD88 : myeloid differentiation primary response 88
NF - kB : nuclear factor kappa B
TRIF : TIR domain containing adaptor inducing interferon ß
NLRs : NOD like receptors
NLRP : with pyrin domain
RLR : RIG ( retinoic acid inducible gene ) like receptors
TNF : tumor necrosis factor
AP 1 : activator protein 1
CRP : C reactive protein ( pentamer )
SAP : serum amyloid P
APPs : acute phase proteins
MAC : membrane attack complex
MBL : mannose binding lectin
MASP : mannan binding lectin serine protease
CF : cystic fibrosis
CFTR : cystic fibrosis transmembrane receptor
AMP : antimicrobial peptides
HDP : host defense peptides
ICAM 1 : intracellular adhesion molecule
LFA 1 : leukocyte function associated antigen 1
Fc portion : fragment crystallizable portion
Fab portion : fragment antigen binding portion
cDC : conventional dendritic cell
pDC : plasmacytoid dendritic cell
ADCC : antibody dependent cytotoxicity
CDRs : complementarity determining region
sIgA : secretory IgA
BAFF : B cells activating factor from TNF family
BLyS: B lymphocyte stimulator
CR2 : complement receptor 2
ITAM : immunoreceptor tyrosine based activation motif
HAV : hepatitis A virus
IVIG : Intravenous immunoglobulin
TCR : T cell receptor
BCR : BCR
PALS : periarteriolar lymphatic sheath
Diseases
~ Abnormalities or absence of thymus > higher susceptibility to infections especially viral ones ( Digeorge syndrome ( CATCH 22 ))
~ Splenectomy > higher susceptibility to encapsulated bacteria infections
~ Complement system abnormalities > higher susceptibility to infections + autoimmune diseases ( systemic lupus erythematosus )
~ Inability to form inflammasomes > higher susceptibility to infections
~ Abnormally low concentrations of neutrophils > neutropenia
~ CFTR deficiency + increased mucus viscosity > cystic fibrosis ( defective resistance to many pathogens )
~ Defective cilia movement > primary ciliary dyskinesia + repeated respiratory infections
~ Defective skin barrier due to inflammation > eczema + recurrent skin infections
~ Damage of Bcl -2 gene > cancers ( especially chronic lymphocytic leukemia)
General important info + comparisons
# of :
Proteasomes : 28 subunits
TLR : 1-9
NLRs : 20
Chemokines : 50
Pentraxins : pentamers
Collectins / ficolins : trimeric / hexametric
Integrins : heterodimeric
Antibodies : 2-3 g per day
hyper variable regions : 3 stretches in light chains / 3 stretches in heavy chains
C type lectin receptor : soluble / cell bound ( dendritic/ macrophages/ some other cells )
Carbohydrates; mannose + dectin
Scavenger receptors : cell bound ( macrophages)
lipids ; microbial diacylglycerides
N - formyl met-leu-phe : neutrophils + macrophages
NOD 1 , 2 : sense peptidoglycan
Inflammasome : activation of IL -1b / IL -18 through caspase 1
RLR : sense viral RNA
TNF : apoptosis , proliferation ( AP1 ) , acute inflammation ( activation NF-kB )
IL - 6 : in addition to the other well known systematic effects , it induces the differentiation of IL -17 producing T helper cells
Macrophages activation :
IL 3,4 > M2a
TLR agonists > M2b
IL10 , glucocorticoids > M2c
IFN gamma & LPS > M1
The classical pathway of the CS > activated by pentraxins + Fc domain of antibodies
PRR = C1q
PRR > C1q > C1r , C1s > C2b C4b ( C 3 convertase )
The lectin pathway of the CS > activated by :
PRR = Mannose binding lectin ; activation by oligosaccharides terminated by mannose , fructose
PRR = Ficolin ; activation by N- acytelglucosamine or lipoteichoic acid
PRR > MASPs > C2b C4b ( C 3 convertase )
C5 convertase > C4b2b3b or C3b Bb C3b
mucus = mucin + IgA + lactoferrin + lysozymes + antimicrobial peptides
Special T lymphocytes
Regulatory T lymphocytes> suppress immune responses
Natural T lymphocytes > innate immune system
Follicular helper T lymphocytes > germinal centers in peyer’s patch
intraepithelial T lymphocytes > between epithelial cells ( innate immune system )
The differences between 1 ) intraepithelial T lymphocytes/ 2) adaptive immunity T lymphocytes
1)) receptors > gamma & delta chains / limited diversity / don’t depend on MHC
representation / don’t express CD4 nor CD 8
2)) receptors > alpha + beta chains / wide diversity ( more specific ) / depend on MHC representation / express either CD4 or CD8
Chemokines increase the affinity & the avidity of integrins
CXC8 ( interleukin 8 )
Recruitment of MDSC ( decreased T cell nutrients / decreased T cells homing )
Recruitment of neutrophils ( decreased T cell nutrients/ ECM degradation by proteases )
Promotion of angiogenesis
** All these participate in the progression & the sustainment of cancer ( tumor cells )
Potency
C5a > C3a as proinflammatory mediators
Adaptive immunity > innate immunity
Tissue + circulating dendritic cells > secondary lymphoid resident dendritic cells on T lymphocytes
Neutrophils respond faster than macrophages but macrophages are the dominant phagocytes in the late phase of innate immunity
IFN alpha / beta : antiviral state ( pDC / virally infected cells )
IFN gamma : macrophages activation ( M1) (NK cells / T helper cells )
Interleukins
IL 3,4,10 : immunoregulation / inhibition ( suppressors )
IL 1,6,17 : pro inflammatory
IL 12, 15 : NK cell activating cytokines
Cellular receptors :
GPCR : cytokines mainly chemokines
Tyrosine kinase : NK activating receptor
After the exposure of B cells to antigens both avidity and affinity change due to class switching and affinity maturation respectively
3 distinct concepts
Somatic maturation ( random germline genes recombination )
Somatic mutation ( new v region , same specifics , affinity maturation )
Class switching ( constant region )
B cells immune response
~ Localization of B cells in Lymph nodes & spleen : chemokine CXCL 13 / its receptor on B cells is CXCR5
~ the interaction between B follicular cells & antigens in secondary lymphoid organs
Directly > soluble / less than 70 kd antigens
Sinus macrophages ( large antigens ) > follicular B cells
Resident dendritic cells ( medium sized antigens ) > follicular B cells
CR2 ( marginal B cells / immune complexes )> follicular B cells
Follicular dendritic cells ( immune complexes ( antigen - antibody / antigen - opsonization complement protein )) > follicular B cells
~ B - 1 B lymphocytes > develop from fetal liver derived HSCs
~ CCL 19 & CCL 21 are ligands for CCR7
Natural antibodies > carbohydrates, lipids but not proteins
~ Marginal B & B1 B cells produce natural antibodies
~ CD40L & chemokines + cytokines > initially clonal expansion & short lived plasma cells production( extrafollicular ) but later induction of B cells differentiation into B memory cells & plasma cells ( intrafollicular )
~ The interaction T helper cell & B cell induces the differentiation of T cell into T follicular helper cell which induce further activation of B cells in the germinal centers
Maternally acquired antibodies :
IgG : transplacental
IgA : breast milk + through the colostrum