Par coeur Immuno Flashcards
What are the roles of interferon in viral infections?
1) active immune cells
2) induces antiviral protein to block virus replication
3) causes apoptosis of virus infected cells
What are the innate lymphoid cells?
Tissue resident lymphocytes w/o LT AG-R activated by cytokines
Group 1-2-3 produce same cytokine as Th1, Th2 and Th17
What are the components of innate immunity?
Epithelial barriers
Phagocytes
Dendritic cells
Complement
NK cells
Nod-Like-R signal via what?
NLR = recognize substance from damaged cell (uric acid, ATP, K+, microbes)
Signal via inflammasome, active caspase 1 + IL1
Utility of C-type lectin (CLR)
On plasma membrane of macro and DC = detect fungal glycans
Utility of Rig-like-R
In cytosol = detect a.n of viruses that replicate in cytoplasm = induce prod of antiviral cytokines
What is the pathway activated by cytosolic-R for microbial DNA
STING = prod of antiviral cytokine IFNa
Overactivation = interferonopathies
Utility of G-coupled-R
On neutro and macro = recognize short bact peptide with N-formylmethionyl residues = chemotaxis
Utility of mannose-R
Recognize microbial sugars = phagocytosis
Of what is composed the inflammasome?
Of a sensor protein ex: NLRP3
An adapter
Enzyme caspase 1 converted from inactive to active
What R is expressed on NK?
What do they secrete?
Regulated by what cytokines?
Express CD16 = R for IgG Fc tails = lyse IgG coated cells
NK inhibitory-R = recognize CMH I
Secrete IFNy = active macro
IL2, IL15 = stimule prolif of NK
IL12 = activates killing of target cells and secretion of IFNy
Role of humoral and cell-mediated adaptive immunity
Humorale = protects against EC microbes (LB and AC)
LB = neutralize microbe, phagocytosis, complement activation
Cell-mediated = defense against IC microbes and cancer (LT)
T-helper = active macro, inflamm, prolif of LT and LB
CTL = killing of infected cell
Treg = suppress immune response
In adaptive immunity, how is AG-R diversity made?
Generated by somatic recombination of genes that encode AG-R
During lymphocytes maturation = recombination of DNA sequence introduced at sites where segments are joined
ENZYME IN CHARGE = RAG-1 et 2 (defects = failure to make mature lymphocytes)
= distinguish polyclonal and monoclonal (neoplasic) by assessing rearrangement diversity
To what bind CD4+ and CD8+
CD4+ = cytokine secreting helper cell = binds CMH II
CD8+ = CTL binds CMH I
Distribution of LT and LB in NL and spleen
LB = germinal center
LT = paracortex
FollicleDC active LB and paracortex DC present AG to LT
LB in white pulp
LT periarteriolar lymphoid sheaths
What plays an important role in grafts rejection?
HLA haplotype polymorphisms (expression of CMH)
HLA-D = Class II
HLA-A à C = Class I (expressed on all nucleated cells and platelets)
Cytokines playing a role in innate immune responses (produced by macro, DC, ILC, NL, endo/epithelial cells)
TNF
IL1
IL12
IFN type 1
IFNy
Chemokines
Cytokines playing a role in adaptive immune response (produced by CD4+ LT)
IL2 = role in differenciation of naive LT to effector and memory LT
IL4
IL5
IL17
IFNy
Terminate response : TGFB, IL10
Principal costimulator of LT
B7 protein (CD80-86) = recognize CD28-R on naive LT
CD4+ effector cells secrete distinct cytokines :
Th1
Th2
Th17
Th1 = IFNy = active macro
Th2 :
IL4 = stimule LB differenciation into IgE secreting plasmocytes
IL5 = production of eosinophils
Induce alternative pathway of macro = repair + fibrosis
Th17 = IL17 = recruits neutro and monocytes
Th1 :
Cytokines produced :
Cytokines inducing this subset :
Immuno rx :
Defense against :
Role in dz :
Cytokines produced : IFNy
Cytokines inducing this subset : IFNy, IL12
Immuno rx : macrophage activation
Defense against : IC microbes
Role in dz : immune-mediated chronic inflamm dz (autoimmune)
Th2 :
Cytokines produced :
Cytokines inducing this subset :
Immuno rx :
Defense against :
Role in dz
Cytokines produced : IL4, IL5, IL13
Cytokines inducing this subset : IL4
Immuno rx : stimule production of IgE, active mast cells and eosinophils
Defense against : helminthic parasites
Role in dz : allergies
Th17 :
Cytokines produced :
Cytokines inducing this subset :
Immuno rx :
Defense against :
Role in dz
Cytokines produced : IL17, IL22
Cytokines inducing this subset : TGFB, IL6, IL1, IL23
Immuno rx : recruitment of neutro and monocytes
Defense against : EC bacteria and fungi
Role in dz : immune-mediated chronic inflamm dz (autoimmune)
Differenciation of LB by LT helper and other stimuli into 3 categories + roles
1) AC secretion (plasma cells = IgM)
2) Class switching (IgG)
3) Affinity maturation (high affinity IgG, memory LB)
ROLES of AC : neutralize microbes and toxins, opsonization and phagocytosis, AC-dependent cytotoxicity (NK-Fc-R), complement activation (lysis of microbes, phagocytosis, inflamm)
HyperS type 1
IMMEDIATE
Th2 cells, IgE AC, mast cells, release mediators + vasoactive amines
Vascular dilation, edema, smooth muscle contraction, tissue injury, mucus
HyperS type 2
AC MEDIATED
Secrete IgG, IgM, promote phagocytosis
Phagocytosis and lysis of cells, inflamm, fct derangment with or w\o tissue injury
autoimmune hemolytic anemia
HyperS type 3
IMMUNE COMPLEX
IgG and IgM bind AG = complex deposit in tissue = neutro and monocyte recruited + release of lysosomal enzyme
Fibrinoid necrosis
Lupus, glomerulonephritis
HyperS type 4
CELL MEDIATED
Th1, Th17 and CTL
perivascular cell infiltrate, edema, granuloma
Contact dermatitis, sclerosis, type I diabetes, tuberculosis
2 phases of hyperS type 1
Immediate = vasoD, vascular leakage, smooth muscle spasm, glandular secretion
Late-phase = infiltration of tissues by eosino, neutro, baso, monocytes, CD4+
Action of IL4, IL5 and IL13 in type 1 hyperS
IL4 = act on LB to class switch to IgE and dev more Th2 cells
IL5 = eosinophils
IL13 = enhance IgE production + mucus secretion
Content of mast cells responsible for immediate and late-phase rx
IMMEDIATE : vasoD, vascular leakage, smooth muscle spasms
Granule content (histamine, protease)
Membrane phospholipids (AA -> PGD4 et Leukotriene B4, C4, D4) (PAF)
LATE PHASE : leukocytes, epithelial damage, bronchospasms
Secreted cytokines and chemokines
Impact of leukotriene C4, D4
Most vasoactive, spasmogenic + chemotaxis
Impact of PGD2
Bronchospasms, mucus secretion
Role of PAF
Platelet aggregation, histamine release, bronchospams, vasoD, permeability
Mechanisms of AC-mediated type II hyperS
A) Opsonization and phagocytosis : opsonization by C3b (C3b-R binds Fc on phagocytes)
B) Complement activation -> C5a, C3a -> neutro, enzymes, ROS -> inflamm + tissue injury
C) AC-mediated cell dysfct : AC inhibits binding to neurotransmitters-R OR stimulates R without hormone
Mechanisms of cell-mediated IV hyperS
- Cytokine mediated inflamm : APC to CD4+ -> cytokines (Th1 macro, Th17 neutro) -> inflamm + tissue injury
- T-cell mediated cytolysis : APC to CD8+ -> cell killing and tissue injury
Autoimmune dz :
1) diabetes type 1
2) sclerosis
3) SLE
4) Goodpasture syndrome
1) diabetes type 1= autoreact LT against B cells of pancreatic islets
2) sclerosis = autoreact LT against SNC myelin
3) SLE = diverse AC against DNA, platelets, GR, prot/phospho complex
4) Goodpasture syndrome = AC to basement membrane of lungs and kidney
What is central tolerance?
Immature self-reactive LT recognize self-AG during maturation and signal for apoptosis = NEGATIVE SELECTION
Process stimulated by AIRE protein
Some LT become Treg
Immature self-reactive LB reactive AG-R gene rearrangement to express new AG-R = RECEPTOR EDITING
What is peripheral tolerance?
Silence autoreactive LT and LB in peripheral tissue
1) ANERGY = not enough costimulator
To be activated need = AG-CMH (reconnait), 2nd signal from APC (CD28 + B7 costimulator)
CTLA-4 binds B7 and PD1 = knockout lead to systemic inflamm dz
LB recognize self-AG w/o Thelper = anergy
2) SUPPRESSION BY TREG developped in thymus (CD4+ express high CD25, IL2-R, FOXP3)
Suppress immunity by secreting TGFB and IL10
3) DELETION BY APOPTOSIS = autoreactive LT express BIM (proapopto) w/o Bcl2 = apoptosis mitochondrial pathway
Fas-Fas ligand engagement = apoptosis by death pathway (LT and LB)
What is molecular mimicry?
APC presents microbial peptide that resemble self-AG = autoimmunity
In SLE, antinuclear AC (ANA) are developed against what?
Double stranded DNA, UI-RNP, SMith AG, Ro/La nucleoprots, anti-PL, ANA
Detection by immunofluorescence
Mechanism of peracute graft rejection
Preformed AC (IgM) Sp for AG of graft (blood transfusion)
Deposition of AC on endothelium active complement = thrombosis
Mechanism of acute graft rejection
Mediated by LT and AC that are activated by alloAG in the graft
CTL may directly destroy graft or CD4+ cytokines induce inflamm
Damaged glomeruli and small vessels
Mechanism of chronic graft rejection
Indolent, leading to progressive loss of graft fct (sclerosis)
What are the different type of amyloid?
LIGHT CHAIN (AL) = secreted by monoclonal plasmocytes (associates plasmocytoma)
AMYLOID ASSOCIATED (AA) = unique protein made by liver associated with chronic inflammation (proteolysis of SAA)
B-AMYLOID (AB) = core of cerebral plaques in Alzheimer dz
TLR2 ligand + microbial source
Ligand (source) :
Lipoprotein (bacteria)
Peptidoglycan (gram+)
Zymosan (fungi)
LPS (lepto)
GPI anchor (trypanosomes)
Lipoarabinomannan (Mycobacterium)
Phosphatidylinositoldimannoside (Mycobacterium)
TLR3 source + ligand
Double stranded DNA (virus)
TLR4 ligand + source
LPS (gram-)
HSP60 (chlamydia)
TLR5 source + ligand
Flagellin (bacteria)
TLR6 source + ligand
CpG DNA (bacteria, protozoan)
TLR7 et TLR8 source + ligand
Single stranded RNA (virus)
TLR9 source + ligand
CpG DNA (bacteria, virus)
TLR11 et TLR12 source + ligand
Profilin (toxoplasma, uropathogenic bacteria)
TLR13 source + ligand
rRNA (bacteria)
ILC group 1
Activating molecules
Effector molecules
Effect
Activating molecules : IL7, IL15, TBX21, E4BP4
Effector molecules : IFNy, TNF
Effect : cytotoxicity (cancer, virus), IC bacteria and protozoa
ILC group 2
Activating molecules
Effector molecules
Effect
Activating molecules : GATA-3, RORa, NOTCH
Effector molecules : IL4, IL5, IL13
Effect : parasitaire, atopy
ILC group 3
Activating molecules
Effector molecules
Effect
Activating molecules : ROR
Effector molecules : IL17, IL22
Effect : development of lymphoid tissue, response against EC bacteria
On what is expressed CD68
Langerhans cells
Myeloid dendritic cells
Osteoclasts
Tissue macrophages
Mast cell mediators and their actions
VasoD + permeability : histamine, PAF, LTC4-D4-E4, protease, PGD2
Smooth muscle spasm : Leukotriene, histamine, PG, PAF
Cellular infiltration : cytokines (TNF), LTB4, PAF
