medical immunology and application

1. Adaptive Immunity

2. Antigen-Presenting Cells Have Characteristic
Costimulatory Properties
• Only pAPCs Dendritic cells, activated Macrophages & activated Bcell express high levels
of MHC II required for Tcell activation
• In early stage of response in Sec Lymphoid Org Tcell meet two types of pAPCs
• Mature DC activated by microbial component via their PRRs and so express specific
peptide complex with high levels of MHC II & costimulatory molecules
• Resting Bcells residing in follicles gain Tcell activation by BCR binding to Ag= up-
regulation of MHC II & costimulatory molecule present to Tcell at border of follicle and
Tcell zone Unique ability to internalize Ag & present via MHC II makes most efficient
activator
• Bcell pairing with Tcell helps Tcell to Bcell proliferate, differentiate & memory cell
generation
• Ag activated macrophage & some reactivated memory cells at site of infection via MHC
costimulatory and cytokine production like IFN-γ activate specific effector Tcell

5. The Endogenous Pathway of APC:
• Intracellular proteins are degraded by proteasomes a ATP
dependant process
• Proteins are targeted for proteolysis when tagged with Ubiquitin
• Immuno-proteasomes(β1i, 2i & 5i) found in pAPC are different
structurally from constitutive(β 1, 2 & 5) ones
• LMP2 & LMP7 genes located in Class I region response to
cytokines convert constitutive to immuno-proteasomes
• Immuno-proteasomes turnover more rapid than standard ones
• Increasing production of peptides that bind more efficiently with MHC I

7. Transporter
• The transporter protein, TAP (for transporter
associated with antigen processing), is a
membrane-spanning heterodimer consisting of
two proteins: TAP1 and TAP2
• Peptides generated by Proteosome in cytosol are
translocated to RER by TAP
• TAP has affinity for peptides c 8-16 AA
• Optimal peptide for Class I is 9
• Longer peptides are trimmed by ERAP

8. Assembly of MHC class I with Peptide by
Chaperones:
• Require peptide in the binding groove of class I molecule to exit RER
• Calnexin* (ER pr.) act as 1st molecular chaperone to assemble class I MHC
• When β2 microglobulin binds to α chain, calnexin released and class I
associates with Calreticulin and Tapasin(TAP Asso. Pr.)
• Tapasin brings TAP closer to Class I & allows it to acquire Ag peptide
• ERAP1 removes amino terminal residues to optimize the size**
• Peptide binding to groove leads to stability of Class I and dissociates from
all the chaperones & proceed to cell surface via Golgi complex

9. Moves
to cell
surface
via GC

10. The Exogenous Pathway of APC
• APC can internalize by either simple phagocytosis or receptor
mediated endocytosis
• Macrophage and Dendritic cells can internalize by endocytosis or
phagocytosis B-cell by receptor mediated endocytosis
• Most other APCs usually do by endocytosis or pinocytosis

11. Peptides generated by Endocytosis
• The endocytic Ag processing pathway
appears to involve several increasingly acidic
compartments(early endosomes etc)
• APCs have unique Late Endosomes*
• Oligopeptides of 13-18 AA meet up and bind
to MHC class II
• Early endosomes in periphery move to
centre to become final lysosome
• Eventually return to periphery to merge
with cell membrane = receptor recycled

12. Prevention of Antigen Switching
• When class II MHC molecules are synthesized within the RER, these class II
chains associate with a protein called the invariant chain (Ii, CD74).
• Invariant chain Ii CD74 conserved non-MHC encoded protein interacts with
class II molecules after synthesized in RER
• Interacts with peptide binding groove prevent endogenous peptide to bind
• Folding of class II a and b chains
• Involved in their exit from RER
• Routing of Class II molecules to endocytic pathway from Trans-Golgi network

13. Peptide Assemble with Class II
• Invariant chain is degraded as the proteolytic activity of
each compartment increases except a short fragment CLIP
• CLIP prevents any premature binding of antigen-derived
peptide
• A nonclassical class II MHC protein called HLA-DM* catalyse
exchange
• Unlike class II molecules it is non-polymorphic
• Normally not expressed at cell membrane
• Predominantly found on the endosomal compartment
• Like MHC I, peptide binding is required to maintain
structure & stability of MHC II
• Once transported to cell membrane neutral pH makes
complex to assume compact and stable form irreplaceable
by other class II peptides

14. Self-Tolerance in APCs
• Unlike HLA DM, HLA DO plays a negative regulator role
• Modulate role of HLA DM changing repertoire of peptides that
preferentially bind to Class II especially self Ag tolerance
• Both are expressed and associate with ER
• HLA DO play role in self tolerance as well as presentation of Auto-Ag
to self-reactive T cells
• DO is down regulated in presence of Ag allowing HLA DM to act

16. Cross-Presentation of
Exogenous Antigens
• As pAPCs express costimulatory molecules = CD4 with Class II (Tcell) activation
• Infected cells generally process, present peptides via Class I MHC on cell surface but
ĉout activated pAPC they will not get costimulatory molecule to activate naïve CD8*
• Subsets of DC are recognized as cross presenters resides in Secondary Lymphoid
• Two possible models or Hypothesis,
• First Hypothesis - Cross presenting cell has special machinery that allows loading of exogenously
derived peptides onto class I MHC
• Second – specialized endocytosis can internalize Ag directly to an organelle where peptides can
be loaded onto class I MHC
• Advantage - APC can capture virus exogenously without infection & process the Ag
and activate CTL
• Role of CD4 in regulation of cross presentation is first DC present to CD4 and they in
turn induce costimulatory molecule and cytokine = second opinion

17. Activation of naïve Tc cells by exogenous
antigen requires DC licensing and cross-
presentation.

18. Presentation of Nonpeptide Antigens
• Various types of T cells (expressing as well as T–cell receptors) can
react against lipid antigens, such as mycolic acid
• Ag are presented by CD1 family of nonclassical Class I
• Structurally similar to MHC Class I but functionally overlap with Class II
• Like Class II move in endosomes and asso with exogenous Ag
• CD1 expressed in Thymocytes, B cells and DC even in Hepatocytes & Epi. Cells
• Grooves are lined by Non-polar AA and are deeper and narrower, which bind
to Glycolipid or Lipopr Ag and Hydrophilic part exposed to be recog. by T cells
• Low affinity self-lipids are loaded in ER & replaced by foreign long-chain Lipids
in late endosomes or phagolysosomes

19. Lipid antigen binding to the CD1 molecule

20. Receptors and Signalling
B and T cell Receptors

21. Concepts in Lymphocyte Signalling
• Binding of Ligand induces clustering of receptors and signaling molecules into
regions of the membrane referred to as lipid rafts
• Causes the activation of receptor-associated tyrosine kinases, which
phosphorylate receptor-associated proteins.
• Binding of downstream adapters to phosphate group on adapter protein creates
scaffold at membrane = activation of PLCγ, PI3 Kinase
• PLCγ cleaves PIP2 to IP3 which interacts with ER vesicles to release Ca++
• Ca++ activate Calcineurin which dephosphorylates NFAT which allows it to nucleus
• DAG from PIP3 activates PKc which activates enzymes leading to degradation of
transcription inhibitor of NF-κB
• Binding of RAS-GRP to signalling complex = GEF and SOS activation = MAP kinase
activation = third set of Transcription factor AP1 activation & entry to nucleus

23. Steps of Receptor Activation
• The First step is ligand binding which induce conformational change
• Or they can result in clustering of the receptors
• Since B & T cell receptors have short cytoplasmic component and so
intracellular receptor asso molecule bring the signal transduction
• Igα/Igβ in B cell and CD3 complex in T cell asso with respective Ag rec
• Both of them has cytoplasmic tail contain multiple copies of Immuno-
receptor Tyrosine Activation Motif or ITAM*
• B & T cell receptors also interact with other molecules on pathogen
• B cell CD19/21 complex bind to complement Attached to Ag
• T cell CD4/8 bind to nonpolymorhic Ag presenting MHC molecule=transduct.
• Finally co-rec CD28 on Tcell interact CD80 & CD86 for full Tcell activation

25. Frequently Encountered Signalling Pathways
• On Ag stimulation, ITAM tyrosine phos’ryltion of
CD3 rec complex or CD79= localization of LAT* to
mem
• LAT phos’rylted & PLCγ1# then binds to LAT
• This allows PLC to localize and acts site subs PIP2
• Ca released by IP3 activates Calcineurin, which
dephosphry. NFAT
• Conform. Ch. Reveals nuclear localization sq.
• Sq. directs NFAT* to enter nucleus & activate
Transcr
• Eg Interleukin2 = proliferation of T Cell

26. The Ras/Map Kinase Cascade
• RAS* binds to GTP = conform ch = active state
• Binds & activates number of serine/threo kinases
• GEFs activate RAS by inducing release of GDP accept GTP
• GAP inhibit RAS intrinsic GTP ase
• DAG binds and activates RAS-GRP that recruits GEF, SOS
• RAS-GTP binds to MAPKKK Raf which activates MAPKK
• MAPKK/MEK phosphry Erk Extracellular signal Related
Kinase = gains ability to pass thr nuclear mem
• Erk phosphorylates and activates Elk-1 activates Fos gene
= Erk activated Fos pr with its partner Jun forms major
transcription factor AP-1 = IL-2

27. PKC Activates the NF-κB Transcription Factor
• NF-κB heterodimeric Trans Factor each dimer activates
repertoire of promoters
• NF-κB mediated transcr asso with proinflam events
• In resting cell NF-κB inhibited by IκB(Inhibitor NF-κB)
• Cell activation induces phosphry of IκB by IκB kinases
• DAG recruits ser/thre kinases PKCθ to membrane
• DAG-PKCθ phosphry adap pr Carma1 recruit TRAF6
• TRAF6 ubiquitinates and activates IKK
• Other T Cell mediated signal activate TAKI complex
which phosphry IKK = phosphry IκB = activation of NF-
κB

28. B-cell
Activation, Differentiation and Memory Generation

29. Clonal Selection:
• Immature B-cell has Ig receptors on surface and all are identical
specificity for a single Ag
• Ag stimulation = mature B-cells = Migrate to lymphoid organs
• Clonal descendants bears same receptors as parental B-cell and
secrete Ab with identical Ag specificity
• At the close of immune response Bcells bearing receptors for
stimulating Ag remain in the host, these memory Bcell capable of
mounting attack = sec response
• Bcells with receptors for self Ag are deleted during embryonic
development

30. Maturation and clonal selection of B lymphocytes. B-cell maturation, which occurs in the absence of antigen, first produces immature B
cells bearing IgM receptors. Each Bcell bears receptors of one specificity only. Any B cell with receptors specific for antigens expressed in
the bone marrow are deleted at the immature B cells stage (indicated by clone 4). Those B cells that do not express self-reactive
receptors mature to express both IgM and IgD receptors and are released into the periphery, where they recirculate among the blood,
lymph, and lymphoid organs. Clonal selection occurs when an antigen binds to a B cell with a receptor specific for that antigen. Clonal
expansion of an antigen-activated B cell (number 2 in this example) leads to a clone of effector B cells and memory B cells; all cells in the
expanded clone are specific for the original antigen. The effector, plasma cells secrete antibody reactive with the activating antigen.

31. T-Dependent B-Cell Responses
• Mature Bcells migrate to Lymphoid follicles Directed by CXCL13 secreted FDC
• Receptor for CXCL13 is CXCR5 expressed on Bcell surface
• Bcell not only reside there but recirculate in blood & lymph and back there
• At inni. Bcell binds Ag via its Ig receptors & that bound Ag is internalised processed re-
expressed as peptides presented in Ag binding groove Class II MHC
• Previously Dendritic cell-Ag activated Tcell bind to MHC & presented peptide in Bcell
• Tcell secretory apparatus activated = release activating cytokines
• Tcell CD40L bind to Bcell CD40 and Tcell CD28 coreceptor engage Bcell CD80 & 86
• Bcell integrates the signal move to specialized region of LN or spleen diff to plasma cell
• Some Activated Bcell move to border with Tcell & diff to cluster of Bcell= Primary Foci
• Here Bcell complete differentiation to plasma cell and 4days post-stim migrate to medullary
cord or red pulp of spleen to secrete Ab
• Some of the plasma cell after inni. response take up long term residence in bone marrow

32. T-Dependent B-Cell Responses
• Some Ag stimulated Bcell enter follicles instead of primary foci = differentiation
• Follicles swell with Ag-specific Bcells change their appearance = Germinal centers
• In this GC Bcell variable region go Somatic HyperMutation (SHM)
• In addition on going signal from Tcell, Bcell are directed to produce Ab isotypes a
process called Class Switching Recombination (CSR)
• Both SHM and CSR are dependent on GC enzyme Activation-induced Cytidine
Deaminase(AID)
• At close primary response memory cells, a daughter of stimulated Bcell remain with
same BCR
• At the end host is left with two sets of long-lived Bcells
• Plasma Cells in bone marrow
• Memory Bcells circulating through lymphoid organs

33. • B cells T-dependent activation first encounter Ag-specific T cells outside of the B-cell follicles. Some activated B cells differentiate into Ab-producing
plasma cells in primary foci outside the follicles= migrate to the medullary cords of the LN, or the BM, where they continue to secrete Ag-specific AB.
Other Ag-activated B cells enter the follicle where they divide and differentiate. As the follicle fills with proliferating B cells, it develops=germinal
center,
• Characterized by a light zone, in which follicular dendritic cells reside, and a dark zone in which the cell density is particularly high. Within the
germinal center, the immunoglobulin genes undergo class switching, in which constant regions are replaced by constant regions of other isotypes.
The variable region is subject to somatic hypermutation, and the mutated variable regions are subject to antigen-mediated selection within the
germinal centers. Low-affinity and autoimmune receptor-bearing B cells die, and those B cells with enhanced receptors leave the germinal centers
for the periphery.

34. B Cells Encounter Antigen in the
Lymph Nodes and Spleen
• Ag enter spleen or LN alone or with Ag transporting cells
• Small soluble Ag are directly acquired by Follicular Bcells
• Small Ag diffuse btw subcapsular macrophages, that line the sinus, to Bcell
• Larger complex Ag bind with surface molecules of SCSMacrophage
• Ag specific Bcells acquire these Ag and become activated
• FDCs provide reservoir of Ag to Bcells as they undergo, mutation, selection
and differentiation to pathway of memory cells

35. • Lymphatic fluid containing antigens (red) and cytokines and chemokines (blue) reaches the lymph node
• Subcapsular sinus has porous border and SCS macroph prevent free flow of lymph fluid
• Larger Ag and cytokines attach to SCS Macroph and are presented to Bcells
• Smaller 70KDa Ag or Cytokines pass through pores or through conduits

36. Somatic Hypermutation
• SHM occurs after Ag contact and in variable region of heavy & light chains requiring Tcell
• Requires interaction Bcell & Tcell via CD40-40L binding
• Mutational process was focussed on certain sp genes of variable region i.e rapidly
transcribed
• Activation-Induced Cytidine Deaminase (AID) necessary for SHM and CSR
• AID induced loss in amino gr in cytidine residue located in Mutation Hotspot = uridine
• DNA replication apparatus interprets deoxyuridine as deoxythymidine A-T instead G-C
• Or uridine excised by U-Glycosylase error-prone polymerase fill the gap as excision repair
• Or mismatch repair =excision of longer stretch of DNA=repaired by error-prone DNA
polymerase η leading to series of mutation
• Those mutation that resulted in increased Ag affinity were selected and survived

37. Antigen-Induced Selection of B Cells
with Higher Affinity
• Bcells with higher Ag affinity capture Ag & process and interact with
cognateTFH cells=so advantageous mutation to competitors for better able to
Tcell interaction
• Higher affinity Bcell actually steal Ag from lower affinity Bcell
• In absence of positive survival signal lower affinity Bcell undergoes apoptosis
• Survival signal delivered by Tcell by CD40 on Bcell surface in addition BCR-
induced P13 kinase activation of serine/threonine kinase=inhibit apopt=GC
Bcell to cell-cycle
• Since self proteins are expressed at extreme high conc in LN so Bcell reactive
to the undergo apoptosis

38. Class Switch Recombination Occurs Within the
Germinal Center
• Naïve Bcell express both IgM & IgD & both are encoded on the same long
transcript so the decision to translate μ versus δ made at RNA splicing
• In contrast switching from IgM to other class occur at DNA level referred as CSR
• Bcell must receive costimulatory signal from CD40 or Bcell Toll-like receptors(TLR)
• Cytokine signal determines the class of Ig Bcell will make
• These Cytokines induce transcription from germline promoters upstream 5’ of
respective Donor & Acceptor switch region
• Class switch occurs by induction of recombination btw donor & acceptor switch S
regions 2-3kb upstream from each CH region process inni by AID deaminates
within both donor/acceptor site previously activated by cytokine signal

40. Specific cytokines signal B cells to undergo CSR
to different heavy-chain classes

41. Some Germinal Center Cells Complete Their
Maturation as Plasma Cells
• At approx. 5-15 days of Ag encounter GC Bcells begin to upregulate IRF-4*
• IRF-4 induces the generation of transcr repressor BLIMP-1** = downregulates genes for
Bcell proliferation, CSR and SHM and upregulates synth and secretion of Ig
• As GC Bcell diff to mature Plasma cell it CXCR5 and express CXCR4
• It enables nascent plasma cell to leave LN and circulate within peripheral tissue
• Plasma cells localized in medullary cords LN, red pulp of spleen and bone marrow which
has niche occupied by fully matured plasma cell beside Bcell
• Survival of Bone marrow Plasma cell is need of CXCL12# and TNF family APRIL
• Other plasma cell asso with gut lymphoid tissue share some imp characteristics with
Granul-Monocyte linages produce TNFα and Inducible NOsynthase
• In order to continually produce these mediators IgA producing Plasma cell must remain in
contact with gut stromal cells and subject to microbial co-stimulation

43. Functional differences between primary and
secondary B cells

44. T-Independent B-Cell Responses
• Ag capable of eliciting Tcell independent Ab response are polyvalent, repeating
determinant shared among many microbial species
• Ag are recogn by B-1 Bcell as well as Marginal zone subsets
• T-Independent 1 Antigens
• Exemplified by bacterial polysaccharides LPS
• TI-1 bind to innate immune receptors in B1 cells and at high Ag doses capable of mitogenic for all
Bcell bearing the responding innate receptors TLR4
• Since Bcell stimulation by innate receptors only small quantity of Ab produced can bind TI1 Ag
• At lower doses TLR4 unable to sufficient Ag to stimulate Bcell but those bind via Ig crosslink and
are able to secrete Ab that are specific to TI-1 Ag

45. Cont….
• T-Independent Antigen 2
• Unlike TI-1, TI-2 capsular bacterial polysaccharide or polymeric flagellin are
not mitogenic
• Capacity to activate Bcell by ability to present antigenic determinants in
flexible and remarkably multivalent array= extensive crosslinking
• In addition most TI-2 Ag characterised by ability to bind complements C3d
C3dg
• Also by crosslinking BCR and CD21 on Bcell surface
• Monocyte, macrophage and dendritic cells facilitate Bcell responses to TI-2 Ag
by expressing BAFF membrane bound homology of TACI(transmem activator
and CAML interactor)
• Tcell can also enhance Bcell activation to produce Ab in response to TI-2
• Tcell cytokines also help the Bcell to switch class from IgM
• Unlike TI-1 TI-2 cannot stimulate immature Bcell and not act as polyclonal
activators

46. Properties of thymus-dependent and thymus-
independent antigens

47. T-Cell
Activation & Regulation

48. T-Cell Activation and
The Two-Signal Hypothesis
• CD4 and CD8 cells leave Thymus and enter circulation G0 resting mature cell
• If naïve cells meet APC expr MHC-peptide to which it can bind = activation = produce
diverse array of cells that orchestrate efforts to clear infection
• The TCR/MHC complex & coreceptor aggregate at central part of synapse ( central
supramolecular activation complex or cSMAC)
• Low intrinsic affinity btw TCR/MHC stabilized by several molecule(Primary Signal)
• Coreceptors CD4 & CD8 stabilize by binding to MHC II & I respectively
• Interaction btw LFA-1/ICAM-1 and CD2/LFA-3 sustain signal & form Peripheral pSMAC
• Even above interaction is not sufficient so interaction btw costimulatory molecule on Tcell
(CD28) and similar on Dendritic cells (CD80/86) provide Second, required signal
• Third set by local cytokine(Signal3) directs Tcells to differentiate into distinct effector cells

51. Costimulatory Signals Are Required for
Optimal T-Cell Activation and Proliferation
• In absence of APC isolated high affinity TCR/MHC = non-responsive = Tcell Anergy
• Dendritic & APC become activated by Ag binding to PRR = express costimulatory
and cytokines that enhance their ability to activate Tcell
• CD28 glycopr homodimer expressed by naïve Tcell, CD4 and 50% CD8 = enhances
TCR-induced proliferation & survival by pro-prolifer IL-2 & prosurvival bcl-xl
• CD80/86 Ig superfamily by intracellular domain generate signal to influence APC
• pAPC have capacity to express CD80/86
• Mature Dentritic cells best activator of naïve Tcell constitutively express CD80/86
• Macrophage & Bcells have capacity to upregulate them on Ag encounter

53. Signals
• The TCR/MHC-peptide interaction, along with
CD4and CD8 coreceptors and adhesion molecules,
provide Signal 1.
• Costimulation by a separate set of molecules,
including CD28 provide Signal 2.
• Together, Signal 1 and Signal 2 initiate a signal
transduction cascade that results in activation of
transcription factors and
• Cytokines (Signal 3) that direct T-cell proliferation (IL-
2) and differentiation (polarizing cytokines).
• Cytokines can act in an autocrine manner, by
stimulating the same cells that produce them, or
• In a paracrine manner, by stimulating neighboring
cells

54. Cytokines
• IL-2 is one of the best-known cytokines involved in T-cell activation and plays
a key role in inducing optimal T-cell proliferation, particularly when antigen
and/or costimulatory ligands are limiting.
• Costimulatory signals induce transcription of genes for both IL-2 and the
chain (CD25) of the high-affinity IL-2 receptor & signals also enhance the
stability of the IL-2 mRNA.
• The combined increase in IL-2 transcription and improved IL-2 mRNA stability
results in a 100-fold increase in IL-2 production by the activated T cell.
Secretion of IL-2 and its subsequent binding to the high-affinity IL-2 receptor
induces activated naïve T cells to proliferate vigorously.
• Polarizing cytokines(APC, NK cell & others), that play central roles not just in
enhancing proliferation, but also in determining what types of effector cells
naïve T cells will become.

55. Other Positive Co-stimulators
• Like CD28, the closely related Inducible CoStimulator (ICOS) provides positive
costimulation for T-cell activation.
• ICOS binds to another member of the growing B7 family, ICOS-ligand (ICOS-L)
• Unlike CD28, ICOS is expressed in Memory & effector Tcells not in naïve Tcells
• CD28 plays key role in initiation of activation of Tcell while ICOS plays crucial role
in maintaining the activity of already differentiated effector & memory Tcell

56. Negative Costimulatory Receptors
• CTLA-4(CD152) CD28 family also capable of binding to CD80/86 but antagonizes Tcell
• CTLA-4 not expressed constitutively on resting Tcells, induced 24hrs after activation
• Peak levels of CTLA4≤CD28 but has higher affinity for CD80/86
• Program Death or PD-1(CD279) & B&T lymphocyte attenuator BTLA(CD272) new boys
• PD-1 expressed by both B&Tcells & binds to PD-L1(B7-H1) & PD-L2(B7-DC)
• PD-L2 expressed predominantly by APCs while PD-L1 more broadly to mediate Tcell
tolerance in non-lymphoid tissue=both regulate Tcell differentiation
• BTLA broadly expressed TH cells, γδTcell, regulatory Tcell, NK cells, some macrophages
and dendritic cells and most highly in Bcells
• BTLA primary ligand is TNF family Herpesvirus-entry Mediator(HVEM) plays role in
downregulating inflammation and autoimmune response

57. Clonal Anergy
• In vivo, the requirement for costimulatory
ligands to fully activate a T cell decreases the
probability that circulating autoreactive T cells
will be activated and become dangerous.
• Unfortunately, negative costimulation may also
contribute to the T cell “exhaustion” during
chronic infection, such as that caused by
mycobacteria, HIV, hepatitis virus, and more.
Tcells specific for these pathogens express high
levels of PD-1 and BTLA, and are functionally
anergic

58. Immunosuppressive
1. Azathioprine (Imuran) is a potent mitotic inhibitor along with
Cyclophosphamide, Mycopheolate & Methotrexate
2. Cyclosporin A (CsA), tacrolimus, and rapamycin (sirolimus)
i. blocking the activation and proliferation of resting T cells
ii. prevent transcription of several genes encoding important T-cell activation
molecules, such as IL-2 and the high-affinity IL-2 receptor (IL-2R).
3. ATG can be used to deplete lymphocytes in recipients prior to Tx
4. OKT3 mAb used against CD3 of TCR Fc portion & phagocytose Tcell
5. Basiliximab specific for IL-2 receptor CD25 Tcell Proliferation
6. Rituximab Anti CD20 deplete Bcell thus AMR
7. CTLA-4 fused to human IgG1 block CD80/86
8. Efalizumab block LFA1-ICAM
9. Alemtuzumab Anti CD52 compliment mediated Tcell lysis
10. Abetacept & Belatacept CD80/86 blocker
11. JAK inhibitors Ruxolitinib, Tofacitinib, Baricitinib, etc.
1
2
4
5
7
10
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59. Thank You !
For your patient hearing