Immunology Rapid Review

Lymphatic Tissue Primary -Bone Marrow Vertebrae, Flat bones of skull, Pelvis & Long Bones -Thymus T-cell development of alpha beta, NOT gamma delta Secondary Lymph Nodes Spleen *Encapsulated bacteria entering blood removed at the spleen to large to enter lymph, opsonized by IgG and complement and cleared MALT, GALT Peyers patches Adenoids Tonsils *If there is a B-cell deficiency can get hypo- nodes/adenoids/tonsils Innate Immune System (nonspecific and constitutive) Cells Natural Killer - a lymphocyte - marker CD16/56 - induced by Interferon alpha and beta - can be given antigen specificty, ADCC Complement System: -Clear Ag-Ab complex -Opsonization of pathogens, Fc receptor synergize -Attraction of phagocytic cells -Lysis -Synergize B cell activation-CR2 Complement components from liver result in systemic inflammatory response Complement components from macrophages result in local response C5a>C3a>C4a are: anaphylotoxins Increase vascular permeability Chemoattractant (bind to R, we are here!! come help) Mediate degranulation of mast cells, leukocytes, & macrophage

Immunology Rapid Review

Alternative Complement Pathway-1st to act!! -C3 cleaved to C3a and C3b, expose thiolester bond that becomes covalently linked to pathogen, Factor B(need Mg2+)->C3bB, Factor D->C3bBb -C3bBb- c3 convertase -(C3b)2Bb- c5 convertase -coat with C3b to opsonize or clear from blood (CR1) Classical Complement Pathway Ag(1-IgM, 2-IgG)-Ab complexes serve as start points C1q,r,s like MASP (stabilized by Ca2+) onto Ag-Ab complex through globular tails at constant region 2 this occurs due to the Ag-Ab binding causing a change in Fc portion of Ig C4->C4b->C2(need Mg2+)->C4b2b C4b2b- c3 convertase C4b2b3b- c5 convertase -coat with c3b to opsonize or clear from blood (CR1) -Factor P- positive regulatory protein of alternate pathway -Complement are heat sensitive(microbio lab) -C3 convertase are short lived, but makes c.2000 C3b/min -Lysis of cells through c5 convertase, C567(insert into outer leaflet of membrane)8(disrupt lipid bilayer)9(n)-MAC pore -Regulation Factor H: prevents B or Bb Factor I: C3b->iC3b->C3dg + C3c->C3d + C3g, cleave c4b DAF: prevent C3b from binding on mammalian cells responsible for paroxysmal nocturnal hemoglobinuria when deficient MCP: C3b inhibition on mammalian cells C1NH: covalently bind to c1r defieciency responsible for hereditary angioneurotic edema Vitronectin: prevent C5b67 insertion HRF and CD59: prevent C9 binding -Receptors for C3 fragments, the opsonins CR1- bind C3b and C4b clearance when on erythrocyte on monocytes/macrophages, granulocytes, FDC, B cells CR2- bind C3d B cells & FDC

Immunology Rapid Review

CR3 and CR4- bind iC3b (FOR EATING) on professional phagocytes C5-C9 deficiency-susceptibility to Neisseria infections C3-increased susceptibility to Type III hypersensitivity, frequent bacterial infections C4 deficiency- most common, associated with poor clearance of Ag-Ab complex Complement Measurement CH50 assay: is it present, if so is MAC formation efficient? 150-300Uml-1 normal if high hyperactivity, if low mssing dilution of patients serum required for lysis of 50% of Ab-RBC, measure hemoglobin Adaptive Immune System Comes into play when innate system cant clear Antigen Receptor 1)T lymphocyte receptor 2)Immunoglobulin Antibody B cell receptor Immune response 1)Humoral mediated increase immunoglobulins TD or TI neutralize toxins immobilize bacteria, H antigen on flagelin clearance & opsonization 2)Cell-mediated increase T-lymphocyte require presentation- CTL, Th (1 & 2) B-cells Development -In the bone marrow, trophic factor IL-7 and stromal contact -ProB to PreB to Naive B -IgM & IgD as BCR (through differential splicing) -Negative Selection

Immunology Rapid Review

If autoreactive, redo LC until possibilities run out-death if not fixed, has made new specificity Anergic response (reaction with soluble antigen) results in a B cell with LOW IgM and normal IgD Escape from negative selection results in autoimmunity XLA Bruton Tyrosine kinase mutation, impaired signal transduction no B cells, decreased immunoglobulins, no CD19 in serum RAG 1/2 deficiency-SCID or Ommen Syndrome Receptor Genesis (INDEPENDENT of Antigen exposure) -Heavy Chain chromosome 14 Light Chain chromosome 22(l),2(k) preferred 2:1 -Heavy Chain VDJ, Light Chain VJ -Heavy chain synthesized first, preBcell receptor has VpreB (light chain substitute), if heavy chain yields signal transduction can move on ALLELIC EXCLUSION and start light chain synthesis -RSS with 12/23 spacers label cut points for RAG -RAG 1/2, only combine 12/23 not of similar -DJ Ist than V-DJ -CDR3 most diversity, not in genome because of hairpin fix Naive B cell encounter antigen.. -activation synergized with cd19/cr2 coreceptor -What happens depends on cytokines and/or T cells -TI Ab response (need additional help since no Tcell aid) -B1(CD5+) cell- Ag+TLR Natural IgM secretion -TI-2 Ag, repeated epitope -W/ T cell (Germinal Reaction, production of Secondary follicle) -Light zone centrocytes are quiescent, Dark Zone centroblasts are dividing -B cells competing for Ag bound to FDC, best man wins -Tcell need to recognize MHCII and a CD40/L stimulation -Somatic Hypermutation (leads to greater affinity) and Isotype Switching at Switch region (depends on what T cell had in mind given its knowledge of the antigen) -make plasma cell(has no surface Ig), differential splicing leads to secreted Ab -make memory cell a direct descendent of B cell, AID works on Switch regions if Switch region activated by IL-4 make IgE if IFN-y make IgG -naive IgM B cells prevented from activation due to IgG binding (Rh hemolytic disease-Rhogam)

Immunology Rapid Review

HyperIgM-X linked CD40L, or autosomal AID , CD40 missing can not class switch

T-cells alpha beta Cd4+ alpha beta Cd8+ Development -At subcapsular region are double negative with no CD3 Very Similar to B cell Development- B synonymous to heavy, A synonymous to light become double positive Followed by Positive Selection: -favor T cells that recognize self-MHC -takes place in the cortex -Cortical epithelial cells express MHC I & II, if recognize continue of not die death by neglect -results in MHC restriction Bare lymphocyte syndrome-only one typ of Tcell due to absence of MHC of a type Negative Selection -dependence on AIRE
defect causes autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy -medullary dendritic cells present -strong->apoptosis, weak->mature

-result in self-tolerance Interactions Adhesins (LFA-1,CD2), CD3+TCR, CD45(adhesion activator), CD28(co-stimulatory NEEDED for activation) -dendritic cell primes -transduction express high affinity IL-2(alpha added), acceptance -> proliferation -CTLA-4, instead of CD28 -upregulation of adhesins -VLA4 to site of infection -downregulation L-selectin->away from lymph -Production of Tem(tissue, quick hrs, good for latent infections in tissue) and Tcm(lymph, quick days)

Immunology Rapid Review

-Effector T cells CTL -recognize MHCI, has FasL and adhesins, set up transport to target release granules and induce apoptosis of target Immunodeficiency with albinism-Chediak-Higashi Immunoglobulins -are not heat sensitive (microbio lab) Fab -antigen binding -results from pepsin cleavage(monomenric), (Fab)2 results from papain cleavage Fc -denotes effector action -confirmation change when antigen bound -portion available to bind receptors FcgammaR FcepsilonR IgM-on naive B cells, in serum is pentameric, activate complement IgD-on naive B cells, susceptible to proteolytic cleavage IgG-major opsonizer, activate complement, blocks naive B cell from activation IgE-allergy & parasite IgA-dimeric if secretory, monomeric if in serum found in all mucosal surfaces (GI, urogenital,skin...), secretory protein prevents it from proteolytic cleavage