Week2 Flashcards
Allelic exclusion
Ab expresses light chain either encoded by either k (chrom 2) or lambda (chrom 22)
Not both!
IgM
10% of blood Ig Pentamer 2 light, 2 mu, linked by J 5 binding sites Monomeric form is BCR Activated classical cascade Functions at very low titers 1st secreted Ab in primary immune response
IgG
75% of blood Ig Major Ab in interstitial fluid 2 light 2 gamma 4 subclasses (y1,2,3,4) Secondary immune response Acticates classical complement at higher [ ]
IgA
Seromucous secretions: immunity at mucosal surfaces 15-20% of Ig blood sIgA highest Ig level Heavy chain: IgA1/IgA2 + J chain Dimer Secretory component
IgD
Monomer
Membrane-bound BCR on naïve B cells
Unknown function
Epitope
LC + HC + 3D epitope
Ab-Ag binding
Non-covalent: Electrostatic forces Hydrogen bonds Van der Waals Hydrophobic forces
Affinity
Single Ag-Ab bond strength
Low affinity Ab bind Ag weakly & dissociate while high affinity Ab bind tightly
Avidity
Multivalent Ab-multivalent Ag bonding strength
Greater than the sum of individual affinities
Total interaction strength btwn Ab-Ag
Chronic inflammation cells
Lymphocytes
Macrophages
Plasma Cells
Margination
Leukocytes are found near the vascular endothelium of capillaries
Fermentation
Homolactic acid- lactobacilli/strep, muscle
Mixed acid- enteric bacteria (products differentiate)
Deoxidise NADH to NAD
Low pH
Clostridium : gas gangrene
Shigella: gas negative
Respiration
E- transport & ox phos
Pyruvate used for ATP production
Insertion sequences
DNA can replicate by non homologous recombination
Transposase
Inactivate genes they insert into
Transposons
IS segments flanking structural gene
Encodes antibiotic resistance
Antigenic variation
Varying surface molecules
Phase variation
On or Off switch
Conjugative plasmids
Tra+
Transfer enzymes & sex pilli
RTF + R determinants = R plasmids
High Fiber diet
Protection against insulin resistance
Guy microbe fermentation —> SCFAs (butyrate, acetate, propionate)
SCFAs tell bone marrow to make myeloid cells
—> GLP-1 —> inc insulin/ inhibit glucagon
Helps glucose control
Inc access to complex carbs
High sat fat diet
Decrease insulin sensitivity
Postprandial lipidemia —> inc inflammation/LPS —> absorption
Chylomicrons bring it in
Meat, egg, dairy, fish diet
L-carnitine and choline
—> TMA/TMAO
Insulin resistance
GI cancer
Acetate
Activate PNS
Inc insulin, ghrelin, hyperphagia, obesity
Metabolic syndrome
ILCs
No Ag specific receptors
React to PAMPs/DAMPs
Cross talk w microbiome and adaptive immune system
Nutritive media
Grow lots of non fastidious organisms
No selective
Soy, nutrient, blood
Differential media
Distinguish
Blood agar - hemolytic patterns
Selective media
Support growth of one, inhibit others Antimicrobials, dyes Mannitol salt Chocolate (inhibits G+) MacConkey (lactose)
Basophil activation
IgE cross linking activation
Ectoparasites
Basophil OC specific granules w myelin figures
1 Degranulation (histamine, heparin sulfate, ECF/NCF)
2 cytokines (IL4/13)
3 phospholipase membrane cleavage (arachadonic acid pathway)
Macrophages
Activated by IFNy
APCs
Secrete IL1, IL6, GMCSF, TGFa
Factors H & I
Present in serum, H binds C3b
Inactivated by Factor I
C5a / C3a
Anaphylatoxin Neutrophil attractor Activates vascular endothelium Chemoattractant Phagocyte activator (respiratory burst & inc C1 R)
Opsonization
CR1 binds C3b
CR3 binds iC3b
Early complement deficiency
C1, 2, 4 Recurrent bacteria infections Can’t opsonise (no C3b) SLE Immune complex disease
C3 deficiency
Extracellular bacterial infections
Immune complex disease
Late complement deficiency
C5, 6, 7, 8
Nisseria gonorrhea infections
Meningitis
G- bacteria esp susceptible to MAC
C1 INH Deficiency
Hereditary angiodema Excessive C4 activation —> C2 lining Have an Ab of acquired later in life Dec C4 Dysfunctional C1 esterase inhibitor
CH50 test
Lower CH50 means more serum needed for lysis
Means at lease 1 dec complement component
Normal levels = no change
No lysis = congenital C1-C8 deficiency
Dec lysis= systemic complement activation due to autoimmune issue/ partial deficiency
Low C4
Classical complement issue
Low C3
Classical or alternative complement issue
Dec CH50, C3, C4
Complement hypercatabolism
Immune complex issues
Dec synthesis
Inc CH50, C3, C4
Systemic inflammation
Cancer, diabetes, MI
Hyper metabolic state (hyperthyroidism, pregnancy)
Immunohistochemistry
Tissue on a slide
Microscopy
Localisation of Ag
Flow cytometry
Cells in suspension
Quantities
Can separate single sub populations
Western blot
Tissues on a gel
Visual
Reactivity
CD14
Binds LPS+LPS-BP complex
Then interacts w TLR4
IFNy
Type II IFN
Made by T Cells & NK cells
Activated macrophages
Made early in infection, activate adaptive immunity
Bactericidal
Used in neutropenia, meningitis, endocarditis
Concentration dependent drugs
Peak:MIC ratio
Infrequent high doses
MIC (minimum inhibitory concentration) - lowest [ ] at which visual bacterial growth is inhibited
Metronidazole, aminoglycosides
Concentration-independent drugs
Time above MIC
Constant levels are ideal
Frequent small doses
Beta lactams, vancomycin, tetracycline
SS (+) RNA virus
Can act as mRNA
Polio, west Nile
Viral RdRp uses + to make - and then more +
SS (-) RNA Virus
Influenza & measles
Viral RdRp makes + mRNA —> translation
Diff transcripts
Makes mult templates Viral RdRp
dsRNA virus
Rep/rota
Viral RdRp transcribes + ssRNa —> protein or parental ds DNA
Genome segments make unique RNA
Small viruses use cellular DNA polymerase
Larger viruses encode their own
ssDNA virus
Parvo
Use host machinery (host DNA polymerase)
dsDNA virus
Use host machinery
Introns/Exons
Overlapping reading frames
Circular, linear
IFNa/B
A: dendritic cells/macrophages B: fibroblasts Type I IFN Stimulated by viral nucleus acids Recognized by TLRs Effects: dec protein production, inc viral replication resistance, inc virus cell killing Inhibit life cycle steps, don’t kill directly Inc MHC I Activate NK Cells
NK Cells
Activating + inhibitory (binds MHC I) Rs : missing self CD16 binds to IgG Fc receptor (ADCC) Perforin, Granzyme Fas:FasL Secret me IFNy —> macrophages Innate lymphocyte
Parvovirus B-19
Fifth Disease Small DNA, naked 4-15yrs Late winter, spring Biphasic: flu—> then rash, arthralgia (non infectious) IgM/IgG No treatment
Rubella
ss+ RNA Buds One serotype Respiratory or vertical transmission (first 20wks) Prodromal flu —> viremia + Ag-Ab complexes in skin Winter/spring Rash IgM : congenital MMR (live attenuated)
Roseola (Herpes 6,7)
dsDNA large
Saliva spread
Fever, rash 1-2 days Tcell response
Latent, reactivated w immunosuppression
Cross reactivity
Failure to Distinguish self from non self
Molecules share similar epitopes
Pathogens w molecular mimicry
Ab-Ag binding
Electrostatic
H bonds
Can der Waals
Hydrophobic
Papain cleavage
2 Fab (Ag bonding) 1 Fc (effector)
Cleaves at hinge
Fc allows complement binding
Pepsin cleavage
Below hinge
(Fab’)2
Has both Ag binding regions
Paratope
Ab region contacting epitope
HV & CDRs
VDJ recombinase
RAG1/2 Early B/T cell development TdT Daughter cells have same Ag specificity Random rearrangement
Somatic hypermutation
HV regions undergo high mutation rates
+ antigenic selection —> affinity maturation (occurs for B cells in germinal center)
Won’t change Ab specificity
Clonally selects those w higher affinity
Pro B cells
First committed to B lineage
HC rearrangement
Pre-B cells
Cytoplasmic u (mu) HC Combine w surrogate LC (lambda5, VpreB) Allows for LC formation
Iga/IgB
Cell signalling after Ag binding Transphosphorylation & activation of Btk, Blk, Fyn, Lyn ITAM phosphorylation Docking sites for adaptor proteins
MHC I
Unregulated by Iga/B a3 binds CD8 A/B/C B2 microglobulin Promiscuous binding Anchor residues secure peptide into binding groove (same for MHC II)
MHC II
Unregulated by IFNy
CD4 binds B2
DP/DR/DQ
Hyper IgM Syndrome
No CD40L
B cells can’t isotope switch
T cell independent Ag
Polysaccharides
Lipopolysaccharides
Proteoglycans
Little isotope switching, somatic mutation, or memory
