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Cell Mediated vs. Humoral Immunity
- Cell Mediated
o Interaction btw. cells required
o Ex. CD8+ T-cell killing virus infected cell
- Humoral
o “fluids” = humors/blood serum
o Does not require cells, b/c of soluble Abs in serum

Antibody Production
- B1 cells and marginal zone B-cells
o Produce low-affinity (non-specific) Abs
o No interaction w/T-cells required
o Produced in absence of infection
o B/c they are non-specific, act more like collectins and other generic opsonins than like traditional Abs
- Follicular Zone B-cells
o Found in 2° lymphoid tissue
o Interact w/activated, mature T-cells
o Interaction w/T-cells → clonal expansion and differentiaition
o All make IgM-type Abs

Functions of Abs
- Neutralizing: Abs stick to pathogen antigens and prevent pathogen from causing problems
- Opsonization
o Fc receptor on macrophages interacts w/Ab Fc region → phagocytosis
- Complement Activation
o C1 binds to Fc region of Ab → complement cascade and the creation of MAC on microbe surface
- Effector Functions
o Stimulate other cells to act
o Ex. Opsonization and IgE
IgE-bound to surface of parasite—-eosinophil degranulation
Structure of Abs
- Heavy and Light Chains
o Each Ab made of 2 heavy chains and 2 light chains
o Antigen binding region made of 1 heavy and 1 light chain
o Both binding sites bind same antigen
- Fc Region: conserved region
doesn't change no matter what the epitope sticks to
o Can vary btw classes of Abs isotopes
- Fab Region
o Contains antigen binding site
Variable domain
• Variability is determined by same mechanism as a TCR (VDJ recombination and during mitosis)
Antigen Binding
• Proteins, Carbohydrates and Lipids
- Hinge Region
o Links the Fc region to the Fab region via chain of small aa’s
o Makes Abs flexible allows binding of antigens very close to each other

Classes of Antibodies = “Isotypes”
- Different isotype properties b/c of different heavy chains, different Fc regions
- IgG
o Most common isotype found in blood
o Binds very avidly to antigens
o “free antibody”: not attached to cell surface
o Transported across placenta
o “Passive Immunity”: “acquired” immunity to pathogen form pre-formed antibody from someone else
- IgM
o Forms pentamers
o Does not bind as avidly as IgG
But multiple binding sites increase avidity
o As a flat molecule IgM pentamer not bound by C1
But when bound to microbe, makes a “tent” allowing C1 to bind
o 1st isotype of Ab to be secreted by B-cell
o IgM bound to B-cell surface = receptor part of B-cell receptor
- IgE
o Mast Cells: inflammatory mediators
o Eosinophils: antimicrobial peptides

Additional Antibody Information
- T-cell Independent: AB responses: B1 marginal zone B-cells spontaneously producing non-specific Ab
- T-cell Dependent: Ab production induced by T-cell receptor presenting antigen to B-cell in secondary lymphoid tissues → relies on clonal expansion of T-cells
- Like in T-cell recognition, IgM-antigen binding site diversity is a result of VDJ recombination
- T-cell presents antigen to B-cell receptor → prolonged contact → somatic hyper mutation
o Somatic hypermutation
Cytidine deaminases convert C → U
In this case act on V segment of gene that’s coding for this particular B-cell receptor
Very high rate of random mutation in V segment
Tweaked B-cell receptor than expressed on B-cell
Gives a better match btw B-cell receptor and T-cell → Abs are then secreted by B-cell, since IgM secreted 1st it binds less well to the antigen
- Then heavy chin gene expression changes - isotype switching
o Mainly IgG secreted
o Plasma cell - terminally differentiated B-cell secreting lots of Ab
o Plasma cells can live > several years
o Plasma cell maintenance and differentiation b/c of IL-6
- Some perfect fit B-cells don’t become plasma cells, don’t secrete antibody = Memory B-cells: can live for decades → re-exposure causes differentiation to plasma cells (no hyper-mutation or recombination, much faster)

- Type 1 Hypersensitivity/Anaphylactic Type
o IgE against worst target, inappropriate Ab against common environmental antigen
Ex. Allergies or Asthma
o Allergies higher in “cleaner” environments b/c we don’t get enough exposure to parasites = Hygiene Hypothesis
o Always make IgE whether its logical or not
- Type II/Cytotoxic Type
o You make IgG or IgM against own antigens, kill own cells w/CD8+ T-cells
Ex. Organ Transplantation Rejection
Ex. Some prolonged bacterial infections → Abs against shared bacterial/self epitopes
• Syphilis (T. pallidum) bacteria shared lots of epitopes w/human cells
- Type III/Immune Complex
o Make IgG or IGM against own free antigens
o Clots of Ab and antigen block small vessels
Ex. Lupus
- Type IV/Cell Mediated
o Delayed: takes ~48 hours after exposure to have reaction, b/c reaction is against antigens from intracellular pathogens, that’s had its antigens presented to T-cells by APCs if re-exposed CD8+ T-memory cells recruited to site of re-exposure

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