Exam 3

Thin layer makes it hard to have inflammation, no TNF α

• 1. Gut associated lymphoid tissues 
• 2. Effector component:
• a. where eosinophils, MACs, plasma cells, effector T cells, etc. reside.
• b. this is part of Lamina propria
• 3. Mesenteric Lymph nodes: not apart of GALT
• a. lagest lymph nodes in body.
• b. dedicated to protecting gut.
• 4. Inductor compartment:
• right below the epithelial layer (before effector component): where antigen, dendritic cells, and lymphocytes interact (adaptive immune system)

• 1. entrance to gut and airways
• 2. susceptible to over-infection and removal.
• a. this can cause issues in adult hood with lack of mature IgA produced.

• 1. location: small intestine only
• 2. dome-like lymphocytes aggregates.
• 3. f(x): this is where a lot of our mucosal activation occurs.
• 4. M cell: a trap. A cell that produces no mucus or covered with mucus.
• 5. 5-200 lymphoid follicles

Both use a microfold cell for transcytosis so that bacteria can be recognized by the immune system.

• 1. located: small and large intestine
• 2. consists of more B cells.
• 3. Good amount of gram negative bac.
• 4. Found in large intestine
• 5. Produce copious amounts of IgA
• 6. Transfers to lumen

• Occurs in lamina propria.
• (below inductor compartment)
• 1. bacteria gain access thru endocytosis
• 2. local effector cells respond, dendritic cells travel to mesenteric lymph nodes
• 3. highly specific effector b and t cells colonize area
• 4. no inflammation
• A. innate immune response:
• a. a lot of chemokines made for each innate cell
• i. activated by TLR/NLR that produce NFKB
• b. MACS do NOT produce TNF-alpha. do not perform respiratory burst.

• 1. tlr's and nods create transcription factor NFKB
• A. create chemokines for different innate cells.
• 2. no resp. burst or tnf-alpha from macs

• 1. M cells: allows for transcytosis of small euk. pathogens
• A.Allows dend. Cells to process these pathogens.
• B.Allows b cells to process antigen directly
• 2. Intraepithelial lymphocyte:
• a. cd8 ARE specialized to remove viral cells
• b.Cd8 also plug the hole so cells can regenerate and not leak fluid.
• c.Some ppl have mast cells in intestines. Fortunate for parasitic infection. Also contribute to allergic responses.
• 3. Intestinal dendritic cell:
• A. dend. Cells can do some sampling in the lumen.
• B.Idea is to reach commensals, remove pathogens, but not identify food.

• 1. IgA/IgM: cannot opsonize since fc regions are bound.
• A. Use complement
• 2. See more IgA than IgG in tract.
• A. gut lumen cell recycles Fcreceptor region to transport IgG from gut to lamina propria

• IgE: only one that can bind to antigen receptor in absence of antigen
• A.Usually associated with helminths but can go with others.
• B.Helminths are from animalia kingdom. IgE will damage both your cells and helminths.
• C. FC epsilon receptor: found mostly on mast cells
• D. These receptors can be found on eosinophils, but this population fluctuates more dramatically than mast cells.
• E. As soon as something binds, there is an immediate dumping of histamines.

• 1. Fluid leakage: we need physical expulsion. If start a large current, going to try to flush it out.
• 2. If physical expulsion doesn’t work, then brings in eosinophils
• 3. Eosinophils: drops Major basic protein onto target organism.
• 4. Mbp, is not a tight release, so it can very easily hit your cells.

• Four dif. Types of this.
• 1.Type I: allergic responses (IgE)
• A. binds to Fc epsilon Receptor on mast cell to release histamine (IgE, mast, eosinophils, basophils, Th2)
• 2.Type II: IgG:
• A. When IgG binds to YOUR target cell.
• 3. IgG: antibody attaches to antibody.

• 1.Type III: IgG. Binds to a small complex (protein, nucleic acid, etc.) when antibody binds to your antibody. Binds to something soluble. Will lodge in blood vessels. Associates with protein or other small molecule
• A.trypanosomes. Ex/ secretes antibodies that IgG binds to which lodges in brain
• B.Serum sickness: antibodies from another species (usually horse) horse anti-venim. Can eventually make an antibody against the antibody, if it is recognized as “foreign”.
• 4.TH1-> MAC’s enhanced TNF alpha-> TNF-alpha produces a lot of inflammation.

• 1.Common allergens.
• 2.How it works: IgE binds to high affinity FC Epsilon Receptor
• a. Eosinophil’s try to release Major Basic Protein
• 3. ECP also released
• 4. Mast cell ‘s histamine try to hit the dander, but misses.

• 1. location: resident in mucosal, epithelial, and vascularized tissue
• 2. pre-formed granules (50-200 in cytoplasm)
• 3. age: long lived, and retain FCepsilon Receptors.
• 4. Side effects: Histamine:
• a. wheezing, coughing, vomiting, diarrhea, 
• b. increased vascular permeability
• 5. other chemicals released:
• A. leukortrienes: same effect as histamine, 100X more potent
• B. prostaglandins: vessel dilation and permeability
• 6. side effects in certain areas: 
• A.GI tract:
• a.increased fluid secretion
• b. peristalsis (vomiting, diarrhea)
• B. Airways:
• a. increased mucus secretion
• C. Blood vessels: 
• a. increased vessel permeability, edema
• b . increased blood flow

• 1. cross reactivity of similar antigens such as dust mite, german cockroach, grass pollen, etc.
• 2. genetic predisposition: caucasians
• 3. mother to child: elevated levels of IgE in amniotic fluid

• 1. most common is hay fever
• 2. mast cells in the nasal mucosae
• 3. Histamine: fluid leakage , mucous discharge, edema

• 1. symptoms: wheezing
• A. if chronic inflammation, eosinophils, th2, and neutrophils are involved
• 2. causes: mast cell

• 1. mast cells in skin
• 2. usually caused by topical or bloodborne contact
• 3. eczema- not well understood

• 1. react to a small amount of peptides.
• 2. GALT mast cells
• 3. reaction:
• A. mucosal mast cells react to ingested antigen
• B. mast cells trigger smooth muscle, epithelial, and blood vessel response.
• C. urticaria (hives),

• 1. wheel and flare
• A. immediate response: histamine
• B. later response: leukotrienes, and prostaglandins
• 2. only works for type 1, or IgE involvement

• 1. over the counter: (de-sensitization)
• A. anti-histamines
• 2. allergy shots:
• A. switch IgE to IgG

• 1. Type 3:
• A.Usually have good peripheral tolerance (FoxP3), just absence of Reg T cells.
• 2. Not uncommon: 5% of pop has this
• 3. Failures of self tolerance
• 4. Who is at fault: anitbodies or T cells

• 1. (hint heme-rbc)
• 2. what: Type II AID
• A. this means IgG and IgA bind to surface (surf. part defines type 2)
• 3. victim: rbc
• A. Erythrocytes are originally bad. Can be from penicillin, bad transplant, mutations
• 4.Anemia-when rbc is destroyed

• Two diseases: grave's disease and hashimoto's thyroiditis
• **thyroid regulates basal metabolic rate**
• 1. G.D:
• A. antibody binds to receptor, mimics ligand
• B. overproduction of thyroid hormones
• C. antibody = antagonist
• 2. Hashimoto:
• A. Th1 and abs attack thyroid
• B. hypothyroidism: unable to make thyroid hormones

• 1. what type: Type ii(bc abs bind to receptors of cells, muscle cells)
• 2. causes: inhibits nerve and muscle interaction
• A. gradual weakening of muscle
• B. impairs breathing
• 3. remedy: immunosuppressants

• 1. caused by: received animal antibodies (such as anti-venom prod. in horses) 
• A. IgG attaches to these abs and lodge in vascular tissue
• B. accumulate in kidneys leading to kidney damage
• C. also recruits too many neutrophils
• 2. Type 3 aid!

• 1. Failure of central and peripheral tolerance.
• 2. affects almost every cell in body
• 3. IgG antibodies against nucleoproteins and nucleic acids of cells
• A. Type 3: reacts to a fragment/protein NOT cell
• 4. releases soluble antigens that accumulate in areas such as kidneys, joints, etc

• 1. Basophils are the source of this IL-4
• A. because drives Th2 response which secretes IL-4

• 1. what: type 4 (involving T cells)
• 2. why its bad: destruction of Beta cells that produce insulin
• 3. European descent
• 4. What happens:

There are other type 1 diabetes this is just the more common

T-cells activate macrosphages (Th1)

Destroys islet cells of the pancreas

-> sugar levels get too high. ->

• 1. who affected: 1-3% women in 20-40 range
• 2. Can be a type 4 type 3 , or type 2. a lot of cells involved.
• 3. Ex/ I make anti-foreign IgG, and anti-you IgG.
• 4. How it works: Make antibodies against antibodies.
• 5. what type: Type iV
• 6. rheumatoid factor: (autoantibodies against Fc region of IgG)
• 7. why its painful:
• th1 activates macs which release a lot of tnf-alpha
• a. prostaglandins and leukotrienes emitted
• Lodge in various locations.
• 8. treatment tactic: immunosuppressant, reduce TNF-alpha stimulation

• 1. what type: type iV (due to Th1 activity)
• 2. macs secrete cytokines and proteases that demylineate proteases
• Damages myleage sheath. Allows neurons to signal faster, so damaging this leads to slower signaling.

• 1. Type iV
• 2. Th1 activates macrophages which attack small intestinal cells 
• 3. triggered by gluten
• 4. **take-home message: causes villi atrophy from effector cells.
• 5. cd4 response as well...

• 1. recap: aire is a transcription factor that allows "self antigens" that are extremely specific and not common in body to be apart of negative selection.
• 2. so ppl with a problem of this do not have T cells that were eliminated due to reactivity of highly specific body functions

• 1. a T regulatory autoimmune disorder
• 2. prevent activation of self reactive T cells
• 3. express FoxP3

• 1. increase is a sign of AID
• 2. secrete IL-17
• A. stimulates release of cytokines for inflammatory cell recruitment

• 1. autoimmune diseases approx. 20% of population with a particular HLA (usually HLA-II) are predisposed to AID
• 2. accounts for 50% of genetic predisposition cases

• 1. smoking/physical trauma
• 2. disrupts tissue -integrity, lungs more accessible to leukocytes

• 1. environmental factors
• A. trauma/injury/smoking
• B. molecular mimicry
• 2. infection-> inflammation-> uptake in mhc 1 presentation-> more diverse antigens -> not enough t cells to respond-> leads to presentation on non-typical cells

• 1. Location: spleen, mucosal, lymph nodes
• 2. express igA, igG, igE on surface
• 3. higher levels of B7 (co-receptor) & MHC-2 (makes sense, secondary response is faster)
• 4. higher avidity
• 5. continue affinity maturation process
• 6. stop immune response
• 7. mechanism: activated differently: do not co-stimulate CD28
• 8.

• 1. activated differently: do not need co-stimulation of CD28
• 2. activated in tissue and not just bloodstream
• 3. negative signals given to naive B cells so that memory b cells can give their better signal

• 1. when mother is -, father +, which produces a + baby
• 2. first pregnancy of + baby not really affected. (primary response slow)
• 3. secondary response: kills rbc of baby due to placental + cells crossing over and mama antibodies crossing over in response destroying them
• 4. rhogam is given in response

pustules, jenner, boy cowpox

• Pros:
• 1. most robust immune response
• 2. most effective 
• 3. skin administration
• 4.

• 1. safe
• 2. protective
• 3. sustained protection
• 4. induces neutralizing antibodies
• 5. induces t-cell response
• 6. practical

• 1. toxoid
• A. stimulate antibody-mediated toxin neutralization
• B. lacks longevity
• 2. live attenuated
• A. all components
• B. CAN replicate
• C. most effective
• D. could revert back (highest risk)
• E. most modern
• 3. killed: 
• A. all components
• B. cannot replicate
• C. safe for AID patients
• 4. component
• A. against polysaccharides, heavily encapsulated bacterium
• B. most concern for lack of longevity
• C. recombinant dna technology
• D. good against pneumococcal.
• E. difficult to attach complement on heavily encapsulated bacteria
• F. pcv: has polysaccharides and peptides for t cell activation

• 1. a vaccine ingredient
• 2. prereq for good immune response: inflammation (recruitment)
• A. MAC will pick up if there is a good immune response
• 3. types:
• A. freund's complete adjuvant: a little too stimulatory for some
• B. AlOH common

• 1. Hg -based (50% Hg)
• 2. removed for vaccinations under 2. due to exceeding recommended daily dose

• 1. Problems:
• A. huge capsule, 
• B. 91 different capsule antigens
• C. with vaccine it only protects against 13 of these antigens. leaving 78 unprotected
• 2. failure type: pathogen evasion

• 1. pathogen evasion
• 2. genetic immunodeficiency
• 3. acquired immunodeficiency

• 1. type: pathogen evasion
• 2. if antigenic binding site mutates like in flu virus, can still get flu

• 1. trypanosomes alter surface antigens thru gene rearrangement
• 2. sheds antigens as they are being recognized by abs
• 3. small protein /abs interaction can be dangerous. these can get lodged into vascular tissue in brain...no good!
• 4. neurological damage-> african sleeping sickness, chagas disease

• 1. HSV. 
• A. attacks epithelial cells
• B recedes back in neural cells-where no MHC1 is located therefore won't be destroyed.
• 2. VZV (chicken pox)
• A. only one reaction after decades of latency.
• B. dorsal root ganglia
• 3. EBV- early childhood
• A. infection of B lymphocytes (b cells also have few MHC 1 molecules)
• B.

• 1. tuberculosis:
• A. prevents fusion of phagosome and lysosome of MAC.
• 2. Listeria
• A. escapes from phagosome
• 3. toxoplasma
• A. surrounds itself with a vesicle to prevent entrance into lysosome
• 4. syphillis
• A. doesn't fit in phagosome/lysosome
• B. coats itself with human proteins so self attacks itself or does not attack parasite at all

• 1. Herpes & pox
• A. sends out virokines (cytokines) that drive immune response
• B. also send out viral receptors to cause a barren immune response
• (blocks complement and antibody binding)

• create a false link between Tcr and MHC-II. 
• b. Th1 and Th17 are proliferated too much and causes a cytokine storm, lots of inflammation

• 1. ex/ RSV:
• A. th2 produces Ige,
• B. Tfh leads to IgA and IgG
• 2. vaccines that are bad and recruite tissue -damaging eosinophils

• 1. since IL-12 happens first, does not affect NK cells
• 2. in turn IFN-gamma is produced. there is a mac defiency. cannot optimally secrete cytokines

• 1. secreted by macs, acts on nk ells
• A. lose NK cell activity, which is imperative for viral and cancer elimination
• 2. susceptible to intracellular infections
• 3.No macrophage activation due to domino effect
• 4. Th1 cells: adaptive immunity
• A. if Macs not activated, then cannot apc for a th1 to attach

have a back up plan. not end of world

• 1. this is the back up plan, so not good if this occurs
• 2.

• 1. females are carriers
• 2. no antibodies
• 3. dfect in rotein kinase
• 4. IgG therapy

• 1. this provides isotype switching and MACs rely on this to achieve optimum
• 2. result is hyper IgM, (lack of switching,)
• low count of other abs
• 3. mac cannot perform at optimum

• 1. defect in rag proteins, which are essential in antibody / t cell development
• 2. only one b cell and only one t cell

• 1. lack of hla class II
• A. causes no CD4 T cells
• B. causes no optimal
• a. B cells
• b. MACs
• c. neutrophils

• acquired immune deficiency syndrome
• 1. massive reduction in cd4 T cell
• 2. infects Cd4 T cells
• A. die thru apoptosis
• B. somewhat lytic
• C. Nk cells/ ctl's destroy impacted MACs, DC, and Th cells
• D. left with no t cells since thymus is turning into fat
• E. can only protect against pre-exposed diseases. so usually die from something bizarre