HG exam 3 pgs 6-10

- Immune system - adaptive - humoral response 

- Antibody response begins when the APC__ activates a T - cell__ which in turn activates a B - cell__

- B cells die in the ___spleen________ and ___lymph nodes_______

- B cells are generated in the ___bone marrow________ & learn self there

- T - cell finds its B cell match it releases cytokines____ that cause the B cell to divide to become:

- 1. ___plasma cell________ = antibody factories (2,000/second)

- 2. memory cell________= become dormant, respond faster

- immune system - antibodies 

- Made of several polypeptides = encoded by many genes

- Parts of an antibody

- 1. heavy____ chain = the 2 longer polypeptides

- 2. light____ chain = the 2 shorter polypeptides

- 3. constuant____ region = base of the Y, common to all antibodies

- 4. ____variable____ region = tip of the Y, different among antibodies

- 5. Antigen binding site binds the epitope

- Antibody jobs

- ____inactive______ pathogen, neutralize toxins

- clump_____ pathogens together

- ____activate______ complement system

- immune system - antibodies 

- Limitless varieties

- 1. V (variable)

- 2. J (joining)

- 3. D (diversity)

- Heavy chain (chromosome 14) & light chain (chromosome 2 & 22) have 3 gene sections

- Only a few antibody genes, but can make limitless varieties : one for every pathogen you encounter

- Thanks to ______alternative splicing_____________ we can make 10 trillion different antibody combinations

- immune system - antibodies - diseases 

- Immunodeficiency with hyper IgM

- 1. Make too much IgM__

- 2. Make too little ___IgG and IgA__________

- 4. Mutation in _____x chromosome____________

- 5. Mutated T cell protein ligand = no signal_____

- Result = can’t maintain long term immunity

- → recurrent bacterial infections

- → risk of autoimmune disease

- Treatment = IV replacement of IgG, bone marrow transplant

- Important immune cells for a healthy system 

- Mast cells: Release histamine to recruit immune cells, defend against pathogens, cause allergic reactions

- Macrophages: Phagocytoses cancer cells & pathogens

- Natural Killer: Cells Destroys tumor cells & virally infected cells

- Dendritic cells: Phagocytoses invaders

- Neutrophils: Responds to trauma, kills bacteria & fungi

- Basophils: Releases Histamine, fights parasites, causes allergic reactions

- Eosinophils: Kills bacteria & parasites

- B - cells: Attacks all microbes with antibodies

- T -cells: Stimulates other immune cells & attacks cancer or infected cells directly

- immune system - abnormalities - inherited 

- Inherited Immune Deficiencies

- 1. Chronic Granulomatous disease

- →___neutrophils__________ can engulf bacteria, but lack enzyme to destroy

- → Chronic recurrent infections usually bacterial or fungal

- → Enzyme made of 4 different genes = ____all x - linked ___________

- → Treatment: antibiotics & IFN gamma infusion

- → Cure with: Bone marrow transplant or umbilical cord stem cells

- immune system - abnormalities - inherited 

- Severe Combined Immune Deficiencies (SCID) Lack of B - cells and/or T cells

- T - cells cannot mature_____ & activate B -cells

- Affects both Humoral & Cellular immunity

- Half of cases are _____x - linked __________

- Die from severe & diverse infections: viral, fungal (thrush), and bacterial infections before age 3 

- David Vetter – bubble boy – transplant – Epstein Barr

- immune system - abnormalities - inherited 

- Inherited Immune Deficiencies

- 3. Immune defect due to absence of thymus

- No T - cell ___matutation______

- No cytotoxic T - cells for ____viral infections__________

- No helper T - cells to activate ___b-cells_______

- 4. Neutrophil Immuno - deficiency Syndrome

- ___point_____ mutation makes neutrophils defective

- Lots of ____bacterial_______ infections

- Lack of ___pus___ = poor wound healing

- immune system - abnormalities - acquired 

- HIV - genome is 1 millionth of ours, has 9 genes – 9,000 RNA bases, encodes 15 proteins – takes over 200 human proteins

- HIV enters__macrophages_________binds to 2 human coreceptors (CD4 & CCR5), once inside reverse transcribes viral RNA into DNA,

- Makes a double helix, enters nucleus, inserts into chromosomes__________

- Cell fills with viral pieces that assemble into new viral particles that bud from the cell. T-helper_____ cells begin to die off

-Bacteria infections begin because B-cells______ cannot activate to produce antibodies.

- Later HIV variants bind to CXCR4 receptors on cytotoxic______ T cells and kill them which allow for cancer and viral infections to take hold.

- immune system - abnormalities - acquired 

- Example :HIV

- Steps in infection

- 1. Binds receptor, enters cell

- 2. Reverse Transcription RNA to DNA__

- 3. Make dsDNA

- 4. Incorporates DNA into ___host genome____

- 5. Viral genes transcribed to mRNA

- 6. Viral mRNA to viral proteins

- 7. Capsid surrounds viral genome

- 8. Buds from cell

- How to stop it?

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- HIV-Treatment

- HIV has no replication repair system so mutates every 5,000 bases.

- Immune system cannot keep up with this ever- changing virus.

- HIV variants arise so quickly that HIV drugs can become useless in days.

- Bone marrow produces 2 billion T & B cells a day, but HIV replicates and buds 1 million to 1 billion new particles a day.

- Combination drugs with different actions offer the best treatment working at different points of infection to slow down HIV = slow lifelong treatable illness.

- Scientists are now looking at people who are resistant to HIV infection. Found variants in 4 receptors or the molecules that bind to them and can block HIV entry. Many had similar homozygous recessive 32 base deletion in CCR5 gene.

- Advantageous mutations

- Chromosome 3

- Heterozygous – delayed__________

- Homozygous recessive –_____no infection__________

- Bone marrow transplant

- Gene therapy

- immune system abnormalities - autoimmunity 

- Immune system makes antibodies that attack your own cells

- Polygenic, 5% of the US population, can develop at any age

- Example: Lupus →Autoantibodies attack connective tissue____________

- Example: Ulcerative colitis →Autoantibodies attack ___colon tissue_______

- How does autoimmunity arise

- 1. viral______ infection–host cell proteins

- 2. Immune cells escape thymus____

- 3. Antigen resembles self___- heart valves & Streptococcus

- 4. Skewed ______x-inactivation_______- females have increase in autoimmune

- immune system abnormalities - allergies 

- What happens when you have allergies?

- 1. You are exposed for the 1st time to an allergen, but you have no allergic reaction

-B-cells bind the allergen, secrete antibodies (IgE) that bind ___mast____ cells

- 2. You are exposed to the allergen a subsequent time, you have an allergic reaction

-When allergen binds to IgE on Mast cells, it causes them to release ____histamine______ in large amounts

- immune system abnormalities - allergies 

- Allergies are an immune response to an allergen___ that is not actually a threat

- Ranges from:

-Hay fever–larger -upper respiratory

-Asthma–small–penetrate lung

-Anaphylactic Shock: IgE binds antigen and causes massive amount of histamine_____ to be released = contraction of bronchial muscles and vasodilation = leaky vessels

- Allergens activate _____T-helper cells______ which in turn release massive amounts of cytokines so both the humor & cellular immunity take part in an allergic response.

- immune system - how to alter it - vaccines 

- Smallpox (first one, sort of) 1796 Edward Jenner

- Vaccines = stimulate a__primary______ response to make secondary____ response better (so you are really just tricking your immune system into recognizing it earlier)

- Herd immunity

- 1. Reduces pool

- 2. Limits spread of things 

- Smallpox on 3,000 year old mummy

- 1500’s take smallpox scabs grind up to smoke or rub in skin

- immune system - how to alter it - immunotherapy 

- Monoclonal antibodies (Mab)

- 1. Recognition– B cells recognize antigen

- 2. production_____– by a B cell of one specific antigen

- 3.___specific______–for only that particular antigen

- Useful for ___diagnosis_______ and ____treatment_________ because they are very specific (pregnancy test– hCG)

- Cytokines

- 1. Interferons = cancer cells, warts

- 2. IL - 2 = administer by IV, treat kidney cancer

- 3. Colony stimulating factor = boost WBC production (AIDs, chemo)

- 4.Tumor necrosis factor = stops binding to self (arthritis)

- mabs & the downside 

- ____immune reaction potential_______________ - the antibody type determines the “Immunogenicity potential”

- _____infection potential______________ - Inhibits your ability to fight off infections caused by viruses, fungi, bacteria & TB

- Act only for a short time

- Must be delivered precisely otherwise overdose or side effects

- Will need numerous infusions over time

- immune system - how to alter it - transplants 

- Types of transplants

- 1. ___autograft________ = same person (leg vein to coronary artery)*least chance of rejection

- 2. ___isograft________ = identical people (Monozygotic twins)

- 3. ____allograft_______ = non-identical people (kidney)

- 4. ____xenograft_______ = different species (pig heart valve)

- Rejection or acceptance

- 1. It’s a match ____HLA______________

- 2. Drugs _________supress t-cells______________

- 3. Graft v host disease ___transplant attacks_________

- 4. Too good a match ______doesn’t recognize disease________

Genetics of development, behavior, & neurogenetics 

- development 

Sex is determined upon ______________ (female = X, male = X or Y)

- Oocyte = female germ cell (egg cell)

- Odds are against us all to be here:

- -84/100 oocytes will be fertilized

-of those that are fertilized 68 will be able to implant in the uterus

- of those that implant 42 will survive 1 week

- of those that survive 1 week, 37 will survive 6 weeks

- of those that survive 6 weeks 30 will be born

- The 70 that did not go on ½ have ________chromosome abnormalities__________________so severe development couldnnot proceed

- Within 12 hours of fertilization =

- 1) 2 different nuclei (one mom, one dad) replicate their individual DNA

- 2) 2 nuclei fuse__ = form genetic instructions for a new individual

- 3) Now called a ___zygote______ chromosome abnormalities

- Before birth a female’s million oocytes arrest in prophase I until after puberty. This means when your grandmother was pregnant with your mom the oocyte that would become you was already there.

- Stages of development 

- ___germinal_______ Stage

-Fertilization begins this stage

- Covers conception → 2 weeks