Thursday, July 19, 2012

July 19 Level 3 Immunodefense continued

Review: Note fill out chart and show professor.....

 Specific Defense:

Cell-Mediated Immunity
  1. First initiated (1-2 days)
  2. T-cell activation and cloning 
  3. Specific cytotoxic T-cells go throughout body
Humoral Immunity
  1. Delayed initiation (2-5 days)
  2. B cell activation and cloning to plasma cells
  3. Plasma cells release antibodies
  4. Antibodies go throughout body 

Humoral immunity: fig 16.14
* activation of B cells:
* MHC - 2 or B cell receptors ( = antibody molecule) in membrane, binds to antigen)

T- dependent: most common
*APC enters lymph node:
   *stimulates Th0 to create to Th2
   *Th2 activates virgin B cells to clone (bind to MHC 2 and B cell)
Fig 16.18

T-independent (rare)
   * B cell receptors bind directly to large, repeating antigens (fig 16.16)






 




* Cloned B cells  differentiate into: 

-majority: plasma cells- producers of antibodies (cause swollen lymph nodes)
     - show up 5 days into infection
     - up to 2000 molecules per second!

- minority: B memory cells (Bm)
                 - dormant plasma cells

*************draw on diagram****






TH0 converts to TH2..........activation happens LATER then T helper 1
        ....... they activate B cell... they clone, most become plasma cells, some are B memory, all stay in lymph nodes, primary job is to secrete antibodies and then the antibodies leave the lymph node........which is significantly later then the T c cells.... then ??? will add more later.......


When the threat is over: 

* Antibodies last for 1-7 weeks: are broken down and recycled.

* Plasma cells die (several days)

* Bm cells remain in the lymph node forever (?)

* second exposure:
     - Primary response as normal. PLUS
     - Bm respond to same antigen quicker (without APC)
           - convert to plasma cells: secrete antibodies in 1-2 days

***** add memory cells to diagram************

while in lymph node: Bm converts into Plasma cell when it encounters pathogen (or antigen from MHC from APC, just have to have antigen touch Bm cell)....plasma cell secrete antibodies...leave lymph node and carries out same five killing activities we are about to talk about and the back up normal process will still happen......

B cells and T cells live in the same lymph nodes....

*** you should be able to fill out everything on chart except for five actions*** note to self: fill out and email professor for corrections after class***

Antibody Structure

y shaped based molecule: protein
* globulin group of proteins, known as gamma globulins or immunoglobulins (Ig)

if you are exposed to Hepatitis A, you need to get a gamma globulin shot (its not a vaccine but harvested from someone's blood) to avoid liver damage....

globulin means folded proteins...

layman: antibody
doctor: gamma globulin
scientist: immunoglobulin
** same thing** different names

* all variations/ combinations of monomer


* Monomer is "Y" shaped protein: two long amino acid chains and two short amino acid chains

two active sites per monomers...bottom have nothing to do with antigen, just the two top parts bind to the antigen....

*tips of Y (Fab) portion = Fraction which is Antigen- Binding (fig 16.5)
          * variable
       * bond lock and key with specific antigen
*Base of Y (Fc) (never changes, constant)
       - Fraction which is crystalizable or constant



http://www.beltina.org/pics/immunoglobulins.jpg






Antibody Types (table 16. 1)
* IgG: monomer; found in blood, tissues, and fetus: highest percentage in circulation (80%)


*IgM: pentamer; found in blood only (5-10%)


*IgA: functions as dimer; found in blood, tissues, and SECRETIONS: (10-15%) (monomer in plasma cells travel into blood into capillaries and in the glands they are put together into two (dimers) and secreted out: tears, saliva, mucus, vagina, intestines, small in sweat (not as much), mother's milk up until age 2... think about what breastfeeding does: deliver large amount of antibodies to baby when they can not produce it to themselves....clostrum: high fat and high antibodies)

************break*********

*IgE: monomer; found in blood and tissues*: (<1%) involved in allergic reactions

(talk about allergic reaction monday, bind to own cells... not significant response in immunoresponse in developed nations; asterisk * present but not that helpful and concentration will be different by B cell concentration from parents: if neither parents are allergic then you will be less likely to be allergic)

*IgD: monomer; B cell surfaces (receptor) (<0.5%) 

five antibody types, concentration and location in the Bocy: IgG, IgM, and secretion: IgA.....

First versus Subsequent Exposure (fig. 16.19)
*first exposure:
    -virgin B cells: lag. then IgM first, followed by IgG

*Subsequent exposure:
   - LOTS of memory B cells release IgG (large amounts) and IgM - both earlier
   - A few virgin B cells: lag, then IgM first and later IgG





Antibodies' actions: 

  1. Agglutination - clumping (fig 16.6d): 
  • Fab bind to different antigen-bearing cells, causing clumping of cells
  • Helps fight: 
    • flagellar antigens of bacteria (paralyze)
    • bacteria in general (big enough to attract lots of phagocytes)



2. Opsonization (fig. 16.6b)
  • Fc end binds to phagocyte
  • Fab ends bind to invaders' antigens
  • Helps fight




3. Natural Killer activation (fig. 16.6 c)
* Fab binds to invaders' antigens
*Fc binds to NK cell surface
*directs abnormal cell killing process
*works best against: Eukaryotic abnormal cells (yeast, worms, cancer cells, etc)


4. Complement activation: 
*Fab on cell surface antigen (fig 15.8, 15.9, 15.10)
*Fc ends bind to loose complement: stimulates chain reaction of bindings
*causes: opsomization, inflammation, MAC 
* Use to fight cellular pathogens: bacteria, infected self cells, yeast, protozoa and worms

**** try draw picture: bacterial cell with antigen on surface = triangle....

antibody binds by the Fab end binds, Fc end points up... complement proteins: example C1... C5... C7.....three things can occur:

 1. opsomization..... the cell now has complement protiens attached: phagocyte can eat it better, make surface stickier...

2. inflammation.... cell with antibody on it... complement protiens affect mast cells and basophiles in the area and release histamine

3. MAC = membrane attack complex.... some stick cell surface and make pore....and that pore allows cell to leak out fluid and die....mainly made of complement 9***********

***remember about inflammation/ level 2: phagocytes and NKC increase by increase blood flow******

virus, endotoxin, exotoxins::: how does the body fight things smaller then bacteria? 


Last process......

5. Neutralization Fig 16.6a

* Antigen still present, but no longer dangerous:
       - Fab grabs, antigens, prevents binding
      - Use to fight: toxins, enzymes, viruses

*** draw enzyme, active site... antibodies bind to active site so now the substrate is unable to bind because antibody occupies active site... with viruses: capsid with capsomeres... host cell.***




**add five process to first diagram... Agg, 

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