C2006/F2402 '05 -- Outline for Lecture 24

(c) 2005 Deborah Mowshowitz . Last updated 04/25/2005 02:23 PM

Handouts: You need 23A & B  from last time & 24.

I. Kidney Function, cont. (See notes  & handouts of Lecture 23)

See problems 12-9 & 12-15.

II. Regulation of kidney function

    A. Regulation of release of ADH from post. pituitary (See Purves 51.14 [51.15])

1. Sensors -- 2 types, since regulating two different variables

a. Stretch receptors in arteries (sensors for blood volume) -- this comes into play only if large volume change

b. Osmo-receptors in HT (sensors for solute levels in blood) -- this is the primary sensor

2. Response: ADH release up if osmolarity of blood up or stretch receptors (way) down

3. Thirst: ADH release & thirst both triggered by same receptors.

4. Feedback Loop: ADH release (& thirst up) --> water intake up, water loss down in kidney, & constriction of arterioles in extremities --> restore blood volume, reduce osmolarity (and restore blood pressure)

4. Speed: This is fast -- no prot. synthesis required

    B. Autoregulation by kidney -- flow through kidney (GFR) must be adequate to keep kidneys functioning properly. Flow is adjusted through local effects and overall control of blood pressure.

1. GFR Adjustments -- dilate/constrict afferent arteriole

Low BP (low flow through kidney)  --> dilation of afferent arteriole (to glomerulus) --> increases flow through kidney ----> increase in GFR (glomerular filtration rate). High BP has opposite effect.

See problem 12-4.

2. Renin/Angiotensin/Aldosterone System

a. Low BP or GFR in Kidney --> kidney secretes renin

b. Renin catalyzes rate limiting state in conversion of angiotensin precursor (in blood) --> angiotensin II (active)

c. Effects of Angiotensin II

(1). Acts on adrenal cortex --> aldosterone --> Na+ reabsorbed in kidney and elsewhere

(2). Acts directly to raise BP -- is vasoconstrictor. (Also stimulates thirst & release of ADH)

(3). Note that effects of aldosterone are slower than others as they involve steroid --> protein synthesis

See problem 12-8.  By now you should be able to do all of problem set 12 except 12-5. (For 12-5 & 12-14, consider the max. osmolarity of urine. It's 1200 mOsm -- less than sea water.)

III. Regulation of Blood Pressure.

Multiple sensors, effectors, and feedback loops are involved in control of both contents of blood and pressure/volume. Many have already been discussed. Major circuit (in addition to those already discussed ) -- uses PS/S system to adjust heart rate & constriction/dilation of arterioles in response to sensors (primarily) for arterial BP. IC = cardiovascular control center in medulla (brain stem);  integrates information from arterial sensors and from other parts of brain. Additional details are in the texts and/or notes of 2004.

IV. Specific (= Acquired) Immune Response -- Major cells and parts Features??

    A. Intro. What are major proteins of the specific immune system? 

1. Antibodies. Already discussed antibodies as chemical reagents. What are antibodies really needed for physiologically? To combat infection and maybe to prevent cancer.  (Details on antibody structure will be covered later.)

2. What other proteins are involved? 

a. Immune system uses 3 types of proteins that have a common evolutionary origin and certain features in common. These are antibodies, TCR and MHC. Roles & structures will be explained below.  For pictures see Purves 18.10 (19.11) for antibodies & Purves 18.13 (19.14) for TCR.

b. All 3 types of proteins have a "constant" part and a "variable part." Constant part determines where protein is (cell surface? What kind of cell? etc.) and its general function. Variable part determines what antigen/epitope will bind to the protein.

    B. Specific Immune system has 2 branches

1. Humoral response -- binding and destruction of antigen done by proteins in "humors" = antibodies in blood and secretions (for ex. milk, tears).

2. Cellular or cell-mediated response -- binding and destruction of antigen done by whole cells bearing a TCR. (TCR on cell surface, not soluble antibody, binds to antigen and triggers a response.)

    C. What are the Important Features to explain?

1. Specificity & Diversity -- each Ab or TCR is directed against one epitope or antigenic determinant (= piece of antigen -- see Purves 18.6 (19.6), and there are many, many different antigens. How can you make so many different Ab's or TCR's, each specific for a particular antigen or piece of it?

2. Memory -- secondary response is faster, larger, better than primary response. In secondary response, make more Ab, Ab is more effective (binds better to Ag because of slight changes in amino acid sequence of Ab), and Ab response lasts longer. (Purves 18.8 (19.8)) How is this done?

3. Tolerance -- can distinguish self/nonself or normal/abnormal -- make Ab only to foreign/abnormal stuff (except in disease states). TCR only directed against infected cells, not normal ones. How does this work?

4. Response is adaptable -- response depends on amount and type of antigen. How do you "know" which antibody (or TCR) to make in response to a particular antigen?

5. Where does MHC fit in?

    D. What Cells are involved?  White blood cells (leukocytes) -- contain no hemoglobin. WBC divided into two main types

1. Phagocytes -- macrophages, dendritic cells, etc. ( See Purves  18.2 (19.2)). Involved in processing antigens as will be explained. 

2. Lymphocytes. Found in lymph nodes and elsewhere. Do actual production of antibodies and/or execution of cellular immune response.

a. Divided into B and T cells.

(1). Both B & T cells come from same line of stem cells in bone marrow.

(2). B cells mature in bone marrow; T cells in thymus

(3). B cells produce & secrete antibodies. Major players in humoral response.

b. There are 2 types of T cells

(1). Helper T's (TH) -- These are required for function of both TC's and TH's as will be explained.

(2). Cytotoxic T's (CTL or TC ) -- Responsible for destructive part of cellular immune response.

(3). T cells have TCR's on their surface -- TCR's are not secreted or released from cell surface.

    E. Major features of 2 branches of specific immune system -- see table on handout 23B & below:

1. Action of B cells to combat infection:

B cells --> release antibody --> Ab (antibody) binds Ag (antigen -- usually on surface of microbe) --> trigger destruction of microbes (microbes are engulfed by phagocytes or lysed) often with the help of complement . (See Purves 18.11 (19.12))  Allergies are a side effect of this system.

2. Action of  (cytotoxic) T cells

T cells --> TCR on surface; TCR's bind to Ag on surface of virus infected eukaryotic cell --> destroy target cell by triggering apoptosis. Cytotoxic T cells can trigger apoptosis by juxtacrine signaling; alternatively they can use proteins called perforins to make holes in their targets. Then other proteins enter the holes and trigger apoptosis.  Note complement is similar to perforins but works on prokaryotic invaders; perforins work on rogue eukaryotic cells. (See Purves 18.14 (19.15)) This is why grafts fail; foreign cells of graft look like infected (defective?) cells and are destroyed. (*See section on MHC below -- foreign MHC looks like host MHC plus antigen.)

3. Role of helper T cells -- needed for function of both B and cytotoxic T cells; details below.

    E. Major features of 2 branches of specific immune system

Immune Response Type



Cell involved in Response

B cells

T cells

Protein Made by Cell

Antibody (Ab)

T cell receptor (TCR)*

Location of Protein

In serum, tears, etc. (released by B cell) or on cell surface.

Always on cell surface (attached to T cell)

Protein Recognizes

Free Antigens (Ag) or Ag attached to microbial surfaces

Antigens attached to surfaces of eukaryotic cells

Aide in killing targets



Usual targets (for killing)

Microbes, soluble proteins

Infected or cancerous cells (for Tc or CTL)

Side Affect


Graft rejection

*T cell receptor is NOT the receptor for T cells -- it is the protein on the T cells that is the receptor for an antigen. It is the receptor of T cells, not the receptor for T cells. (By analogy, antibody attached to B cells is sometimes called "the B cell receptor" or BCR instead of antibody. BCR and TCR both act as receptors for antigen -- they allow antigen to trigger the immune response, as explained below. So they are also referred to as B or T cell receptors for antigen.)

** Complement = a series of proteins found in blood. Activation of complement involves a cascade of activations similar to that involved in blood clotting. Complement binds to antibody-antigen complexes attached to microbes and triggers phagocytosis or lysis of the microbe bearing the complex.

V. Clonal Selection -- How do you account for the "important features" listed above?

    A. B cells (See Purves fig. 18.7 (19.7))

1. Each cell differentiates --> produces a single type of Ab on surface ("virgin" or "naive" B). Each cell rearranges its DNA during differentiation, so each cell has a unique set of Ab coding genes and makes a unique antibody -- that is, with a unique set of "grabbers."

Note: As B cells mature and specialize, changes in the antibody they make may occur because of alternative splicing and/or additional rearrangements of the DNA. Structure & rearrangement of Ab coding genes and antibodies will be discussed in detail next time.

2. Ab on surface of cell acts as a "trap". Surface antibody (also called BCR or B cell antigen receptor) acts as trap/receptor for Ag.

3. Activation or destruction of B cell is triggered by binding of Ag to surface Ab (BCR)

a. Destruction. If Ag is perceived as "self" --> cell destroyed or suppressed (--> tolerance).

b. Activation. If Ag is perceived as foreign --> cell divides --> clonal expansion, further differentiation into

(1). Effector cells -- short lived but secrete lots of Ab --> destroy or inactivate targets; class of Ab determines fine points. (In earlier lecture we explained how alternative splicing can allow cell to switch from making surface bound Ab to secreted Ab.)

(2). Memory cells -- long lived and more specialized to make Ab; wait for next time (responsible for memory). 

c. Whether antigen is perceived as "self" or "foreign" depends on time of exposure (embryonic vs adult) and additional factors. (This turns out to be very complicated, so we are ignoring the "additional factors.")

4. What's the point?

a. Clonal Selection: Each cell makes a little Ab before any Ag present. Each cell makes a different Ab. This antibody stays on the cell surface and acts as BCR = trap for antigen. Ag acts as a trigger -- binding of Ag to "trap" stimulates only those cells that happen to make Ab that binds to that particular trigger. (This is the selection part that accounts for specificity, diversity, and adaptability.)

b. Clonal expansion: The cells triggered by binding of Ag grow and divide --> (more) effector cells  & memory cells. Both types of cells make only the antibody that binds to the trigger Ag. (This is the clonal expansion part that accounts for memory & tolerance -- memory when Ag triggers multiplication, and tolerance when Ag triggers destruction or suppression).

5. Why do you need helper T cells? For most antigens, helper T must bind to B cell-Ag complex in order to activate B cell (step 3b above; details next time).

Try Problem 13-4.

    B. T cells -- similar process as with B cells -- DNA rearrangement occurs so one type of protein with unique binding site made per cell -- but there are differences/complications to be explained next time.