Download Packet 14- Acquired Immunity

Lecture 14: Acquired Immunity
Silverthorn Chapter 24
Acquired immunity-- Antigen specific response mediated primarily by lymphocytes…
LYMPHOCYTE PLAYERS
1. T Cells
A. CELL-MEDIATED response
B. Born in the bone marrow
C. Mature in the thymus
D. Educated in thymus
E. Each has a special T-cell receptor
2. B Cells
A. HUMORAL response
B. Born in the bone marrow
C. Mature in the bone marrow
D. Probably educated in bone marrow
E. Each has a special antibody
Antibodies
Antibodies ATTACH TO foreign substances (antigens)
1. Structure (fig 24-12)
A. 1x108 different antibodies possible (Immunology, Goldsby)
B. Variable regions are built from separate genetic sections that can be combined in a huge # of ways…VISUAL…IP 10:
http://portal.mypearson.com/cclogin.jsp (email)
2. Antibody Functions:
A. Increase “visibility” of antigen (make it easier for immune cells to find bad guys)
B. Coat bacteria and promote phagocytosis by other immune cells
C. Causes antigens to CLUMP together, making phagocytosis easier!
D. Can inactivate bacterial toxins…
E. Enhance/INITIATE inflammatory response
F. Can initiate complement!
MHC
MHC (Major Histocompatability Complex) PRESENTS foreign substances (antigens)…(and in the case of transplants, can BE foreign
substances!)
1. MHC-I proteins found on the cell surface are the key players in REJECTION of transplants.
A. Found on the surface of all nucleated cells.
B. MHC-1 platforms are used by cells to display SELF…when it displays NON-SELF, it triggers a signal to DESTROY the
cell. Watch video! http://student.ccbcmd.edu/courses/bio141/lecguide/unit5/intro/mhc/mhcone_dend.html
i. How foreign stuff is displayed on MHC-I
a. Phagocytosis of foreign invader
b. Invader is digested…
c. SOME proteins from invader leak into the cytoplasm
d. These proteins are digested by proteosomes…
e. Invader protein fragments are taken to the ER where they are attached to MHC-I proteins that were built by DNA!
f. After processing in ER and Golgi apparatus, it is “exocytosed” onto cell surface…
C. Transplant tissue has the MHC-I proteins from someone else…
i. Great genetic diversity in MHC-I proteins!
ii. The body immediately id’s the MHC-I protein as NON-SELF and mounts an immune response!
iii. Try to find as close a MATCH as possible…takes time.
iv. SFO study…1000 subjects
a. Over 50% had unique MHC-I proteins!
b. 111more had only ONE shared allele with another!
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c. Most common combo was found in only 11 folks. Source: http://users.rcn.com/jkimball.ma.ultranet/
BiologyPages/T/Transplants.html
2. MHC-2 (Major Histocompatability Complex class II) molecular platform, for DISPLAY.
A. Only a few cells have MHC-2 platforms…(macrophages, B lymphocytes, and dendritic cells)…
B. All cells with MHC-2 platforms are “antigen presenters”.
C. Found only on antigen presenting cells… used to activate acquired immunity.
D. MHC-2 used by antigen presenting cells to SHOW antigens to lymphocytes and activate them.
E. Only a few cells have MHC-2 platforms…(macrophages, B lymphocytes, and dendritic cells)…
F. All cells with MHC-2 platforms are “antigen presenters”.
Lymphocyte Selection/Maturation
This important process takes place in thymus and bone marrow:
1. Shuffle genes to make unique receptor (antibody OR T-cell receptor=TCR)
2. POSITIVE SELECTION: Each one must have viable receptors, evidenced by the ability to bind with the MHC platform on
dendritic cells…(immunocompentant)
A. This is because ALL must bind to MHC before they can be activated!
3. NEGATIVE SELECTION: Each one must NOT bind with self molecules found on the MHC II platform…(self-tolerant)
A. If they bind to SELF molecules, then they are TOO sensitive, and would attack self!
B. This is distinguished by the STRENGTH of binding…(stronger bond means T cell is bonded to both MHC-II AND the
SELF proteins on the MHC-II platform…)
4. 19/20 T cells do NOT pass the training, and commit suicide (apoptosis)
5. Cells that pass the test become NAÏVE (B and T) LYMPHOCYTES, and enter circulation, looking for the SPECIFIC antigen
that matches their antibody (or TCR) to stimulate activation…
A. Naïve T cells can be of different subtypes:
i. CD4 differentiate into helper T’s
ii. CD8 differentiate into killer T’s
B. Naïve B cells all become either plasma or memory cells upon activation
6. Once they graduate from school, they go out looking for “their” antigen...activation cannot happen until they find it. Where
might they find it?
A. In the blood…
B. In the lymph nodes…
HUMORAL RESPONSE = ANTIBODY PRODUCTION
1.
2.
3.
4.
5.
Occurs when the invader is OUTSIDE the cell…
Main player: B lymphocyte
Involves the mad production of antibodies
Relies on ANTIGEN PRESENTING CELLS to activate
Basic steps in the Humoral Immune Response:
A. Naïve B cell encounters ANTIGEN that matches the antibodies on its surface
B. Naïve B cell ingests antigen…digests it.
C. Naïve B cell places antigen parts onto MHC-2 (Major Histocompatability Complex class II) molecular platform, for
DISPLAY.
D. Now antigen presenting B cell must be activated…
i. Helper T cells that can bind to the antigen do the deed
ii. B cells increase the chances of meeting their matching Helper T cell by circulating through the lymph nodes
iii. The Helper T binds to antigens on MHC-2 platform, and ACTIVATES B cell
E. Activated B cell undergoes CLONAL EXPANSION, dividing into:
i. PLASMA CELLS (produce MAD antibodies 2000/sec!)
ii. Memory cells= B lymphocytes which are ready to rock and roll, and wait for another attack…(VACCINES)
a. Upon future attack by the same antigen, the memory cells activate the acquired response MUCH FASTER
b. This is the theory behind the use of vaccines…
CELL MEDIATED RESPONSE = DIRECT ATTACK
1. Takes place within individual infected cells…
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2.
3.
4.
5.
Main player: T lymphocytes
Involves the destruction of infected SELF cells
Relies on the fact that SELF cells constantly display intracellular proteins on their MHC-1 platforms
Basic steps in the Cell Mediated Immune Response:
A. Naïve T cell encounters a dendritic cell presenting an antigen (on MHC-2 platforms) that matches the T cell’s antigen
receptors.
B. Naïve T cell is ACTIVATED after binding with dendritic cell’s MHC-2
C. If naïve cell was CD8:
i. Cytotoxic T cells (Killer T cells)
a. Begins scanning all “self” cells
b. Recognize the body parts of an ingested bad guy displayed on MHC-1
c. Initiates apoptosis in cell by producing granzymes (which activate an enzyme cascade that causes the cell to
commit suicide) and perforin (which pokes a hole in the cell).
D. If naïve cell was CD4:
i. Helper T cells
a. Secrete cytokines to enhance the immune response, when they encounter an immune cell presenting stuff on their
MHC-I.
b. Activate B cells by binding to the MHC-II on the B cells
c. Can play a role in activating cytotoxic T cells (because usually dendritic cells are powerful enough by themselves
to activate helper T’s, but they need help to activate the killers…)
E. Memory T cells
i. Upon future exposure, divide into more killer and helper cells
Blood Types
RBC do not have MHC-I!
Instead, have AB antigens (and Rh…)
1. Instead, have AB antigens (and Rh…)
A. A antigens = Type A blood…but there are B antibodies in the plasma!
B. B antigens = Type B blood…but there are A antibodies in the plasma!
C. AB antigens = Type AB blood…and NO antibodies in the plasma!
D. NO antigens = Type O blood…but there are A and B antibodies in the plasma!
2. What about Rh factor?
A. Rh antigens = + blood (and there are NO Rh antibodies in the plasma)
i. Rh + blood = Rh antigens on RBC
ii. Rh – blood = NO Rh antigens on RBC…and usually NO Rh antibodies either, unless a person is somehow EXPOSED
to the Rh antigen…
B. There are many Rh antigens…but one form (Rh-D) is problematic during pregnancy
i. IF a Rh- mom has Rh antibodies, AND carries a Rh+ child, the antibodies can CROSS THE PLACENTA and attack the
child (Erythroblastosis fetalis)
ii. How does mom get Rh antibodies?
a. Exposure to Rh+ previous child’s Rh+ blood!
iii. Why do Rh antibodies harm a fetus?
a. Rh antibodies are type G (IgG). These small antibodies CAN cross the placenta!
iv. Why don’t AB antibodies harm a child?
a. AB antibodies are type M (IgM). They are bigger, and CANNOT cross the placenta. (http://users.rcn.com/
jkimball.ma.ultranet/BiologyPages/B/BloodGroups.html)
3. So who can donate to whom?
4. And keep in mind, you donate PARTS of your blood at any one time! You don’t give someone WHOLE BLOOD, unless they
have EXACTLY the same blood type as you. This is because:
A. Plasma (has antibodies)
B. RBC (has antigens)
C. Platelets (not a problem! Only last 5 days though…)
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External Brain 14: Acquired Immunity
Study Guide Questions
5. Compare and contrast innate and acquired immunity.
6. Compare and contrast humoral and cell mediated immune responses.
7. Clearly contrast B and T cells (of all types).
8. Describe the process by which T cells are selected during “education” in the thymus.
9. Contrast between positive and negative selection of lymphocytes in the thymus.
10.What is an antibody? How is antibody diversity obtained?
11. What is a membrane histocompatibility complex? Contrast MHC I and MHC II.
12.Be able to clearly describe the basic steps of the humoral immune response.
13.Understand the implications of MHC in organ transplants…
14.Be able to clearly describe the basic steps of the cell mediated immune response.
15.Understand the significance of blood types.
16.Given information about tests run on a blood sample, be able to determine the blood type.
17.Know who can donate blood to whom. Know what blood “parts” can be donated to which people.
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