Transcript
Chapter 17: Adaptive Immunity
• Adaptive = acquired = specific immunity– Defense against a particular microbe– Response has a memory which is enhanced
upon re-exposure– Immunity based on Ab production– Begins at birth
Adaptive Immunity: Antigens
• Antigen (Ag) stands for Antibody Generator = any chemical substance capable of stimulating the immune system and provoking an immune response– Recognized as non self by the immune
system– Are large macromolecules and are easily
phagocytized by macrophages– Most common Ags – proteins,
polysaccharides, rare – nucleic acids, lipids
Adaptive Immunity: Antigens
• Antigen – The immune system recognizes a small part of the
Ag called an antigenic determinate or epitope which is the part that binds with a specific Ab or T-cell receptor
– May be part of microbe, pollen, egg whites , blood cell, transplanted tissue or organs
– Haptens are Ags that are too small to stimulate Ab formation unless they are attached to a larger carrier molecule – now can stimulate Ab formation pg 505
Antibodies, Antigens, “Epitopes”
Adaptive Immunity: Antibodies
• Antibody (Ab) or immunoglobulins = a protein produced by lymphocytes in response to the presence of an antigen and is capable of combining specifically with the antigen– Each Antibody has 2 identical antigen binding
sites
Adaptive Immunity: Ab structure
• Each Ab consists of 4 polypeptide chains– 2 identical heavy chains and 2 identical light
chains joined together by disulfide (S-S) linkages to form a Y shaped structure
• Each chain (light or heavy) consists of:– Constant region wh/ is identical among
different types of Abs– Variable region wh/ is uniquely shaped to
combine w/ a specific Ag – binds to epitopes on the antigen
Adaptive Immunity: Ab type
• 5 types of Ab (Ig = immunoglobulin) pg.507 for pix and table
1. IgM – largest Ab (M stands for macromolecule), 5 – 10% of Ab in serum (fluid portion of blood), pentimer
a. First to appear after B cell stimulation, they decline rapidly
b. Principal component of primary Ab response1) If found in serum indicates recent infection
Adaptive Immunity: Ab type
c. It is one of the Abs bound to the B lymphocyte as a cell surface receptor
d. IgM generally stays in the blood vessels and does not enter surrounding tissue because of its size
e. Predominant Ab in ABO blood group Ag rxs, agglutination and complement rxs
Adaptive Immunity: Ab type
2. IgG = gamma globulin – monomer
a. 80 % of total Ab content in normal serum
b. appears 24 - 48 hours after antigenic stimulation
c. booster vaccines raise the level of this Ab
d. provides long term resistance to disease as a product of a memory B cell
e. crosses blood vessel walls to enter tissue fluids
Adaptive Immunity: Ab type
f. maternal IgG crosses the placenta – passive immunity to fetus and forapproximately 6 months after birthg. protects against circulating bacteria and
viruses, neutralizes toxins, triggers complement system, binds to Ag to enhance phagocytic action
Adaptive Immunity: Ab type
3. IgA is 10–15% of total Ab in normal seruma. 2 types – prevent attachment of pathogens to mucosal surfaces – this is important because mucosal surfaces are portals of entry
1) serum IgA – monomer2) secretory IgA
a) 2 monomers (dimer) joined by a J chain
b) predominant in GI fluids, nasal secretions, saliva, tears,
colostrum - 1st milk (passive immunity)
Adaptive Immunity: Ab type
4. IgE – 0.002% total serum Abs, monomera. plays a major role in allergic rxs by sensitizing cells to certain Ags by binding the Fc stem to basophils and mast cells which release chemical mediators such as histamineb. these inflammatory rxs attract IgG and
phagocytic cellsc. binds to parasitic worms (Helminths)
Adaptive Immunity: Ab type
5. IgD – 0.2 % total serum Ab, monomer
a. it is a cell surface receptor on the B lymphocytes together with IgM
Imm
unog
lobu
lin C
lass
es Longest lived Ab & present in colostrum.
Associated with allergies.
Most abundant class (except in serum).
Adaptive Immunity: Lymphatic System
1. The lymphatic system is anatomically intertwined with the cardiovascular system – both systems circulate body fluids
2. Cardiovascular system circulates blood w/in the BVs
a. Certain components of the blood move into tissue spaces and now the fluid is called interstitial fluid
b. Interstitial fluid is picked up by the lymph system and is now called lymph
c. Lymph is drained back into the blood
Adaptive Immunity: Lymphatic System
3. Lymph nodes contribute to both innate and adaptive immunity and are situated along the path of lymphatic vesselsa. Swollen lymph nodes in the armpits, groin, or neck indicate an active immune response to infectionb. these nodes contain both B cell and T cell lymphocytes and are the site of antibody productionc. they also contain phagocytes which destroy
microbes and stimulate the adaptive immunity response
Prim
ary
Lym
phoi
d O
rgan
s The primary lymphoid organs,
are bone marrow and the thymus, where lymphocytes
originate and/or mature
(depending on type).
Sec
onda
ry L
ymph
oid
Org
ans
The secondary lymphoid organs, such as Lymph Nodes, are the
sites of interaction among immune
system cells including with
antigens presented by
Antigen Presenting Cells.
Adaptive Immunity: Lymphocytes
Lymphocytes = small WBCs with a large
nucleus that develop from stem cells in the fetal liver or in the red bone marrow
of adults
1. B lymphocytes (B cells) – mature in the bone marrow and then migrate to lymphoid tissue – lymph nodes, tonsils, adenoids
a. responsible for Ab mediated immunity that reacts with microbes, Ags, and non self cells
Adaptive Immunity: Lymphocytes
2. T lymphocytes (T cells) – mature in the thymus gland then migrate to lymphoid tissue via the blood and lympha. the thymus is a flat, bi-lobed organ that lies behind the sternum and above the heartb. have surface cell receptors called T cell receptorsc. responsible for cell mediated immunity that reacts w/ eukaryotic pathogens, antigen marked cells (virus infected cells, transplant cells)d. recognize and destroy non self cells (esp. Ca)
Adaptive Immunity
The specific immune system is divided into two categories: humoral and cell mediated
1. Humoral (Ab mediated) immunity – B cell
a. most Ags are large protein molecules associated w/ microbes, tumor cells, damaged cells, pollens, dust, food
b. they trigger the production of Abs specific for that Ag
Adaptive Immunity
2. Cell mediated immunity (CMI), T-cella. Ags trigger the production of T lymphocytes
directed against that Agb. T lymphocytes have a role in both humoral and cell mediated immunityc. there are several T cell types and each has a
specific role and is identifiable by the cluster of differentiation (CD) molecules acquired in the thymus during the T cell maturation process.
T cells and Cell Mediated Immunity
1. Directed against intracellular Ags not exposed to circulating Abs (viruses, some bacteria, protozoans)
2. Before an inactive T cell can attack Ags, the T cell must become sensitized to recognize the Ag
3. Sensitization involves macrophages wh/ phagocytize and present the partially digested Ag on the macrophage surface to the T cells
a. macrophages secrete interleukin–1 and interferons wh/ stimulate T cell growth and divisionb. most of the time T cells are inactive
T cells and Cell Mediated Immunity
4. Once T cells are sensitized they increase in size and # to produce a clone = a group of identical cells which then differentiate into various cell types
Each T lymphocyte has a specific role Id by the cluster of differentiation
Cell Type CD (receptors) Fx T helper cell CD4 Activates B cell
to produce Abs and activates cytotoxic T cells
Cytotoxic T-cell – killer cell that works against cells w/ foreign intracellular Ags
CD8 Goes to invasions site and secretes perforin – causes cell lysis
T suppressor cell (regulatory)
CD8 stops immune rx w/otherTcells
B cells and Ab mediated Immunity (humoral immunity)
1. Humoral immunity is mediated by Absa. Abs are products of B cells in response to
Agsb. the binding of Abs to Ags facilitate the
destruction of the Ag bearing microbe
2. Ab secreting cells are called plasma cells3. T helper cells are required to help B cells
produce Abs by releasing cytokines that causes clonal expansions of the B cells
B cells and Ab mediated Immunity (humoral immunity)
4. Some B cells develop into long lived memory B cells which frequently provide life-long immunity to a microbe or vaccine-Ag encountered earlier in life
a. they respond more rapidly and forcefully to a future encounter with the Ag
5. B cells don’t leave the lymphoid tissue
a. a macrophage processes and presents an Ag to the B cell in the lymphoid tissue
B cells and Ab mediated Immunity (humoral immunity)
6. B cells are specific for the Ag they are sensitized to
a. some of them enlarge, divide and develop into plasma cells which secrete Abs into your circulation
Clo
nal S
elec
tion
The
ory Applies to
both B and T cells.
B cells are associated with Ab (Ig) production.
T cells are associated with cell-mediated immunity.
Takes place in 2° lyphoid organs.
Ant
igen
Pre
sent
atio
n by
B C
ell
Results in production of
Abs against T-Dependent
Antigens (no T-helper binding, then no Ab).
Note binding by only one-half of the “Y”.
Antigen-Antibody Interaction (forms complex)
1. Neutralization = Abs that alter toxin molecules and inactivate viruses by blocking their attachment to host cellsa. neutralizing of toxins increase their size making them more susceptible to phagocytosis and they are less likely to be able to diffuse through the cell
2. Opsonization = Abs coat bacteria preventing them form attaching to cells and enhancing phagocytosis
Antigen-Antibody Interaction
3. Agglutination = Abs react with Ag on surface of bacteria causing them to clump together making them easier to phagocytize
a. IgM is the main Ab because it has more binding sites (lg. molecule)
4. Precipitins = Ab that react w/ dissolved Ag and convert them to solid precipitates wh/ inactivates them and makes them more easily phagocytized
Antigen-Antibody Interaction
5. Activation of complement system – triggered by IgG or IgM Abs
a. Abs attach the complement to the bacteria resulting in cell lysis,
also causes inflammation
Imm
unog
lobu
lin A
ctio
ns
These are now available
for phago-cytosis.
This is a host cell, covered
with foreign
antigens and
therefore with
antibody.
Pilus as well as
flagellum binding.
Recall that C3b can bind directly to cell.
Prevents binding to host tissues.
Pos
& N
eg T
Cel
l Sel
ectio
n Both T cells and B cells are derived from hematopoietic stem cells found in bone marrow.
T cells migrate to the thymus for further development (and hence the “T” in T cells, though the “B” in B cells stands for Bursa).
T cells, during their development in the thymus, are subject to two round of selection.
The first round is Positive Selection where only T cells that can bind MHC are retained.
The second round is Negative Selection where T cells that recognize self antigens in association with MHC are deleted.
The resulting T cells, both helper and cytotoxic, consequently can bind MHC (II or I, respectively), but only if complexed with non-self antigens.
Ant
igen
Rec
ogni
tion
by T
Cel
ls
Recognition by Cytotoxic T cell (CD8
receptor)
Recognition by Helper T cell (CD4 receptor)
Cyt
otox
ic C
onse
quen
ces
Apoptosis is cellular
suicide which here is
induced by the CTL.
I.e., they tell their “friends”
(other cytotoxic T cells).
Stimulating T-Helper Cells
Macrophages and Dendritic cells present antigens to, and thereby stimulate, T-helper cells.
Adaptive ImmunityGood summary of Adaptive Immunity!
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