Chp.17

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!