Microbiology - Las Positas Collegelpc1.clpccd.cc.ca.us/lpc/zingg/Micro/lecture...

17Adaptive

Immunity:

Specific

Defenses

of the Host

Copyright © 2010 Pearson Education, Inc.

SLOsDifferentiate between innate and adaptive immunity, and humoral and cellular immunity.

Define antigen, epitope, and hapten.

Explain the function of antibodies and describe their structural and chemical

characteristics. Name one function for each of the five classes of antibodies.

Compare and contrast T-dependent antigens and T-independent antigens.

Differentiate between plasma cell and memory cell.

Describe clonal selection.

Describe how a human can produce different antibodies.

Describe four outcomes of an antigen-antibody reaction.

Differentiate between helper T and cytotoxic T

Define apoptosis.

Define antigen-presenting cell.

Describe the role of antibodies and natural killer cells in antibody-dependent cell-

mediated cytotoxicity.

Identify at least one function of each of the following: cytokines, interleukins, interferons.

Distinguish a primary from a secondary immune response.

Contrast the four types of adaptive immunity.


Immune System Overview

Innate immunity: An individual’s genetically predetermined resistance to certain diseases.

Adaptive immunity: Ability of the body to react to specific microbial infection.

Adaptive immunity

is antigen specific, has memory

is made up of two branches

Humoral Immunity (B cell mediated)

Cellular Immunity (T cell mediated)

collaborates with innate immunity

has ability to ignore healthy “self” molecules (tolerance)


Vocabulary

Antigen (Ag): A substance that causes the body to produce specific antibodies or sensitized T cells.

Antibody (Ab): Proteins made in response to an Ag; can combine with that Ag.

Serology: The study of reactions between antibodies and antigens.

Antiserum: A generic term for serum because it contains Ab.

Globulins: Serum proteins

Immunoglobulins (= Gamma () globulins): Serum antibodies

Complement:


Serum Proteins

Fig 17.18


Antibodies recognize and react with antigenic determinants or epitopes on an antigen

Fig 17.1

Antigens and

antigenic

Determinants

The Nature of Antigens


Haptens Fig 17.2

Definition: Small separable part of an antigen that

reacts specifically with an antibody but is incapable

of stimulating antibody production except in

combination with a carrier protein molecule


The Nature of Antibodies

Fig 17.3

Immunoglobulin Structure: 4 polypeptide chains (2 heavy and 2 light) Variable regions

Constant regions

Fig 17.3


IgG antibodies

Monomer

80% of serum antibodies

Activate complement

In blood, lymph, and intestine

Cross placenta

Enhance phagocytosis; neutralize

toxins and viruses; protects fetus

and newborn

Half-life = 23 days


IgM Antibodies

Pentamer

5-10% of serum

antibodies

Fix complement

In blood, lymph, and on

B cells

Agglutinates microbes;

first Ab produced in

response to infection

Half-life = 5 days


IgA Antibodies

Dimer

10-15% of serum

antibodies

In secretions

Mucosal protection

Half-life = 6 days


IgE Antibodies

Monomer

0.002% of serum

antibodies

On mast cells,

basophils, and in blood

Allergic reactions; lysis

of parasitic worms

Half-life = 2 days

Monomer

0.2% of serum

antibodies

In blood, lymph, and on

B cells

On B cells, initiate

immune response

Half-life = 3 days

IgD Antibodies


B cells and Humoral Immunity

Effective against free antigen (toxins, bacterial surface structures, viruses in between cells)

B cell receptors (mostly IgM and IgD)

Activated B-cells go through clonal expansion leading to

1.Plasma cells (effector cell for antibody production) and

2.Memory cells

Clonal Selection

Fig 17.5

ANIMATION Humoral Immunity: Clonal Selection and Expansion

humoral_clonal.html


Response to T – dependent antigens

B cells require help of T cells for most protein antigens (T-dependent ag)

B cells internalize antigen and present it to T-helper cell in combination with MHC class IImolecules

If T cell recognizes antigen it activates B cell clonal expansion plasma cells and memory cells

Review

Fig 17.4

Antigen Presentation by B-cell

Compare to Fig. 17.4


Response to T – Independent Antigens

No T-helper cells involved

Polysaccharides (bacterial capsules) and LPS

Weak response

with no memory

cells

Young children

react poorly

Fig 17.6


Antibody Diversity

1015 different B-cell receptors

How many genes in human genome?

Mechanism of antibody diversity: somatic recombination

(during embryonic development)

Primarily through Gene rearrangement (mix and match)

Susumu Tonegawa

Nobel Prize 1987


Antigen—Antibody Binding and its Results

Affinity: Strength of bond between Ag and Ag.

Specificity: Ab recognizes a specific epitope.

Antibody function:

1. agglutinate and precipitate

2. opsonize

3. neutralize (immobilize and prevent adherence)

4. activate complement

5. Antibody-Dependent Cell-mediated Cytotoxicity(ADCC) via NK cells and eosinophils

Protective outcome disposal of antigen

(based on antigen-antibody binding)


The Results of Ag-Ab Binding

Fig 17.7


T Cells and Cellular Immunity

T cells have TCR on surface.

TCR does not recognize free antigen. Ag must be presented in association with MHC on an antigen-presenting cell (APC).

Antigens are processed by APC and positioned on the surface of the APC.

Compare to

Fig 17.10

APCs

Digest antigen

Ag fragments on APC surface with MHC-II

B cells

Dendritic Cells

Macrophages

Activated macrophages: Macrophages stimulated by ingesting Ag or by cytokines.

ANIMATION Cell-Mediated Immunity: Helper T Cells

cell_mediated_helper.html


Classes of T cells

Helper T Cells (CD4, TH)

are activated by antigen presented by MHC class II. After binding to Ag presented by APC, CD4 cells secrete cytokines activating other T cells and B cells

TH1 cells activate cells involved in cellular immunity

TH2 stimulate production of eosinophils, IgM, and IgE ( associated with allergic reactions and parasitic infections)

Cytotoxic T cells (CD8, TC, CTL)

activated by endogenous antigens and MHC class I

When activated transform into CTLs and memory cells

CTLs lyse target cell or induce apoptosis

Antigen Recognition by

T Cells

MHC Class I on all

nucleated cells

MHC Class II on

surface of APCs

(Macrophages, B-

cells, dendritic

cells)


Mechanism of

Action of CTL

Perforin molecules

create protein channels

in target cell membrane

Granzymes enter and trigger

apoptosis in target cell

Similar but different

from MAC !!

Destruction of cells

displaying MHC-I-Ag

complexes

Compare to Fig. 17.11

http://www.nature.com/nrm/journal/v9/n3/extref/nrm2312-s1.mov

http://www.nature.com/nrm/journal/v9/n3/extref/nrm2312-s1.mov


Natural Killer (NK) Cells

Granular leukocytes.

Not immunologically specific.

Lyse virus-infected and tumor cells.

Kill target cell in absence of MHC-I (early stages of virus infection and tumor cells)

Similar mechanism to CTLs

In Antibody-Dependent Cell Mediated Cytotoxicity (ADCC) NK cells and macrophages lyse antibody-coated cells (protozoans and helminths)

Fig 17.15


Immunological Memory Amount of antibody in serum is called the antibody titer.

1 response: Response of the body to the first contact with an antigen. Mostly IgM

2 response: any subsequent contact with the same antigen. Rapidly very high antibody titer. Mostly IgG

Fig 17.16


Self Tolerance: Negative Selection

Goal: eliminate B and T cells, recognizing “self” molecules

Clonal deletion of B cells taking place in bone marrow apoptosis

Negative selection of T cells in thymus

Failure results in auto-antibodies and autoimmune disease


Types of Specific Immunity

Active immunity

Protection via introduction of antigen into responsive host, e.g.:

Naturally acquired via infection or

Artificially acquired via vaccination


Passive Immunity

Protection via transfer of antibodies or immune cells into a non-immune host, e.g.:

Naturally acquired: Fetus receives mothers antibodies via placenta

Artificially acquired via vaccination injection of immune serum after exposure (snake bite, Rh+ child with Rh-mother etc.)

Compare to

Fig 17.17


Cellular Immunity Review

T-cells specific surface receptors (TCRs)

TCR cannot bind free ag. Ag must be presented by APCs

Activated T-cells go through clonal expansion effector and memory T cells.

CTLs directly kill virus infected and tumor cells

T-helper cells help the humoral and cellular immunity

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