Chapter 18: Adaptive Specific Host Defenses

Third Line of Defense

Includes specific host defenses that must be developed uniquely for each microbe through the action of specialized WBCs. This form of immunity is marked by its activity toward specific pathogens and development of memory.

• B and T lymphocytes, antibodies, cytotoxicity

• Acquired, specific

Adaptive Immunity

• Learned/developed

• Specificity

• Memory

• Ability to distinguish b/w self and non-self

• B cells and T cells

• Slow

Humoral-Mediated Immunity

Primary defense against extracellular pathogens; extracellular bacteria, circulating virus.

• Antibody-mediated

• B Lymphocytes

• Antibodies circulating in serum

Immunogen

Any substance capable of inducing specific immune response

• Immunogenicity

Immunogenicity

• Foreignness

• High molecular weight

  • 10,000 Da

• Chemical nature

• Molecular complexity

  • Homopolymers vs. Heteropolymers

Antigen

a molecule that stimulates an adaptive immune response

• Immunogen

• ALL _______ ARE NOT IMMUNOGENIC

• Has multiple epitopes

Epitope/Antigenic Determinant

Small part of an antigen that can be recognized by T-cell or B-cell receptors.

• An antigen has many epitopes

Haptens

Small foreign molecules that are not immunogenic by themselves

• Combine with carrier molecule, which contributes to the size of the complex

Antibodies

Y-shaped glycoprotein molecule produced by B cells that binds to specific epitopes on an antigen.

• Composed of 4 polypeptide chains:

  • 2 identical heavy chains (H)

  • 2 identical light chains (L)

• Antigen binding sites

• Variable regions (V) and Constant regions (C)

• Surface receptors for antigens

  • B cell receptors - Igm and IgD

• Five classes

  • IgG, IgM, IgA, IgE, and IgD

    • Based on their constant region structure and immune function.

Antibody-Antigen Interactions

• Neutralization

• Opsonization

• Antibody-dependent cell-mediated cytotoxicity (ADCC)

• Agglutination

Major Histocompatibility Complex (MHC)

AKA human leukocyte antigen (HLA)

• Recognize ‘self’ and reject ‘non-self’ (foreign) tissue

• Transmembrane glycoproteins

• Genetically determined- important in tissue transplants (Histocompatibility)

2 types

• Class 1 MHC (MHC-1)

• Class 2 MHC (MHC-II)

MHC-I

All body cells (except RBCs)

MHC-II

Only on APCs

• Macrophages, dendritic cells, and B cells

Antigen-presenting cells (APC)

T-Cell dependent antigens must be processed by phagocytes called…

Immunocompetence

The ability of the body to produce an immune response following exposure to an antigen.

B cells

Production of antibodies to inactive, neutralize, target antigens.

• Bone Marrow

• Immunoglobulin MHC-I and MHC-II

• Low numbers in blood

• Immunoglobulins D and M

• Plasma cells and memory cells product of antigenic stimulation

T cells

Regulate immune functions, kill foreign and infected cells, synthesize cytokines.

• Thymus

• T-cell receptor, CD molecules, MHC I

• High numbers in the blood.

• T cell receptor (TCR)

• Helper and cytotoxic T cells and memory cells product of antigenic stimulation

Cytotoxic T cell

Kill virus-infected and damaged cells.

• Surface CD8 molecules

• Activates APCs or infected nucleated cells presenting antigens associated with MHC I

• Function

  • Destroy cells infected with intracellular pathogens.

Helper T cells

Help cytotoxic T Cells and B cells in their immune functions.

• Surface CD4 molecules

• Activates APCs presenting antigens associating with MHC II

• Function

  • Orchestrate humoral and cellular immunity

  • Involved in the activation of macrophages and NK cells

Lymphocyte Receptors

Role in surveillance and recognition is a function of their receptors

• Confer the specificity and identity of a cell.

B cell receptors (BCR)

T cell receptors (TCR)

B-cell receptor (BCR)

Bind-free antigens: immunoglobulins (Ab)

T-cell receptors (TCR)

Bind processed antigens together with MHC molecules on the cells that present antigens to them.

• 2 parallel polypeptide chains small, not secreted CD (Cluster of differentiation) receptors; another class of ______ _____ _____ function in cell signaling

  • CD4 and CD8

Cell mediated Immunity

• Requires the direct involvement of T lymphocytes

• T cells act directly against Ag and foreign cells when presented in association with an MHC carrier

• Helper T cells secreted cytokines that act on other cells

• Sensitive T cells proliferate into long-lasting memory T cells.

Ex: HIV attacks and destroys the CD4 cells (Helper T cells)

Effector Cells

activated cells of cellular immunity that are involved in the immediate immune response, primarily to defend the body against pathogens.

Memory B cell

an activated and differentiated B cell that is programmed to respond to secondary exposures to a specific antigen

Memory Helper T cell

a long-lived T cell programmed to recognize and quickly mount a secondary response to a specific pathogen upon re-exposure

Naive Mature B cell

a B cell that has not yet been activated

Naive Mature T cell

a T cell that has exited the thymus after thymic selection but has not yet been activated.

Natural Killer Cells

Lack antigen specificity and can target any infected or malignant cell.

Superantigens

Bridge used to bind the MHC II and TCR molecule.

• Reaction has drastic consequences

• _____ are a form of virulence factor

• Provoke overwhelming immune responses by large numbers of T cells (non-specific, uncontrolled activation)

  • Massive cytokine release

Superantigens stimulates…

• Excessive inflammatory response

• Blood vessel damage

• Toxic shock

• Multiorgan damage

• Potential death.

Clonal Selection Theory

Undifferentiated lymphocytes undergo a continuous series of divisions and genetic changes that generate millions of different cell types.

• Each cell has a particular/unique receptor specificity.

T cell dependent activation

require the assistance of T cells (helper T cells) to initiate antibody production, leading to stronger and memory-forming immune response.

T cell-Independent activation

Have repeating epitopes that can induce B cell recognition and activation without involvement from T cells.

• Immune response

• Short-lived

• No memory cells

Passive Natural Acquired

Immunity acquired from antibodies passed in breast milk or through placenta

Passive Artificial Acquired

Immunity gained through antibodies harvested from another person or an animal

Active Natural acquired

Immunity gained through illness and recovery

Active Artificial Acquired

Immunity acquired through a vaccine

Variolation

Inoculation of smallpox (live virus) into the skin (18th century)

Vaccination

• Inoculation of cowpox to protect people from smallpox (Edward Jenner)

• Inoculation with rabies virus (Louis Pasteur)

Vaccine

A preparation that stimulates the body’s immune system to develop immunity against a specific disease by exposing it to a killed, attenuated, or fractionated version of a pathogen.

Herd Immunity

Reduced probability of an individual becoming infected when it is part of a vaccinated population

• Less likely that a nonimmunized person will encounter the pathogen.