Study Notes on Host Defenses II: Microbiology

Chapter 16: Host Defenses II

Adaptive Immunity

  • Adaptive immunity is the third line of defense against pathogens and is characterized by specificity and memory. It occurs after an immunizing event, such as an infection.

  • Immunocompetence: This refers to the body's ability to respond to a vast range of foreign substances.

Characteristics of Specific Immunity

  • Specificity: Specifically targets the antigen.

  • Memory: The immune system’s ability to remember past infections and respond more rapidly upon re-exposure to the same pathogen.

Principal Stages of Immunologic Development and Interaction

  1. Lymphocyte development and differentiation

  2. Presentation of antigens

  3. Antigen challenge of B and T lymphocytes

    • B-lymphocyte response: Production and activities of antibodies

    • T-lymphocyte response: Engages in cell-mediated immunity

Major Stages in the Development of B and T Cells

- Stem cells in the bone marrow differentiate into granulocytes, monocytes, or lymphocytes.

  • B cells: Stay in the bone marrow to develop.

  • T cells: Migrate to the thymus for maturation.

    • Each lymphocyte develops a unique antigen receptor for specific antigens and migrates to lymphoid tissues.

    • Naive lymphocytes are equipped to respond to a unique antigen upon reaching lymphoid tissues.

Surface Markers on T Cells

  • T-cell receptors: Specific to antigens, formed by genetic modification.

  • CD3 markers: Assist in the binding of the T-cell receptor.

  • CD4 and CD8 coreceptors:

    • CD4: Found in helper T cells, binds to MHC class II molecules.

    • CD8: Found on cytotoxic T cells, binds to MHC class I molecules.

  • Continuous circulation between lymphatic and circulatory systems.

Properties of B Cells vs. T Cells

Feature

B Cells

T Cells

Site of maturation

Bone marrow

Thymus

Specific surface markers

Immunoglobulin

T-cell receptor

Concentration in blood

Low numbers

High numbers

Receptors for antigen

B-cell receptor

T-cell receptor

Location in lymphoid organs

Cortex (follicles)

Paracortical regions

Require antigen with MHC

No

Yes (except gamma-delta T cells)

Result of antigen stimulation

Plasma and memory cells

Activated T cells and memory cells

Major Histocompatibility Complex (MHC)

  • A set of genes coding for human cell markers.

  • Produces glycoproteins (MHC molecules) found on all cells except red blood cells.

  • Also known as human leukocyte antigen (HLA), crucial for self-recognition and foreign tissue rejection.

Concept of Clonal Selection

  • Clonal Selection Theory: Describes how lymphocytes develop and diversify, becoming specialized through selection of clones based on antigens encountered.

Immune Tolerance

  • Tolerance to self: Self-antigens are not attacked by the immune system.

  • Removal of harmful clones through clonal deletion may cause autoimmune diseases due to the survival of “forbidden clones.”

Antigen Presentation

  • Antigens: Substances that provoke an immune response.

  • Immunogens: Antigens that elicit a response from the immune system.

  • PAMPs: Pathogen-associated molecular patterns recognized by the innate immune response.

Types of Antigens

  • Characteristics: Must be perceived as foreign; immunogenicity increases with complex molecules (e.g., proteins).

  • Epitopes: Small parts of the antigen that are recognized by lymphocytes.

  • Haptens: Small molecules that cannot elicit a response unless bound to a carrier molecule.

  • Alloantigens: Antigens from one individual that provoke an immune response in another individual.

Role of APCs in Antigen Processing

  • Antigen-Presenting Cells (APCs) include dendritic cells, macrophages, and B cells.

  • They engulf and process antigens then present them on MHC molecules to T cells.

Activation of T Helper Cells

  • Activation occurs via MHC II and requires additional signals (e.g., CD28 interacting with CD80).

  • T helper cells (CD4) produce IL-2, proliferating and assisting other immune cells (B cells and T cells).

Types of T Cells

  1. Helper T cells: Activate macrophages and B cells.

  2. Regulatory T cells: Control immune response and maintain tolerance.

  3. Cytotoxic T cells: Kill infected host cells and foreign cells.

  4. Gamma-delta T cells: Respond quickly to PAMPs.

B-Cell Activation and Antibody Synthesis

  • Upon activation, B cells proliferate into plasma cells and memory B cells, producing antibodies.

  • Antibodies mark antigens for destruction/neutralization.

Immunoglobulin Structure

  1. Ig: Composed of four polypeptide chains (two heavy and two light chains).

  2. Fab region: Antigen-binding, varies in structure.

  3. Fc region: Binds to immune cells and can activate complement.

Functions of Antibodies

  • Opsonization: Enhances phagocytosis by coating pathogens.

  • Neutralization: Prevents pathogen attachment and function.

  • Agglutination: Clumps antigens to enhance phagocytosis.

  • Lysis: Antibodies can activate complement to rupture pathogens.

Classes of Immunoglobulins

Class

Number of Binding Sites

Molecular Weight

Percentage of Serum Antibody

Crosses Placenta?

Function

IgG

2

150,000

80%

Yes

Long-term immunity

IgA

4 (dimer) / 2 (monomer)

170,000-385,000

13%

No

Secretory antibody

IgM

10

900,000

6%

No

First response

IgD

2

180,000

1%

No

B-cell receptor

IgE

2

200,000

0.002%

No

Allergy and parasitic infections

Primary and Secondary Immune Response

  • Primary response: Initial exposure with a lag phase, production of IgM, followed by IgG gradually peaking.

  • Secondary response (amnestic response): Faster production of IgG due to memory B cells surviving from the primary exposure.

Passive vs. Active Immunity

  • Active Immunity: Long-term immunity from exposure to antigens (natural or artificial).

  • Passive Immunity: Short-term immunity obtained from another individual’s antibodies (e.g., maternal antibodies or serum treatments).

Types of Vaccines

  1. Whole Organism Vaccines:

    • Killed/inactivated: Pathogens killed by heat or chemicals (e.g., injected flu vaccine).

    • Live attenuated: Live organisms with reduced virulence (e.g., MMR vaccine).

    • Vector-based: Harmless virus delivering pathogenic antigen information (e.g., mRNA COVID-19 vaccines).

  2. Antigenic Component Vaccines: Consist solely of antigenic components extracted from pathogens (e.g., Hepatitis B vaccine).

  3. Toxoid Vaccines: Contain inactivated bacteria toxins to elicit immunity.

Requirements for an Effective Vaccine

  • Minimal adverse effects, effective against virulent form, stimulates both B cell and T cell responses, longevity of immunity, economical, and easy to administer.

Vaccine Side Effects

  • Common: Local soreness, mild flu-like symptoms.

  • Severe: Rare occurrences of anaphylaxis (example: COVID-19 vaccine).