Activation of Th Cells

Characters of Adaptive Immunity

• Adaptive immunity discriminates between "self" and "non-self" structures.
• It is highly specific for the invading organism and can respond specifically to millions of antigens.
• Adaptive immunity requires previous exposure to pathogens.
• It has memory, meaning re-exposure to the same antigen results in a faster and stronger response, sometimes leading to lifelong immunity.

Types of Adaptive Immunity

Passive Immunity

• Involves the transfer of readymade antibodies to an individual.
• Provides rapid protection but is short-lasting.
• Can be naturally acquired (e.g., from mother to fetus through the placenta or in breast milk) or artificially acquired (e.g., through injection of specific antibodies).

Active Immunity

• Involves the individual's active production of their own antibodies or sensitized lymphocytes specific to a foreign antigen.
• Immunity develops slowly but lasts for a long time due to the development of immunologic memory.

Mechanisms of Adaptive Immune Response (Active Immunity)

Humoral (Antibody-Mediated) Immune Response (HI)

• Directed mainly towards defense against extracellular microbes and their toxins, leading to their extracellular elimination or destruction via different cells (e.g., phagocytes and NK cells).

Cell-Mediated Immune Response (CMI)

• Responsible for a wide variety of protective mechanisms, including:
  • Resistance to viruses, protozoa, fungi, and intracellular bacteria (e.g., TB and Brucella).
  • Resistance to tumors.
• However, CMI can also play a role in harmful conditions, such as:
  • Graft rejections.
  • Type IV hypersensitivity.
  • Autoimmune diseases.

Stages of Specific CMI Immune Response

Antigen Processing and Presentation

• Antigen-presenting cells (APC) (e.g., macrophages) bind, ingest, and digest antigens into peptide fragments (Ag determinants or epitopes) and present them in association with MHC class II molecules on the cell surface to be recognized by TCR of Th cells.

T Cells Activation

• Th cells are activated in association with MHC and costimulatory molecules.
• Activated Th cells secrete cytokines (e.g., IFN-γ), which activate macrophages and NK cells, increasing their killing effects against antigens.

Activation of Tc Cells

• Tc cells are activated in association with expression of cytotoxins (e.g., graft cells, tumor cells).

Activation of Th Cells

• Th cells are activated by two signals:
  • The first signal: Ag epitopes associated with MHC II on the surface of APC.
  • The second signal: Costimulatory molecules (e.g., CD28 on Th cells and B7 on APC).
• Activated Th cells undergo proliferation and differentiation into effector cells, secreting cytokines (e.g., IFN-γ and IL-2) that activate macrophages and NK cells.

Activation of Tc Cells

• Tc cells are activated by two signals:
  • The first signal: Ag epitopes associated with MHC I on the surface of target cells.
  • The second signal: IL2 produced from activated Th cells.
• Activated Tc cells undergo proliferation and secrete cytotoxins to kill target cells (e.g., graft cells, tumor cells, infected cells).

Specific B Cells Activation (T-Dependent Activation)

• Specific B cells (acting as APC) are activated by two signals:
  • The first signal: Interaction between TCR on Th and Ag epitopes associated with MHC II on the surface of B cells.
  • The second signal: Costimulatory molecules (e.g., CD40 on B cells and CD40L on Th cells).
• Activated B cells differentiate into antibody-producing plasma cells and memory cells.

Contraction Phase (Homeostasis)

• Occurs when the effective immune response eliminates the microbe that initiates the response.
• In this stage, expanded lymphocyte clones die, and homeostasis is restored.
• This response is regulated by Treg cells.

Memory Cells Formation

• Some activated Th, Tc, and B cells become memory cells that can respond to exposure of the same antigen.

Superantigens (SAgs)

• Definition: Antigens capable of activating multiple clones of T helper cells.
• Characteristics:
  • Bind to class II MHC molecules on APC and the TCR β chain on Th cells outside the peptide binding groove.
  • Activate Th cells even at very low concentrations.
  • Can cause lymphocyte exhaustion and systemic toxicity.
• Examples: Staphylococcal enterotoxins and toxic shock syndrome toxins, Streptococcal pyrogenic exotoxin, and some viral superantigens (e.g., nucleoprotein of rabies virus).