Adaptive Immunity Notes: Mechanisms of Humoral and Cell-Mediated Responses

Describe the interactions and differences between humoral and cellular immunity.
Outline how plasma cells and memory cells are generated in the primary immune response.
Sketch the structure of an antibody (implicitly covered by description).
Summarize the role of MHC proteins in the adaptive immune response.
Compare how cell-mediated pathways function versus humoral pathways.

The immune system "remembers" infections, allowing for a faster and stronger response upon subsequent exposure.
Primary Immune Response:
- Occurs a few days after the initial infection.
- Involves the production of antibodies and T cells specific to the detected antigen.
- Generates Effector cells which actively carry out the immune attack.
- Generates Memory cells which retain a "memory" of the attack for future encounters.
Secondary Immune Response:
- Triggered if infected with a previously-encountered pathogen.
- Characterized by a very rapid and robust response due to the presence of memory cells.

B cell activation:
- A "naïve" B cell is activated when it binds to a specific antigen.
- The bound antigen is then presented to a helper T cell (TH cell).
- The helper T cell promotes B cell clonal selection through the release of cytokines.
Clonal Selection and Differentiation:
- Activated B cells undergo clonal propagation (proliferation).
- They differentiate into two main types of cells:
  - Plasma cells: These are effector cells responsible for producing and secreting large quantities of antibodies (also known as immunoglobulins).
  - Memory B cells: These cells persist in the body, providing immunological memory.
Antibody Structure:
- Composed of 4 protein chains.
- Held together by disulfide bridges.
- Possess 2 antigen binding sites.

Variable regions:
- These unique regions on the antibody allow for specific binding to particular antigens.
Constant regions:
- These regions can anchor the antibody in the B cell membrane if the antibody is not freely circulating.
Antigen Binding Capabilities:
- An antibody can bind to $2$ antigens simultaneously.
- Agglutination: Antibodies can bind to multiple antigens, causing them to clump together.
  - This clumping effect makes antigens easier targets for phagocytes (immune cells that engulf and digest foreign particles).
  - Agglutinated antigens also attract Natural Killer (NK) cells.

Vaccinations work by triggering a primary immune response in a safer, controlled manner.
This process allows the immune system to generate memory cells without exposure to the full-strength pathogen.
Consequently, if the vaccinated individual is later exposed to the real pathogen, their immune system can mount a fast secondary response.
Herd Immunity:
- Achieved when a high percentage of the population, typically $90\%+$ , is vaccinated.
- This significantly reduces the spread of infectious diseases, protecting even those who cannot be vaccinated (e.g., infants, immunocompromised individuals).
Examples of diseases preventable by vaccination:
- Measles
- Mumps
- Influenza
- Chickenpox
- Tetanus
- Polio
- Whooping cough

T cells possess surface receptors for antigen recognition, similar to B cells.
Key Distinctions from B cell receptors:
- T cell receptors are not immunoglobulins.
- They are glycoproteins.
- Each receptor contains 2 polypeptide chains: an $\alpha$-chain and a $\beta$-chain.
- They contain both constant and variable sites.
Crucial Difference: T cell receptors only bind to antigens that are presented by an MHC protein.

Major Histocompatibility Complex (MHC) proteins are essential for presenting antigens to T cells.
T helper (TH) and T cytotoxic (TC) cells:
- Both types of T cells bind to antigens displayed on Antigen Presenting Cells (APCs).
- Response to antigen binding differs based on T cell type:
  - TH cells (Helper T cells) lead to the activation of the overall adaptive immune response.
  - TC cells (Cytotoxic T cells) induce the death of the cell displaying the antigen.
Determining T cell binding: The type of T cell that binds to an APC is determined by which class of MHC protein is presenting the antigen (MHC class I or class II).

MHC Class I:
- Present on the surface of all nucleated cells in the body.
- Primarily presents antigens to TC cells.
- Examples of antigens presented:
  - Viral fragments from internally infected cells.
  - Abnormal proteins found in cancer cells.
MHC Class II:
- Found on the surfaces of specialized Antigen Presenting Cells (APCs) such as B cells, macrophages, and dendritic cells.
- Presents antigens that these cells have ingested from external pathogens.
- Primarily presents antigens to TH cells.

Activation Mechanism:
- TC cells become activated when their receptors bind to antigens presented by MHC-I proteins.
- A common example is binding to a virus-infected cell displaying viral antigens on its MHC-I proteins.
Clonal Propagation and Function:
- Upon activation, there is clonal propagation of TC cells that have the same specific receptor.
- When activated TC cells bind to target cells (e.g., infected cells or cancer cells), they perform two main actions:
  - Release perforin, a protein that creates pores in the target cell membrane, leading to lysis (bursting) of the cell.
  - Stimulate apoptosis (programmed cell death) in the target cell.

Activation Mechanism:
- TH cells are activated when they bind to antigens presented by MHC-II proteins (typically on APCs like macrophages or B cells).
Clonal Propagation and Cytokine Release:
- Upon activation, clonal propagation of specific TH cells occurs.
- Activated TH cells then release various cytokines.
Role of Cytokines:
- These cytokines act as signaling molecules to stimulate other immune cells:
  - TC cells (enhancing cell-mediated responses).
  - NK cells (Natural Killer cells).
  - Macrophages (enhancing phagocytosis and antigen presentation).
  - B cells (promoting their activation and antibody production, thus linking to humoral immunity).

An Antigen Presenting Cell (APC), such as a macrophage or B cell, encounters and internalizes a pathogen.
The APC processes the pathogen and presents its antigens on MHC-II proteins to TH cells.
Activated TH cells then release cytokines that perform several functions:
- Stimulate TC cells to enhance cell-mediated killing.
- Stimulate B cells to produce antibodies (humoral response).
- Attract NK cells to the site of infection.
- Attract other phagocytes (e.g., macrophages) to enhance pathogen clearance.

Humoral Immune System:
- Primarily a response mediated by B cells.
- Produces circulating antibodies.
- Mainly active against extracellular bacteria and viruses (those found outside cells).
Cellular Immune System:
- Primarily a response mediated by T cells.
- Directed towards parasites, fungi, intracellular viruses (those living inside cells), and foreign tissues (e.g., in organ transplants).
- Cytotoxic T cells (TC) are the "workhorses" of the cellular immune system, directly killing infected or abnormal cells.

(Reference: Principles of Life - 3rd edition - Hillis et al. MacMillan, Fig. 36.11)