Human Physiology Week 2b - Immune System

Understanding the Immune System

• The immune system is complex, involving various cells and chemicals essential for managing inflammation in physical therapy.
• Key understanding of the immune system aids in the management of immune-mediated diseases such as rheumatoid arthritis, myasthenia gravis, and Guillain-Barre syndrome.

Key Terminology

• Antigen: A substance that triggers an immune response, typically proteins or polysaccharides found on foreign invaders.
• Antibody: A protein produced by the immune system in response to an antigen, functioning to neutralize or inhibit the antigen's negative effects.
• Epitope: A specific sub-region of an antigen that antibodies bind to.
• Pathogen: A microorganism that causes infectious diseases, characterized by various antigens with associated epitopes.

Immune System Cells

• Leukocytes (white blood cells): Main players in the immune response, classified into granular and agranular types.

  • Granular leukocytes:
    • Eosinophils: 2-4% of white blood cells, stain red.
    • Basophils: 0.5-1%, stain blue/purple.
    • Neutrophils: 60-70%, neutral staining, dominant white blood cell type.

• Agranular leukocytes:

  • Lymphocytes: Include B-cells and T-cells, essential for adaptive immunity.
  • Monocytes: Larger cells that differentiate into macrophages, which engulf cellular debris and pathogens.

Immune System Branches

• Innate Immune System:

  • Non-specific, includes physical barriers like skin and mucus membranes.
  • Components like phagocytes (e.g., macrophages, neutrophils) respond rapidly (within hours) to any perceived threat without discrimination between harmful and harmless substances.

• Acquired (Adaptive) Immune System:

  • Specific immunity involving lymphocytes, particularly B-cells (produce antibodies) and T-cells (mediators of cell-mediated immunity).
  • Takes days to mount a response, recognizing and targeting specific pathogens, often after an innate response.

Functions of Immune Cells

• B-cells: Produce antibodies that circulate and bind to specific antigens on pathogens.
• T-cells: Help coordinate immune responses; may kill infected host cells and support B-cell antibody production.

Immune Response Dynamics

• Innate immunity acts quickly upon exposure to pathogens, while adaptive immunity has a delayed but targeted response.
• Adaptive immunity involves:
  • B-cell activation: Upon recognizing an antigen, B-cells proliferate and differentiate into antibody-producing plasma cells.
  • T-cell activation: T-cells become activated through interactions with antigen-presenting cells (e.g., macrophages), leading to proliferation and targeted immune actions.

Summary of Immunity Types

• Cell-mediated Immunity: Primarily refers to the functions of T-cells.
• Humoral Immunity: Relates to B-cells and the antibodies produced in response to antigens.

Overall Structure

• The immune system is organized into specific branches (innate and adaptive), with distinct roles and collaborative interactions to effectively combat infections.### Adaptive Immune Response
• Effector T cells are the final outcomes of the initial phases of the adaptive immune response, taking days to develop.
• Antigen presenting cells (APCs), primarily macrophages, collect cellular debris and antigens to activate immune responses by other immune cells.

Antigen Presenting Cells

• Macrophages function like "garbage bags," engulfing and presenting antigens from various sources, including bacteria and innocuous materials.
• Antigens presented by APCs interact with lymphocytes to determine whether an immune response is necessary.
• Cytokines released during the interaction between APCs and lymphocytes trigger either an inflammatory response or halt the immune reaction.

T Cells Development

• T cells originate from pluripotent hematopoietic stem cells in the bone marrow and mature in the thymus.
• Mature immunocompetent T cells can differentiate into:
  • Helper T cells: Activate other white blood cells and enhance the inflammatory response.
  • Regulator T cells: Control and suppress the immune response to prevent overactivation.

Effector and Memory T Cells

• Cytotoxic T cells: Primarily kill virus-infected and pathogenic cells.
• Memory T cells: Provide long-term immunity by rapidly responding to previously encountered antigens.

B Cells Development

• B cells mature in the bone marrow and are vital for producing antibodies.
• They differentiate into:
  • Plasma cells: Secrete immunoglobulins (antibodies) to target specific pathogens.
  • Memory B cells: Retain information about encountered antigens for quicker responses in the future.

Humoral Immunity

• Humoral immunity is facilitated by B cells, primarily targeting extracellular microbes.
• B cells produce antibodies that bind to specific antigens, neutralizing pathogens or marking them for destruction by phagocytosis.
• Antibodies can inhibit pathogen function, recruit complement proteins, or facilitate engulfment by neutrophils and macrophages.

Cell-Mediated Immunity

• Cell-mediated immunity involves T cells responding to intracellular pathogens, such as viruses.
• Helper T cells, upon recognizing antigens presented by APCs, release cytokines that promote T cell proliferation and activation.
• Activated cytotoxic T cells destroy infected host cells through direct apoptosis or other mechanisms.

Summary of Lymphocyte Functions

• B lymphocytes: Key for antibody production, neutralization of pathogens, and tag pathogens for destruction by phagocytes.
• Helper T lymphocytes: Interact with APCs to activate macrophages, B cells, and further T cell proliferation, initiating inflammatory responses.
• Cytotoxic T lymphocytes: Identify and eliminate infected cells through antigen recognition and subsequent activation.

Key Terms

• Cell Mediated Immunity: T cell response.
• Humoral Immunity: B cell response, primarily targeting blood and extracellular fluids.
• Immunocompetent: Capability to respond to antigens.
• Cytokines: Signaling molecules that mediate immune responses.### Immune Cell Functions
• Cytotoxic T lymphocytes (CTLs) destroy infected cells, acting as the immune system's executioners.
• Regulatory T lymphocytes (Tregs) regulate and suppress the immune response to prevent overactivity.
• Natural killer (NK) cells inherently target and kill antigen-presenting cells without prior activation.

Role of Dendritic Cells in Immune Activation

• Dendritic cells, a type of macrophage, transport antigens to lymph nodes via lymphatic vessels.
• Naive T and B cells, which have not encountered antigens, are activated in the lymph nodes when presented with antigens by dendritic cells.
• Activation leads to the proliferation and differentiation of T and B cells into effector or memory cells.

T Cell Activation and Response

• Effector T cells exit lymph nodes into circulation to perform immune functions, including assisting phagocytes and causing inflammatory responses.
• Helper T cells have a critical role in activating B cells, boosting antibody production through signals.

B Cell Immunity

• B cells produce antibodies, which bind specifically to epitopes on antigens.
• Initial antibody production starts with Immunoglobulin M (IgM), followed by class switching to produce more specific Immunoglobulin G (IgG) antibodies.
• Memory B cells are formed for long-term immunity after the initial exposure to pathogens.

Antibodies Overview

• Antibodies (or immunoglobulins) are proteins produced by B cells that bind antigens.
• There are five main types of antibodies:
  • IgG: Most abundant, found in body fluids, protects against bacteria and viruses.
  • IgA: Located on mucous membranes, such as in the eyes.
  • IgM: First antibody produced during an infection; present in blood and lymph.
  • IgE: Involved in allergic reactions.
  • IgD: Found in small amounts in blood; its function is not well understood.

Active vs Passive Immunity

• Active immunity results from exposure to antigens and the body producing its own antibodies.
• Passive immunity provides antibodies directly, without prior exposure; occurs naturally (e.g., maternal transfer) or artificially (e.g., convalescent plasma therapy).
• Maternal antibodies (like IgG and IgA) transfer to the fetus through the placenta or breast milk, offering protection during early life.
• Convalescent plasma therapy involves transferring antibodies from recovered patients to help newly infected individuals, such as those with COVID-19.