Introduction to Immunology

Introduction to Immunology

• Immunology is the study of the immune system
• John James, Associate Professor, is the instructor
• [email protected] is the instructor's email address

Lecture Learning Outcomes

• Describe the development of an immune response to infection
• Understand the differences between innate and adaptive immune responses
• Know the main functions of different immune cell types

The Function of an Immune System

• The immune system maintains a healthy equilibrium with the environment
• It defends the host against a range of pathogenic agents
• Protection against tumour formation is also a function of the immune system

The Function of Our Immune System

• The immune system defends against infectious agents of varying sizes
• Examples of these agents include viruses, bacteria, fungi, and parasites
• Viruses range in size from 50-500 nanometers
• Bacteria range in size from 0.5-50 micrometers
• Fungi range in size from 0.05-1 millimeter
• Parasites range in size from 0.1-100 centimeters

Maintaining a Fine Balance

• The immune system doesn't respond to every foreign particle (tolerance)
• A healthy immune system's 'setpoint' is crucial to maintaining homeostasis
• Individuals have diverse setpoints, defining how/when the system is set, and what this means.

Out of Balance

• Imbalances in the immune system can lead to various health problems
  • Psychological disorders (e.g., Alzheimer's, PTSD, depression, bipolar disorder)
  • Cardiovascular diseases (e.g., atherosclerosis, hypertension, stroke)
  • Metabolic disorders (e.g., diabetes, fatty liver disease)
  • Autoimmunity (e.g., IBD, osteoporosis)
  • Aging
  • Immune deficiency
  • Allergies
  • Chronic Obstructive Pulmonary Disease (COPD)
  • Muscular dystrophy
  • Cancer
  • Transplantation tolerance

Flowchart of an Immune Response

• The immune response follows a specific pathway
• Pathogen encounters a physical barrier
• Infection leads to innate recognition, antigen transport, and pathogen removal
• Receptor selection/evolution of adaptive immune response is triggered by bad things
• Tolerate chronic infection

Cells of the Immune System

• Immunological cells including B cells, T cells, Granulocytes, platelets, macrophages, monocytes are involved
• Adaptive and innate immune cell types exist
• Cells are derived from a common stem cell

Flowcharts of an Immune Response (Repeated)

• Similar to previous flowchart: pathogen, physical barrier, innate recognition, antigen transport, etc. This section repeats the processes involved in the immune response

Physical Barriers

• Physical barriers prevent infection
  • These barriers are crucial for interaction with the environment
• Without these interactions, the immune system wouldn't be needed. Infections would be difficult to avoid.

Where We are Likely to Be Infected

• Micro-organisms enter the body through entry points
  • Respiratory, reproductive, and gastrointestinal tracts
  • Wounds, abrasions, and bites disrupt anatomical barriers

Physical Prophylaxis

• First anatomical barriers to infection are epithelial surfaces (e.g., skin epidermis, bronchial epithelium, gut epithelium)
• Chemical barriers including lysozyme, mucus, surfactants, and acidity of the stomach also exist

Innate Cells are the First Responders

• Innate cells have sensors to detect pathogens
  • Genetic receptors trigger direct detection
• Innate cells are phagocytic (eat and destroy) pathogens
• Complement is a system of soluble factors. Factors within this system are not discussed.

Sensors: Pattern Recognition Receptors

• Membrane-bound and Cytoplasmic Pattern Recognition Receptors (PRRs) include Toll-like receptors (TLRs), C-type lectin receptors (CLRs), NOD-like receptors (NLRs), and RIG-I-like receptors (RLRs)

Neutrophils are Short-Lived Innate Effector Cells

• Inflammation is involved in expressing adhesion proteins on blood vessel cells
• Neutrophils are efficient macrophages, but die quickly
  • They are a primary component in inflammatory responses and are efficient in eliminating pathogens
• Neutrophils can form extracellular traps from excreted DNA to capture bacteria.

Innate Response is Not Always Sufficient

• The innate response effectively controls most infections - However, if the innate response is insufficient, it recruits specialised innate cells (e.g. neutrophils) - If problems persist, an adaptive response is triggered

Adaptive Immunity

• The immune system can recognise nearly any potential pathogen
• Evolutionary selection processes can directly kill pathogens or recruit others to do so
• Lymphocytes (T and B cells) provide long-lasting memory against some pathogens.

Lymphocytes

- T cells are the key gatekeepers of adaptive immunity, developing in the thymus
- Activated T cells (effector T cells) include cytolytic and regulatory T cells, that can activate B cells
- Activated B cells produce high-affinity antibodies that block pathogens or activate innate responses

Lymphocyte Antigen Receptors

• T-cell and B-cell antigen receptors (TCR and BCR) are not genetically encoded
• Somatic gene recombination generates nearly limitless receptor combinations
•  TCR and BCR share similar structures but have different functions

Antigen Receptors are Unique Structures

• Adaptive immune cells use evolutionary strategies to select sequences of antigen receptors
  • This means that each receptor in the body is unique
    • Each T cell is a "clonotype"

T cells initiate the adaptive immune response

•  Activated T cells play crucial roles in the immune system
  • Helper T cells help other immune cells, such as B cells
  • Cytotoxic T cells directly kill infected cells

Antibody-mediated effector functions

• Antibodies have various functions like neutralisation, opsonisation, and complement activation that neutralize pathogens, identify them for destruction, and activate the complement system.

Repeated Pathogen Encounters

• Repeated exposures lead to the development of memory B and T cells persisting for years
  • These "memory" cells quickly initiate a powerful response upon repeated pathogen exposure
• An enhanced innate and adaptive response eliminates infection often with a more rapid clearance
  • Antibodies are usually central to the enhanced response.

Take Home Messages

• A healthy immune system maintains homeostasis with environment
• The immune system responds to pathogens from 50nm viruses to 50mm worms.
• Innate responses are rapid but limited to encountering the pathogens in the area of the body where they are present
  • It usually focuses on initial responses.
• Innate cells either destroy pathogens directly or send out signals to indicate infection
• Adaptive immune responses have a longer latency period, but they provide a powerful response to control an infection and potential prophylaxis

Consolidation/Talking Points

• Vaccine effectiveness depends on factors specific to the vaccine
• Pregnancy and immune response relationship are complex. Immune response adaptations are needed
• Scientific understanding of the immune system constantly expands

Explore the functions and development of the immune system in this quiz on immunology. You'll learn about innate and adaptive immune responses, as well as the roles of various immune cells in defending against infections. Test your understanding of how the immune system maintains equilibrium and protects against diseases.