Revision Lectures on Immunology from University of Portsmouth

Revision Lectures Overview

• Lecture 1: Basic and advanced immunology, innate immunity
• Lecture 2: The Complement System, MHC and antigen presentation
• Lecture 3: B cells and T cells
• Lecture 4: Atopic dermatitis
• Lecture 5: Hypersensitivities
• Lecture 6: Rheumatoid arthritis, cystic fibrosis

Expectations for Team-Based Learning

For this lecture using Team-Based Learning (TBL), the focus is on active participation, critical thinking, and collaborative problem-solving rather than passive learning. Here's what you should expect:

You should:

• Review the fundamental concepts of Innate and Adaptive Immunity before class (reading materials, lecture slides, or pre-recorded content).
• Be familiar with key differences, functions, and roles of both immune systems.
• Be ready to apply this knowledge in team discussions.

Revision Lecture: Basic and Advanced Immunology

Innate Immunity Concepts

METTE M33310 and M33522 Revision Lecture Basic and Advanced Immunology Innate Immunity

Learning Outcomes

By the end of this lecture, students will be able to:

• Understand the fundamental principles of the immune system, distinguishing between innate and adaptive immunity.
• Explain the components and functions of innate immunity

Basic and Advanced Immunology

METTE Basic and advanced immunology

Key Concepts of Cellular Basis of Immunity

• Immunology - study of immunity (response of immune system to infection).
• Primary function of immune system is to prevent infection and eradicate an established infection.
• 2 arms:
1. Innate response - first line of defense, non-specific, no memory
2. Adaptive response - final stage of response, specific, memory

Innate and Adaptive Immunity Attributes

TABLE 4-1 Innate and adaptive immunity

Attribute Comparison

Attribute Innate immunity Adaptive immunity Response time Minutes/hours Days Specificity Specific for molecules and molecular patterns associated with pathogens and molecules produced by dead/damaged cells Highly specific; discriminates between even minor differences in molecular structure of microbial or nonmicrobial molecules Diversity A limited number of conserved, germ line- encoded receptors Highly diverse; a very large number of receptors arising from genetic recombination of receptor genes in each individual Memory responses Some (observed in invertebrate innate responses and mouse/human NK cells) Persistent memory, with faster response of greater magnitude on subsequent exposure Self/nonself discrimination Very good; no microbe-specific self/nonself patterns in host Very good; occasional failures of discrimination result in autoimmune disease Soluble components of blood Many antimicrobial peptides, proteins, and other mediators, including cytokines Antibodies and cytokines Major cell types T cells, B cells, antigen-presenting cells Phagocytes (monocytes, macrophages, neutrophils, dendritic cells), natural killer (NK) cells, other leukocytes, epithelial and endothelial cells

Phases of the Immune Response

Response Time and Duration

Response Typical time after infection to start of response Duration of response Innate immune response Inflammation, complement activation, phagocytosis, and destruction of pathogen Minutes Days Interaction between antigen-presenting dendritic cells and antigen-specific T cells: recognition of antigen, adhesion, co- stimulation, T-cell proliferation and differentiation Hours Days Activation of antigen-specific B cells Hours Days Formation of effector and memory T cells Days Weeks Adaptive immune response Interaction of T cells with B cells, formation of germinal centers. Formation of effector B cells (plasma cells) and memory B cells. Production of antibody Days Weeks Emigration of effector lymphocytes from peripheral lymphold organs A few days Weeks Elimination of pathogen by effector cells and antibody A few days Weeks Immunological memory Maintenance of memory B cells and T cells and high serum or mucosal antibody levels. Protection against reinfection Days to weeks Can be lifelong

Functions and Characteristics of Immune System Cells

Macrophage Role

Macrophage Resident in tissues Phagocytosis Bacterial killing mechanism e.g. NO production Antigen processing and presentation

Dendritic Cell Role

Dendritic cell Antigen recognition/uptake Antigen presentation-produce cytokines to direct T cell response e.g. IL-12

Neutrophil Role

Neutrophil Only enter tissues when instructed Phagocytosis Bactericidal killing mechanism e.g. respiratory burst

Additional Immune Cell Functions

Eosinophil Function

Eosinophil Attack and killing of large antibody coated parasites such as worms

Basophil Function

Basophil Smallest WBC in circulation Function largely unknown; may be similar to mast cells

Mast Cell Function

Mast cell Mainly found in tissues Release of granules containing histamine and other compounds Important in inflammation and allergy

Lymphatic System Cells

Natural Killer (NK) Cell Function

Natural killer (NK)cell Important in innate immune response Recognises foreign/infected cells Destroys them by release of toxic granules Releases cytokines e.g. IFNy

Immature T Cell Function

Immature T cell

Mature Helper T Cell Function

Mature helper T cell CD4 T cells: Important in specific immune response Produce cytokines to activate macrophages and B cells and to regulate the immune response

Mature Cytotoxic T Cell Function

Mature cytotoxic T cell CD8 T cells: Important in specific immune response Recognise and kill infected cells in a specific manner Produce cytokines

Lymphatic System Overview

• Lymphoid organs are either primary (central) or secondary (peripheral)
• Primary lymphoid organs:
• Major sites of lymphocyte development i.e. thymus and BM
• Secondary lymphoid organs:
• Spleen, lymph nodes, mucosal-associated lymphoid tissues (MALT) including tonsils and Peyer's patches

Lymphoid Organs in Adults

Fig 1. The lymphoid organs in adults Primary lymphoid organs Secondary lymphoid organs Neck (cervical) lymph nodes Thymus Armpit (axillary) lymph nodes Spleen Peyer's patches Red bone marrow Groin (inguinal) lymph node

Humoral Mediated Immunity Components

• Cytokines - glycoproteins that co-ordinate immune response (interleukins, growth factors)
• Antimicrobial peptides - broad-spectrum anti- infectives against wide ranges of bacteria
• Complement - approx. 30 when activated promote bacterial cytolysis, phagocytosis and inflammation
• Acute phase proteins - contribute to acute response to infection by binding pathogens such as bacteria and facilitating complement activation

Key Aspects of Humoral-Mediated Immunity

• Humoral-mediated immunity is a key aspect of the immune response that involves various components in the body's fluids (humors) to defend against infections. These components, including cytokines, antimicrobial peptides, the complement system, and acute phase proteins, work together to eliminate pathogens.
• Cytokines:
• Definition: Cytokines are glycoproteins that act as signaling molecules, helping to coordinate the immune response by regulating the activity of immune cells.
• Types of Cytokines:
• Interleukins (ILs): Facilitate communication between white blood cells, playing roles in the activation and differentiation of T cells and B cells. For example, IL-1 promotes inflammation, and IL-2 is important for T cell proliferation.
• Growth Factors: Stimulate the growth and differentiation of immune cells.
• Tumor Necrosis Factor (TNF): A cytokine that induces fever, inflammation, and apoptosis in infected cells.
• Function: Cytokines regulate immune responses, ensuring that immune cells are activated, recruited to infection sites, and work in harmony to eliminate pathogens.
• 2. Antimicrobial Peptides:
• Definition: Antimicrobial peptides (AMPs) are small, broad-spectrum molecules produced by the immune system that act as anti-infective agents.
• Examples: Defensins and cathelicidins are well-known AMPs.
• Function:
• AMPs target a wide range of bacteria, fungi, and viruses, disrupting microbial membranes and inhibiting their growth.
• They are part of the innate immune response and are often found in mucosal surfaces, skin, and body fluids.
• Clinical Relevance: AMPs are an essential defense mechanism at barrier sites such as the skin and gut, preventing infections before they can establish themselves.

Complement System and Acute Phase Proteins

3. Complement System

Definition: The complement system is a group of approximately 30 proteins that circulate in the blood in an inactive form. Upon activation, they enhance the ability of antibodies and phagocytic cells to clear microbes.

Activation Pathways

Activation Pathways: Classical Pathway: Triggered by antibody binding to a pathogen. Alternative Pathway: Directly activated by microbial surfaces. Lectin Pathway: Activated by mannose-binding lectin binding to pathogen surfaces.

Functions of Complement System

Functions: Bacterial Cytolysis: Formation of the Membrane Attack Complex (MAC) that punches holes in bacterial membranes, leading to cell death. Phagocytosis (Opsonization): Complement proteins coat pathogens, making them easier for phagocytes to recognize and engulf. Inflammation: Complement activation leads to the release of inflammatory mediators that recruit immune cells to the infection site. Clinical Relevance: Deficiencies in the complement system can lead to increased susceptibility to infections, especially by bacteria.

4. Acute Phase Proteins

Definition: Acute phase proteins are produced by the liver in response to inflammation or infection and contribute to the acute immune response.

Examples of Acute Phase Proteins

Examples: C-reactive protein (CRP): Binds to bacterial surfaces, promoting phagocytosis and activating the complement system. Mannose-binding lectin (MBL): Recognizes carbohydrates on pathogens and helps activate the lectin pathway of complement.

Function of Acute Phase Proteins

Function: These proteins act as opsonins, binding to pathogens like bacteria to mark them for destruction. They also play a role in enhancing complement activation and thus, contribute to the immune response against infections. Clinical Relevance: Elevated levels of acute phase proteins like CRP are used as markers of inflammation or infection in clinical settings.

Inflammatory Responses

• Provide immediate protection against tissue injuries and foreign substances
• Crucial for health and well-being
• Cause visible symptoms and can rid the body of harmful organisms
• Tissue damages may result from excessive inflammatory responses

Body's Defense Mechanisms

Inflammation is one of the body's immediate defense mechanisms against tissue injuries and foreign substances. It plays a crucial role in protecting our health and well-being, but it's a double-edged sword-while it can rid the body of harmful organisms, excessive inflammation can also cause tissue damage.

Immediate Protection Against Tissue Injuries

Immediate Protection Against Tissue Injuries and Foreign Substances: .Function: Inflammation provides rapid protection by activating immune cells and directing them to the site of injury or infection. .Process: When tissues are damaged, immune cells like macrophages and neutrophils release signaling molecules, triggering an inflammatory response. .Without inflammation, the body wouldn't be able to effectively respond to infections, injuries, or harmful stimuli. Inflammation often causes redness, swelling, heat, and pain, which are classic signs of the immune system in action. These symptoms are the result of increased blood flow and immune cell recruitment to the site of injury. Immune cells recruited during inflammation, such as neutrophils and macrophages, engulf and destroy harmful organisms, such as bacteria or dead cells, clearing the infection or damage. .While inflammation is protective, an overactive or prolonged inflammatory response can cause tissue damage.Conditions like chronic inflammation in autoimmune diseases (e.g., rheumatoid arthritis) or persistent infections can lead to significant tissue damage. Clinical Relevance: Managing inflammation is crucial in conditions where an overactive immune response can do more harm than good, such as in allergies, asthma, or chronic diseases like inflammatory bowel disease (IBD).