Lecture 17 of HUBS2601: Human Infection and Immunology covers immunology.
Instructor: Dr. Alexandra Spencer (Alex)
Learning Objectives
Define the role of the immune system in maintaining health.
Describe the two arms of the immune system and the major cell types involved in each.
Identify the major organs and tissues that make up the immune system.
Constant Exposure to Pathogens
Every day, we are exposed to pathogens such as bacteria, viruses, fungi, and parasites.
The immune system helps us overcome these infections.
Importance of the Immune System
Infectious diseases are a major cause of death globally.
The WHO releases an annual list of top 10 causes of death.
In 2019, infectious diseases accounted for a significant percentage of global deaths, especially in children under five and in low to middle-income countries.
Coevolution with Microorganisms
Microorganisms predate animal life, and we have coevolved with them.
An immune system is necessary to limit damage caused by microorganisms.
Eukaryotes have developed some form of an immune system.
Adaptive immune systems became necessary when animals started consuming other animals, leading to exposure to more microorganisms and viruses.
Intracellular Bacteria, Protozoa, and Parasites: Able to get inside of the cell and use the cell machinery to replicate. Examples: mycobacterium leprae (leprosy), mycobacterium tuberculosis (tuberculosis), Plasmodium falciparum (malaria), Toxoplasma gondii.
The required immune response depends on the type of pathogen.
Extracellular pathogens: Aim to stop replication and growth, the production of antibodies.
Intracellular pathogens: Require killing of infected cells, involving T cells and NK cells.
The immune system is varied and specific, involving both immediate and specialized responses.
Phases of Immune Response
Immediate/Early (0-4 hours): Barrier mechanisms and antimicrobial peptides are in place.
Early Induced Response: Activation of innate immune cells that recognize common pathogen features, leading to inflammation.
Adaptive Immune System: A later response that is highly specialized and involves antigen-specific T cells and B cells.
Innate vs. Adaptive Immune System
Innate Immune System (natural/native/nonspecific):
Early response.
Cells are ready and waiting.
Barriers on the surface.
Recognizes common pathogen features.
Generates a broad spectrum response, leading to inflammation.
Adaptive Immune System (acquired/specific):
Later response.
Tailored to the pathogen.
Involves B cells (antibodies) and T cells (direct killing).
Discrimination Between Self and Non-Self
Immune cells recognize small components of molecules or proteins.
Innate Immune System: Receptors recognize common pathogen features (e.g., proteins on bacterial cell walls, double-stranded RNA, LPS).
Adaptive Immune System:
Each cell expresses a unique receptor that recognizes one type of antigen.
Cells that recognize self-proteins are deleted during development.
Development of Immune Cells
All immune cells originate from the bone marrow.
Hemopoietic stem cells differentiate into innate and adaptive immune cells.
Common lymphoid progenitors make T cells and B cells.
Common myeloid progenitors give rise to dendritic cells and granulocytes.
Types of Immune Cells
Granulocytes (contain granules):
Neutrophils: Multi-lobe nucleus, involved in antibacterial processes.
Eosinophils: Bilobed nucleus, involved in killing parasites.
Basophils: Bilobed nucleus, involved in anti-parasitic responses and allergic reactions.
Agranulocytes:
Lymphocytes: Adaptive immune system, large nucleus.
Monocytes: Kidney-shaped nucleus.
Functions of Immune Cells
Phagocytic Cells: Macrophages and dendritic cells engulf proteins and present them to adaptive immune cells.
Neutrophils: Involved in antibacterial processes and destroying extracellular pathogens.
Eosinophils & Basophils/Mast Cells: Anti-parasitic responses and allergic reactions.
Natural Killer (NK) Cells: Direct killing of infected cells.
Inflammation
Innate immune system activation leads to inflammation.
Macrophages release chemokines and cytokines, leading to vasodilation and increased permeability.
Inflammation recruits more immune cells, causing swelling, redness, and pain.
Adaptive Immune System Activation
Activation of antigen-specific cells leads to proliferation and differentiation.
Clonal selection: Only antigen-specific cells respond.
Antigen Specificity of T and B Cells
B Cells: Unique receptor from immunoglobulin genes. Different combinations of genes lead to differences in receptors. B cell receptor is surface-bound immunoglobulin, whereas antibodies are secreted immunoglobulin.
T Cells: Unique receptor from T cell receptor genes. The T cell receptor is made up of an alpha and a beta chain. It needs to be expressed with coreceptors for intracellular signaling.
T Cell Activation
T cell receptor recognizes a peptide sequence bound on a major histocompatibility complex (MHC) molecule.
Antigen-presenting cells (APCs) break down proteins into peptide sequences that bind to MHC.
Diversity in Immune System
Diversity is achieved through combinations of MHC genes.
MHC Class I: presents peptides to CD8 molecules.
MHC Class II: presents peptides to CD4 T cells.
Control of Adaptive Immune System
Antigen-specific recognition and co-stimulation are needed for activation.
CD4 T cells: Require antigen presentation on MHC class II by dendritic cells and co-stimulation.
B cells: Receive co-stimulation through T cells.
Antigen-Presenting Cells (APCs)
Professional APCs: Dendritic cells, macrophages, and B cells express MHC class II.
All nucleated cells express MHC class I.
Immune System Organs and Tissues
Primary Lymphoid Organs:
Bone marrow: Hematopoiesis and B cell development.
Thymus: T cell development.
Secondary Lymphoid Organs:
Spleen, lymph nodes, and mucosal-associated lymphoid tissue (MALT).
Promote immune activation by bringing together T cells, B cells, and APCs.
Lymphatics: Connect tissues and organs, filtering lymph fluid through lymph nodes.
Lymph Nodes
Promote immune activation by filtering lymph fluid.
High concentration of T cells and B cells.
Activated APCs migrate to the lymph node to present antigens to T cells.
Structure: T cell zones, B cell zones, afferent lymphatic vessels (fluid drains in), efferent lymphatics (fluid exits).
Spleen
Similar structure to lymph nodes.
Filters blood.
White pulp (T and B cell zones) and red pulp (red blood cell production).
Mucosa-Associated Lymphoid Tissue (MALT)
Located in mucosal sites.
Filters antigens from mucosal sites.
Examples:
Gut-associated lymphoid tissue (GALT), including tonsils, adenoids, appendix, and Peyer's patches.
Nasal-associated lymphoid tissue and Bronchial-associated lymphoid tissue.
Adaptive Immune Response
B Cells: Secrete antibodies that neutralize, opsonize, or activate complement pathways.
T Cells:
CD4 T helper cells recognize antigens on MHC and release cytokines to shape the immune response.
Cytotoxic T cells directly kill infected or abnormal cells via peptide presented on MHC class I.
Kinetics of Immune Response
Innate immune response activates within minutes and lasts a couple of days.
Adaptive immune response takes longer (T cells proliferate within 3 days, peak at 7 days; B cells take longer).
Memory cells develop for a faster response upon subsequent exposure.
Inflammation
Acute Inflammation: Recruit cells to the site of infection and promote wound healing.
Chronic Inflammation: If prolonged or dysregulated, it can lead to disease by disturbing normal cell architecture and function.