unit 4, lesson part 1

• Immunology provides protection against infectious diseases caused by microorganisms like bacteria, viruses, protozoa, fungi, and parasites
• Immunology provides protection against cancer

Pathogen Transmission

• Pathogens can be transmitted through airborne transmission, contact, contaminated water, blood stream, or tissues

The Immune System

• The immune system is divided into the innate and adaptive immune systems

Innate Immune System

• Provides physical defenses like skin, cough reflex, tears, mucosal layers, and stomach acids
• Includes phagocytes such as monocytes, macrophages, neutrophils, NK cells, and dendritic cells

Adaptive Immune System

• Includes T-lymphocytes, specifically helper T-cells, suppressor T-cells, and cytotoxic T-cells
• Contains B-lymphocytes, further divided into clonal B-cells and memory B-cells

Physical Barriers

• Skin is a physical barrier

Secretions

• Secretions contain molecules that can neutralize bacteria
• Secretions include saliva and tears

Mucosal Tissue

• Lungs, airways, and the gut are coated with mucus
• Mucosal tissue traps potential pathogens
• Mobile ciliate hair transports 'contaminants' out

Tissue Resident Immune Cells

• Skin, mucosal surfaces, and airways have cells that fight pathogens

Organisation of the Immune System

• The immune system is comprised of tissues and cells throughout the body

Primary Lymphoid Tissue

• Bone marrow contains pluripotent hematopoietic stem cells and is the source of most cells in the immune system
• T cells produced in the bone marrow must travel to the thymus to complete their maturation

Secondary Lymphoid Tissue

• Lymph nodes
• Spleen

Primary Lymphoid Tissue - Thymus

• Thymus is an encapsulated lymphoid organ
• T cell maturation and differentiation occurs in the thymus
• The cortex is rich with immature T cells, and the medulla contains sparse mature T cells

Secondary Lymphoid Tissue

• Lymph nodes
• Spleen
• Mucosa-associated lymphoid tissue
• Secondary lymph tissues are an important site for adaptive immune responses and contain lymphocytes
• The lymphatic system consists of vessels draining fluids from body tissue
• Lymph nodes monitor lymph for signs of infection
• Mucosa-associated lymphoid tissues are important for mucosal immune response in the gut and airways
• The spleen serves as a lymph node for the blood

Secondary Lymphoid Tissue - Lymph Node

• A lymph node is an encapsulated, trabeculated lymphoid organ that has many afferent and one or more efferent branches
• Lymph nodes act as a filter, storage, activation centre for B and T lymphoid cells, and a centre for antibody production

Lymph Node Components

• Follicles are the site of B cell storage and proliferation
• The medulla is composed of medullary cords and sinuses acting as a filter
• The paracortex is the location of the T cells

Secondary Lymphoid Tissue - Spleen

• Sinusoids are composed of elongated channels with a fenestrated membrane and adjacent macrophages, functioning as filters.
• Periarterial lymphatic sheath (PALS) houses T cells
• Follicles are the site where white pulp houses B cells
• The spleen contains two major units: white pulp and red pulp
• The white pulp is composed of lymphatic tissue and contains mainly WBC which initiate adaptive immune response
• White pulp around the spleen is surrounded by red pulp

Immune Cells

• Immune cells derive from stem cells
• Myeloid progenitor cells produce dendritic cells, macrophages, monocytes, and neutrophils
• Lymphoid progenitor cells make NK-cells, T-cells and B-cells

Immune System Overview

• Innate immunity provides physical and biochemical barriers inside and outside the body
• Innate immunity uses cells with specific functions and responses
• Innate immunity has no memory
• Innate immunity does not use antibodies but does involve a complement system
• Acquired/adaptive immunity provides a specific response to infectious agents, which depends on antigen presentation, recognition, and the antigen-antibody response
• Adaptive immunity has memory and uses antibodies

Innate Immune System Overview

• The nonspecific immune response indiscriminately attacks invaders (virus, bacteria, parasite)
• There is no memory; repeated exposures to the same pathogen generate the same response as the first exposure
• The first line of defense comes from the innate immune system
• Most pathogens enter the body via the respiratory system, gut, or genitourinary tract
• Skin provides an effective physical barrier to pathogens
• Mucus can trap and remove particles and small organisms
• Cilia lining the trachea and main bronchi catch and remove pathogens
• Reflexes (coughing, sneezing, fever) eliminate and destroy pathogens

Innate Immunity - Cell Types

• 2 primary cell types are involved in the innate immune response: natural killer (NK) cells and phagocytes
• Natural killer (NK) cells recognize virally infected and malignant cells, as well as antibody-opsonized cells
• NK cell binding to a target cell releases cytolytic and cytotoxic granules to kill target cells via apoptosis
• Phagocytic cells engulf debris, infectious particles, and bacteria, which are then destroyed and removed
• Neutrophils are efficient phagocytes
• Macrophages are recruited to the site of infection

Innate Immunity - Cells

• Cellular and humoral components make up innate immunity Mast cells and basophils secrete histamines to mediate inflammation
• Mast cells are tissue resident
• Basophils are found in the blood
• Mast cells and basophils play a key role in allergic response (hypersensitivity type I)
• Phagocytosis is carried out by Neutrophils and Macrophages
• These respond to signs of infection (i.e. inflammation) in the tissue
• Phagocytosis Recognizes microorganisms by pathogen-associated molecular patterns (PAMPs) on the microbial surface
• Recognition is carried out by pattern recognition receptors (PRRs), e.g., Toll-like receptors (TLRs)
• This results in neutralisation and phagocytosis

Phagocytes in the Body

• Phagocytes enter an infected site from circulation
• Phagocytes bind, engulf, and kill a wide variety of microbial agents
• Phagocytes produce immunomodulatory substances (cytokines, chemokines), which regulate the immune response
• Phagocytes act as the first line of defense against infection

Cell Surface Proteins of Immune Cells

• Immune cells have cell surface proteins
• Macrophages have MHC II, B7, CD40, CD14
• Proteins have distinct functions, supporting cell interaction and communication
• Macrophages (APC) express MHC II
• MHC II in complex with antigenic peptides bind to T cell TCR

Non-Cellular (Humoral) Innate Immune Response

• Humoral innate immune response attacks pathogens in a rapid, non-specific manner

Complement

• Plasma proteins destroy cell membranes (lytic pore)
• Plasma proteins attract phagocytes & stimulate activity of other immune cells. (C3a, and C5a)
• Plasma proteins promote phagocytosis (Opsonins, C3b/iC3b, C4b)

Fever

• Elevation of body temperature due to pyrogens (COX-2)

Inflammation

• Mast cells release pro-inflammatory cytokines & chemokines
• Blood vessels dilate
• Allows influx of immune cells and fluid (plasma)
• Results in symptoms of pain, swelling, redness and heat

Complement

• The complement system consists of small proteins in the blood that interact with the immune system
• Important in humoral immunity and inflammation
• There are 3 pathways that activate the complement system: classical, alternative, and lectin
• A classical pathway requires antibodies, typically IgG and IgM, bound to antigens
• An alternative pathway requires the presence of antigens, such as endotoxin, or a foreign surface, such as a bacterial surface
• The Lectin pathway requires the presence of bacterial carbohydrates

Adaptive Immune System

• Involves both humoral and cell-mediated immunity
• Cell-mediated immunity relies on direct contact between immune cells and the pathogen
• Humoral immunity is an antibody-mediated response that relies on proteins (antibodies) to convey signals between cells
• Adaptive immunity is specific for a given pathogen
• Repeated exposure causes an enhanced immune response

T and B Cells

• Provide for acquired immunity
• T cells promote cell-mediated activation of B cells and other immune cells (T helper or CD4+ T cells), or direct cell killing (cytotoxic or CD8+ T cells)
• B cells make antibodies: IgM, IgG, IgD, IgE, IgA

Adaptive Immunity - Receptors

• T CELLS carry T cells receptors (TCRs)
• B CELLS carry B cell receptors (BCRs)
• Structures allow for high specificity
• Major histocompatibility complex plays an important role in adaptive immunity
• MHC class I receptors are on all nucleated body cells
• MHC class II receptors are on antigen-presenting cells (APCs)
• Both interact with TCRs

Cellular vs Humoral Adaptive Response

• The cellular adaptive response is mediated by cytotoxic T cells (CD8+)
• Targets infected body cells (e.g. viruses) and malignant cells (e.g. cancer)
• The humoral adaptive response is affected by B cells (antibodies)
• Targets pathogens or antigens in the blood stream or on mucosal surfaces
• Helper T cells (CD4+) are essential as 'gatekeepers'

Cell Surface Proteins of Immune Cells

• T helper cells have CD4, TCR, CD3, CD28, CD40L
• Cytotoxic T cells have CD8, TCR, CD3
• Proteins have distinct functions, supporting cell interaction and communication
• T cell TCR binds and interacts with MHC class I or II

MHC I and II

• An important acquired immunity component is the major histocompatibility complex or MHC
• MHC I and MHC II have distinct functions
• The MHC is a complex of proteins encoded by human leukocyte antigen (HLA) genes
• MHC I is encoded by HLA-A, HLA-B, and HLA-C and expressed on nucleated cells
• MHC II is encoded by HLA-DR, HLA-DP, and HLA-DQ and expressed on antigen-presenting cells (APCs)

T Cell Differentiation

• T cells play an important role in cell-mediated acquired immunity
• T cell precursor cells from the bone marrow travel to the thymus where they differentiate into CD8+ and CD4+ cells
• These cells then travel to the lymph node where they further differentiate:
• CD8+ cells: differentiate into cytotoxic T cells
• CD4+ cells: differentiate into T helper cells

T Helper Cell Subsets

• Th1 guides the adaptive response towards a cellular profile (Cytotoxic T cells, intracellular pathogens)
• Th2 guides the adaptive response towards a humoral profile (B cells, extracellular pathogens)
• Th17 responds to extracellular bacteria and fungi, IL-17
• T regs control the immune response to self and foreign particles (antigens)

The Role of B Cells

• B cells are essential for The primary and secondary antibody response The body produces B cells that express a wide variety of surface receptors (BCRs) of IgD or IgM class

• Humoral adaptive immune reposnse recognizes antigens via antibodies
• An antigen is a substance that elicits an antibody's production, and binds specifically with that antibody
• An antibody are proteins that are classified as immunoglobulins, are produced by plasma cells (B cell derived), and are defined functionally
• Antibodies include IgM, IgG, IgE, IgD, IgA

Antibodies

• Fab fragment: Binds to antigens with light and heavy chains that recognize distinct antigens.
• Fc fragment: Determines the antibody class and fixes complement.

Antibody Function

• Opsonisation - Promotes phagocytosis via Fc receptors recognizing antibody-antigen complexes and binding antibody via its Fc fragment
• Neutralisation - Inhibits the antigen (e.g. bacterial adherence) by blocking a surface protein required for adhering to cell surfaces
• Complement activation - Antibody-antigen complexes bind, triggering the classical pathway of complement
• Complement pathway activation results in opsonins (C4b, C3b) and amplification via the alternative pathway

Antibody Responses

• Primary response involves B cells proliferating into plasma cells, which secrete antibodies and create memory B cells
• IgM is also involved

Secondary Response

• Involves antigen-specific memory, where B cells secrete antibodies and cause isotype switching
• Involves IgG
• Displays higher affinity and higher titre (serum concentration)

Cytokines

• Cytokines are immune mediators
• A particular cytokine's effects occur through its high-affinity binding of its receptor on the surface of a target cell.
• Can stimulate or inhibit the differentiation, proliferation and activity of immune cells

Examples of Cytokines

• Interferon family act as antiviral proteins
• Chemokine family directs cell migration, adhension and activation
• Tumour necrosis factor family regulate inflammatory and immune responses
• Interleukin family vary in action depending on upon interleukin and cell type
• Haematopoietins promotes cell proliferation and differentiation
• Transforming growth factor beta family regulates immune cells

Explore the primary functions of the immune system. Learn about physical barriers, mucosal tissues, and hematopoietic stem cells. Also, understand the roles of the thymus, lymph nodes, spleen, innate immunity and lymphoid tissue.