Understanding Immunity and the Immune System

Concept of Immunity

• Immunology studies how the body defends itself from infectious agents
• Immunity constitutes the ability of an organism to recognize and defend itself against specific pathogens or antigens
• The cells and molecules responsible for immunity make up the immune system
• The collective and coordinated response to foreign substances is called the immune response
• The word Immunology comes from the Latin "immunis," meaning "exempt," which translates to protection from disease or resistance

What is the Immune System?

• It is a biological structure with processes within an organism
• It protects against disease by identifying and killing pathogens and tumor cells
• The immune system detects a wide variety of agents, from viruses to parasitic worms
• It distinguishes these agents from the organism's own healthy cells and tissues

Structure of the Immune System

• The immune system has a multilayered architecture
• Defenses are provided at many levels
• It is a complex network security system of chemicals, cells, tissues, and organs

Functions of the Immune System

• Without an immune system, a human being would be exposed to harmful pathogens and other substances from the outside environment to inside the body

Main Tasks

• Distinguish between body's own cells (self) and foreign cells (non-self)
• Provide defenses against pathogens, including bacteria, viruses, parasites, or fungi
• Distinguish one pathogen from another
• Remove dead or worn-out cells, such as red blood cells
• Identify and destroy abnormal cancer cells
• Protect against autoimmune diseases
• Reject tissue cells with foreign antigens
• Remember previously encountered pathogens
• Respond upon pathogen invasion
• Stop immune response when danger passes

Differentiation Between Self and Non-Self Substances

• Critical for the immune system to differentiate between "self antigen" and "non-self (foreign)" antigen cells, organisms, and aspects of the immune response
• The body should not attack its own healthy cells
• All cells, including pollen, display surface macromolecules that the immune system "senses" to determine foreignness; these chemicals are called antigens
• The immune system's cells, primarily white blood cells, constantly search the body for potential pathogens
• White blood cells are trained to recognize and differentiate body cells (self) from foreign material (non-self), such as invading microorganisms
• White blood cells have a sense of touch
• Self-markers are felt as they determine what is self and what is not
• No response happens when self markers are recognized

Contact with Foreign Cells

• Detection and recognition of foreign cell or virus is the first point of contact with the pathogen
• Pathogen recognition receptor (PRR) detect pathogen-associated molecular pattern molecules (PAMPs)
• Destruction of the foreign cell occurs after the signal has been established

Self and Non-Self Substances

• The immune system defends against foreign or dangerous invaders
• This includes microorganisms, like bacteria, viruses, fungi, and parasites
• It also defends against innocuous substances, transplanted organs/tissues, and cancer cells

Autoimmune Disorders

• Many autoimmune disorders result from the immune system mistakenly attacking the body's own tissues and organs
• Rheumatoid arthritis will cause the body to attack its own joints and tissues, causing pain and loss of function

Immune Activation

• Antigens activate the immune system
• These antigens include proteins on the surfaces of bacteria, fungi, and viruses
• When antigens bind to special receptors on defense cells, a series of cell processes begins
• The immune system recalls stored "memories" for a quicker defense against known pathogens

Immune Tolerance

• Immune tolerance is defined at the state of unresponsiveness of the immune system to an antigen

Self-Tolerance:

• Self-tolerance is defined as the state of unresponsiveness of the immune system to a self-antigen
• Self-tolerance describes a physiological state in an organism
• The immune system proceeds far enough to lose the capacity to attack and destroy its own bodily constituents through self-recognition

Self vs Nonself

• Apoptotic cells use programmed cell death
• Homeostasis maintains a stable internal condition

Normal and Aberrant Immunity

• Immune Hyperactivity: Allergy, autoimmunity, reactions
• Normal Immune System: Specific non reactivity to self, specific reactivity to non-self
• Immune Hypoactivity: Immunodeficiency, infections, and cancers

Terminology: CD Nomenclature

• CD stands for "cluster of differentiation"
• It is a classification system for antigenic determinants on cells
• Surface molecules of different cell types act as markers of differentiation
• CD complexes are given numbers
• Over 300 CD molecules have been named
• Many CD molecules are involved in immune response

Role of Markers and Receptors

• All cells, both foreign and "self," have various surface markers
• These markers play significant roles in detection, recognition, and cell communication
• Cell markers activate different immunity components and contribute to the immune response

Introduction to Immune Cells

• Hematopoietic Stem Cells (HSCs) in bone marrow produce cells of the immune system through haematopoiesis
• Haematopoiesis involves development, production, maturation and differentiation of blood cells
• Erythrocytes, megakaryocytes and leukocytes arise from HSCs
• HSCs differentiate into common myeloid progenitors or common lymphoid progenitor cells in the presence of specific cytokines

Hematopoiesis

• Hematopoietic Stem Cells (HSCs) are self-renewing through cell proliferation that leaves daughter cells as HSCs
• During embryogenesis and fetal development, the yolk sac is the site of haematopoiesis
• After organogenesis, hematopoiesis shifts to the liver, spleen, and then bone marrow, where it remains throughout adulthood

Cytokines

• Cytokines are signaling proteins that facilitate cell communication to initiate and coordinate immune actions
• Most body cells can produce and release cytokines
• Hundreds of cytokines have been identified and are grouped by function
• Pro-inflammatory cytokines can induce inflammation
• Cytokines have become central in clinical medicine as diagnostic, prognostic, and therapeutic agents

Cytokine Types

• Interleukin (IL)
• Tumor Necrosis Factor (TNF)
• Interferon (IFN)
• Colony stimulating factor (CSF)
• Transforming growth factor (TGF)
• Chemokines

Cells of the Immune Response

• Immune responses are mediated by specific cells with defined functions
• CARP is known for each of the specific cells:
  • Cell- Surface Markers
  • Actions
  • Role
  • Products

Myeloid Progenitor Cells

• Common myeloid progenitor cells give rise to:
  • Neutrophils
  • Basophils (mast cells)
  • Eosinophils
  • Monocytes (macrophage precursors)
  • Dendritic cells
  • Platelets
  • Erythrocytes

Mononuclear Cells

• Monocytes (bloodstream) are mononuclear cells
• They are agranulocytes
• Monocytes develop into macrophages (resident in all tissues) after migrating into tissue
• Monocytes make up 1-6% of total WBCs
• Monocytes show presence of foreign surface antigens
• There is no presence of antibodies, and the lifespan is long

Macrophage Location

• In the tissues, mononuclear phagocytes differentiate into different histological forms
• Abundant in liver, spleen, lymph nodes, lungs, and the peritoneal cavity

Macrophage functions

• Phagocytosis (big eater)
• Professional antigen presenting cell (APC)
• Production of proinflammatory cytokines, such as IL-1, IL-6, and TNFα, to signal and recruit other cells to an area with pathogens

Dendritic Cells

• Dendritic cells are found in various tissues and act as "scouts"
• They engulf material in the tissues and bring it to cells of the adaptive immune system for "inspection"
• Dendritic cells develop from monocytes and other cell types

Multinuclear Cells

• Neutrophilic, eosinophilic and basophilic

Neutrophils

• Circulate in the blood
• They are 60-70% of total WBCs
• Highly mobile/very active
• Short lived
• Strong phagocytes that target extracellular pathogens
• Granules contain myeloperoxidases (MPO) which create cytotoxic substances to kill bacteria and pathogens

Eosinophils

• The percentage in blood is 1-3% of total WBC
• It is present in large numbers during worm infections
• It is weakly phagocytic
• They produce toxic proteins against parasites, such as helminths. Although eosinophils are physically too small to ingest and destroy helminths, they can attach to the outer surface of the parasites and discharge peroxide ions that destroy them

Basophils

• Basophils circulate in the blood
• They are non-phagocytes which comprise <1% of circulating WBCs.
• Mast cells are resident in most tissues adjacent to blood vessels
• Mast cells Location: mast cell found in skin, connective tissues & mucosal epithelial tissue that contains histamine and heparin
• They have cell surface receptors (Fc) specific for immunoglobulin IgE

Basophils Function

• Basophils are responsible for the body's allergic response
• Basophils are granulocytes whose granules contain substances such as histamine and heparin
• Heparin thins blood and inhibits blood clot formation
• Histamine dilates blood vessels and increases blood flow, which helps the flow of white blood cells to infected areas
• Also, platelets and RBCs (Non-leukocytes) are produce from common myeloid progenitor cells

Lymphoid Progenitor Cells

• Common lymphoid progenitor cells include B lymphocytes (B cells), T lymphocytes (T cells), and NK cells
• Lymphocytes make up 20-35% of cells
• They participate in innate (NK cell) and adaptive (B & T) immune responses
• Lymphoid organs are spleen, appendix, tonsils, lymph nodes, and thymus
• Lymphocyte proliferation causes the swelling of lymph nodes during an infection

Small Agranular Lymphocyte:

• B lymphocytes (B cells) and T cells have subsets
  • Plasma cell
  • Memory B-cell
  • Regulated B-Cell
• T lymphocyte (T cells) have subsets;
  • T Helper cell (CD4)
  • Cytotoxic cell. (CD8)
  • Regulatory T-cells (Treg) - also called T Suppressor (Ts cell)
  • Memory T-cell