Immune System Physiology: Structure, Function, and Pathology

Immune System Overview

Introduction to Immunology

The immune system is a complex network of cells, tissues, and molecules that protects the body from pathogens and maintains homeostasis. Unlike traditional organ systems, it is distributed throughout the blood, lymph, and tissues.

• Immunology studies physiological defenses that distinguish self from non-self.

• Main functions: removal of abnormal cells, dead/damaged cells, and protection against pathogens.

Why Don’t We Get Sick More Often?

Humans are constantly exposed to microbes, but the immune system and physical barriers prevent frequent illness.

• Physical, chemical, and behavioral barriers are the first line of defense.

• The microbiome (beneficial microbes) also contributes to health by outcompeting pathogens.

Pathogens and Microbes

Types of Pathogens

Pathogens are organisms or agents that cause disease. Not all microbes are pathogenic; many are harmless or beneficial.

• Viruses: Nucleic acids (DNA or RNA) in a protein coat; require host cells for replication.

• Bacteria: Outnumber human cells; most are harmless, some are essential, and some are pathogenic.

• Parasites/Fungi: Examples include Plasmodium (malaria) and Candida auris (multidrug-resistant fungus).

Comparison Table: Bacteria vs. Viruses

Feature	Bacteria	Viruses
Structure	Cellular, with cell wall	Non-cellular, protein coat
Living Conditions	Can live independently	Require host cell
Reproduction	Binary fission	Host-dependent
Treatment	Antibiotics	Antivirals, vaccines

Functions of the Immune System

Main Functions

• Recognition and removal of abnormal "self" cells: e.g., cancer cells.

• Removal of dead/damaged cells: Macrophages perform phagocytosis.

• Protection against pathogens: Bacteria, viruses, parasites; requires recognition of self vs. non-self.

Immune System Pathologies

• Incorrect response: Autoimmune diseases (Type 1 diabetes, Crohn's disease, Hashimoto's thyroiditis).

• Overactive response: Allergies (exaggerated immune response).

• Lack of response: Immunodeficiency (primary/genetic or acquired, e.g., HIV/AIDS).

Functional Anatomy of the Immune System

Distribution and Organization

The immune system is not a traditional organ system but a collection of cells found in blood, lymph, and tissues.

• Lymphoid tissues:

  • Primary: Thymus, bone marrow (site of immune cell development).

  • Secondary: Lymph nodes, spleen, tonsils, GALT (site of immune cell activation).

Role of Lymph Nodes

• Immune defense and response

• Fluid balance

• Waste removal

• Immune cells positioned to detect/intercept pathogens

Blood and Immune Cells

Blood Composition

• Plasma: Water, proteins (albumins, globulins, fibrinogen), other solutes

• Cellular elements:

  • Red blood cells (erythrocytes): >99%

  • White blood cells (leukocytes): <1%

  • Platelets: <1%

Leukocyte Types and Percentages

Type	Percentage	Function
Neutrophils	60–70%	Phagocytosis, inflammation
Lymphocytes	20–45%	Adaptive immunity
Monocytes	3–8%	Phagocytosis, antigen presentation
Eosinophils	2–4%	Parasitic defense, allergy
Basophils	0.5–1%	Inflammation, allergy

Hematopoiesis

• Production of blood cells in bone marrow

• Red bone marrow: Active, contains hemoglobin (25% RBCs, 75% WBCs)

• Yellow bone marrow: Inactive, contains adipose cells

• Controlled by cytokines (e.g., interleukins)

Immune Response Steps

Basic Steps

1. Detection and identification of foreign substances

2. Communication with other immune cells

3. Recruitment and coordination of response

4. Destruction or suppression of the invader

All steps depend on signaling molecules such as cytokines and antibodies.

Defense Against Pathogens

Barriers to Infection

• Physical barriers: Skin, nasal hairs, mucous linings, ciliated epithelium

• Chemical barriers: Lysozyme, acidity, lactoferrin, antimicrobial peptides (AMPs)

• Behavioral barriers: Sneezing, coughing, washing

If these fail, the internal immune response is activated.

Innate and Adaptive Immunity

Innate Immune Response

• Nonspecific responses: Resident macrophages (phagocytosis), NK cells (apoptosis of infected cells)

• Inflammatory response:

  • Attracts immune cells and mediators

  • Produces physical barrier

  • Promotes tissue repair

  • Signs: redness (rubor), heat (calor), swelling (tumor), pain (dolor)

• Antigen-presenting cells bridge innate and adaptive immunity

Adaptive Immune Response

1. Innate immune cells recognize pathogens

2. Inflammatory response is triggered

3. Neutrophils and macrophages arrive

4. Dendritic cells phagocytose pathogen

5. Dendritic cells migrate to lymph nodes

6. Antigen presentation on MHC molecules to naïve T-cells

7. Naïve T-cells become activated

8. Helper T-cells activate B-cells, which produce antibodies

9. Adaptive immunity is fully engaged

Pathogen Recognition

Pattern Recognition

• PRRs (Pattern Recognition Receptors): Detect extra- and intracellular signals

• PAMPs: Pathogen-associated molecular patterns

• DAMPs: Damage-associated molecular patterns

Inflammation

Mechanisms and Signs

• Interleukins: Cytokines that alter blood vessel endothelium, stimulate acute-phase proteins, induce fever, and stimulate other cytokines

• Bradykinin: Initiates pain and tenderness

• Complement proteins: Opsonins, chemotactic factors, membrane attack complex

• Acute-phase proteins: Increase during inflammation (e.g., C-reactive protein)

• Histamine: Increases capillary permeability, causes swelling and redness

• Opsonin: Antibody or substance that binds to foreign cells, enhancing phagocytosis

Classical Signs of Inflammation

• Calor (heat)

• Dolor (pain)

• Rubor (redness)

• Tumor (swelling)

• Loss of function

Fever Mechanism

• Infection or LPS activates monocytes

• Release of pyrogenic cytokines (e.g., IL-1, TNFα)

• Elevated hypothalamic set point via prostaglandins (PGE2)

• Peripheral heat responses increase body temperature

Antigen Presentation and Recognition

MHC Molecules

• MHC class I: Present in all nucleated cells; present endogenous antigens to CD8+ T cells

• MHC class II: Present in antigen-presenting cells (APCs); present exogenous antigens to CD4+ T cells

Antigen Recognition Molecules

• Antibodies: Produced by B lymphocytes

• T cell receptors: Recognize antigens presented by MHC

Antigen Presentation Pathways

Pathway	Antigen Type	Cells Involved	MHC Class	T Cell Type
Exogenous	Extracellular	APCs (dendritic, macrophages, B cells)	II	CD4+ helper T cells
Endogenous	Intracellular	Infected cells	I	CD8+ cytotoxic T cells

Platelets and Hemostasis

Platelet Structure and Function

• Cell fragments from megakaryocytes

• Contain mitochondria, smooth ER, granules (cytokines, growth factors)

• 10-day lifespan

• Essential for blood clotting, immunity, and inflammation

Hemostasis and Coagulation

• Hemostasis: Prevents blood loss via vasoconstriction, platelet plug, and coagulation cascade

• Platelet plug: Platelets adhere to exposed collagen, release factors (PAF, thromboxane A2), aggregate

• Coagulation cascade:

  • Intrinsic (contact activation) and extrinsic (cell injury) pathways

  • Common pathway: Thrombin converts fibrinogen to fibrin

  • Fibrin forms the clot; plasmin breaks down fibrin (fibrinolysis)

Factors Involved in Platelet Function

Chemical Factor	Source	Activated by/Released in Response to	Role in Platelet Plug Formation	Other Roles/Comments
Collagen	Subendothelial extracellular matrix	Injury exposes platelets to collagen	Binds platelets to begin plug	N/A
von Willebrand factor	Endothelial cells, megakaryocytes	Exposure to collagen	Links platelets to collagen	Deficiency causes bleeding disorder
Serotonin	Secretory vesicles of platelets	Platelet activation	Platelet aggregation	Vasoconstrictor
ADP	Platelet mitochondria	Platelet activation	Platelet aggregation	N/A
Platelet-activating factor	Platelets, neutrophils, monocytes	Platelet activation	Platelet aggregation	Role in inflammation
Thromboxane A2	Phospholipids in platelet membranes	Platelet activating factor	Platelet aggregation	Vasoconstrictor
Platelet-derived growth factor	Platelets	Platelet activation	N/A	Promotes wound healing

Coagulation and Fibrinolysis

• Intrinsic and extrinsic pathways converge to activate thrombin

• Thrombin converts fibrinogen to fibrin

• Fibrin forms the clot; plasmin (activated by tPA) breaks down fibrin (fibrinolysis)

Anticoagulants and Pathology

• Anticoagulants: Heparin, antithrombin III, protein C inhibit clotting

• Thrombus: Clot adhering to undamaged vessel wall

• Hemophilia: Deficiency in coagulation factors

Key Equations

• Coagulation cascade: $\text{Fibrinogen} \xrightarrow{\text{Thrombin}} \text{Fibrin}$ $\text{Plasminogen} \xrightarrow{\text{tPA}} \text{Plasmin}$ $\text{Fibrin} \xrightarrow{\text{Plasmin}} \text{Fibrin fragments}$

Summary

The immune system is essential for defending against pathogens, maintaining tissue integrity, and preventing disease. Its complex interactions involve physical barriers, innate and adaptive responses, and specialized cells and molecules. Understanding its structure and function is crucial for recognizing health and disease states in human physiology.