Immunology: Innate and Adaptive Immunity, Antibodies, Immune Pathologies, and Vaccination

The Immune System

Overview of Immunity

The immune system protects the body from pathogens through a complex network of cells, molecules, and responses. It is divided into two main branches: innate immunity (nonspecific, immediate defense) and adaptive immunity (specific, acquired defense).

• Innate Immunity: First line of defense, rapid, non-specific, includes barriers (skin, mucosa), phagocytic cells, and inflammation.

• Adaptive Immunity: Slower to respond, highly specific, involves lymphocytes (B and T cells), and generates immunological memory.

Cytokines and the Inflammatory Response

Cytokines

Cytokines are small chemical messengers that mediate communication between immune cells. They regulate immune responses, inflammation, and cell recruitment.

• Produced by all innate immune cells.

• Increase blood flow to infected areas, facilitating immune cell access.

Inflammation

Inflammation is a hallmark of innate immunity with three main purposes:

• Attract immune cells and chemical mediators to the site of insult.

• Produce a physical barrier to slow infection spread.

• Promote tissue repair after infection is controlled.

Four signs of inflammation: redness, heat, swelling, and pain.

Phagocytic Cells and Antigen Presentation

Phagocytic Cells

Phagocytic cells ingest and destroy pathogens. Major phagocytic cells include:

• Neutrophils

• Monocytes (precursors to macrophages)

• Macrophages (tissue-resident, mature monocytes)

• Dendritic Cells

All of the above are phagocytic.

Antigen Presentation and MHC Molecules

Some innate immune cells (macrophages, dendritic cells) and B cells can present antigens to T cells using MHC (Major Histocompatibility Complex) molecules.

• MHC Class I: Expressed on all nucleated cells; presents endogenous (intracellular) antigens (e.g., viral, cancerous).

• MHC Class II: Expressed only on professional antigen-presenting cells (APCs: dendritic cells, macrophages, B cells); presents exogenous (extracellular) antigens.

T cells recognize antigens only when presented on MHC molecules.

Leukocytes and Their Roles

Types of Leukocytes

• Neutrophils: Most common leukocyte (40–70% of WBCs); numbers increase during infection.

• Lymphocytes: Main mediators of specific (adaptive) immune responses (B and T cells).

• Macrophages, Eosinophils, Basophils: Innate immune cells with specialized functions (e.g., attacking parasites, mediating allergies).

Adaptive Immunity

Lymphocytes: B Cells and T Cells

Lymphocytes are responsible for antigen-specific adaptive immune responses.

• B Cells: Mature in bone marrow; differentiate into plasma cells that secrete antibodies.

• T Cells: Mature in thymus; include cytotoxic (CD8+) and helper (CD4+) subsets.

Each B or T cell clone recognizes a single specific antigen.

Self-Tolerance and Negative Selection

The immune system must distinguish self from non-self to prevent autoimmunity. Lymphocytes that react to self-antigens are eliminated through negative selection and clonal deletion (apoptosis of self-reactive cells).

T Cell Activation

T cell activation requires three signals:

1. TCR-MHC Interaction: Recognition of antigen presented on MHC.

2. Co-stimulation: Additional signals indicating the antigen is dangerous.

3. Cytokine Context: Information about the nature and location of the pathogen.

This multi-step process prevents accidental activation and autoimmunity, and conserves energy.

T Cell Subsets

• Cytotoxic T Cells (CD8+): Destroy infected or cancerous cells presenting antigen on MHC I.

• Helper T Cells (CD4+): Secrete cytokines to activate other immune cells; essential for adaptive responses.

• Regulatory T Cells (Tregs): Suppress immune responses to prevent excessive reactions and autoimmunity.

HIV infects and destroys CD4+ helper T cells, leading to immunodeficiency (AIDS).

B Cells and Antibodies

B cells produce antibodies (immunoglobulins, Ig), Y-shaped proteins that bind specific antigens.

• Antibody Structure: Variable region binds antigen; constant region mediates effector functions.

Classes of Antibodies

Class	Main Features
IgG	Most abundant in serum; secondary responses; crosses placenta
IgA	Found in external secretions (mucus, gut, respiratory tract)
IgE	Defense against parasites; mediates allergies
IgM	First antibody produced in primary response
IgD	Role unclear

Antibody Functions

• Antigen Clumping: Aggregates pathogens for easier clearance.

• Inactivation of Toxins: Neutralizes harmful bacterial toxins.

• Opsonization: Tags pathogens for phagocytosis by innate immune cells.

• Triggering Degranulation: Especially important for IgE in allergies and parasite defense.

Primary and Secondary Immune Responses

• Primary Response: First exposure to antigen; slow, mainly IgM production; takes ~2 weeks to peak.

• Secondary Response: Subsequent exposures; rapid, strong response due to memory cells; mainly IgG, IgA, or IgE depending on context.

This principle underlies vaccination.

Pathogens and Immune Defense Strategies

Different pathogens (viruses, bacteria, parasites) require distinct immune responses due to differences in structure, replication, and location (intracellular vs. extracellular).

• Viruses: Intracellular; require cytotoxic T cell response.

• Bacteria: Often extracellular; targeted by phagocytes and antibodies.

• Parasites: Large, may require IgE-mediated and eosinophil responses.

Immune System Pathologies

Categories of Immune Disorders

• Incorrect Response: Autoimmune diseases (immune system attacks self).

• Overactive Response: Allergies/hypersensitivities (excessive reaction to non-pathogenic antigens).

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

Allergies and Hypersensitivity

• Allergy: Inflammatory response to non-pathogenic antigen (allergen).

• Immediate Hypersensitivity: Antibody-mediated (mainly IgE); occurs within minutes; can cause anaphylaxis (life-threatening, massive histamine release, bronchoconstriction, vasodilation, shock).

• Delayed Hypersensitivity: T cell-mediated; occurs over days.

Autoimmune Diseases

Result from loss of self-tolerance; immune system attacks body's own cells (e.g., multiple sclerosis, myasthenia gravis, type 1 diabetes, Graves' disease).

Blood Types and Immune Response

ABO Blood Groups

Blood types are determined by antigens on red blood cells (RBCs): A, B, AB, or O. Individuals produce antibodies against antigens they do not possess.

Blood Type	Antigens on RBC	Antibodies in Plasma
A	A	Anti-B
B	B	Anti-A
AB	A and B	None
O	None	Anti-A and Anti-B

• Universal Donor: Type O (no antigens, can be given to anyone).

• Universal Recipient: Type AB (no antibodies, can receive any type).

Transfusion of mismatched blood leads to RBC lysis and severe complications.

Vaccination and Herd Immunity

Principles of Vaccination

Vaccines stimulate a mild primary immune response, generating memory B and T cells without causing disease. This prepares the immune system for rapid, strong secondary responses upon real pathogen exposure.

• Types of Vaccines: Live attenuated, killed/inactivated, molecular subunit.

• Routes of Administration: Intramuscular (most common), intranasal, oral (mimic natural infection routes).

• Benefits: Cost-effective, easy to administer, rapid and sometimes lifelong protection.

Herd Immunity

When a high percentage of the population is vaccinated, the spread of pathogens is limited, protecting even unvaccinated individuals. The required vaccination rate depends on the pathogen's infectivity (e.g., measles requires very high coverage).

Examples of Vaccine Success

• Smallpox: Eradicated in 1979 through vaccination.

• Rinderpest: Livestock disease, also eradicated.

Additional info: MHC proteins are also called human leukocyte antigens (HLA). Red blood cells lack MHC because they are non-nucleated. The complement system is another important part of immunity but was not covered in detail here.