Innate Immunity

Key Definitions

• Opsonization: The process by which pathogens are marked for ingestion and destruction by phagocytes. Opsonins (e.g., antibodies, complement proteins) bind to the surface of microbes, enhancing their recognition by phagocytic cells.

• Opsonin: A molecule that binds to a pathogen and enhances its uptake by phagocytes.

• Antigen: Any substance that can induce an immune response, typically a foreign protein or polysaccharide.

• Cytokine: Small proteins released by cells that have a specific effect on the interactions and communications between cells, especially in immune responses.

• Epitope: The specific part of an antigen that is recognized and bound by an antibody or a T cell receptor.

• Interferon: A type of cytokine produced in response to viral infections; interferons help inhibit viral replication and activate immune cells.

• Margination: The process by which leukocytes adhere to the walls of blood vessels at the site of infection or injury.

• Diapedesis: The movement of leukocytes out of the circulatory system and towards the site of tissue damage or infection.

• Pyrogen: A substance, typically produced by bacteria or immune cells, that induces fever by acting on the hypothalamus.

Serum vs. Plasma

• Serum: The liquid portion of blood after coagulation, lacking clotting factors.

• Plasma: The liquid component of blood that contains clotting factors, obtained by preventing coagulation.

• Key Difference: Plasma contains fibrinogen and other clotting factors; serum does not.

Phagocytic Immune Cells

• Neutrophils

• Macrophages

• Dendritic cells

Phagocytosis and Its Role

• Phagocytosis is the process by which phagocytes engulf and digest pathogens and debris.

• Steps: Chemotaxis → Adherence → Ingestion → Digestion → Exocytosis of debris.

• Role: Removes pathogens, presents antigens to adaptive immune cells, and releases cytokines to recruit other immune cells.

Pathogen Recognition by Phagocytes

• Pattern Recognition Receptors (PRRs): Recognize pathogen-associated molecular patterns (PAMPs) on microbes.

• Opsonin Receptors: Recognize opsonized pathogens (e.g., those coated with antibodies or complement proteins).

Cytokines: Types and Functions

• Interleukins (ILs): Mediate communication between leukocytes.

• Interferons (IFNs): Antiviral responses, activate immune cells.

• Tumor Necrosis Factors (TNFs): Inflammation and apoptosis.

• Chemokines: Attract immune cells to sites of infection (chemotaxis).

The Complement System

• A group of plasma proteins that enhance (complement) immune responses.

• Three Main Functions:

  • Opsonization: Coating pathogens to enhance phagocytosis.

  • Cytolysis: Formation of the membrane attack complex (MAC) to lyse pathogens.

  • Inflammation: Attracting immune cells and increasing vascular permeability.

Body Temperature and Microbial Protection

• Normal human body temperature (37°C) inhibits the growth of many environmental microbes, especially those adapted to lower temperatures.

Immune Response and Fatigue

• Energy is diverted to immune processes.

• Cytokines can act on the brain to induce fatigue.

• Fever and inflammation increase metabolic demands.

Normal Microbiota and Immunity

• Normal microbiota compete with pathogens for resources and space, produce antimicrobial substances, and stimulate immune system development.

Lysozyme

• An enzyme that breaks down bacterial cell walls (peptidoglycan).

• Found in tears, saliva, mucus, and other secretions.

Antimicrobial Peptides

• Short proteins that disrupt microbial membranes, found in various body fluids and tissues.

Lymph and Lymphoid Tissues

• Lymph: Fluid collected from tissues, filtered through lymph nodes.

• Primary lymphoid tissues: Bone marrow and thymus (sites of lymphocyte development).

• Secondary lymphoid tissues: Lymph nodes, spleen, MALT (sites of immune activation).

Leukocytes

• Granulocytes: Neutrophils, eosinophils, basophils (contain granules, involved in innate responses).

• Agranulocytes: Lymphocytes, monocytes (lack visible granules).

Monocytes, Macrophages, and Dendritic Cells

• Monocytes: Circulate in blood, differentiate into macrophages or dendritic cells in tissues.

• Macrophages: Phagocytic cells, antigen presentation, cytokine production.

• Dendritic cells: Professional antigen-presenting cells, bridge innate and adaptive immunity.

Lymphocytes

• B cells: Produce antibodies.

• T cells: Cell-mediated immunity (helper and cytotoxic functions).

• Natural Killer (NK) cells: Destroy infected or abnormal cells.

Inflammation

• Primary functions: Recruit immune cells, contain infection, initiate tissue repair.

• Phases: Initiation, amplification, resolution.

• Cardinal signs: Redness, heat, swelling, pain (caused by increased blood flow, vascular permeability, and mediators).

• Chronic inflammation: Prolonged, can lead to tissue damage.

Fever

• Elevated body temperature, induced by pyrogens.

• Useful effects: Inhibits pathogen growth, enhances immune function.

• Generation: Pyrogens act on hypothalamus to raise set point.

• Treatment: Antipyretics (e.g., acetaminophen).

• Fever patterns: Continuous, remittent, intermittent, relapsing.

Adaptive Immunity

Key Definitions

• Antigen: Any molecule that can be specifically recognized by the immune system.

• Epitope: The specific region of an antigen recognized by immune receptors.

• Immunogen: A substance capable of inducing an immune response.

• HLA (Human Leukocyte Antigen): The human version of MHC molecules.

• MHC (Major Histocompatibility Complex): Cell surface proteins essential for antigen presentation.

Immune Specificity, Memory, and Tolerance

• Specificity: Ability to target specific antigens.

• Memory: Enhanced response upon re-exposure to the same antigen.

• Tolerance: Lack of response to self-antigens, preventing autoimmunity.

MHC I vs. MHC II

Antigen Processing and Presentation

• Intracellular antigens: Processed via proteasome, loaded onto MHC I, presented to CD8+ T cells.

• Extracellular antigens: Engulfed, processed in endosomes, loaded onto MHC II, presented to CD4+ T cells.

Immunological Memory

• Primary response: First exposure, slower, lower magnitude.

• Secondary response: Faster, stronger due to memory cells.

T Cytotoxic Cells (CD8+)

• Activated by antigen presented on MHC I.

• Differentiation into effector and memory cells.

• Eliminate infected cells via perforin and granzymes.

Effector vs. Memory Lymphocytes

• Effector: Actively respond to antigen (e.g., plasma cells, cytotoxic T cells).

• Memory: Persist long-term, respond rapidly upon re-exposure.

T and B Cell Receptors

• TCR: Recognizes antigen-MHC complexes; composed of alpha and beta chains; one epitope binding site; requires MHC interaction.

• BCR: Recognizes free antigen; composed of two heavy and two light chains; two epitope binding sites; does not require MHC for antigen binding.

Antibody Functions

• Neutralization: Block pathogen binding to host cells.

• Opsonization: Enhance phagocytosis.

• Complement activation: Trigger complement cascade.

T Helper vs. T Cytotoxic Cells

Activation of T Helper and B Cells

• T Helper: Activated by APCs presenting antigen on MHC II; secrete cytokines to activate other immune cells.

• B Cells: Activated by antigen and T helper cell signals; differentiate into plasma cells (antibody production) and memory B cells.

Cell-Mediated vs. Humoral Immunity

• Cell-mediated: T cells, especially cytotoxic T cells, target infected or abnormal cells.

• Humoral: B cells and antibodies target extracellular pathogens.

Antibody Classes

Isotype Switching

• Process by which a B cell changes the class of antibody it produces without altering antigen specificity.

• Important for effective immune responses and serological testing.

Vaccines and Immunity

Categories of Adaptive Immunity

• Natural active: Infection-induced immunity (long-term protection).

• Natural passive: Maternal antibodies (temporary protection).

• Artificial active: Vaccination (long-term protection).

• Artificial passive: Antibody therapy (temporary protection).

Vaccine Hesitancy

• Reluctance or refusal to vaccinate despite vaccine availability; influenced by misinformation, distrust, or perceived risks.

Smallpox (Variola) Virus

• Mode of transmission: Respiratory droplets, direct contact.

• Incubation period: 7-17 days.

• Tropism: Narrow (primarily humans).

• Innate immune defenses inactivated: Interferon response, complement system.

• Initial APC infected: Dendritic cells.

• Mortality rate: Up to 30%.

• Reservoir: Humans only.

• Year of eradication: 1980.

Vaccine Types

• Live attenuated: Weakened pathogen, strong immunity, risk in immunocompromised.

• Inactivated: Killed pathogen, safer, may require boosters.

• Subunit/conjugate: Specific antigens, fewer side effects.

• Toxoid: Inactivated toxins, protect against toxin-mediated diseases.

• DNA/recombinant vector: Genetic material or vectors induce immunity.

Adjuvants

• Substances added to vaccines to enhance immune response.

Herd Immunity

• When a high proportion of the population is immune, the spread of disease is limited, protecting those who are not immune.

Laboratory Diagnostics

Key Definitions

• Sensitivity: Ability of a test to correctly identify those with the disease (true positive rate).

• Specificity: Ability of a test to correctly identify those without the disease (true negative rate).

• TAT (Turn-Around-Time): Time from specimen collection to result reporting.

Immunological Methods

• Agglutination tests: Detect antigen-antibody reactions by visible clumping.

• PRNT (Plaque Reduction Neutralization Test): Measures virus-neutralizing antibodies by reduction in viral plaques.

• ELISA (Enzyme-Linked Immunosorbent Assay): Detects antigens or antibodies using enzyme-labeled reagents.

• ICA (Immunochromatographic Assay): Rapid tests (e.g., pregnancy tests) using lateral flow technology.

• IGRA (Interferon Gamma Release Assay): Measures T cell release of interferon-gamma in response to specific antigens (e.g., TB diagnosis).

DNA Microarrays

• Allow simultaneous detection of thousands of DNA sequences; used for pathogen identification, gene expression profiling.

Diagnostic Methods Comparison

• Immunological: Fast, specific, can detect past or current infection.

• Biochemical: Detect metabolic products or enzyme activity; less specific.

• Molecular: Detect nucleic acids (e.g., PCR), highly sensitive and specific.

PCR and Variants

• PCR (Polymerase Chain Reaction): Amplifies DNA for detection.

• Real-time PCR: Quantifies DNA during amplification.

• RT-PCR (Reverse Transcription PCR): Converts RNA to DNA before amplification (used for RNA viruses).

Summary Table: Diagnostic Methods