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Immunology Overview

• Immunology: Study of the immune system's structure and function.
• Immune System: Collection of cells, molecules, tissues, and organs providing protection against infections .
• Immunity: State of being protected from infectious diseases.
• Immune Response: A collective and coordinated reaction to foreign substances in an individual mediated by the immune system's cells and molecules.
• Antigen: A foreign substance recognized by the immune system.
• Antibody: Produced by the immune system to recognize foreign substances, also known as Immunoglobulins.

Classes of Human Immunoglobins

• IgG (146,000 daltons): 80-85% of total serum immunoglobulin, half-life of 21 days. Functions include agglutination, precipitation, opsonization, ADCC and complement activation.
• IgM (970,000 daltons): 5-13% of total serum immunoglobulin, half-life of 10 days. Functions include complement fixation, first antibody produced in primary immune response, only class responding to T-independent antigens and agglutination, precipitation and complement activation.
• IgA (monomer 160,000 or secretory 390,000 daltons): 10-13% of total serum immunoglobulin with a 6 day half life. Secreted into saliva, milk, mucus, and other secretions. Its secretory form resists enzymatic degradation protecting mucous membranes by preventing organism attachment.
• IgD (184,000 daltons): Less than 1% of total serum immunoglobulin. Involved with development and maturation of the antibody response. Functions not fully described and has a 3 day half life.
• IgE (188,000 daltons): Less than 0.01% of total serum immunoglobulin. Attaches to mast cells and basophils causing cell to release granule contents when bound by antigen; involved in allergic reactions and ADCC, helps expel parasites and has a 2 day half life.

Antibody Functions

• Neutralization: Antibodies prevent viruses or toxins from binding to cells.
• Opsonization: Antibodies enhance phagocytosis by coating pathogens.
• Complement Activation: Antibodies trigger complement protein activation, leading to inflammation, lysis of foreign cells, and opsonization.
• Immobilization and Prevention of Adherence: Antibodies bind to bacterial flagella or pili, hindering movement and attachment.
• Agglutination and Precipitation: Antibodies clump bacteria or precipitate soluble molecules, enhancing clearance.
• Antibody-Dependent Cellular Cytotoxicity (ADCC): Antibodies tag infected cells, enabling NK cells to kill them.

Immune System Role

• Defense against pathogenic microbes.
• Defense against the growth of tumor cells.
• Homeostasis by destruction of abnormal or dead cells such as dead red or white blood cells, antigen-antibody complexes.

Immune System Classifications

• The immune system is broadly classified into:
  • Innate (Non-specific) immunity.
  • Adaptive (Specific) immunity.
• Innate immunity consists of:
  • Cells: Phagocytes and NK Cells
  • Soluble factors: Complements, Secretions, and Enzymes.
• Adaptive immunity consists of:
  • Cell-Mediated: Th Cells and Tc Cells
  • Humoral (Ab): B Cells

Host Defense Lines

• The first line of defense involves surface protection by anatomical and physiological barriers against microbes.
• The second line of defense involves a cellular and chemical system with phagocytes and inflammation that holds infections in check.
• The third line of defense involves specialized white blood cells providing long-term immunity with memory.

Types of Immunity

• There are two types of immunity:
  • Innate (non-specific) immunity.
  • Adaptive (specific) immunity.

Innate (Non-Specific) Immunity

• The first line of immune response, and a naturally existing defense mechanism.
• It relies on existing mechanisms that have already been formed, and responds rapidly, often within minutes of infection.
• It is not specific, and same kinds of molecules or cells respond to a range of pathogens.
• It has no memory, and same response occurs after repeated exposure.
• It does not lead to clonal expansion.

Host Protective Responses

• Bodies are constantly exposed to bacteria, fungi, parasites, and viruses that can live on and within.
• There is requirement to restrict the normal flora from entering into sterile tissue sites, discriminate between friend and foe, and defend against invading microbes as a military defense.

Innate Immunity Functions

• It acts as a physical and chemical barrier to infectious agents and toxins.
• Recruits immune cells to infection sites through humoral factors like chemokines and cytokines.
• Activates the complement system to mark bacteria and promote clearance of dead cells/antibody complexes.
• Identifies and removes foreign substances via white blood cells (neutrophils & macrophages).
• Activates the adaptive immune system through antigen presentation.

Innate Immunity Components

• Cellular Barriers include:
  • NK cells.
  • Neutrophils.
  • Macrophages.
  • Eosinophil's
  • Dendritic Cells.
• Surface Barriers include:
  • Physical/Mechanical Barriers: Skin, cilia, and mucus production act as barriers.
  • Biochemical/Humoral Barriers: Enzymes, secretions, pH, cytokines, and interferons present barriers.
  • Biological Barriers: Normal flora prevents pathogen growth.
  • Washing Mechanisms: Tears & urine.

Breakdown in Physical & Chemical Barriers

• Skin/mucous membranes: Eczema, burns, or indwelling cannulas.
• Cough reflex: Neurological disease.
• Mucociliary escalator: Smoking, cystic fibrosis, or asthma.
• Washing mechanisms: Bladder outflow obstruction or Reduced secretions.
• Acid pH: Change to the stomach & skin.
• Colonization resistance: Broad spectrum antibiotics.

Inflammatory Reactions

• Any physiological response to exogenous or endogenous stimuli, such as infections, injuries, or cancer cells.
• Can involve local inflammation.
• Vascular and cellular reaction to the presence of invading microorganisms or injury.
• Highly effective defense mechanism in humans and other animals.
• Stages are Initiation, Tissue Response, Leukocyte Response, and Tissue Repair.

Inflammatory Reaction Stages

• Initiation: Damage to tissue or infection triggers the inflammatory response.
• Tissue Response: Damaged tissue releases histamines, causing vasodilation and increased capillary permeability, which leads to redness, heat, swelling, and pain at the site.
• Leukocyte Response: Neutrophils, macrophages, and dendritic cells arrive, engulf microbes and damaged tissue through phagocytosis and post capillary vasoconstriction.
• Tissue Repair: Agent is removed, leading to resolution and complete healing.

Cellular Barriers

• Phagocytic cells (Neutrophils, macrophages/monocytes, or dendritic cells):
  • Produce a wide array of chemicals.
  • Release inflammatory cytokines and enzymes.
  • Act as scavengers/phagocytose pathogens.
  • Act as antigen presenting cells (APCs), activating the adaptive immune system.
• Natural Killer cells:
  • Kill virus-infected or transformed/tumor cells.

Phagocytosis

• Host defense by a process that engulfs pathogenic particle and digesting:
  • Occurs through neutrophils, macrophages, or dendritic cells.
  • Phagocytes recognize:
    • Pathogen-associated molecular patterns (PAMPs) of pathogens such as Lipoproteins & Proteoglycan
    • By their pattern recognition receptors (PRRs).

Adaptive Immunity

• The second line of response, if innate immunity fails.
• Relies on mechanisms that adapt after infection after events like genetic event, cellular growth, or resistance acquired occur.
• Responds more slowly, over a few days.
• Specific.
• Allows recognition of billions of unique structures.
• Results in clonal expansion and exhibits self/non-self recognition. and anamnestic memory leading to faster and stronger responses.

Primary vs. Secondary Adaptive Response

• Primary Response: Production of specific effector T cell and memory clones.
• Secondary Response: More pronounced and faster when stimulated and more effective at limiting infection.

Forms of Adaptive Immunity

• Natural active immunity: Clinical or sub-clinical infection.
• Artificial active immunity: Vaccination.
• Natural passive immunity: Breast milk or placenta.
• Artificial passive immunity: Immune serum or immune cells.

Adaptive Immunity Components

• Is divided into Humoral and Cell Mediated Immunity.
• Humoral Mediated Immunity:
  • Involves antibodies produced by B-lymphocytes to eliminate extracellular microbes and their toxins.
  • B-Cells transform into Plasma Cells, which produce Antibodies.
• Cells (Cell Mediated) Immunity:
  • Involves T-lymphocytes (T-lymphocytes) and consists of TH & T cytotoxic cells.
  • Works to Eliminate microbes that survive within phagocytes or other infected cells

The Humoral Response

• Consists of immunity mediated by B-cells:
  • These recognize specific antigens and proliferate/differentiate into antibody-secreting plasma cells. - Antibodies bind to antigens on microbes and cause destruction.
• B cells recognize the whole pathogen without any need for Antigen processing and have Antigen specific receptors. Some B lymphocytes evolve into the resting state as memory cells.

Cell-Mediated Immune Response

• Is an immune response with antigen specific T cells (T - lymphocyte).
• Types include:
  • Cytotoxic T cells (CTLs)
  • Helper T cells (HTLs)
• Cytotoxic T cells roles involve:
  • Kills infected cells within those infections such as viruses.
  • Kills damaged or dysfunctional cells.
• Helper T cells (HTLs) roles involve: -Regulating both innate and adaptive immune responses.
  • Helps to determine which immune response the body makes to a particular pathogen.

Comparison of Innate and Adaptive Immunity

Altered Immune Responses

• Disorders that alter the normal function of the immune system which includes:
  • Hypersensitivity reaction
  • Immune deficiency
  • Autoimmune disease

Hypersensitivity Reactions

• Inappropriate or excessive immune responses to an antigen.
• Mediated by pre-existing immunity to self or foreign antigen, requiring a pre-sensitized (immune) state.
• Can have require pre-sensitized (immune) state of the host, and may develop in the course of either humoral or cell-mediated responses and is an increased response.

Classes of Hypersensitivity

• Based on mechanism involved and time taken, hypersensitivity is split into four classes:
  • Type I (anaphylactic) reactions
  • Type II (cytotoxic) reactions
  • Type III (immune complex) reactions
  • Type IV (T-cell-mediated) reactions
• Type I, II & III involve the humoral branch are mediated by antibody or antigen-antibody complexes reactions.
• Type IV the cell-mediated branch & is a delayed-type hypersensitivity.

Hypersensitivity Type I (Anaphylactic)

• Also known as immediate hypersensitivity, and occur within minutes of exposure.
• Mediated by IgE, Cross-linking of cell-bound IgE results in degranulation of mast cells or basophils, releasing histamine.
• Release of histamine leads to Dilation and increased permeability of blood vessels, increased mucus secretion, and smooth muscle contraction.
• Can be systemic, resulting in shock, or localized, such as allergic rhinitis, asthma, atopic dermatitis, or food allergies.
• Common allergens are Pollens, Drugs, or Foods.

Hypersensitivity Type II (Cytotoxic)

• IgG or IgM binding causes activation complement system and cytotoxic immune cells and response occurs in minutes to hours.
• Cytolytic or cytotoxic effect d/t organs and tissue as seen in Transfusion reaction or Hemolytic anemia.

Hypersensitivity Type III (Immune Complex)

• IgA antibodies bind to soluble antigen resulting in large antibody-antigen immune complexes formed and not easily cleared.
• This deposition initiates a recruitment of neutrophils, in order to release granular, develops localized reactions, and causes can inflammatory tissue-damaging.
• This is seen in Serum sickness, Glomerulonephritis or Autoimmune diseases & Infections.

Hypersensitivity Type IV (Cell-Mediated)

• Also called as delayed-type hypersensitivity.
• Occurs one or more days after exposure.
• Sensitized lymphocytes release lymphokines which activate leucocytes, macrophages, and is not induced by circulating Ab.
• Reactions frequently displayed on the skin, such as dermatitis. E.g. Mycobacterium tuberculosis or agents like poison, cosmetics, or latex.

Delayed-Type Hypersensitivity Phases

• Sensitization phase occurs of 1–2 weeks, where TH cells are activated and clonally expanded.
• Effector phase, subsequent exposure induces DTH and TH1 cells secrete cytokines, activating macrophages and inflammatory cells.

Immunodeficiency

• Loss or inadequate function of various components of the immune system or body's defensive mechanisms.
• Occurs in any part or state of the immune system, including Physical barriers, phagocytes, B lymphocytes or complement.
• Can be congenital (genetic abnormality/lymphocyte maturation defect).
• Can be acquired (secondary) (infections/treatments).

Autoimmunity

• Failure of an organism in recognizing its own constituent parts as self.
• Autoimmune includes immune system response to self component causes localized or systemic injury or any disease that results from aberrant immune response to recognizing self-cells. Examples are Grave's disease and Rheumatoid Arthritis.
• Mechanisms: Breakdown of immunological homeostasis or regulation, molecular mimicry or sequestered antigens.

Applications of Immunology

• It has significant applications in the field of:
  • Immunization/vaccination

Immunization/Vaccination

• Acquired through active (natural infection) or passive (maternal antibodies).
• Immunity achieved by active or passive immunization/vaccination.
• Can be acquired naturally (mother to fetus transfer) or artificially (injection of antibodies).

Vaccines

• Biological substances that stimulate immune system.
• Prepared from pathogens, raising a protective immune response without causing illness.
• Stimulate immune cells that help create memory cells that mount vigorous immune response to pathogens.
• Ideal vaccines provide the same immune protection, generating long-lasting response, and interrupt infection's spread.
• Vaccines are designed with a goal is to produce the same immune protection which usually follows natural infection.

Types of Vaccines

• In activated vaccines contains still antigenic, but inactivated pathogens.
• Live/altered vaccines contains attenuated microorganisms.
• Purified macromolecules from pathogen, capable of producing an immune response against inactivated toxins.
• There are ones with capsular polysaccharides or recombinant microbial antigens.