Disorders Associated with the Immune System

Microbiology: An Introduction - Disorders Associated with the Immune System

Introduction

  • Focus: Understanding disorders related to the immune system as presented in Chapter 19 of the textbook.

Big Picture: The Hygiene Hypothesis

  • Dysbiosis:

    • Definition: An imbalance that causes adverse effects in humans.

    • Example: Antibiotic therapy kills normal gut microbiota, allowing proliferation of Clostridioides difficile.

    • Linked Conditions: Possible causes of Inflammatory Bowel Diseases (IBDs) such as ulcerative colitis and Crohn's disease.

Allergies and Asthma

  • Observation: Fewer allergies in tribal populations and children from farms vs children in urban settings.

    • Possible Explanation: Greater microbial exposures in farm settings contribute to lower asthma rates.

Inflammatory Bowel Diseases (IBDs)

  • Possible Cause: Lack of normal microbiota metabolic products leads to chronic inflammatory state.

Treatments

  • Treating Crohn’s Disease with Worms:

    • Treatment involves whipworm eggs that suppress T helper cell pathways.

  • Fecal Transplants for C. difficile Infections:

    • Involves taking gut microbiota from a healthy individual and transplanting it into the patient.

Hypersensitivity

  • Definition: Antigenic response that leads to undesirable effects, occurring upon re-exposure to an allergen in sensitized individuals.

  • Types of Hypersensitivity:

    • Anaphylactic (Type I)

    • Cytotoxic (Type II)

    • Immune Complex (Type III)

    • Delayed Cell-Mediated (Type IV)

  • Note: The study of hypersensitivity reactions is called immunopathology.

  • Hygiene hypothesis impact: Suggests that limiting exposure to pathogens may reduce immune tolerance.

Types of Hypersensitivity

Table 19-1: Types of Hypersensitivity

  • Type 1 (Anaphylactic):

    • Time Before Clinical Signs: < 30 min

    • Mechanism: IgE binds to mast cells/basophils, causing their degranulation and release of substances (histamine).

    • Examples: Anaphylactic shock from drugs, insect venom, hay fever, asthma.

  • Type 2 (Cytotoxic):

    • Time Before Clinical Signs: 5-12 hours

    • Mechanism: Antigen causes IgM/IgG antibodies to bind to target cells, leading to cell destruction.

    • Examples: Transfusion reactions, Rh incompatibility.

  • Type 3 (Immune Complex):

    • Time Before Clinical Signs: 3-8 hours

    • Mechanism: Antibodies and antigens form complexes causing inflammation.

    • Examples: Arthus reactions, serum sickness, rheumatoid arthritis.

  • Type 4 (Delaying Cell-Mediated):

    • Time Before Clinical Signs: 24-48 hours

    • Mechanism: Antigens activate CTLs which kill target cells.

    • Examples: Tissue rejection, contact dermatitis, certain chronic diseases like tuberculosis.

Type 1 (Anaphylactic) Reactions

  • Occur minutes after re-exposure to an antigen.

  • Mechanism: Antigens combine with IgE antibodies attached to mast cells and basophils.

    • Degranulation Mediators:

    • Histamine: Increases blood capillary permeability.

    • Leukotrienes: Cause prolonged smooth muscle contraction.

    • Prostaglandins: Affect smooth muscle and increase mucus secretion.

Anaphylaxis

  • Systemic Anaphylaxis (Anaphylactic Shock):

    • Results from re-exposure to an antigen.

    • Affects cardiovascular and respiratory systems, can lead to shock and death.

    • Symptoms include blood vessel dilation, leading to decreased blood pressure.

    • Common triggers: Injected antigens, bee stings.

    • Treatment: Epinephrine to constrict blood vessels and increase blood pressure.

  • Localized Anaphylaxis:

    • Typically affects limited body regions, less severe.

    • Associated with ingested, inhaled, or contacted antigens:

    • Examples: Pollen, dust mites, nuts.

    • Symptoms vary based on entry route (e.g., hay fever, asthma).

    • Treatment: Bronchodilators and leukotriene blockers.

Food Allergies

  • Common allergens: Eggs, peanuts, milk, etc.

  • Symptoms: Hives, gastrointestinal upset, systemic anaphylaxis can occur.

Preventing Anaphylactic Reactions

  • Allergy Testing:

    • Antigens inoculated under skin to observe an inflammatory reaction (wheal).

  • Desensitization:

    • Increasing dosages of antigen injected to produce IgG that intercepts and neutralizes allergens.

Type 2 (Cytotoxic) Reactions

  • Involves activation of complement by IgG/IgM antibodies with antigenic cells, causing lysis.

  • ABO Blood Group System:

    • Involves antibodies against carbohydrate antigens on RBCs (Type O, A, B, AB).

Table 19-2: The ABO Blood Group System

  • Blood Group A: Contains A antigens, Anti-B antibodies, can receive A, O.

  • Blood Group B: Contains B antigens, Anti-A antibodies, can receive B, O.

  • Blood Group AB: Contains both A and B antigens, no antibodies, can receive A, B, AB, O.

  • Blood Group O: Contains no A or B antigens, Anti-A and Anti-B antibodies, can only receive O.

Type 2 - Rh Blood Group System

  • Rh Factor: Present on RBCs for 85% of the population.

  • A mother with an Rh- fetus may produce anti-Rh antibodies post-sensitization.

  • Hemolytic Disease of the Newborn (HDNB):

    • Anti-Rh antibodies damaging fetal RBCs.

    • Prevention: RhoGAM shots at 28 weeks and post-delivery.

Drug-Induced Cytotoxic Reactions

  • Immune Thrombocytopenic Purpura:

    • Drug-platelet complexes form and are destroyed by antibodies.

  • Agranulocytosis and Hemolytic Anemia:

    • Drug-induced immune destruction of granulocytes and RBCs.

Type 3 (Immune Complex) Reactions

  • Occur when antibodies react with soluble antigens, forming complexes that settle in blood vessel walls, activating complement and causing inflammation.

Arthus Reaction

  • Rare side effect of vaccine, usually occurs with already circulating IgG against injected antigen.

  • Serum Sickness: Swelling and inflammation due to foreign serum injection.

Type 4 (Delayed Cell-Mediated) Reactions

  • Cell-mediated immune responses caused by T cells.

  • On first exposure, phagocytized antigens present to T cells sans reaction. On reexposure, memory cells release destructive cytokines, developing over multiple days.

Allergic Contact Dermatitis

  • Haptens provoke immune response via skin contact.

    • Examples include poison ivy and some cosmetics.

Autoimmune Diseases

  • Occur when the immune system responds to self-antigens causing organ damage.

  • Predominantly affects women (80% of autoimmune diseases).

  • Loss of Self-Tolerance:

  • Types of reactions: Cytotoxic, immune complex, or cell-mediated.

Cytotoxic Autoimmune Reactions

  • Multiple Sclerosis:

    • T cells attack the myelin sheath of nerves causing severe symptoms.

    • Etiology remains unclear, potential involvement of genetic factors or infections like Epstein-Barr virus.

Immune Complex Autoimmune Reactions

  • Systemic Lupus Erythematosus:

    • Autoantibodies against cellular components like DNA lead to immune complex formations.

  • Rheumatoid Arthritis:

    • Immune complexes deposit in joints causing inflammation and severe joint damage.

Type 4 Autoimmune Reactions

  • Insulin-Dependent Diabetes Mellitus:

    • T cell-mediated destruction of insulin-secreting cells.

  • Psoriasis and Psoriatic Arthritis:

    • Autoimmune conditions affecting skin and joints.

Role of HLA (Human Leukocyte Antigens)

  • HLA: Major histocompatibility complex (MHC) in humans—important for antigen presentation to T cells.

  • HLA typing: Lab tests for identifying HLAs; certain HLAs linked to specific diseases.

Diseases Linked to Specific HLA Types

  • Multiple Sclerosis: 5 times risk with specific HLA types.

  • Graves’ Disease: 10-12 times increased susceptibility.

  • Addison’s Disease: 4-10 times increase linked with specific HLAs.

Transplant Surgery Implications

  • HLA matching is critical for transplant success to prevent rejection.

  • Privileged Sites: Some tissues (e.g., cornea) can withstand transplants without immune response.

Stem Cells and Transplants

  • Types of Stem Cells:

    • Embryonic Stem Cells (ESCs): Pluripotent stem cells sourced from blastocysts used for tissue regeneration.

    • Adult Stem Cells: Limited differentiation potential; can become induced pluripotent stem cells.

Bone Marrow Transplants

  • Also known as hematopoietic stem cell transplants, aimed at producing healthy blood cells.

    • Risk of Graft-Versus-Host Disease (GVHD) from transplanted immunocompetent cells.

Graft Types

  • Autograft: Tissue from oneself.

  • Isograft: Tissue from an identical twin.

  • Allograft: Tissue from another person.

  • Xenotransplantation: Nonhuman tissue use, e.g., genetically modified pigs.

Immunosuppression for Transplants

  • Prevents immune rejection; drugs include cyclosporine, tacrolimus, sirolimus.

The Immune System and Cancer

  • Cancer cells are often marked by tumor-associated antigens.

  • CTLs, activated macrophages, and NK cells can destroy these cells.

  • Challenges include rapid tumor growth and evasion from immune surveillance.

Immunotherapy for Cancer

  • Treatment Methods:

    • Bacterial endotoxins, vaccines targeting specific cancers (e.g., HPV), and monoclonal antibodies for targeted therapy.

Immunodeficiencies

  • Types:

    • Congenital: E.g., DiGeorge syndrome affecting thymus development and T cell response.

    • Acquired: Developing later in life due to various factors.

Table of Selected Immunodeficiencies

  • AIDS: Caused by HIV destruction of CD4 T cells; leads to opportunistic infections.

  • Common Variable Hypogammaglobulinemia: Decreased immunoglobulins leading to frequent infections.

Acquired Immunodeficiency Syndrome (AIDS)

  • History: Cluster of cases in young homosexual men in 1981 leads to HIV discovery in 1983.

  • Origin of HIV: Crossed from chimps to humans in Africa around 1908, spread due to urbanization.

Structure of HIV

  • Retrovirus with two identical RNA genomes, reverse transcriptase, integrase enzymes, and gp120 glycoproteins.

  • Mechanism of infectivity centers on attachment, entry, reverse transcription, and integration into host DNA.

Stages of HIV Infection

  • Phase 1: Asymptomatic or lymphadenopathy, high RNA levels post-infection.

  • Phase 2: CD4+ T cells decrease, latent form in many cells, subtle symptoms may appear.

  • Phase 3: AIDS develops; CD4+ count drops critically, opportunistic diseases arise.

Diagnostic Methods for HIV

  • Routine testing recommended based on exposure risk; antibodies in blood detected for diagnosis.

    • Positive screening must be confirmed through tests like Western blot.

  • Nucleic Acid Amplification Tests (NAATs): Detect RNA early and monitor viral load.

HIV Transmission

  • Involves transfer through infected body fluids, with sexual contact being the primary mode.

  • Most infective via blood and semen.

Global AIDS Overview

  • 38 million infected worldwide, with the majority in Africa.

    • Transmission commonly occurs through heterosexual contact.

Preventive Measures and Treatments for AIDS

  • Multilayered approach involving biomedical, behavioral, and structural interventions.

    • Highly Active Antiretroviral Therapy (HAART) considered an effective treatment method to manage and minimize HIV progression.

  • Variety of drug inhibitors targeting different phases of the HIV life cycle.

Challenges in HIV Vaccine Development

  • No natural immunity model exists, high mutation rate, and rapid antigenic variation pose significant hurdles in vaccine research.