Chapter 2 Immunity

Learning Outcomes

• Define and apply key immune-related terms

• Differentiate innate vs. adaptive immunity

• Describe lymphocytes, macrophages, and antigen-presenting cells

• Explain primary vs. secondary antibody responses; compare types of T lymphocytes in cell-mediated immunity

• Describe immunoglobulin classes (IgA, IgD, IgE, IgG, IgM)

• Discuss altered immune function: host defense failure, hypersensitivity, autoimmunity, alloimmunity, immunodeficiency

• Apply concepts to clinical models (e.g., lupus, HIV/AIDS)

Stress and Immunity

Stress can negatively affect body homeostasis

Universal experience

Can contribute to development/exacerbation of disease and the tendency to engage in negative behavior

Can arise from many events, including those perceived as positive

Chronic stress weakens immunity, increases disease risk

The Stress Response

Hans Selye observed physiological changes from stress

General adaptation syndrome (GAS)

• alarm stage - the initial reaction, activation of fight or flight, increase in stress hormone release, increased HR and BP

• resistance stage - adaptation to stress response

• exhaustion stage - breakdown of defenses from chronic stress, illness is most likely

Local adaptation syndrome (LAS)

• confines damage to one area

• inflammation after an injury

• predictable

• individual variability

• past experiences and support system can influence

Stress response is somewhat predictable with individual variability

• conditioning factors

• some coping strategies can minimize/eliminate effects

Overview of Immunity

Immunity: recognition & neutralization of foreign substances (antigens)

Immunology: study of immune system & its function

Key principles:

• Specificity → cells seek & destroy invaders

  • antibodies for measles only attack measles, useless against the flu

• Memory → faster response on re-exposure (basis for vaccines)

Core Components

• Antigen = foreign particle that triggers immune response

  • bacteria, viruses, toxins, abnormal cells

• Leukocytes = primary immune cells (innate & adaptive)

  • white blood cells

• Body is constantly under microbial assault

• System is self-regulated & self-limiting → must distinguish self from non-self

Layers of immunity:

• Innate defenses (nonspecific, immediate)

• Adaptive defenses (specific, memory)

• Lymphatic system (organs/tissues coordinating immune responses)

Lymphocytes and Organs of Immunity

Lymphocytes: basic unit of the immune system

Lymphatic system:

• Transports lymphocytes and immune cells

• Lymph nodes act as immune checkpoints

Organs of Immunity

• Primary (Central): Bone marrow & Thymus

  • bone marrow - the training center, development

  • thymus - maturation site

• Secondary (Peripheral): Lymph nodes , Spleen , Tonsils, Appendix

Innate Immunity

Adaptive Immunity

Acquired defenses that target specific antigens

Slower to develop, but provides memory for future protection

Key features:

• Specificity: immune cells target one specific antigen

• Memory: faster, stronger response on re-exposure

• Self vs. non-self recognition prevents autoimmunity

Cellular players:

• B lymphocytes: humoral immunity (antibodies)

• T lymphocytes: cell-mediated immunity (Helper T, Cytotoxic T, Regulatory T)

Activation of Adaptive Immunity

Antigen enters the body

• APCs like dendritic cells and macrophages engulf the foreign particle

Antigen-presenting cells recognize the antigen

• through the MHC molecules

T and B cells become activated

Clonal expansion occurs

• multiplication of T and B cells

• all cells are programmed to respond to the same antigen

• B cells → plasma cells

• Cytotoxic T cells → directly attack

• Helper T cells → support

Effector cells attack the pathogen

Memory cells remain for future protection

Recognition → Present → Activation → Expansion → Attack → Memory

Humoral vs. Cell-Mediated Immunity

Humoral Immunity

• B Cells → Antibodies → Extracellular Pathogens

• Body Fluids and antibodies

Cell-Mediated Immunity

• T Cells → Infected Cells → Intracellular Pathogens

• Target infected cells

Innate vs. Adaptive Immunity: Across the Life Span

Infancy:

• maternal IgG provides temporary passive immunity

• breast milk provides IgA protection

• vaccinations build active immunity

Adolescence:

• hormonal changes influence immune responses

• increased risk for some autoimmune disorders

Older Adults:

• immune senescence (aging of the immune system)

• reduce B- and T-cell function

• increased susceptibility to infection

• reduced vaccine response

Inflammatory Response

Purpose:

• eliminate the cause of injury

• removed damaged tissue

• generate new tissue

Types

• acute → rapid, short-term

  • swelling, heat, localized redness, pain, loss of function

• chronic → prolonged, ongoing

  • may come from unresolved inflammation, persistent infection, autoimmune infection

Medical Terminology

• suffix “itis” = inflammation

• examples: cellulitis, appendicitis

Key Inflammatory Mediators

Histamine - causes dilation of arterioles and increases permeability of venules (redness, warmth, swelling)

Prostaglandins - induce inflammation and potentiate effects of histamine (pain and fever)

Cytokines - induces priming and aggregation of neutrophils, mediators of systemic responses including fever, hypotension, and increased levels of corticosteroid hormones (cell communication and fever)

Cellular Response in Inflammation

Margination (move toward vessel wall) → Transmigration (diapedesis = leave bloodstream) → Chemotaxis (follow chemical signs, guide neutrophils to where they are needed) → Phagocytosis (engulf and destroy pathogens)

Neutrophils: The First Responders

First responder (~90 minutes)

Perform Phagocytosis

Increase during bacterial infections

• immature - bands

• mature - segs

Other Key White Blood Cells in Inflammation

Eosinophils (allergies and parasites)

• increased during allergic reactions

• control the release of chemical mediators

Monocytes (clean up crew)

• second white cell to arrive

• released to act as macrophages

Basophils/Mast Cells (histamine release)

• release chemical mediators

  • histamine - increased vasodilation and vascular permeability

  • heparin

Alterations of the Immune System

Immune system requires all components to function properly

Failure leads to increased risk of disease and death

Major categories of dysfunction

• host defense failure: inability to protect against pathogens

• hypersensitivity: excessive or inappropriate immune response

• autoimmunity: immune system attacks self-tissues (SLE)

• alloimmunity: reaction against foreign tissue (ie transplant rejection)

• immunodeficiency: weakened immune response (congenital or acquired)

Hypersensitivity Reactions - General Overview

Definition: exaggerated or inappropriate immune response that causes tissue injury or disease

Occurs when normal protective immune mechanisms become harmful

Can be antibody-mediated (Types I-III) or T-cell mediated (Type-IV)

Responses may be immediate (minutes to hours) or delayed (days)

Clinical Significance: contribute to allergy, autoimmunity, and transplant rejection

Types of Hypersensitivity

Pathology of Anaphylaxis

Diagnosis of Anaphylaxis

Clinical diagnosis is based on rapid onset of symptoms after allergen exposure

History of allergen exposures (food, drug, insect sting)

Key Findings

• skin and mucosal changes (hives, angioedema)

• respiratory compromise (wheezing, stridor)

• hypotension or syncope

• Labs (not acute): serum tryptase, allergy testing (later)

Clinical Manifestations of Anaphylaxis

Treatment of Anaphylaxis

First-line: IM Epinephrine (0.3-0.5mg adult: 0.01mg/kg child) in mid-thigh

• maybe repeated every 5-15 minutes

Call EMS immediately

Airway and oxygen support, possible intubation

IV fluids for hypotension

Adjunctive meds (used with epinephrine not in place of)

• antihistamines (H1 and H2 blockers)

• Corticosteroids (reduce late-phase reaction)

• Beta-agonists (albuterol for bronchospasm)

Long-term: Epinephrine auto-injector, allergen avoidance, medical alert ID

Autoimmune Disorder: Systemic Lupus Erythematosus (SLE) -Type III Hypersensitivity Reaction

Chronic systemic autoimmune disease

Physical and Emotional Stress may precipitate disease flare ups

• stress does not cause lupus

Stressors trigger exacerbations

Production of autoantibodies (ANA, anti-dsDNA)

Immune complexes deposit in tissues → inflammation and organ damage

Multisystem involvement: skin, joints, kidneys, heart, CNS

Diagnosis of SLE

ANA (antinuclear antibody)

• screening test

• positive result

• it is sensitive but not specific to lupus

Anti-dsDNA and anti-Smith antibodies

• highly specific and sensitive

Labs

• anemia, leukopenia, thrombocytopenia

Urinalysis

• proteinuria, hematuria (lupus nephritis)

Clinical Manifestations

Treatment of SLE

Medications

• NSAIDS → joint pain, inflammation

• Corticosteroids → reduce inflammation (acute flares)

• Immunosuppressants (azathioprine, cyclophosphamide, mycophenolate)

• Hydroxychloroquine (Plaquenil) → for skin/joint symptoms

Lifestyle

• sun protection

• infection prevention

Alloimmunity: Transplant Reactions

Transplant Rejection

Immune system recognizes transplanted tissue as foreign

Better tissue matching decreases rejection risk

Types of rejection:

• hyperacute (minutes-hours)

• acute (days-months)

• chronic (months-years)

Graft-versus-host disease

• donor immune cells attack recipient tissues

• most common with bone marrow transplants

Recipient attacks graft = rejection

Graft attack recipient = GVHD

Immunodeficiency: HIV/AIDS

Diminished/absent immune response → infections

Categories

• primary: present at birth due to inherited immune problems

• secondary: develops later in life from external factors

General Features

• HIV is the most common acquired immunodeficiency disorder

• HIV destroys CD4+ (helper T) cells

• Decreased CD4+ count → increased risk for opportunistic infections

• ART suppresses viral replication and improves outcomes

Pathophysiology of HIV/AIDS

HIV is a retrovirus that targets CD4 helper T cells

Transmission:

• blood

• sexual contact

• perinatal (mother to infant)

HIV enters and replicates inside CD4 cells

Progressive loss of CD4 cells weakens immunity

Increased susceptibility to opportunistic infections

AIDS develops when CD4 count falls below 200 cells/mm³ or an AIDS-defining illness occurs

Diagnosis and Monitoring of HIV

Clinical Manifestations of HIV/AIDS

Acute Infection

• flu-like illness

• fever, sore throat, rash

• high viral load

Clinical Latency

• often asymptomatic

Gradual decline in CD4 cells

AIDS

• CD4 < 200 cells/mm³

• opportunistic infections

• increased risk for certain cancers

HIV progresses from acute infection → latency → AIDS

Classic clues that HIV has progressed to AIDs

• oral candidiasis (thrush)

• pneumocystis jirovecii pneumonia (PCP)

• Tuberculosis

• Kaposi sarcoma

Treatment of HIV/AIDS

Goals of Treatment

• suppress viral replication

• increase/maintain CD4 count

• prevent opportunistic infections

• improve quality of life

Antiretroviral Therapy (ART)

• lifelong treatment

• combination of medications

• must be taken consistently

• decreases viral load and infections, increases CD4

Patient Education

• medication adherence is critical

• safe sex practices reduce transmission

• regular follow-up and monitoring

Immune Response: Disease Prevention and Management

Vaccines and Immune Protection

• vaccines expose the immune system to antigens

• stimulate antibody production and memory cell formation

• provide active immunity

• reduce risk of infection and severe disease

• help protect individuals and communities (herd immunity)

Vaccines work by creating immune memory before exposure to the real pathogen

Practice appropriate infection prevention while allowing normal environmental exposures

Lifestyle strategies:

• smoking cessation

• proper nutrition

• regular exercise

• moderate alcohol consumption

• stress management