1. General Pathology
    2. 1. The Cell as a Unit of Health and Disease
    2. Cellular Response to Stress and Toxic Insults
    3. Inflammation and Repair
    4. Hemodynamic Disorders, Thromboembolic Disease, and Shock
    5. Genetic Disorders
    6. Diseases of the Immune System
    7. Neoplasia
    8. Infectious Diseases
    9. Environmental and Nutritional Diseases
    10. Diseases of Infancy and Childhood
  2. Systemic Pathology: Diseases of Organ Systems
    3. 11. Blood vessels
    12. The Heart
    13. Diseases of White Blood Cells, Lymph Nodes, Spleen, and Thymus
    14. Red Blood Cell and Bleeding Disorders
    15. The Lung
    16. Head and Neck
    17. The Gastrointestinal Tract
    18. Liver and Gallbladder
    19. The Pancreas
    20. The Kidney
    21. The Lower Urinary Tract and Male Genital System
    22. The Female Genital Tract
    23. The Breast
    24. The Endocrine System
    25. The Skin
    26. Bones, Joints, and Soft Tissue Tumors
    27. Peripheral Nerves and Skeletal Muscles
    28. The Central Nervous System
    29. The Eye
General Pathology
6. Diseases of the Immune System
THE NORMAL IMMUNE RESPONSE
Feature
Innate Immunity (Natural/ native immunity)
Adaptive Immunity (Acquired/ Specific immunity)
Definition
Present since birth and already evolved to recognize microbes.
Specific immune response that develops after exposure to antigens.
Defence
First line of defence
Second line of defence
Onset
Immediate (minutes to hours)
Delayed (days to weeks)
Specificity
Non-specific (recognizes general patterns)
Highly specific (recognizes specific antigens)
Memory
No immunological memory
Develops memory → faster and stronger response on re-exposure
Power
Less powerful
More powerful
Response to repeated exposure
Same magnitude each time
Stronger and faster (due to memory cells)
Components
  1. Physical barriers (skin, mucosa)
  2. Phagocytes
  3. Complement proteins
  1. Cellular component
  2. Humoral component
Cells involved
  1. Macrophages
  2. Neutrophils
  3. Natural Killer (NK) cells
  4. Dendritic cells
  1. B lymphocytes (produce antibodies)
  2. T lymphocytes (helper and cytotoxic T cells)
Receptors
Germline-encoded pattern recognition receptors (e.g., TLRs)
Receptors are formed by somatic gene rearrangement (TCR, BCR)
Examples
  1. Inflammatory response to injury
  2. Fever
  3. Phagocytosis of bacteria
  1. Production of antibodies after vaccination
  2. T cell-mediated killing of virus-infected cells
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Feature
IgG
IgA
IgM
IgE
IgD
Subclasses
IgG1, IgG2, IgG3, IgG4
IgA1, IgA2
N/A
N/A
N/A
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Structure
Monomeric
Monomeric(serum) /dimer(glandular secretions)
Pentameric
Monomeric
Monomeric
Size
Two gamma (γ) heavy chains + two light chains
Two alpha (α) heavy chains + two light chains
10 mu (μ) heavy chains + 10 light chains
Two epsilon (ε) heavy chains + two light chains
Two delta (δ) heavy chains + two light chains
Key Features
  1. Present in maximum concentration in human body
  2. Important for secondary immune response
  3. Can cross the placenta
  4. Involved in classical pathway activation (with IgM)
  1. Present in physiological secretions (e.g., saliva, tears, breast milk)
  2. Responsible for activation of alternate complement pathway
  1. Important for primary immune response
  2. Maximum molecular weight and size
  3. Also called 'Millionaire’s antibody'
  4. Functions as B cell receptor
  5. Involved in classical pathway activation (more potent than IgG)
  1. Increased in allergic conditions
  2. Also known as 'homocytotropic antibody'
  3. Also called 'reaginic antibody'
  1. Functions as B cell receptor
Innate Immunity
Components of Innate Immunity
▢ Epithelial barrier:
❖ Locations:
  1. Epithelia of the skin.
  2. Epithelia of the gastrointestinal tract.
  3. Epithelia of the respiratory tract.
❖ Functions:
  1. Provides mechanical barriers to the entry of microbes from the external environment.
  2. Produces antimicrobial molecules like
    1. Defensins
    2. Lymphocytes
▢ Monocytes:
  1. Phagocytes of the blood.
▢ Neutrophils:
  1. Phagocytes of the blood.
  2. Monocytes that enter the tissues and mature are called Macrophages.
    3. ◉ Macrophages:
    1. All tissues have resident macrophages.
      1. Brain → Microglia
      2. Skin → Dendritic cells/ Langerhans' cells
      3. Connective tissue → Histiocytes
      4. Cartilage → Condrocytes
      5. Bone → Osteocytes
      6. Thymus → Hassal's corpuscles
      7. Lungs → Dust cells
      8. Liver → Kuffer cells
      9. Spleen → Sinusoidal cells
      10. Kidney → Messangial cells
▢ Dendritic cells:
❖ Locations:
  1. Epithelia
  2. Lymphoid organs
  3. Most tissues
❖ Functions:
◉ Antigen presenting function: They capture protein antigens and display peptides for recognition by T lymphoctes.
◉ Cytokine secretion: They are endowed with a rich collection of receptors that sense microbes and cell damage and stimulate the secretion of cytokines.
▢ Natural killer cells: They provide early protection against many viruses and intracellular bacteria.
▢ Mast cells:
▢ Innate lymphoid cells:
▢ Proteins of the complement system:
▢ Mannose-binding lectin:
▢ C-reactive protein:
Cellular Receptors for Microbes, Products of Damaged Cells, and Foreign Substances
▢ Pathogen-associated molecular patterns:
▢ Damage-associated molecular patterns:
Actions of Innate Immunity
Adaptive Immunity
Cells of the Immune System
Lymphocyte Diversity
T Lymphocytes
Helper T lymphocytes
  1. Stimulates B lymphocytes to make antibodies and
  2. Activate other leukocytes (e.g., phagocytes) to destroy microbes.
Cytotoxic T lymphocytes (CTLs)
  1. Kill infected cells
Regulatory T lymphocytes
  1. Limit immune responses and prevent reactions against self antigens.
B Lymphocytes
Dendritic Cells
Macrophages
Natural Killer Cells
Innate Lymphoid Cells (ILCs)
Tissues of the Immune System
Generative Lymphoid Organs
Peripheral Lymphoid Organs
Lymphocyte Recirculation
Major Histocompatibility Complex (MHC) Molecules: The Peptide Display System of Adaptive Immunity
Cytokines: Messenger Molecules of the Immune System
Overview of Lymphocyte Activation and Immune Responses
Display and Recognition of Antigens
Cell-Mediated Immunity
Humoral Immunity
HYPERSENSITIVITY: IMMUNOLOGICALLY MEDIATED TISSUE INJURY
Classification of Hypersensitivity Reactions
Feature
Type I: Immediate hypersensitivity
Type II: Antibody-mediated hypersensitivity
Type III: Immune complex–mediated hypersensitivity
Type IV: Cell-mediated (delayed-type) hypersensitivity
Antibody-mediated
Cell-mediated
Antigen
Exogenous, Free
Endogenous, Fixed to tissue
Exogenous or Endogenous, Free
Antibody
IgE fixed on Mast cell and Basophil
IgG or IgM free
IgG or IgM free
Ag-Ab reaction
On Mast cell or Basophil
On Target Tissue
Free immune complex
Immune Mechanism
IgE production → release of histamine and mediators from mast cells → later recruitment of inflammatory cells
IgG and IgM antibodies bind to target antigens → phagocytosis or lysis via complement or Fc receptor → leukocyte recruitment
Formation and deposition of antigen-antibody complexes → complement activation → leukocyte recruitment → tissue damage
Activated T lymphocytes → cytokine release, macrophage activation, and/or direct cytotoxicity by CTLs
Histopathologic Lesions
Vascular dilation, edema, smooth muscle contraction, mucus production, inflammation, tissue injury
Phagocytosis and lysis of cells, inflammation, possible functional disturbance without overt damage
Inflammation, necrotizing vasculitis, fibrinoid necrosis
Perivascular infiltrates, edema, granuloma formation, and cell destruction
Examples / Prototypical Disorders
  1. Anaphylaxis
  2. Allergies (e.g., hay fever)
  3. Bronchial asthma (atopic)
  1. Autoimmune hemolytic anemia
  2. Goodpasture syndrome
  1. Systemic lupus erythematosus (SLE)
  2. Glomerulonephritis (some forms)
  3. Serum sickness
  4. Arthus reaction
  1. Contact dermatitis
  2. Tuberculosis
  3. Type 1 diabetes
  4. Multiple sclerosis
Immediate (Type I) Hypersensitivity
Activation of TH2 Cells and Production of IgE Antibody
Sensitization and Activation of Mast Cells
Mediators of Immediate Hypersensitivity
Late-Phase Reaction
Development of Allergies
Systemic Anaphylaxis
Local Immediate Hypersensitivity Reactions
Antibody-Mediated (Type II) Hypersensitivity
Opsonization and Phagocytosis
Inflammation
Cellular Dysfunction
Immune Complex–Mediated (Type III) Hypersensitivity
Systemic Immune Complex Disease
Local Immune Complex Disease (Arthus Reaction)
T Cell–Mediated (Type IV) Hypersensitivity
CD4+ T Cell–Mediated Inflammation
CD8+ T Cell–Mediated Cytotoxicity
AUTOIMMUNE DISEASES
Immunologic Tolerance
Central Tolerance
Peripheral Tolerance
Mechanisms of Autoimmunity
General Principles
Role of Susceptibility Genes
Role of Infections
General Features of Autoimmune Diseases
Systemic Lupus Erythematosus (SLE)
Spectrum of Autoantibodies in SLE
Etiology and Pathogenesis of SLE
Drug-Induced Lupus Erythematosus
Rheumatoid Arthritis
Sjögren Syndrome
Systemic Sclerosis (Scleroderma)
Inflammatory Myopathies
Mixed Connective Tissue Disease
Polyarteritis Nodosa and Other Vasculitides
IgG4-Related Disease
REJECTION OF TISSUE TRANSPLANTS
Mechanisms of Recognition and Rejection of Allografts
Recognition of Graft Alloantigens by T and B Lymphocytes
T Cell–Mediated Reactions
Antibody-Mediated Reactions
Rejection of Kidney Grafts
Methods of Increasing Graft Survival
Transplantation of Other Solid Organs
Transplantation of Hematopoietic Cells
IMMUNODEFICIENCY SYNDROMES
Primary Immunodeficiencies
Defects in Innate Immunity
Defects in Leukocyte Function
Deficiencies Affecting the Complement System
Defects in Adaptive Immunity
Defects in Lymphocyte Maturation
Severe Combined Immunodeficiency
X-Linked Agammaglobulinemia
DiGeorge Syndrome (Thymic Hypoplasia)
Other Defects in Lymphocyte Maturation
Defects in Lymphocyte Activation and Function
Hyper-IgM Syndrome
Common Variable Immunodeficiency
Isolated IgA Deficiency
X-Linked Lymphoproliferative Syndrome
Other Defects in Lymphocyte Activation
Immunodeficiencies Associated with Systemic Diseases
Wiskott-Aldrich Syndrome
Ataxia Telangiectasia
Secondary Immunodeficiencies