1. IMMUNE PATHOLOGY Decreased, inhibited immunity –One or more functions are missing and/or down-regulated Enhanced and/or dysregulated immunity –One or more functions are up- regulated Disturbed cell differentiation – B, T, NK or other collaborating cells Disturbed cellular function – activation, cell death, signaling, communication Levels of dysregulation – DNA, RNA, protein, post-translational modification, secretory function etc. IMMUNE SYSTEM – genetically encoded elements – developmental programs – continuous generation and death of cells – continuous contact with the environment Genetically determined – Loss of function mutation – Altered gene expression – Genetic predisposition Acquired – Environmental factors – Deviated reactions – Spectral diseases

2. THE IMMUNE RESPONSE TO PATHOGENS

4. PATHOGENS Bacteria, Viruses, Fungi Parasites Unicellular protozoa Multicellular worms REQUIRES HIGH INITIAL DOSE FOR INFECTION ESCAPE MECHANISMS TO AVOID DEFENSE MECHANISMS HUMAN BODY VAST RESOURCE RICH ENVIRONMENT FOR PATHOGENS DEFENSE MECHANISMS Physical barriers/Innate immunity – STOP MOST INFECTIONS WITHOUT CALLING Adaptive immunity Diseases – Medical practice DISEASE DISEASEInnate immunity fails to terminate infection Pathogen spreading into lymphoid tissues and activation of adaptive immunity Successful evasion and subversion of the immune system by pathogens

5. Environment SELF NON-SELF Destructive SELF Immune system Tolerance Immune response MagnitudeQuality

6. DIRECT EXOTOXIN Streptococcus pyogenes Staphylococcus aureus Corynebacterium diphteriae Clostridium tetani Vibrio cholerae ENDOTOXIN Escherichia coli Haemophylus influenzae Salmonella typhi Shigella Pseudomonas aeruginosa Yersinia pestis CYTOPHATHIC Variola Varicella zoster Hepatitis B virus Polio virus Measles virus Influenza virus Herpes simplex virus Tonsilitis Scarlet fever Toxic shock syndrome Food poisoning Diphteria Tetanus Cholera Gram (-) sepsis Meningitis Pneumonia Typhoid fever Baccillary dysentery Wound infection Plague Small pox Chicken pox, shingles Hepatitis Polyiomyelitis Measles Subacute sclerosing panencephalitis Influenza, cold sores MECHANISMS OF TISSUE DEMAGE INDUCED BY PATHOGENS DISEASE

7. CYTOPATHIC – CYTO-PROLIFERATIVE INFLAMMATION Acute and chronic inflammation Death of individual cells No or weak host – mediated inflammation Virus inclusion bodies – CMV, adenovirus, Ebola Fused multinucleated cells Modification and proliferation of epithelial cells Epithelial and lymphoid dysplasia – tumorigenic viruses INFLAMMATORY RESPONSES TO INFECTIOUS AGENTS NECROTIZING INFLAMMATION Toxin – mediated lesions Clostridium, HBV-infected hepatocytes, HHV neurons CHRONIC INFLAMMATION HBV cirrhosis in liver Schistosoma – fibrosis in liver

8. INCLUSION BODIES IN THE LIVER AFTER EBOLA VIRUS INFECTION

9. MULTINUCLEATED CELL IN HIV INFECTION

10. INDIRECT IMMUNE COMPLEX Hepatitis B virus Malaria Strreptococcus pyogenes Treponema pallidum Most acute infections ANTI-HOST ANTIBODY Streptococcus pyogenes Mycoplasma pneumoniae CELL-MEDIATED IMMUNITY Mycobacterium tuberculosis Mycobacterium leprae Lymphocytic chorio- meningitis virus Borrelia burgdorferi Schistosoma mansoni Herpes simplex virus Kidney disease Vascular deposits Glomerulonephritis Kidney demage in secondary syphilis Transient renal deposits Rheumatic fever Hemolytic anaemia Tuberculosis Tuberculoid leprosy Aseptic meningitis Lyme arthritis Schistosomiasis Herpes stromal keratitis MECHANISMS OF TISSUE DEMAGE INDUCED BY PATHOGENS DISEASE

11. INFLAMMATORY RESPONSES TO INFECTIOUS AGENTS Diversity in pathogens and inflamatory mediators Common features of histology and morphologic patters POLYMORPHONUCLEAR INFILTRATION Acute tissue demage  Increase vascular permeability  Neutrophilic exudation (pus)  Pyogenic bacteria  Chemoattractant f-Met peptides  Chemoattractant C5a  LPS-mediated macrophage activation MONONUCLEAR INFILTRATION Effector cell infiltration  Plasma cells (Syphilis lesions)  T cell infiltration  virus infection – acute  intracellular bacteria – acute  Helminths, spirochetes – chronic  Granulamotous inflammation M. tuberculosis, Schistosoma  Spectral diseases M. leprae, Leishmania Strong response, many lymphocytes Few pathogens and macrophages Weak response, few lymphocytes Many pathogens and macrophages

12. Seen here is vasodilation with exudation that has led to an outpouring of fluid with fibrin into the alveolar spaces, along with PMN's. The series of events in the process of inflammation are: 1.Vasodilation: leads to greater blood flow to the area of inflammation, resulting in redness and heat. 2.Vascular permeability: endothelial cells become "leaky" from either direct endothelial cell injury or via chemical mediators. 3.Exudation: fluid, proteins, red blood cells, and white blood cells escape from the intravascular space as a result of increased osmotic pressure extravascularly and increased hydrostatic pressure intravascularly 4.Vascular stasis: slowing of the blood in the bloodstream with vasodilation and fluid exudation to allow chemical mediators and inflammatory cells to collect and respond to the stimulus. The cardinal signs of inflammation are rubor (redness), calor (heat), tumor (swelling), dolor (pain), and loss of function. Seen here is skin with erythema. ACUTE INFLAMMATION

13. The arm at the bottom is swollen (edematous) and reddened (erythematous) compared to the arm at the top. Acute inflammation is marked by an increase in inflammatory cells. Perhaps the simplest indicator of acute inflammation is an increase in the white blood cell count in the peripheal blood, here marked by an increase in segmented neutrophils (PMN's). As in the preceding diagram, here PMN's that are marginated along the dilated venule wall (arrow) are squeezing through the basement membrane (the process of diapedesis) and spilling out into extravascular space.