Transcript immune system

IMMUNE PATHOLOGY
IMMUNE SYSTEM
•
– genetically encoded elements
– developmental programs
– continuous generation and death of cells
– continuous contact with the environment
Decreased, inhibited immunity
•
– One or more functions are missing
and/or down-regulated
Enhanced and/or dysregulated
immunity
– One or more functions are upregulated
Genetically determined
Acquired
– Loss of function mutation
– Environmental factors
– Altered gene expression
– Deviated reactions
– Genetic predisposition
– Spectral diseases
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.
THE IMMUNE RESPONSE TO PATHOGENS
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
Innate 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
Environment
Immune system
Tolerance
SELF
NON-SELF
Destructive
SELF
Immune
response
Magnitude
Quality
MECHANISMS OF TISSUE DEMAGE INDUCED BY
PATHOGENS
DIRECT
EXOTOXIN
ENDOTOXIN
CYTOPHATHIC
Streptococcus pyogenes
Staphylococcus aureus
Corynebacterium diphteriae
Clostridium tetani
Vibrio cholerae
Escherichia coli
Haemophylus influenzae
Salmonella typhi
Shigella
Pseudomonas aeruginosa
Yersinia pestis
Variola
Varicella zoster
Hepatitis B virus
Polio virus
Measles virus
Influenza virus
Herpes simplex virus
DISEASE
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
INFLAMMATORY RESPONSES TO INFECTIOUS AGENTS
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
NECROTIZING INFLAMMATION
Toxin – mediated lesions
Clostridium, HBV-infected hepatocytes, HHV neurons
CHRONIC INFLAMMATION
HBV cirrhosis in liver
Schistosoma – fibrosis in liver
INCLUSION BODIES IN THE LIVER AFTER EBOLA VIRUS
INFECTION
MULTINUCLEATED CELL IN HIV INFECTION
MECHANISMS OF TISSUE DEMAGE INDUCED BY
PATHOGENS
INDIRECT
IMMUNE COMPLEX
Hepatitis B virus
Malaria
Strreptococcus pyogenes
Treponema pallidum
Most acute infections
ANTI-HOST ANTIBODY
CELL-MEDIATED IMMUNITY
Streptococcus pyogenes
Mycoplasma pneumoniae
Mycobacterium tuberculosis
Mycobacterium leprae
Lymphocytic choriomeningitis virus
Borrelia burgdorferi
Schistosoma mansoni
Herpes simplex virus
DISEASE
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
INFLAMMATORY RESPONSES TO INFECTIOUS AGENTS
Diversity in pathogens and inflamatory mediators
Common features of histology and morphologic patters
POLYMORPHONUCLEAR
MONONUCLEAR
INFILTRATION
INFILTRATION
Acute tissue demage
Effector cell infiltration

Increase vascular permeability

Plasma cells (Syphilis lesions)

Neutrophilic exudation (pus)

T cell infiltration
 Pyogenic bacteria
 virus infection – acute
 Chemoattractant f-Met peptides
 intracellular bacteria – acute
 Chemoattractant C5a
 Helminths, spirochetes – chronic
 LPS-mediated macrophage
activation
 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
ACUTE INFLAMMATION
The cardinal signs of inflammation are rubor (redness), calor (heat), tumor
(swelling), dolor (pain), and loss of function. Seen here is skin with erythema.
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 arm at the bottom is swollen
(edematous) and reddened (erythematous)
compared to the arm at the top.
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.
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).