fk 2014 im2micr
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IMMUNITY TO MICROBES
Prof. Dr. dr. Djoni Djunaedi, SpPD, KPTI
General feature of immune response to microbes:
• Defense against microbes is mediated by the effector mechanisms of innate and adaptive immunity
• The immune system respons in distinct and specialized ways to different types of microbes to most effectively combat these infectious agents
• The survival and pathogenicity to microbes in a host are critically influenced by the ability of the microbes to evade or resist the effector mechanisms of immunity
• In many infections, tissue injury and diseases may be caused by the host response to the microbe and its products rather than by the microbe itself
Microbe Exam.of human diseases Mechanisms of pathogenicityStaphylococcus aureus
Skin and soft tissue infections, lung abscess; systemic: toxic shock syndrome, food poisoning
Skin infections; acute inflammation induced by toxins; cell death caused by pore-forming toxinsSystemic: enterotoxin (“superantigen”)-induced cytokine production by T cell causing skin necrosis, shock, diarrhea
Streptococcus pyogenes (grA)
PharyngitisSkin infections: impetigo, erysipelas; cellulitisSystemic: scarlet fever
Acute inflammation induced by various toxins, e.g., streptolysin O damages cell membranes (antiphagocytic action of capsular polysaccharides)
Streptococcus pyogenes (pneumococcus)
Pneumonia,meningitis Acute inflammation induced by cell wall constituents; pneumolysin is similar to streptolysin O
Escherichia coli Urinary tract infections, gastroenteritis,septic shock
Toxins act on intestinal epithelium and cause increased chloride and water secretion; endotoxin (LPS) stimulats cytokine secretion by macrophages
Vibrio cholerae Diarrhea (cholera) Cholera toxin ADP ribosylates G protein subunit, which leads to increases cyclic AMP in intestinal epithelial cells and results in chloride secretion and water loss
Immunity to extracellular bacteria
• The principal mechanisms of innate immunity to extracellular bacteria are complement activation, phagocytosis and the inflammatory response
• Humoral immunity is the principal protective immune response against ectracellular bacteria, and it functions to block infection, eliminate the microbes, and neutralize their toxins
• The principal injurious consequences of host responses to extracellular bacteria are inflammation and septic shock
Adaptive immune responses to extracellular microbes
Adaptive immune responses to extracellular microbes, such as bacteria, and their toxins consist of antibody production and the activation of CD4+ helper T cells. Antibodies neutralize and eliminate
microbes and toxins by several mechanisms. Helper T cells produce cytokines that stimulate B cell responses, macrophage activation, and inflammation.
Immunity to intracelullar bacteria
Microbe Examples of human diseases Mechanisms of pathogenicityMycobacterium Tuberculosis, leprosy Macrphage activation resulting in
granulomatous inflammation and tissue destruction
Listeria monocytogenes
Listeriosis Listeriolysin damages cell membranes
Legionella pneumophila
Legionnaires’ disease Cytotoxin lyses cells and causes lung injury and inflammation
• The innate immune response to intracellular bacteria is mainly mediated by of phagocytes and natural killer (NK) cells
• The major protective immune response against intracellular bacteria is T cell-mediated immunity
Innate and adaptive immunity to intracellular bacteria
The innate immune response to intracellular bacteria consists of phagocytes and NK cells, interactions among which are mediated by cytokines (IL-12 and IFN-). The typical adaptive
immune response to these microbes is cell-mediated immunity, in which T cells activate phagocytes to eliminate the microbes. Innate immunity may control bacterial growth, but
elimination of the bacteria requires adaptive immunity.
Immunity to fungi
Microbe Examples of human diseases Mechanisms of pathogenicityCandida albicans Candidiasis Unknown; binds complement proteins
Aspergillus fumigatus
Aspergillosis Invasion and thrombosis of blood vessels causing ischemic necrosis and cell injury
Histoplasma capsulatum
Histoplasmosis Lung infection caused by granulomatous infalmmtion
Microbe Examples of human diseases Mechanisms of pathogenicityInfluenza Influenza pneumonia Inhibits host cell protein synthesis (tropism
for ciliated epithelial cells)
Herpes simplex Various herpes infections (skin, systemic) Inhibits host cell protein synthesis; functional impairment of immune cells
Hepatitis B Viral hepatitis Host CTL response to infected hepatocytes
Epstein-Barr virus
Infectious mononucleosis; B cell proliferation, lymphomas
Acute infection: cell lysis (tropism for B lymphocytes)Latent infection: stimulates B cell proliferation
Human immuno-deficiency virus (HIV)
Acquired immunodeficiency syndrome (AIDS)
Multiple: killing of CD4+ T cells, functional impairment of immune cells
Immunity to viruses
• The principal mechanisms of innate immunity against viruses are inhibition of infection by type I IFNs and NK cell-mediated killing of infected cells
• Adaptive immunity against viral infections is mediated by antibodies, which block virus binding and entry into host cells, and by CTLs, which eliminate the infection by killing infected cells
Innate and adaptive immune response against viruses
Immunity against viruses functions to prevent infection and to eradicate established infection. Innate immunity is mediated by type I IFNs, which prevent infection, and NK cells, which
eliminate infected cells. Adaptive immunity is mediated by antibodies and CTLs, which also block infection and kill infected cells, respectively
AgIMMUNE RESPONSE
IL-12/1L-1
FAST
TNF-β, IFN-γ
IL-2, IFN-γ
IL-16
Th-2IL-4
IL-6
IL-5
Abnormal cell
IFN-γTh-1
IL-2
NK cell
Activated NK cellLysis
cellCYTOKINE
Abnormal cell
FC-R
CTL B-lymph
Memory cell
MHC-I
MHC-IIAPC
DV
DV
DV
DV
DV
DVMo
Dengue virus infection of human monocyte
RESPONS IMUN PADA INFEKSI VIRUS DENGUE
TH CD8
T CD8
TH CD4
T CD4
Mo
Mo
DVMo
IL-1 TNFαTissue factor
Chemical mediators
IFNγ
IL-2, other lymphokines
T cell activation
Dengue virus-antibody complex
Complement activation
C3a, C5a
Endothelial cells
Plasma leakage
Shock
Hemostatic system
Hemorrhage