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