Immunity to Microbes

Fadel Muhammad Garishah

Infection and Immunity

Faculty of Medicine Diponegoro University

How do you describe this?

Microbe

NeutrophilePMN Cell

General features

• Defense against microbes via innate and adaptive immunity

• Responds in distinct and specialized ways to different types of microbes

• survival and pathogenicity of microbes influenced by the ability of the microbes to evade or resist the immunity

• tissue injury and disease may be caused by the host response to the microbe and its products rather than by the microbe itself.

Microbes• Prion• Viruses• Bacteria• Parasites

Immunity to Extracellular Bateria

Extracellular Pathogenic Bacteria

Extracellular bacteria Human Diseases Pathogenicity

Staphylococcus aureus Skin/soft tissue infection, lung abscess, Systemic: toxic shock syndrome, food poisoning

Enterotoxin superantigeninduced

Streptococcus pyogenes Group A

Pharyngitis, Skin impetigo;Cellulitis, Scarlet fever (rheumatic fever)

Streptolysin-0

Streptococcus pneumonia

Pneumonia, Pneumococcusmeningitis

Pneumolysin, Capsule

Escherichia coli UTI, Genteritis, Septic shock LPS Endotoxin

Vibrio cholerae Diarrhea cholerae Cholera toxin (cAMPincreases)

Clostridium tetani Tetanus Tetanus toxin

Neisseria meningitidis Meningococcus meningitis Endotoxin

Corynebacteriumdiphtheriae

Diphtheria Diphtheria toxin

The extracellular bacteria

• Extracellular bacteria defined as the bacteria that capable to replicate outside the host cells, e.g. in blood, connective tissue, airway/gastrointestinal tract

• The bacteria may either 1) induce inflammation or 2) produce toxins that destruct the body tissue

• E.g. of toxin: Endotoxin of gram-negative or lipopolysaccharide (LPS).

Innate immunity to extracellular bacteria

• Principles: complement activation, phagocytosis and inflammatory response.

• Complement activation

• Activation of phagocytes and inflammatory response

Adaptive immunity to extracellular bacteria

• Humoral immunity: block infection, eliminate microbes and neutralize toxins

• CD4+ produces cytokines that induce local inflammation and activate phagocytic function and microbicidal activities of Macrophages and Neutrophiles

Humoral Immunity

Cellular Immunity

Polyclonal activation of T cells by bacterial superantigens

Extracellular bacteria evasion

• A mechanism used by bacteria to evade humoral immunity.

• Genetic variation of surface antigen (E. coli, N. gonorrhoeae, S. typhimurium)

• Resistance to phagocytes (Pneumococcus)

• Destruction to ROS (Catalase producing Staphylococci)

Immunity to Intracellular Bacteria

Intracellular bacteria

• A characteristic of facultative intracellular bacteria is their ability to survive even replicate within phagocytes.

• Requires cell-mediated immunity

Intracellular bacteriaMicrobe Human Diseases Pathogenicity

Mycobacteria species Tuberculosis, Leprosy Macrophage activation,granulomatous inflammation, tissue destruction

Listeria monocytogenes Listeriosis Listeriolysin damages cell membrane

Legionella pneumophila Legionnaires’ disease Cytotoxin lyses cells

Innate and Adaptive Immunity

• The innate immune response to intracellular bacteria consists mainly of phagocytes and NK (natural killer) cells.

• The major adaptive-protective immune response against intracellular bacteria is cell-mediated immunity

• The macrophage activation in response to intracellular microbes is capable of causing tissue injury

Figure 15-5 Naive CD4+ T lymphocytes may differentiate into TH1 cells, which activatephagocytes to kill ingested microbes, and TH2 cells, which inhibit macrophage activation.The balance between these two subsets may influence the outcome of infections, asillustrated by Leishmania infection in mice and leprosy in humans.

Mechanisms of Immune Evasion by Bacteria

• Inhibition of phagolysosome formation (Mycobacterium tuberculosis, Legionella pneumophila)

• Inactivating reactive oxygen and nitrogen intermediates Mycobacterium leprae(phenolic glycolipid)

• Disruption of phagosome membrane, escape into cytoplasm Listeria monocytogenes(hemolysin protein)