Immunity To Microbial Infection

Immunity to microbial infection

Bacteria • Extra cellular • Intracellular

Extracellular bacteria • Innate Immunity • Adaptive Immunity

Innate Immunity • 1) Phagocytosis – PAMPs  microbial molecules – PPRs  Receptors

• 2)Alternative pathway

Pattern-Recognition Receptors(PRRs) on and in Defense Cells

Physiologic Action of Lipopolysaccharide (LPS) from the Gram-Negative Cell Wall

Toll-Like Receptors Responding to Lipopolysaccharide (LPS) from the Gram-Negative Cell Wall

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on the surface: TLR-2 - recognizes peptidoglycan, bacterial lipoproteins, lipoteichoic acid, and porins TLR-4 - recognizes lipopolysaccharide (LPS) from gram-negative cell wall, fungal mannans, viral envelope proteins, parasitic phospholipids, heat-shock proteins TLR-5 - recognizes bacterial flagellin • within endosomes (phagolysosomes): TLR-3 - recognizes viral double-stranded DNA TLR-8 - recognizes viral single-stranded RNA TLR-9 - recognizes viral and bacterial unmethylated CpG sequences • in the cytoplasm: NOD-2 - recognizes muramyl dipeptide from bacterial peptidoglycan RIG-1 - recognizes viral RNA

pattern-recognition receptors (PRRs ) • recognize PAMPs • a. Endocytic Pattern-Recognition Receptors – promote the attachment of microorganisms to phagocytes

• b. Signaling Pattern-Recognition Receptors – toll-like receptors (TLRs) • 1. signaling PRRs found on cell surfaces (1) (2) • 2. Signaling PRRs found in the membranes of the endosomes (3)

Adaptive Immunity • HIR • ActivateB-cell and T4-cell • Produce Antibody – Opsonization – Cytolysis by the Membrane Attack Complex (MAC) – Neutralization of Exotoxins – Neutralization of Viruses – Preventing Bacterial Adherence – Agglutination of Microorganisms

Opsonization (Enhanced Attachment), Step-1

Opsonization (Enhanced Attachment), Step-1

Cytolysis by the Membrane Attack Complex (MAC)

Cytolysis of Gram-Negative Bacteria, Step-2

Neutralization of Exotoxins Neutralization of Exotoxins

Preventing Bacterial Adherence Bacterial Adherence Via Pili

Agglutination of Microorganisms • IgM and IgA

Intracellular bacteria • Innate immunity • Adaptive immunity

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Adaptive immunity • CMIR • Th1 cells IFN-gamma • CTLs

Immunity to virus

Immunity to virus • Innate Immunity • Adaptive Immunity

Innate Immunity • 1) Produce IFN-α/β by Infected cell • 2)NK-cell

Antiviral Action of Interferon

Activation of NK Cells • activate  (IL-2) and (IFN-gamma) • produce large amounts of IFN-gamma • cell under stress, are turning into tumors, or are infected  MICA and MICB • killer-activating receptor enables the NK cell to kill • killer-ihibitory receptor prevents the NK cell from killing that cell • antibody-dependent cellular cytotoxicity or ADCC • lead to apoptosis

Adaptive Immunity • HMI • CMICTLs • HMI+CMI

Immunity to fungi

Immunity to Fungi • Innate Immunity • Adaptive Immunity

Innate Immunity • Neutropil – granules contain various agents for killing microbes MPO – kill microbes intracellular lysozyme , lactoferrin , collagenase, and elastase

• MQs

Adaptive Immunity • CMIMajor defenseCTLs • HMInot established

Immunity to parasites

Immunity to parasites • Protozoa • Helminths

Immunity to Parasites • Innate Immunity Ineffective • Adaptive Immunity

Adaptive Immunity • • • • •

Protozoa w/n MQs Th1 stimulation Insite cells host CTLs Helminths IgE and EosinophilTh2 stimulation

Th2 stimulation • Interleukin-4 (IL-4) and interleukin-13 (IL-13): • IL-13 increased mucus production and peristalsis in the gastrointestinal tract for the removal of helminths • Stimulate B-lymphocytes to produce  immunoglobulin E (IgE). • IgE: – Serves as an opsonizing antibody to bind eosinophils to helminths

Fig. 9: Opsonization of a Helminth by IgE and Eosinophils

A major function of the cytokines produced by Th2 cells is to enable Blymphocytes to activate eosinophils and produce increased amounts of a class of antibodies called IgE against helminths (parasitic worms) and arthropods. IgE act as an opsonizing antibody to stick phagocytic eosinophils to helminths for extracellular killing of the helminths. The Fab portion of IgE reacts with epitopes on the helminth while the Fc portion binds to Fc receptors of activated eosinophils. The lysosomal proteases of eosinophils are able to destroy the tough integument of helminths. IgE also promotes inflammation to recruit phagocytes.