Immune Response to Pathogens

What are the range of pathogens the immune system has evolved to combat?

All kinds; extracellular, intracellular, multicellular, unicellular, etc.

What are microbe survival and pathogenicity in a host influenced by?

Ability of the microbe to evade or resist effector mechanisms of immunity

The host can cause what in response to microbes?

Tissue injury and disease; off-target effects

What immune mediators are included in extracellular pathogen infections?

Phagocytes, complement, AMPs, cytokines, and antibodies

How must the immune system respond to extracellular pathogens?

With extracellular tools to recognize and attack the pathogen

What is required to combat intracellular infections?

Mechanisms that recognize infected host cells

What do inctracellular pathogens activate in host cells?

If in vesicles or endosomal spaces, PRRs and TLRs

If in cytosol, cytosolic PRRs

With intracellular pathogens that are in vesicles, what response is expected?

A vigorous Th1 response

With intracellular pathogens in cytosol, what response is expected?

Cytokine secretion, inflammasome activation, and induction of cytotoxic NK cells and CTLs

How does innate immunity react to bacterial infections?

Complement system with the alternative and lectin pathways

Natural antibodies

Phagocytes and acute phase proteins

Hoes does adaptive immunity react to bacterial infections?

With B cell/NK cells and T cells

How do B-cells and NK cells react to bacterial infections?

Activation of the complement system through the classical pathway

Antigen-specific antibodies

Antibody-dependent cell-mediated cytotoxicity (ADCC)

What T cell subsets respond to bacterial infections?

CD4+ TH1 and Th17

CD8+ CTLs

How do CD4+ T cells respond to bacterial infections?

Th1 secretes IFN-gamma to activate macrophages

Th17 secretes IL-17 to recruit neutrophils and anti-microbial peptides

How do CD8+ CTLs respond to bacterial infections?

By killing cells infected with intracellular bacteria

What do antibodies cause in response to extracellular bacteria?

Neutralization

Opsonization and Fc receptor-mediated phagocytosis

Complement activation

What does complement activation result in?

Phagocytosis of C3b-coated bacteria

Inflammation

Lysis of microbes

What do T cells cause in response to extracellular bacteria?

Inflammation

Macrophage activation for phagocytosis and bacterial killing

Antibody response

What cells are activated in response to intracellular bacteria?

Neutrophils, NK cells, macrophages, and CTLs

NK cells and CTLs help activate macrophages

What are the steps of CTL lysis of infected cells?

Infected cells degrades intracellular pathogen into peptides

Peptides are loaded into MHC-I and presented to CTls

CTLs induce apoptosis or lysis of the cell

What is the order of events when there's an M. tubercuolsis (intracellular pathogen) infection?

Macrophages are activated -> IL-12 secreted -> Th1 activation -> IFN gamma secreted -> enhance macrophage bacterial killing

How do bacteria evade the immune system?

Antigenic variation

Inhibition of complement activation

Resistance to phagocytosis

Scavenging of reactive oxygen intermediates

How do bacteria resist phagocytosis?

Disruption of phagosome membrane allowing escape

Inactivation of reactive oxygen and nitrogen species

Inhibition of phagolysosome formation

Decreased MHC II expression

Polysaccharide capsule

How do viruses typically enter a host cell?

Through a cell-surface receptor

What happens once a virus enters a host cell?

They start to replicate, triggering humoral and cell-mediated adaptive immunity mechanisms

How does the innate immune system react to viral infections?

Effector functions with nonspecific defenses prevent or eliminate viral infections

During a viral infection, PPRs indue what?

Type 1 interferon expression, inflammasome complex assembly, and NK cell activation

What does Type I interferon do in viral infections?

Binds to IFN receptors to start a JAK-STAT pathway leading to antiviral activity and resistance to viral replication

What innate immune effector functions are used in viral infections?

Complement, AMPs, recognition of PAMPs

How does adaptive immunity react to viral infections?

Producing virus-specific antibodies and CTLs

What four genes are turned on by type I interferon?

Protein kinase R (PKR)

2',5'-Oligoadenylate synthetase

Mx group proteins

IFIT proteins

How does type I interferon mediate a potent antiviral response?

Inhibition of viral protein synthesis

Degradation of viral mRNA

Inhibition of viral gene expression and virion assembly

When do NK cells appear in viral infections, and what do they do?

Early in infection

Kill viral infected cells and tumor cells; secrete IFN-gamma to activate macrophages

How does a NK cell recognize a virus infected cell?

Lack of MHC I expression

How does adaptive immunity respond to viral infections?

Release antibodies to provide protection

Use antibody-dependent cell-mediated cytotoxicity to kill cells

Use of CTLs to eradicate the infection

How do viruses evade the immune system?

Genetic recombination

Inhibition of antigen processing and presentation

Production of cytokine receptor homologs

Latency

Lytic viruses

Immunosuppression

What are ways that viruses inhibit antigen processing and presentation?

Downregulate MHC to escape presentation

Epitope mutation to escape the immune system and reduce MHC presentation

How does Feline Immunodeficiency Virus evade the immune system?

Infects CD4+ T cells and slowly destroys adaptive immunity

What type of immunity is required to protect against fungal infections?

Cell-mediated immunity

What subset of T cells respond to fungal infections?

Th1 and Th17 to activate macrophages and neutrophils

What is a common fungal skin infection in veterinary species and humans?

Ringworm

How do fungi evade the immune system?

Some are too large to be phagocytosed

Express complement and reactive oxygen inhibitors

Escape or alter phagolysosome

Complex glycan coat

What T cell subset is used in helminth infections?

CD4+ Th2

What do CD4+ Th2 induce?

Mucosal eosinophil and mast cells

IgE production

What are helminths vulnerable to?

ADCC involving eosinophils, neutrophils, and macrophages