L20 - Bacteria and Fungi Immunity

How do host cells block attachment by bacteria?

Secreting IgA antibodies

R. equi

Intracellular pathogen

• Has lipoprotein → allows it to go inside of the cell

• DC and Macrophages → secrete IL-23 → promotes Th17 → secretes IL-17 → makes macrophages to kill extracellular bacteria

• Th1 → IFN-y → CD8 → kills intracellular bacteria

Th17 protect against _____ by ______

extracellular bacteria and fungi

triggering inflammation

Iron sequestering

Lactoferrin: (milk, saliva, tears)

Transferrin: blood plasma

Ferritin: cells

*All bind to iron and don’t let bacteria have free access to it → bacteria death

Immunity to Tuberculosis and Vitamin D

Mycobacterium is IC pathogen → can’t treat with antibiotic

Macrophage can be converted to Cathelicidin if they have Vitamin D → makes hole in bacterial cell wall

1. Macrophage has TLR 2 → binds to bacteria

2. Increases Vitamin D receptor

3. Animal exposed to sunlight → Vitamin D binds to receptor

4. Macrophage becomes Cathelicidin (antimicrobial peptide)

5. Bacteria goes into macrophage

6. Cathelicidin makes hole in bacteria → bacteria dies

5 Mechanisms of Adaptive Immunity to Bacteria

1. Antibody neutralization of toxins

2. Classical Complement Pathway

3. Opsonization

4. Activated Macrophages

5. Cytotoxic T cells and NK Cells

How does the immune system combat toxigenic bacteria?

• Toxigenic bacteria

• Immune system must stop invading bacteria and neutralize toxin

• Neutralize by Ab preventing toxin from binding to its receptor on a target cell (competition b/w receptor and antibodies for toxin)

• Ex. Clostridium tetani and Bacillus anthracis

How does the immune system combat invasive bacteria?

• Invasive: bacteria that enters bloodstream

• Mediated by antibodies against surface antigens

• Antibodies activate classical complement pathway via C3b → opsonize

• Antibodies also have direct effects on bacteria

  • E.coli → antibodies prevent them from binding to intestinal wall and binding to iron

  • IgM and IgG against Lyme → damage surface proteins

Heat Shock Proteins

Invasive acteria expresses heat shock proteins when exposed to fever from host

• Ex. HSP 90, 70 and 60

• Highly antigenic → lots made during infection, processed by APCs, induce cytotoxic T cells and NK cells

Macrophage function and what immune system they’re part of

• Garbarge collectors → innate

• APCS via MHC → bridge innate and adaptive

• Vicious killers → adaptive

What protects against intracellular bacteria?

• M1 Macrophages → phagocytosis of bacteria

  • Activated by IFNy

What cells are involved in immunity to Listeria?

CD4 and CD8

Can intracellular bacteria be killed by unimmunized animals?

No, M1 macrophages must be activated by IFNy, will occur about 10 days post infection

• Inappropriate Th2 response → only antibodies → gets chronic disease

If vaccinated → have antibodies and cytotoxicity → kills IC bacteria

Type I Interferons - what are they released in response of and what do they do?

• Released in response to bacterial PAMPs

• Increase macrophage responses (produce IFNy, NO and TNFa)

What are the primary granules and what do they do?

Direct microbial killing (via degranulation, NETosis or phagocytosis)

• Myeloperoxidase

• Defensins

• Lysozyme

• Proteases

What is lipopolysaccharide?

Endotoxin found on gram negative bacteria

Johne’s Disease (how it spreads, how immune system responds)

MAP → agent

• Mycobacterium grows and infects intestine

• Subclinical adult → secretes in fecal matter → calf gets some → bacteria phagocytized by macrophages → immune response activated

  • Acute infection → TH1 and CD8 → bacteria killed

  • Chronic/Persistent infection→ TH2 → can’t remove bacteria because it’s an intracellular pathogen

What TH does extracelluar vs. intracellular bacterial killing?

TH1 → intracellular

TH2 → extracellular

Immunity to Fungal Infections

IL-23 converts TH0 into TH17 → produces IL-17 → activate granulocytes and neutrophils to kill fungal cells

• IL-17 also works with TH1 → inflammatory response to fungi