MOD 8 - IMMUNITY TO BAC. AND FUNGAL INFECTIONS

What prevents most microorganisms in an animal’s environment from invading tissues and causing disease?

The combined efforts of the innate and acquired immune systems.

What factors influence whether disease will develop in an animal?

1. Response of host

2. presence of damaged tissues

3. location of bacteria in the body

4. virulence of the bacteria

What happens when there is an imbalance between host immunity and bacterial virulence?

It can result in disease or even death.

What immune system components work together to stop microbial invasion?

innate and acquired immune systems

antimicrobial immunity consists of:

1. innate response

2. sustained adaptive response

recognition of the microorganism is through TLRs will induce

1. inflammation

2. cytokine release

3. complement activation

the roles of the dendritic cells and macrophages are very important especially in ingesting the invading bacteria and later on triggering both T and B cell responses.

acquired immunity

What are TLRs responsible for recognizing?

microorganism

What cells play an important role in ingesting invading bacteria in acquired immunity?

dendritic cells and macrophage

What do dendritic cells and macrophages trigger after ingesting bacteria?

T and B cells responses

5 basic mechanisms by the acquired-immune response to combat bacterial infections

1. Neutralization of toxins or enzymes by antibody

2. the killing of bacteria by antibodies and complement

3. Opsonization of bacteria by antibodies and complement resulting in phagocytosis and destruction

4. Intracellular destruction of bacteria by activated macrophages

5. direct killing of bacteria by cytotoxic T cells and NK cells

What results from the opsonization of bacteria by antibodies and complement?

phagocytosis and destruction of bacteria

What cells are responsible for intracellular destruction of bacteria?

activated macrophages

What immune cells are involved in the direct killing of bacteria?

cytotoxic T cells and NK cells

What mechanism involves antibodies preventing harmful effects of bacterial products?

Neutralization of toxins or enzymes by antibody.

bacteria that can produce toxins

toxigenic bacteria

examples of toxigenic bacteria

1. clostridia

2. B. anthracis

What limits the effectiveness of antibodies against toxins?

Antibodies are relatively ineffective once the toxin has already bound to its receptor.

What is required for antibody-mediated neutralization of a bacterial toxin to be effective?

The antibody must act before the toxin binds to its receptor.

What enhances phagocytosis by marking bacteria for recognition by immune cells?

layer of opsonin: antibodies, C3b, MBL

What do neutrophils and macrophages recognize to promote phagocytosis?

layer of opsonin (MBL, C3b, antibodies) on the bacterial surface

What activates complement and leads to the binding of C3b to the bacterial surface?

alternative and lectin pathways

What may neutralize the antiphagocytic properties of a bacterial capsule?

Antibodies directed against the capsular (K) antigens.

What acts as opsonins in nonencapsulated bacteria?

Antibodies directed against O antigens.

What antigens are targeted by antibodies in certain strains of E. coli to block pathogenicity?

pilus antigens such as K88 (F4) and K99 (F5)

What is the effect of antibodies interfering with pilus antigen expression in E. coli?

Deletion of the genetic material responsible for pili formation.

What happens to E. coli strains when adherence pili are deleted?

They cannot bind to the intestinal wall and become nonpathogenic.

What bacterial disease highlights the importance of the capsule in immunity?

anthrax caused by bacillus anthracis

What two features make B. anthracis particularly harmful?

1. capsule

2. exotoxin

What type of immunity is protective against anthrax but slow to develop?

antitoxic immunity

What prolongs toxin production in B. anthracis infections?

The difficulty phagocytic cells have in eliminating the encapsulated bacteria.

What does the anthrax vaccine for animals contain?

unencapsulated but toxigenic strain of B. anthracis given in the form of spores.

What form is the unencapsulated strain of B. anthracis given as in the vaccine?

spores

HSP

heat shock protein

What are present in all organisms at very low levels under normal temperature conditions?

heat shock protein (HSPs)

What triggers an increase in HSP production?

mild stress

What effect do HSPs have on cells under high temperature conditions?

They increase thermotolerance, allowing cells to function at high temperatures.

What are examples of heat-shock proteins that serve as dominant antigens in certain infections?

HSP90, HSP70, and HSP60.

What bacterial pathogens are known to induce HSP60 as a dominant antigen?

1. Mycobacteria

2. Coxiella burnettii

3. Treponema'

4. Borrelia

What type of immune response may be a major defense against bacterial pathogens?

the anti-HSP response

highly antigenic and readily processed by antigen-presenting cells

HSPs

What type of immune cells do many intracellular bacteria survive and grow within?

macrophages

What allows Listeria monocytogenes to avoid exposure to extracellular fluid?

Its ability to travel from cell to cell directly.

What do some bacteria use to resist lysosomal enzymes?

resistant coat

What do some bacteria prevent from assembling to evade macrophage killing?

NOX complex.

What process is blocked by some bacteria to prevent phagolysosome formation?

Phagosome maturation.

What do some intracellular bacteria manipulate to suppress T cell responses?

The host’s cytokine responses.

What cytokines are induced by some bacteria to suppress immune responses?

IL-6, IL-10, and TGF-β.

What cytokine is especially effective at inhibiting macrophage activation and downregulating MHC class II expression?

IL 10

What kind of vaccine cannot induce protective immunity against intracellular bacteria?

vaccines containing killed bacteria

What kind of vaccine is required to induce protective immunity against intracellular bacteria?

Vaccines containing living bacteria.

What type of T helper cells are stimulated by live Brucella abortus?

Th1 cells that secrete IFN-γ

What cytokine is more strongly stimulated by killed Brucella organisms compared to live ones?

IL 1

What innate immune mechanism activates neutrophils in response to fungal infections?

Activation of the alternative pathway of the complement system

What immune cells attempt to ingest invading fungal hyphae or pseudohyphae?

NEUTROPHILS

What prevents neutrophils from fully ingesting fungal hyphae or pseudohyphae?

their large size

What causes damage to fungal hyphae even if neutrophils can't fully ingest them?

Enzymes released by neutrophils into the tissue fluid.

What immune cells can destroy small fungal fragments or spores?

1. macrophages

2. NK cells

What type of immunity is involved in the later destruction of fungal infections?

T-cell-mediated (acquired) immunity.

What is the primary function of T cells during fungal infections?

Activating macrophages and promoting epidermal growth and keratinization.

What cells can exert a direct cytotoxic effect on yeasts such as C. neoformans and C. albicans?

1. some T cells

2. NK cells