Host-commensal and pathogen interactions and Specimens and mechanisms of identification

What is pathogenicity?

Ability of microbe to cause disease

What is virulence?

The degree of damage caused by a microbe to its host and measure of capacity of the organism to cause disease

What is the virulence factor?

Measurable trait to promote self-growth at expense of host (e.g. secreted protein toxin)

What is colonization?

Organism lives/grows without interfering with normal host function

What is a disease/infection?

Interaction leads to damage to host

What is a strict pathogen?

Always associated with human disease, cause infection regardless of host immune system or microflora (not commensal)

What is an opportunistic pathogen?

Do not produce disease under normal circumstances

What happens to opportunistic pathogen under certain circumstances?

Infections like barrier breach, immune deficiency

What are commensal bacteria?

Bacterial “microflora” typically do not cause disease and live symbiotically with host

Is there injury to host from commensal bacteria?

No injury to host unless they “move” to different body site (“opportunistic”)

What are the roles of the commensals?

• aid in food digestion

• aid immune system by defending against pathogens 

• provide vitamins to host

What is local or generalized inflammation?

Reaction to wall off injury or pathogen, immune cells recruited: destruction (pathogen)

What is commensal interference?

Direct defense, competition for nutrients and space or secreted products that kills others

What is a mechanical host defense?

Physical barriers or removal of microbe

What is a chemical host defense?

antimicrobial agents: lysozyme, H202, cytokines, bile, antibodies, complement

host cells secrete antimicrobials: e.g. cecropin, cathelicidin

What is a cellular host defense?

Neutrophils(WBC): primary phagocyte

Monocytes: Macrophages found in many tissues

Lymphocytes: T and B cells

What are some immune defense mechanical barriers?

skin, mucus, cilia, stomach acid, bile, eyelashes

What are some innate immune defense?

Non-specific responses to pathogen like fever, macrophages, interferon

What are some antigen-specific immune defense?

Specific for a particular pathogen, antibody and T-cells attack and eliminate invader

Are the two types of immune responses?

Cellular (T cell specific killing) and Humoral (antibody mediated)

What are B-cells?

Produce antibodies, internalize and process antigen, present antigen to T cell

What are T cells?

Directly kill invader, activate/control immune response through cytokine release

Which cells are antigen presenting?

Dendritic cells, Macrophages, and B-cells

What is a neutrophil?

phagocytic, destroys bacteria

What are monocytes?

precursor to macrophages and dendritic cell

What do macrophages and dendritic cells do?

Phagocytic, antigen-presenters. secrete cytokines

What are some mechanisms by which antibodies (humoral) protect the host?

Agglutination of pathogen, Opsonization, Neutralization

What is agglutination of pathogen?

Antibodies bind and cross-link bacteria → clumps from → phagocytes destroy

It is a type of “immunoprecipitation”

What are the steps of agglutination of pathogens?

1. Specific antibodies bind antigen

2. Cross link antigen (bacteria)

3. Ab-ag complex: very large precipitates of solution

4. “Clump” of Ab-Ag forms

What is the purpose of a clump of Ab-Ag forms?

The body doesn’t like clumps

What is opsonization?

Binding of antibody to surface bacteria which triggers organism for phagocytosis

What is neutralization?

Specific antibodies can bind to bacteria, toxins or, virus and prevent activity like dividing and growing

What is the complement pathway?

Non-specific, pathway triggered when the body detects the presence or formation of antibody-antigen complex and bacterial products or surface molecules

What results in the activation of the complement cascade (pathway)?

• phagocytes recruited to site of infection

• increase permeability of blood vessels

• binding of complement proteins to pathogen/product to promote opsonization

• some complement proteins lyse certain gram-negative bacteria

What are the three complement pathways?

Classical, Alternative and Lectin Pathway

How is the classical pathway activated?

activated by complex of antibody-antigen

How is the alternative pathway activated?

activated directly by bacteria/bacterial product

How is the lectin pathway activated?

Mannose binding protein bind mannose sugar on pathogens

What do complement proteins do?

Activate immune response and recruit immune cells. Sequentially bind to plasma membrane of bacteria

What does the last stage of cascade create?

Membrane attack complex (MAC); drills hole in membrane; the bacteria lyse and are killed

What is the initial barrier of bacteria in the skin and mucous membrane?

Skin

Why is skin relatively hostile?

Mechanical defense: dry, exposure to UV rays, washing

Chemical defenses: fatty acids, lysozyme, IgA antibody

Commensal interference

Local immune system: keratinocytes (antimicrobial peptides) and dendritic cells (antigen presenters), and IgA secretory antibodies

What does commensal interference on skin mean?

Normal commensals found on skin compete with “invaders”

What are the predominant type of microflora in the respiratory tract?

Mostly anaerobes bacteria

What are the defenses in the upper respiratory tract?

Commensal interference, mechanical: expulsion, chemical

What are some chemical defenses in the upper respiratory tract?

Lysozyme (saliva) degrades certain peptidoglycans

IgA- secretory antibody found most mucosal surfaces

What are the lower respiratory tract defenses?

Mechanical: trapping action of mucus and cilia; cellular: many macrophages in lungs

Is the lower respiratory tract normally colonized by microflora?

Yes answer used to be no

What are some examples of lower respiratory tract pathogens?

Staphylococcus aureus, Klebsiella pneumoniae

What are the defenses of the upper GI tract?

Stomach: very acidic; small intestine: acidic, bile salts, lysozyme, IgA

What are interferences in the upper GI tract?

Microflora produce antimicrobials

normal flora: produces bacteriocins (small, antibacterial)

host (human) produces cecropins and other antibacterials

Is the normal flora in upper GI tract anaerobic or aerobic?

Mostly anaerobic

What is the major defense of the large intestine?

Interference from normal flora

When does infection occur in larger intestine?

Flora disrupted because of antibiotic use, Pathogens exposed to GI

Are there colonized areas in Genitourinary tract?

Permanently colonized areas.