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Immune defence of mammals against bacterial pathogens

26 important questions on Immune defence of mammals against bacterial pathogens

What is innate immunity?

A form of non-specific host defence against invaders and forms the first line of defence. Always ready to respond without induction of time.

What is adaptive immunity?

More specific and long-lasting immunity

The innate and adaptive immune responses differ in a number of ways?

The innate system is constitutively present, while the adaptive system response takes some time to develop
The innate system is not specific
The adaptive system exhibits immunological memory

Differences in susceptibility of animals to pathogens could be due to

Absence of specific tissue or cellular receptor for attachment to the pathogen
Temperature of the host and ability of the pathogen to grow
Lack of exact nutritional requirements to support pathogen growth
Lack of a target site for a microbial toxin
Individual resistance

Age, sex, diet, stress, trauma, drugs

What is the mucus layer?

A thick layer of mucin glycoprotein secreted by specialized globet cells in the epithelium.
It is constantly made and removed by peristaltic flushing
Two structural layers: The outer layer contains bacteria and the inner layer without bacteria

What is the intestinal epithelium?

- The most important physical barrier
- A layer of intra epithelial cells (IECs) that seperates the lumen from the lamina propria (LP)and the inside of the body

The cells of the intestinal epithelium are renewed by?

Stem cells in the crypts of Lieberkuhn, and they are shed when they die

What are tight junctions?

The most apical of cell- to-cell junctions and seal the intercellular space between adjacent cells, creating a selective barrier keeping microorganisms out. Some pathogens can disrupt or go around the tight junctions

What do pattern recognition receptors (PRRs) do?

With them the epithelium senses microbial content of the lumen and sends out a potent array of cytokines and chemokines

Where are PRRs expressed?

Along the entire GI-tract by enterocytes, Paneth cells and immune cells

What are NOD1 and NOD2

intracellular proteins that contain an N-terminal caspase recruitment domain (CARD), nucleotide-binding oligomerization domain (NOD) and a C-terminal regulatory domain with leucine rich repeats

Which mechanisms help avoid excessive immune responses?

- Regulation of TLR expression

In the absence of inflammation, TLRs are only highly expressed in the crypts

- TLR localization

Activation of the TLR pathways leads to different responses depending on the location of the stimulus. Basolateral stimuli activate, while apical prevents

- Differential apical and basolateral TLR signaling

- Negative feedback regulation of the NF-kB pathway
- Reduction of NF-kB activation by commensal bacteria

Non-virulent bacteria can inhibit the NF-kB pathway by blocking degradation and thus promoting attenuation of inflammatory responses

What do paneth cells secrete?

A diverse range of antimicrobial pepties and proteins, referred to as antimicrobial peptides (AMPs)

What is a major group of the AMPs?

- The defensins
- small, highly basic peptides that show antimicrobial activity against gram negative and positive bacteria

Where does the antibacterial acitivity come from defensins?

- interaction with the bacterial outer membrane
- the defensin displaces the lipid, weakening the membrane and forming deadly pores -> the carpet wormhole mechanism

What do defensins also serve as?

Chemo-attractants for leukocytes

What is the antimicrobial factor Reg3B protein?

- has been proposed to kill gram-negative bacteria and a number of gram-positive bacteria
- Their effect is growth phase-dependent
- in case of gram-negative bacteria: It involves binding to the lipid Anchor of lipopolysaccharide (LPS)

What are the cathelicidins (AMPS)?

- Produced by enterocytes
- cationic peptides that kill bacteria by binding to the bacterial membrane via electrostatic interactions, creating pores.

What is immunoglobin A?

- An antibody that plays a role in the immune function of mucous membranes.
- Protects against microbes in the intestine by maintaining the integrity of the epithelial barrier and shaping the composition of commensal bacteria.
- Produced by plasmacells in the lamina propria

The IgA complex passed through the cell and gets secreted on the luminal side epithelial cell.....

Ther it comes loose from the receptor, leaving a piece called the secretory component, into the lumen

What does the secretory component do?

It protects the sIgA from being degraded

How does sIgA act?

- By blocking epithelial cells
- Sterically hindering attachment to epithelial cells
- immune exlusion

What is immune exclusion?

Immune exclusion traps pathogens or clears them peristaltically by crosslinking them with antibody
- Via immune exclusion, sIgA helps to shape the bacterial community

What are other mechanisms for sIgA?

- removal of antigen complexes formed in the lamina propria, reducing inflammation
- Neutralizes pro-inflammatory complexes like LPS
- Can interact with antigens presented by pathogens in endosomes during transport through epithelial cells
- It does not activate the classical complement cascade like other antibodies do

How can the complement system be initiated?

- The classical pathway
- the lectin pathway
- the alternative pathway

-> Inefficient activation is associated with susceptibility to infection; overstimulation can lead to autoimmunity

How does the complement system distinguishes self from non-self?

Via a range of cell-surfaces and soluble proteins that belong to a family called the regulators of complement activation (RCA) or complement control proteins (CCP)
- They keep the system from damaging the host while directing it towards foreign particles

The question on the page originate from the summary of the following study material:

Microbial disease mechanisms summary

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