Infection and innate immunity Flashcards
(35 cards)
What is innate immunity and how does it differ from adaptive immunity?
Innate immunity is our first line of defence to pathogen invasion. It is a very fast response, does NOT adapt and has no memory. It also is primordial has been there for 500 million years.
What is a virus and how to defend them?
A virus is an intercellular pathogen that occurs INSIDE the body. Antibodies and cellular immunity.
Give examples of a virus vs bacteria.
Virus: Influenza, Polio, Smallpox, Varicella, HIV. Bacteria: Staph aureus, Mycobacterium tuberculosis (Intracellular) these live inside the macrophages, Strep pyogenes , Yersinia pestis , Vibrio cholerae
What is a bacteria?
Bacteria are extracellular pathogens. Because they occur outside of the cell, phagocytosis and the innate system makes it easier to target them.
Describe the features of parasite and Protozoa.
Parasites are large and multicellular in which phagocytosis can’t engulf them. Instead of phasgotisis, myeloid cells will release chemicals called histamine to kill the parasite. Basophils and mast cells have granules which contain hisamtine (singanlling molecule).
What is the process called of releasing granules outside the cell?
Degranulation
Describe the difference between Gram positive and Gram negative.
Gram positive is a stain showing that the bacteria will have a thick peptidoglycan layer(strong, but no outer membrane). Gram negative have a thin peptidoglycan layer but has an outer membrane.
Why can’t the MAC complement kill the gram positive bacteria?
Because it cannot get through the strong peptidoglycan layer.
What type of antibiotic inhibit the synthesis of peptidoglycan layer?
β-lactam antibiotics such as penicillin which works efficiently on Gram positive because it relies on the thick peptidoglycan layer.
Name the five steps of neutrophil extravasation (neutrophils finding bacteria).
- Activation = Chemokines activate near capillary endothelium cells.
- Tethering = Nuetrophils start rolling and selecting on the endothelium upregualte (increase). sLexis acarbohydrate antigen on the neutrophil will bind to the selectin.
- Adhesion = integrins on the neutrophils surface and ICAM-1 molecule on the endothelium surface will bind together.
- Diapadesis = Neutrophil will squeeze through the interstitial space of endothelium.
- Chemotaxis = Neutrophils will follow a chemical gradient (chemokine), with higher concentrations at the injury site and lower near the endothelium.
How is chemokine activated?
From opsonization (marking of the pathogen), tissue
injury or inflammation.
What is a type cell adhesion molecule?
Selectin
What happens during the adhesion step?
Neutrophils loses its ability to move as it is firmly stuck to the endothelium cells. It also flattens.
What happens during the complement innate response?
As there is injury near the tissue, it release complement proteins like C5. C5 breaks down into C5a, the C5a acts as a chemoattractant. It will create a chemical gradient where there will be more C5a near the infection site and less further away. Neutrophils will have receptors that detect it and migrate up the gradient.
How do the neutrophils to move to the site of infection?
Actin filaments polymerisation will join together at the leading edge (front). At the trailing edge (back), actin filaments depolymerize — they break down, allowing the cell to contract and move forward.
What is the complement protein that is on the surface of the pathogen, marking it? This process is called optimisation.
C3b which acts as an opsonin (a molecule that marks the pathogen).
What binds to C3b? (Initiates phagotosysis)
CR1 is the main receptor on the neutrophil (myeloid cell). It is specific to C3b. Others are CR2, CR3, CR4. The binding triggers phagocytosis.
What initiates phagocytosis on neutrophils?
Cross-linking of the surface CRs.
What are the 3 important pathways for complement mediated phagotosis? This means how is the immune system triggered to initiate complement mediated phagotosis?
Triggered by 3 pathways.
- Classical antibody pathway mediated by the antibodies.
- Lectin pathway which is triggered by unique sugar molecules on the bacteria.
- Alternate pathway where complement C3 can activate the bacteria itself.
What do all pathways do?
So all pathways are activated and undergo a cascade of activating other complement proteins. The main thing is that it all leads to a complement protein being activated called C3, which is cleaved in C3a and C3b. C3b covalently binds to the surface of the pathogen, which acts like a opsonin (making the pathogen). Nutrophils will then bind to the C3b because of its CR1 receptor.
What are Anaphylotoxins?
During the cascade of the complement proteins activating such as C3, C4 and C5. A small region of C3, C4 and C5 is cleaved releasing anaphylotoxins which are C5a, C4a ,C3a. These attract neutrophils to the site of infection (neutrophil extravasation). Remember that C5a is the most potent one (powerful).
What is the entire sequence of nuuetrophils getting activated?
- Complement activation →
- C3b opsonizes the pathogen →
- C5a attracts neutrophils →
- Neutrophils extravasate →
- Neutrophils bind to C3b (via CR1) → 6. Phagocytosis happens
What is MAC (Membrane Attack Complex) and where does it fit into the complement system?
So after the complement C5 is activated,remember how C5 cleaves into C5a and C5b. C5a is a Anaphylotoxin but C5b will go activate other molecules such as C6, C7, C8, and C9. This forms a complex called MAC.
How does the Fc Receptor (antibody) mediated phagocytosis?
This process occurs in simpler steps.
1. The antibody (IgM or IgG) will bind to the surface of bacteria of the antigenic epitope.
2. This binding exposes the Fc region on the antibody, which is a section of the body.
3. The Fc reception on the surface of neutrophils will bind to the Fc region on the antibody. Multivalent Fc means that multiple antibodies (each having an Fc region) can be bound by these Fc receptors at the same time.
4. This will draw the bacteria in and Activates phagocytosis.
