Tuesday, 4 October 2022

Immunology Q&A

Innate immunity

~Open-Ended questions~

1. Describe the speci city of Innate Immune system.

Answer: Speci city of innate immune system refers to its speci city for structures shared by di erent
types of microbes. This is due to speci c receptors, for example TLR-4 is speci c for LPS, but it
reacts the same way to all bacterial LPSs. Speci city of immune system is not clonal.

2. What are two principal types of reactions carried out by innate immune system?
Answer: In ammation a & antiviral defense.

3. Describe the process of In ammation.

Answer: In ammation occurs at the site of infection.

* Microbe enters the tissue.

* Resident dendritic cells engulf the invaders

* Dendritic cells produce cytokines.

* Cytokines stimulate endothelial cells which causes the expression of selectins on the endothelial
cells.

* Selectin binds to carbohydrates on the surface of neutrophils, slowing neutrophils down “rolling”
occurs.

* In ammatory signals trigger neutrophils to express molecules called integrins.

* Integrins lock on adhesion molecules called ICAM I and VCAM I

* Tight adhesion stops the rolling.

* Damaged tissue cells at the site of infection release bradykinin which acts upon endothelial cells to
create small gap between them.

* Neutrophils squeeze through the gaps of endothelial cells - Extravasation.

* Neutrophils go to the infected tissue (chemotaxis) and phagocytosis occurs.

* Bradykinin molecules also bind to mast cells.

* Mast cells release histamine, which further loosens the endothelial cells, causing the “leak” of the
plasma causing swelling.

* Bradykinins also force endothelial cells to synthesize prostaglandins, which stimulate the nerve
endings causing pain.

- Five cardinal signs of in ammation are: Redness, Warmth, Pain, Swelling and altered function at
the a ected site

4. Describe antiviral defense.

Answer: Antiviral defense is mainly responsibility of interferons and NK cells.

* Specialized dendritic cells - plasmacytoid dendritic cells produce type I interferons.

* Type I IFNs produce signals for the viral replication to stop and also to enhance the activity of the
NK cells.

5. What are PAMPs and DAMPs?

Answer: PAMP - Pathogen Associated Molecular patterns, which means that pathogens have
patterns which are recognized by adaptive immunity.

DAMP - Damage Associated Molecular Patterns, which means that damaged host cells also have
di erent types of patterns which are then recognized by the innate immune system.

6. What are PRRs?

Answer: PRRs - Pattern recognition receptors, by which the innate immune system recognizes the
PAMPs or DAMPs.

7. Why doesn’t the innate immune system react against healthy cells?
Answer: Several features of innate immunity account for it’s stability not to react to healthy cells:

* The innate immune system has evolved to respond do substances of microorganisms and
damaged cells, not the substances produced by the healthy cells.

* Second, receptors of immune system which recognize the nucleic acids are located on the
endosome, so the contents of the healthy cells and therefore nucleic acids do not reach them.

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* Normal, healthy mammalian cells express regulatory mechanism that doesn’t allow innate immune
system to act upon them.

8. How do epithelial cells chemically defend the organism?

Answer: By producing defensins and cathelicidins, which kill bacteria.

9. What are some features of innate immunity that distinguish it from the adaptive immunity?
Answer: There are several features:

* Speci city for adaptive immunity means that every cells receptors are di erent from each other, and
are speci c for di erent antigens. Whereas in innate immunity, speci city means that the receptors of
the innate immunity recognize the PAMPs, they may be speci c for the microbial structural
component, or the composition.

10. We know that the innate immune system reacts to the microbe at every stage of invasion,
describe on what stages and how innate immune system responds to invading pathogen?
Answer:

* At the portals of entry in microbes - epithelial cells at these sites provide mechanical and chemical
defense system.

* In the tissues - macrophages, dendritic cells, mast cells.

* In the blood - plasma proteins, complement system.

11. Where are TLRs located?

Answer: Some are located in the plasma membrane of the whole cell, some are located in the
endosomal membrane.

12. Where are NLRs located?

Answer: In the cytoplasm.

13. What are in ammasomes and how are they stimulated?

Answer: In ammasomes are protein complexes. They’re composed of:

* Caspase -1 - an enzyme which cleaves and activates IL-1 and IL8.

* Oligomers of a sensor - usually NLRs, sense many things like the presence of microbes themselves
or changes in the overall molecular composition of the cell.

* Adaptor that links the two.

NLR sensors oligomerize with adaptor protein, —> this activates Caspase-1. —> caspase-1
activates IL-1 and IL-8. —> acute in ammation and fever.

14. Describe the cooperativeness of the macrophage and NK cell.

Answer: Macrophage ingests microbes —> macrophage produces IL-12 —> IL-12 activates NK cells
—> NK cells secrete IFN - gamma —> IFN-gamma activates the macrophages to kill the ingested
microbes.

15. What is NFkB?

Answer: NFkB are transcription factors activated by TLRs, they are essential for expression of
various cytokines and endothelial adhesion molecules, therefore important for the in ammation
process.

16. Activating receptor of NK cells NKG2D recognizes…?

Answer: Molecules that resemble MHC proteins and they’re expressed to many types of cellular
stress.

17. CD16 is speci c for…?

Answer: IgG antibodies, bound to cells. Results in Antibody Dependent Cellular Cytotoxicity.

18. Describe the monocyte activation pathways.

Answer: There are two pathways of monocyte activation (turning it into a macrophage):

* Classical pathway - in classical pathway, monocytes are called the M1, these are important for the
in ammation. This activation pathway is triggered by IFN-gamma.

* Alternative pathway - in alternative pathway, the monocytes are called the M2, these cells are
important for termination of in ammation. This activation pathway is triggered by IL-4 and IL-13.

19. What is a complement system?

Answer: Complement system is a collection of circulating and membrane-associated proteins, which
are important in defense against microbes. Many of these proteins are proteolytic enzymes.
Complement system has three main functions: Triggering the Opsonization and phagocytosis(C3b);
in ammation (C5a and C3a), and cell lysis (C6-9).

20. Describe the possible pathways that can activate the complement system.
Answer: There are three pathways that can activate the complement system:

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* Alternative pathway - Triggered when some complement proteins are activated on the microbial
surfaces and cannot be controlled. Component of the innate immunity.

* Classical pathway - Triggered by antibodies that bind to microbes. Component of the humoral
adaptive immunity.

* Lectin pathway - Triggered when Mannose-binding lectin, binds to carbohydrates on the microbes,
then lectin activates the classical pathway, but because there is no antibody involved in initiation of
the lectin pathway, it is still considered as a component of innate immunity.

21. Function of C3b.

Answer: Opsonization and phagocytosis. C3b coats microbes and the phagocytes have receptors
for C3b, therefore C3b is important for opsonization and phagocytosis.

22. Function of C5a and C3a.

Answer: In ammation. C5a and C3a are chemoattractants for leukocytes, they also activate the
endothelial cells and mast cells.

23. MHC molecule role in recognition of infected cells by NK cells.

Answer: NK inhibitory receptors are speci c for self MHC I molecules, therefore expressing MHC I
molecules stops the NK cells from destroying self cells. Whereas in infected cells, virus inhibits the
expression of MHC I and therefore, NK cells can distinguish infected cells.

24. How does the Innate immunity stimulate the adaptive immunity?
Answer: Lymphocytes require 2 signals for activation, 1 is antigen itself and the 2nd is the innate
immune response. Second signal can be:

* Increased expression of costimulators on the dendritic cells, which bind to TCRs and activate the
naive T cells.

* Production of cytokines such as: IL-1; IL-12; and IL-6.

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