Lecture 9 The Genitourinary System PT2 - Immune response

Question 1

Question: What are lymphocytes?

Answer 1

Answer: Lymphocytes are a type of white blood cell crucial for the immune system. They include T cells, B cells, and Natural Killer (NK) cells, each with different roles in immunity.

Question 2

Question: What are NK cells, and what do they do?

Answer 2

Answer: NK cells are lymphocytes of the innate immune system that detect and kill virus-infected and tumor cells by recognizing stress signals or the absence of MHC class I molecules on target cells.

Question 3

Pattern Recognition
Receptors (PRRs)

Answer 3

PRRs are receptors on immune cells that recognize Pathogen-Associated Molecular Patterns (PAMPs) on pathogens, triggering an innate immune response.

==> are proteins found on or inside (for intracellular pathogens) certain immune cells that recognize Pathogen-Associated Molecular Patterns (PAMPs)

can be found extracellular (cell membrane), cytosolic (cytoplasm inside the cell) and endosomal (nucleus)

Main type is TLRs

A lot are found on resident and innate immune cells such as macrophages because its their role to detect the pathogens

PRRs have broad specificity. This means that a single PRR can recognize a common molecular pattern found on a wide variety of pathogens.

CDSs = a type of PRRs. usually DNA in nucleus so if DNA is detected in cytosol, something is happening, virus occuring, senses this

Question 4

PAMPS

Answer 4

Pathogen Associated Molecular Patterns (PAMPs)
PAMPs are conserved molecular structures found on pathogens like bacteria and viruses. They are recognized by the immune system’s PRRs as signals of infection.
Structures common to many different
pathogens which are not present in healthy
cells

[PAMPs recognised by innate receptors, germ line encoded (germ line encoded genetic information is inherited from your parents and is the same in all individuals of a species.)
Antigens recognised by adaptative, specific immune cells receptors, ]

Question 5

Natural Killer (NK) Cells

Answer 5

Type: Innate lymphocyte
Circulation: Circulate in the blood and are recruited to sites of infection by chemokines.
Location: Found in HSV (Herpes Simplex Virus) lesions.
Function: Recognize and lyse virally infected cells, particularly those with downregulated MHC class I molecules (Missing self hypothesis).
Cytotoxic Mechanism: Use the same cytotoxic mechanisms as CD8+ T cells, releasing perforins and granzymes to induce apoptosis in target cells.
Cytokine Release: Release cytokines like IFN-gamma, which helps enhance the adaptive immune response and activates macrophages.
Activation = NK cells are activated when MHC is present or absent (pathogens may try to hide their MHCs to evade immune response but NK cells counteract that)

Question 6

PRRs mechanism of action

Answer 6

1. Detection of Pathogens = responsible for recognizing PAMPs
2. PRRs trigger a signaling cascade that leads to the production of proinflammatory cytokines such as TNF (Tumor Necrosis Factor), IL-6 (Interleukin-6), and IL-1β (Interleukin-1 beta). = cytokines promote inflammation to contain pathogen and recruit additional immune cells to infection site
3. Production of type 1 interferons == induce an antiviral state in neighboring cells, limiting viral replication and spread.
   4.Induction of Apoptosis == some PRR activation can lead to (apoptosis) of infected or damaged cells
4. Enhancing Adaptive Immune Response: PRR signaling can activate and direct the adaptive immune response.

Question 7

What do PRRs sense during a viral infection?

Answer 7

Viral Replication: Viruses replicate inside host cells, limiting the targets available for PRRs.
Viral PAMPs: PRRs can detect specific viral components known as PAMPs, including:
- Viral RNA (e.g., double-stranded RNA)
- Viral DNA
- Viral glycoproteins

Primary Response: The major response to PRR recognition of viral PAMPs is the production of Type I Interferons (e.g., IFN-α, IFN-β), which help establish an antiviral state in neighboring cells.

Secondary Response: Following Type I Interferon production, PRRs also trigger the release of cytokines like TNF, IL-12, and IL-1β, which further drive inflammation and the immune response.

Question 8

What are the types of Interferons (IFNs)?

Answer 8

Type I Interferon: IFN-α and IFN-β
Type II Interferon: IFN-γ
Type III Interferon: IFN-λ

Main Sources:
* IFN-α: Dendritic cells and macrophages
* IFN-β: Fibroblasts
* IFN-γ: NK cells and T cells

Question 9

What is the function of Type I Interferons (IFN-α and IFN-β)?

Answer 9

1. Secreted from virally infected cells to induce an antiviral state in surrounding uninfected cells.
   type 1 sends signal to neighbour cells, warning== create an inhospitable environment for virus, walled off, stop the spread
2. When a cell is infected by a virus, it secretes IFN-α and IFN-β, which bind to receptors on nearby cells, signaling them to upregulate antiviral genes
   ==> Interferon-Stimulated Genes: Induce genes that encode antiviral enzymes and shut down host cell metabolism.
3. MHC-I Expression: Increase MHC class I expression, enhancing the detection of infected cells by CD8+ T cells.

Question 10

How does HSV evade Type I Interferon responses?

Answer 10

HSV Evasion Mechanisms: HSV encodes gene products that inhibit the induction of Type I IFN and disrupt IFN signaling, helping the virus evade the immune response.

Question 11

How does the immune system respond to Chlamydia trachomatis?

Answer 11

Infection Site: Infects epithelial cells.
Associated Conditions: Can cause mucopurulent cervicitis, pelvic inflammatory disease, and non-gonococcal urethritis.
Immune Response: The immune response is largely responsible for the symptoms of the infection.

Question 12

How does the immune system respond to Neisseria gonorrhea?

Answer 12

Immune Response: Strong immune response leads to symptoms such as pus/discharge, and potentially scarring, which can result in infertility.
Neutrophil Role: Neutrophils are recruited to phagocytose the bacteria, but Neisseria gonorrhea can survive inside neutrophils, potentially facilitating transmission.

Neisseria gonorrhea == affect neutrophils
Cause pus, contiaining bacteria, if in contact, the pus has the live agent to infect someone else

Question 13

How does the immune system respond to Treponema pallidum?

Answer 13

Infection Characteristics: The chancre (ulcer) contains replicating spirochetes (spiral looking bacteria) surrounded by immune cells, including T cells, plasma cells, and macrophages.

Immune Response: The immune response can clear the local infection through macrophage phagocytosis, but Treponema pallidum can spread systemically and evade the immune system through antigenic escape (Spirochetes can change, antigenic escape).

Question 14

How does the immune system respond to Trichomonas vaginalis?

Answer 14

Inflammatory Response: Triggers inflammation.
Neutrophil Role: Can be broken down and killed by neutrophils.

Question 15

1. How will viral PAMPs differ from bacterial PAMPs?

Answer 15

Viral PAMPs: Include features like double-stranded RNA (dsRNA), viral DNA, and viral glycoproteins.
Bacterial PAMPs: Include structures like lipopolysaccharides (LPS), peptidoglycan, and flagellin.
Key Difference: Viral PAMPs are often nucleic acids or viral proteins, while bacterial PAMPs are typically cell wall components or surface molecules.

Question 16

Why are there so many PRRs?

Answer 16

Diverse Pathogen Detection: Different PRRs recognize a wide range of PAMPs, allowing the immune system to detect and respond to various pathogens (viruses, bacteria, fungi, parasites).
Broad Coverage: Having multiple PRRs ensures that the immune system can respond to many different types of infections quickly and effectively.

Question 17

Will Type I Interferon inhibit bacteria?

Answer 17

Not Directly: Type I interferons (IFN-α, IFN-β) primarily target viruses by inducing an antiviral state in cells. They do not directly inhibit bacterial growth, but they can modulate the immune response, which might indirectly affect bacterial infections.

Question 18

Why is low Type I Interferon associated with COVID-19 severity?

Answer 18

Impaired Antiviral Response: Low levels of Type I interferon lead to a weaker antiviral response, allowing the virus to replicate more freely and cause severe disease. This is consistent with the role of Type I interferons in controlling viral infections.

Question 19

What is required for an NK cell to kill a virally infected cell?

Answer 19

Detection of Stress Signals: NK cells detect stress-induced ligands on infected cells.
“Missing Self” Recognition: NK cells recognize the downregulation of MHC class I molecules on infected cells.
Summation of Signals: The balance of activating signals (from stress ligands) and lack of inhibitory signals (from MHC-I) leads to NK cell activation and the killing of the infected cell.

Question 20

How can we ensure antigen-specific T cells traffic to sites of infection?

Answer 20

Chemokine Signals: Chemokines produced at the infection site attract antigen-specific T cells.
Upregulated Adhesion Molecules: T cells express adhesion molecules that interact with endothelial cells at the site of infection, facilitating their migration into the tissue.
Lymph Node Activation: T cells are activated in lymph nodes and then follow chemokine gradients to the site of infection.

Question 21

how do bacteria and virus differ when infecting the body

Answer 21

Bacteria infect the body by entering through various routes, adhering to and colonizing host tissues, producing toxins, and evading the immune system. They can live and reproduce independently.
Viruses infect by entering host cells, taking over the cell’s machinery to replicate, and then spreading to other cells. They rely entirely on the host cell for replication and survival.