Innate Immunity Overview

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Questions and Answers

Which component of innate immunity serves as a physical barrier to infection?

Cytokines

Complement proteins

Neutrophils

Skin (correct)

What is the role of lysozyme in the innate immune response?

Enhances T cell activation

Produces antibodies

Facilitates phagocytosis

Hydrolyzes peptidoglycans (correct)

Which type of immune cell is primarily responsible for phagocytosis during an infection?

B cells

Basophils

T cells

Macrophages (correct)

What type of immune mechanism do antimicrobial peptides utilize?

Destabilize bacterial membranes Signup and view all the answers

Which of the following is NOT a part of the soluble innate immune recognition elements?

Phagocytes Signup and view all the answers

What role do neutrophils play within the leukocytes of innate immunity?

Produce respiratory burst Signup and view all the answers

What is the main advantage of commensal bacteria in the context of innate immunity?

They compete with pathogens. Signup and view all the answers

Which substance is NOT produced during the respiratory burst of neutrophils?

Cytokines Signup and view all the answers

What best describes the role of opsonins in the immune response?

They coat bacteria and promote phagocytosis. Signup and view all the answers

Which of the following conditions is characterized by a mutation that prevents lysosome-phagosome fusion?

Chediak-Higashi syndrome Signup and view all the answers

Which enzyme is primarily responsible for the production of reactive oxygen species during the respiratory burst?

NADPH oxidase Signup and view all the answers

In Chronic Granulomatous Disease, which of the following is a common feature due to the underlying genetic mutation?

Formation of granulomas due to infections Signup and view all the answers

Which of the following mechanisms is employed by some bacteria to evade phagocytosis?

Formation of carbohydrate capsules Signup and view all the answers

Which of the following functions is NOT associated with phagocytosis?

Production of antibodies Signup and view all the answers

What role does lysozyme play in the immune system?

It hydrolyzes peptidoglycans in bacterial cell walls. Signup and view all the answers

What characterizes the respiratory burst in phagocytes?

Production of highly reactive radicals. Signup and view all the answers

What is the primary function of perforin in NK cell activity?

Forming pores in the target cell membrane Signup and view all the answers

Which type of recognition is involved when NK cells detect cells missing MHC-I molecules?

Missing-self recognition Signup and view all the answers

What do ILC2 cells primarily produce to support anti-helminth responses?

IL-5 and IL-13 Signup and view all the answers

Which receptor on NK cells recognizes antibodies opsonizing infected cells?

FcγRIII (CD16) Signup and view all the answers

What determines whether a NK cell will kill a host cell?

The balance of inhibitory and activating signals Signup and view all the answers

In what type of tissue are ILC3 cells primarily found?

Mucosal tissue Signup and view all the answers

What is a common feature of tumor cells in relation to NK cell recognition?

They constitutively express ligands for activating NK cell receptors Signup and view all the answers

Which of the following statements is true regarding granzymes?

They induce apoptosis or osmotic lysis within the target cell Signup and view all the answers

Which of the following best describes a potential issue with leukocytes in the context of bacterial infections?

They cannot phagocytose bacteria efficiently. Signup and view all the answers

What is a consequence of leukocytes being unable to recognize bacterial components released into the cytoplasm?

Compromised immune response to the bacteria. Signup and view all the answers

Which statement is true regarding the cytokine production of leukocytes when faced with bacterial products?

They cannot produce cytokines and other inflammatory mediators. Signup and view all the answers

What does it indicate if leukocytes are more susceptible to viral infections?

A possible dysfunction in their overall immune capabilities. Signup and view all the answers

What role do reactive oxygen species play in the function of leukocytes?

They are crucial for killing pathogens and regulating inflammation. Signup and view all the answers

Why might a deficiency in producing reactive oxygen species in leukocytes be problematic?

It may prevent effective killing of pathogens. Signup and view all the answers

Which of the following is a characteristic of leukocytes during an immune response?

They have the ability to adapt to various pathogens. Signup and view all the answers

What might be a consequence of leukocytes failing to produce inflammatory mediators when encountering bacteria?

Prolonged times for recovery from infections. Signup and view all the answers

Which process is most directly affected if leukocytes cannot phagocytose bacteria?

Pathogen clearance from the infection site. Signup and view all the answers

Which type of pathogen is most likely to evade leukocyte activity if leukocytes cannot recognize bacterial components?

Bacteria Signup and view all the answers

What is the primary function of Toll-Like Receptors (TLR)?

Signal microbial presence and initiate inflammation Signup and view all the answers

Which type of molecule do RLR primarily recognize?

Viral genomes (ssRNA and dsRNA) Signup and view all the answers

What can chronic activation of the cGAS/STING pathway lead to?

Autoimmune disorders like Aicardi–Goutières syndrome Signup and view all the answers

Nod-like Receptors (NLR) are primarily involved in which action?

Cytoplasmic recognition of microbial products and danger signals Signup and view all the answers

How do TLR contribute to adaptive immunity?

By presenting antigens and inducing cytokine production Signup and view all the answers

Which of the following is a consequence of TLR activation?

Induction of co-stimulatory molecules Signup and view all the answers

What role do pro-inflammatory cytokines play following RLR activation?

They promote inflammation and antiviral responses Signup and view all the answers

Which statement about TLR is incorrect?

TLR exclusively recognize proteins from pathogens. Signup and view all the answers

Study Notes

Innate Immunity

First line of defense against infection.
Composed of physical, chemical, and biological barriers.

Physical Barriers

Skin and mucus membranes act as a physical barrier to pathogens.
Mucus and cilia in the lungs and intestines help remove particles.

Chemical Barriers

Lysozyme: breaks down peptidoglycans in bacterial cell walls. Found in tears, saliva, and produced by neutrophils.
Phospholipase 2A: hydrolyzes membrane phospholipids.
Antimicrobial peptides: short peptides with a positive charge that interact with bacterial membranes, disrupting their integrity.
Acid pH of the stomach and bile salts act as chemical barriers.

Biological Barriers

Commensal bacterial flora (microbiota): competes with pathogens for resources and space.
These barriers recognize an infection once it gets past the epithelial barrier.

Microbicidal Mechanisms

Soluble innate immune recognition elements: collectins, ficolins, and complement activation.
Sentinel innate immune cells of tissues: neutrophils, macrophages, mast cells, NK cells, and dendritic cells.
Phagocytosis: engulfment and destruction of pathogens.
Toxic products:
- Nitric oxide (iNOS2)
- Hydrogen peroxide
- Superoxide anions (O2-) produced by NADPH oxidase in neutrophils (respiratory burst).

Leukocytes of Innate Immunity

Polymorphonuclear Leukocytes (PMNs):
- Neutrophils:
  - 40-70% of all white blood cells.
  - First to arrive at the infection site.
  - Short-lived, with 10^11 produced daily.
  - Highly phagocytic and microbicidal.
  - Produce respiratory burst.
  - Bind to many microbial ligands.
  - Receptors for apoptotic cells.
Functions:
- Destruction of pathogens
- Exposure of microbial products
- Antigen presentation
- Removal of necrotic/apoptotic cells

Opsonization

Opsonins, like complement proteins or antibodies, coat bacteria and enhance phagocytosis by opsonin receptors.

Chediak-Higashi Syndrome

A rare, autosomal recessive disorder characterized by:
- Recurrent bacterial infections including pyogenic infections.
- Oculocutaneous albinism.
- Progressive neurologic abnormalities.
- Mild coagulation defects.
Mutation in a lysosomal trafficking regulator prevents lysosome-phagosome fusion.

Phagocytosis and Production of Toxic Radicals

Phagocytosis is coupled to the "respiratory burst": production of toxic radicals that kill microbes.
Phagocyte oxidase (NADPH oxidase): produces reactive oxygen intermediates (superoxide anion, hydrogen peroxide).
Myeloperoxidase: produces hypochlorous acid.
Inducible Nitric oxide synthase (iNOS): produces reactive nitrogen intermediates (NO).

Chronic Granulomatous Disease (CGD)

Genetic disease caused by mutations in NADPH oxidase enzyme complex of neutrophils.
Most common form is X-linked.
Recurrent infections, particularly by intracellular bacteria, leading to pneumonia, abscesses, and arthritis.
Granulomas form due to the inability to kill phagocytosed bacteria.

Oxygen-Independent Killing in the Phagolysosome

Effector Molecule: | Function:
Antimicrobial peptides | Damage to microbial membranes
Lysozyme | Hydrolyzes peptidoglycans in the cell wall
Lactoferrin | Deprives pathogens of iron
Hydrolytic enzymes (proteases) | Digests killed organisms

Microbial Evasion of Phagocytosis

Some bacteria avoid engulfment by phagocytes through strategies like:
- Masking bacterial surface: using a carbohydrate capsule, M protein, and fimbriae to prevent antibody recognition.
- Attract cells to infection site and induce migration of DC to lymph nodes: to facilitate spreading.

Toll-Like Receptors (TLR)

Recognize microbial products (PAMP) on the cell surface or endosomal compartments.
Humans express 10 TLRs.
TLR evolved to recognize PAMPs derived from viruses, bacteria, fungi, and protozoa (self/non-self discrimination).
TLR are expressed on the cell surface or endosomal compartments.
TLR also recognize endogenous molecules ("danger signals" (DAMP)).
Activation of TLR leads to:
- NF-κB activation
- Production of pro-inflammatory mediators

Toll-Like Receptors (TLR) - Linking Innate and Adaptive Immunity

TLR signaling:
- Signals the presence of microbes.
- Initiates inflammation:
  - Cytokine/chemokine production
  - Upregulation of adhesion molecules
- Initiates and instructs the adaptive immune response:
  - Antigen presentation (DC maturation)
  - Induction of co-stimulatory molecules
  - Induction of cytokines that guide Th cell polarization

Rig-like Receptors (RLR)

Cytoplasmic recognition of viral genomes.
RLR recognize ssRNA and dsRNA that constitute the genome of viruses.
Induce production of proinflammatory cytokines and interferons.

cGAS/STING

Cytoplasmic recognition of DNA.
Chronic activation of cGAS/STING due to presence of host DNA in the cytosol can lead to autoimmune disorders (Aicardi–Goutières syndrome).

Nod-like Receptors (NLR)

Cytoplasmic recognition of microbial products and "danger signals".
NLRs are part of a multiprotein complex called the "inflammasome".
Inflammasome activation leads to activation of caspase-1 and production of proinflammatory cytokines IL-1β and IL-18.

Natural Killer (NK) Cells

Part of the innate immune system that provides a first line of defense against viral infections and tumors.
They can kill infected or cancerous cells without prior sensitization.
NK cells possess small granules in their cytoplasm containing perforin and the proteases granzymes.
They have two main mechanisms for killing:
- "Missing-self recognition": Infected or transformed cells lose expression of MHC-I, leading to NK cell activation and killing.
- "Altered-self recognition": Infected or stressed host cells induce the expression of endogenous self molecules that act as ligands for activating NK cell receptors.
The balance between inhibitory and activating signals determines whether an NK cell will kill a target cell.

NK Cell Killing Mechanisms

Perforin-Granzyme pathway: NK cells release perforin, which forms pores in the cell membrane of the target cell. Granzymes then enter the cell, inducing apoptosis or osmotic lysis.

Antibody-Dependent Cellular Cytotoxicity (ADCC)

Infected cells are opsonized with antibodies.
Antibodies bound to antigens can be recognized by FcγRIII (CD16) receptors expressed on NK cells, resulting in NK activation, release of cytolytic granules, and induction of apoptosis.
This is the major killing mechanism of some monoclonal antibodies like rituximab (Rituxan) and ofatumumab (Azzera).

Innate Lymphoid Cells (ILCs)

Recently discovered cells that promote functions associated with T helper cells.
Do not share the same surface markers as T cells (e.g., T cell receptors).
Three main groups:
- ILC1: Includes NK cells and ILC1 cells, both known for IFN-γ production, tumor surveillance, and inflammation.
- ILC2: Produce IL-5 and IL-13, promoting anti-helminth responses and allergic lung inflammation.
- ILC3: Found in mucosal tissue like the intestinal tract, interacting with microbiota.

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Description

Explore the crucial aspects of innate immunity, including its first line of defense against infections. This quiz covers physical, chemical, and biological barriers that protect the body, along with the mechanisms through which they operate. Test your knowledge on how these elements work together to combat pathogens.