Immune Response Overview

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Questions and Answers

What is the primary role of the innate immune system in response to infection?

It resolves inflammation and returns to homeostasis.

It rapidly controls pathogen replication. (correct)

It is responsible for memory cell production.

It provides a slow, specific response to pathogens.

Which statement best describes the adaptive immune system's response to a reinfection?

It operates independently of prior infections.

It does not produce memory cells.

It starts as quickly as the innate response but is more powerful. (correct)

It is slower than the innate immune response.

Which of the following is NOT a requirement for a successful immune response?

Recognition of pathogens through receptors.

Production of effector mechanisms.

A rapid increase in pathogen replication. (correct)

Activation of immune cells.

What role do memory cells play in the adaptive immune response?

They enable faster and more effective responses upon re-infection. Signup and view all the answers

How do cytokines contribute to the immune response?

They provide direct cytotoxicity through digestive enzymes. Signup and view all the answers

Which HLA molecule is associated with rheumatoid arthritis?

HLA-DR4 Signup and view all the answers

What is the first step in the endogenous antigen presentation pathway?

Protein synthesis and ubiquitination Signup and view all the answers

In which type of antigen presentation are extracellular antigens primarily involved?

Exogenous pathway Signup and view all the answers

What role does TAP play in the endogenous pathway?

Transports peptides into the endoplasmic reticulum Signup and view all the answers

Which of the following cells are considered professional antigen-presenting cells (APCs)?

B cells Signup and view all the answers

What is the primary function of proteasomes in the endogenous pathway?

To degrade proteins into short peptide fragments Signup and view all the answers

Which mechanism do antigen-presenting cells use to capture exogenous antigens?

Phagocytosis Signup and view all the answers

What happens to peptides after they are loaded onto MHC class I molecules?

They are transported to the cell surface Signup and view all the answers

What is the primary function of matrix metalloproteinases (MMPs) in basement membrane transmigration?

To degrade the basement membrane Signup and view all the answers

Which type of receptors are crucial for recognizing molecular patterns associated with pathogens?

Pattern recognition receptors (PRRs) Signup and view all the answers

What type of molecular patterns do PAMPs represent?

Structural components found on microbes Signup and view all the answers

Which TLR is responsible for detecting lipopolysaccharide (LPS) from gram-negative bacteria?

TLR4 Signup and view all the answers

What signaling pathway is activated by the binding of ligands to extracellular TLRs?

NF-κB pathway Signup and view all the answers

Which TLRs are known for recognizing viral nucleic acids in intracellular membranes?

TLR3, TLR7, and TLR8 Signup and view all the answers

What type of cytokines does the MyD88 signaling pathway primarily produce?

Pro-inflammatory cytokines Signup and view all the answers

What do DAMPs release when cells are stressed or dying?

Molecules like ATP and HSP proteins Signup and view all the answers

How do chemokines function in the immune response?

They guide leukocytes to the site of infection Signup and view all the answers

What role do TLRs play in the immune response?

They activate immune response pathways for pathogen detection Signup and view all the answers

What is the primary role of negative selection in T cell development?

Eliminate T cells that recognize self-antigens too strongly Signup and view all the answers

Which cells present tissue-restricted antigens for negative selection?

Medullary thymic epithelial cells (mTECs) Signup and view all the answers

What characterizes regulatory T cells (Tregs)?

They are involved in maintaining immune tolerance Signup and view all the answers

What process occurs when T cells that recognize self-antigens with intermediate affinity are not deleted?

Conversion into regulatory T cells Signup and view all the answers

Which transcription factor is crucial for the expression of tissue-specific antigens in the thymus?

AIRE Signup and view all the answers

What is a result of reduced presentation of self-antigens in the thymus?

Development of more autoreactive T cells Signup and view all the answers

After successful selection in the thymus, what type of T cells exit into peripheral blood circulation?

Mature naive CD4+ and CD8+ T cells Signup and view all the answers

What is the significance of AIRE expression in medullary thymic epithelial cells?

It facilitates clonal deletion of autoreactive T cells Signup and view all the answers

What percentage of T cells is estimated to die during maturation in the thymus?

95% Signup and view all the answers

Which process is specifically associated with T cells that escape negative selection?

Anergy Signup and view all the answers

What occurs first when a pathogen is phagocytosed?

Activation of NADPH oxidase Signup and view all the answers

Which enzyme converts superoxide to hydrogen peroxide?

Superoxide dismutase Signup and view all the answers

What is the primary function of hypochlorous acid (HOCl)?

To serve as a powerful oxidizing agent Signup and view all the answers

Which of the following is NOT a reactive oxygen species (ROS)?

Prostaglandin (PG) Signup and view all the answers

What is the role of enzymatic scavengers in phagocytic cells?

To neutralize excess reactive oxygen species Signup and view all the answers

M1 macrophages are primarily involved in which of the following functions?

Host defense against intracellular pathogens Signup and view all the answers

What type of macrophages are induced by anti-inflammatory signals?

M2 macrophages Signup and view all the answers

Which reactive oxygen species is considered the most reactive and destructive?

Hydroxyl Radical (OH·) Signup and view all the answers

Which cytokine is NOT typically associated with M1 macrophage activation?

IL-10 Signup and view all the answers

What is one main way that reactive oxygen species kill pathogens?

Through lipid peroxidation leading to membrane damage Signup and view all the answers

What is the lifespan of macrophages typically described as?

Months to years Signup and view all the answers

Which signal induces M2 macrophages to promote tissue remodeling?

IL-4 Signup and view all the answers

What type of macrophages can develop from monocytes based on local cues?

Monocyte-derived macrophages Signup and view all the answers

What initiates the classical pathway in humoral adaptive immunity?

Binding of C1q to antibodies on microbial surfaces Signup and view all the answers

In the alternative pathway, what is the role of factor D?

To assist Bb in binding C3b to the pathogen Signup and view all the answers

What is a key characteristic of the spontaneous hydrolysis of C3 in the alternative pathway?

It continuously occurs regardless of pathogen presence Signup and view all the answers

Which component is NOT directly activated in the classical pathway cascade?

C5 Signup and view all the answers

How does the alternative pathway distinguish between self and foreign microbes?

Based on the absence of regulatory proteins on pathogens Signup and view all the answers

Which cytokine is essential for NK cell development and proliferation?

IL-15 Signup and view all the answers

In the development of NK cells, which transcription factor is primarily associated with lineage commitment?

T-bet Signup and view all the answers

Which receptors on NK cells primarily recognize self-molecules to prevent attacking healthy cells?

Inhibitory receptors Signup and view all the answers

Which NK cell state is associated with a higher expression of cytotoxic cytokines?

CD56 dim Signup and view all the answers

What results from the interaction between inhibitory receptors of NK cells and MHC class I molecules?

Prevention of cell killing Signup and view all the answers

What drives the maturation and activation of NK cells after their development?

IL-2 and IL-12 Signup and view all the answers

What is the primary role of ILC2 cells in the lung?

Responding to allergens and helminths Signup and view all the answers

Which type of signal primarily influences ILC3 activation?

Short-chain fatty acids from gut microbes Signup and view all the answers

Neuro-immune interactions can significantly activate which type of ILCs?

ILC2 Signup and view all the answers

What type of plasticity allows ILCs to adapt to changes in their environment?

ILC3 to ILC1 transition Signup and view all the answers

What distinguishes CD56 bright NK cells from CD56 dim NK cells?

Ability to kill target cells Signup and view all the answers

Which function of NK cells allows them to respond quickly to compromised cells?

Killing with granzymes Signup and view all the answers

What role do memory NK cells play in the immune system?

Improving recognition of previously encountered pathogens Signup and view all the answers

How do ILCs influence the gut barrier function?

Through cytokine production modulation Signup and view all the answers

What primarily defines the rapid response capability of NK cells?

Direct recognition of damaged cells Signup and view all the answers

What could trigger the functional flexibility of ILCs in response to environmental changes?

Cytokines like IL-12 Signup and view all the answers

Which of the following statements accurately describes follicular dendritic cells (DCs)?

They do not present protein antigens to T cells. Signup and view all the answers

What characteristic is true for immature dendritic cells?

They exhibit high phagocytic activity. Signup and view all the answers

What is the primary function of conventional dendritic cells?

Capture and presentation of antigens to CD8+ T cells. Signup and view all the answers

Which feature distinguishes plasmacytoid dendritic cells from conventional dendritic cells?

They originate from lymphoid precursors. Signup and view all the answers

Which transcription factor is associated with cDC1s?

BATF3 Signup and view all the answers

What distinguishes Langerhans cells from other types of dendritic cells?

They have a unique surface marker, Langerin. Signup and view all the answers

In what way do immature dendritic cells optimize their role in antigen capture?

Via high phagocytic activity. Signup and view all the answers

Which cytokine is characteristic of conventional dendritic cells?

IL-12 Signup and view all the answers

What is a primary role of plasmacytoid dendritic cells during viral infections?

Secretion of type I interferons. Signup and view all the answers

What TLRs role is most relevant in dendritic cells?

Detects pathogen-associated molecular patterns. Signup and view all the answers

What is the primary role of chaperone proteins in the endogenous antigen presentation pathway?

To assist in peptide loading onto MHC class I molecules. Signup and view all the answers

Which function is carried out by the proteasome during endogenous antigen processing?

It degrades proteins into shorter peptide fragments. Signup and view all the answers

In the exogenous antigen presentation pathway, how are antigens primarily internalized by professional antigen-presenting cells?

Through receptor-mediated endocytosis. Signup and view all the answers

What environmental condition within the lysosome facilitates the degradation of engulfed antigens in exogenous antigen processing?

Low pH and proteolytic enzymes. Signup and view all the answers

What type of antigens does the endogenous pathway primarily present?

Intracellular antigens such as viral proteins. Signup and view all the answers

Which specific step follows proteolytic processing in the exogenous antigen presentation pathway?

Peptide loading onto MHC class I molecules. Signup and view all the answers

Which of the following correctly describes the role of HLA-DQ2 and HLA-DQ8 in the immune system?

They are associated with celiac disease due to gluten sensitivity. Signup and view all the answers

What is a crucial feature of the Major Histocompatibility Complex (MHC) molecules during antigen presentation?

They present peptides for recognition by specific T cells. Signup and view all the answers

Study Notes

Innate vs Adaptive Immune Response

The innate immune system provides a rapid but non-specific response to pathogens, controlling replication while activating adaptive immunity.
Adaptive immunity is slower, but highly specific to individual pathogens.
Memory cells are produced by the adaptive immune system after the first infection, allowing for a faster and more potent response during reinfection.

Components of Immune Response

Recognition of pathogens via receptors.
Immune cell activation in response to infection.
Effector mechanisms for killing pathogens:
- Direct cytotoxicity: Killing through enzymes, etc.
- Indirect communication: Signaling to other immune cells.
Resolution of inflammation and return to homeostasis.
Basement membrane transmigration for leukocyte migration.

Pattern Recognition Receptors (PRRs)

PRRs are critical for detecting pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs).
They initiate an immune response to clear infection or repair damage.
Types of PRRs:
- Toll-like receptors (TLRs):
  - Located on the cell surface or within endosomal membranes.
  - Recognize diverse components from bacteria, viruses, and fungi.
  - Signal through MyD88 or TRIF pathways, leading to pro-inflammatory or antiviral responses.
- Other PRRs:
  - A wide range of PRRs exist with distinct functions.

Reactive Oxygen Species (ROS)

NADPH oxidase: Produces superoxide radicals by transferring electrons from NADPH to oxygen.
Superoxide dismutase (SOD): Converts superoxide into hydrogen peroxide.
Myeloperoxidase (MPO): Catalyzes the production of hypochlorous acid from hydrogen peroxide and chloride ions.
ROS functions:
- Damage microbial proteins, lipids, and nucleic acids.
- Contribute to pathogen killing via oxidative burst.

Macrophages

Versatile immune cells involved in defense, tissue homeostasis, and inflammation.
Development: Derived from yolk sac or monocytes.
Lifespan: Long, months to years.
Plasticity: Adopt different phenotypes based on signals.
Polarization:
- M1 (classically activated): Pro-inflammatory, induced by IFN-γ, LPS, and TNF-α.
- M2 (alternatively activated): Anti-inflammatory, induced by IL-4, IL-13, IL-10.

Antigen Presentation

MHC Class I:
- Presents intracellular antigens (viral or tumor-derived proteins) to CD8+ cytotoxic T cells.
- Involves proteasomal degradation of proteins and peptide transport via TAP complex.
MHC Class II:
- Presents extracellular antigens (bacteria, fungi, etc.) to CD4+ helper T cells.
- Involves antigen uptake via phagocytosis, endocytosis, and proteolysis.

T Cell Development in the Thymus

Double-negative (DN) stages: T cell progenitors lack CD4 and CD8 expression.
Double-positive (DP) stage: T cells express both CD4 and CD8.
Positive selection: Survival of T cells that weakly recognize self-MHC molecules.
Negative selection: Elimination of T cells that bind too strongly to self-antigens, preventing autoimmunity.
Regulatory T cells (Tregs): Develop from T cells that recognize self-antigens with intermediate affinity and suppress immune responses to self.

AIRE (Autoimmune Regulator)

Transcription factor expressed by medullary thymic epithelial cells (mTECs).
Enables the expression of tissue-specific antigens, allowing negative selection against a broad range of self-antigens.
Plays a critical role in preventing autoimmunity.

T Cell Lineage Commitment and Exit

After positive and negative selection, mature naive T cells exit the thymus:
- CD4+ T cells: Help other immune cells fight infections.
- CD8+ T cells: Directly kill infected cells.
These T cells remain in a resting state until encountering their specific antigen.

Classical Pathway

A major effector mechanism of humoral adaptive immunity.
Detects antibodies (IgM, IgG) bound to microbes and binds to their Fc region.
C1r and C1s become active, initiating a proteolytic cascade.
Antibodies are produced first, followed by complement molecule binding to C1.
Activates C4/C2, resulting in C4b/C2b.
Further activates C3, generating C3a and C3b.

Alternative Pathway

C3 undergoes spontaneous hydrolysis.
Recognizes LPS, triggering a continuous activation process.
Distinguishes self from foreign microbes based on regulatory proteins.
Pathogens lack inhibitory proteins, leading to activation.
C3 generates C3b, which binds to the pathogen.
Bf activates Bb, which further binds to C3b on the pathogen.
This creates an amplification loop with pathogen activation.

Tissue-Specific Cues

ILC2 are primed to respond to allergens and helminths in the lungs.
ILC3 are more responsive to bacterial signals in the gut.

Metabolic and Microbiota Signals

Short-chain fatty acids (SCFAs) produced by commensal microbes modulate ILC activation.
SCFAs influence cytokine production and barrier function.

Neuro-Immune Interactions

Neuronal signals (VIP, neuromedin U) directly activate ILCs.
These signals influence allergic reactions and tissue repair processes.

ILC Plasticity

ILCs can switch from one type to another under certain conditions.
ILC3 can transform into ILC1 in response to IL-12, associated with intestinal inflammation.
This allows for functional flexibility in response to environmental changes and diseases.

NK Cells

Type of ILC critical for defense against virally infected cells and tumors.
Do not require prior sensitization or antigen-specific receptors.
Rapidly respond to stressed cells showing changes through direct killing and cytokine secretion.
Exhibit different killing mechanisms, with granzymes being the fastest.
CD56 level distinguishes two subtypes:
- Bright CD56: Killing NK cells.
- Dim CD56: Cytokine producing NK cells.
Can become memory cells.
Found in blood, with mature cells expressing dim CD56, exhibiting pro-inflammatory functions.

NK Cell Functions

Produce IFN-γ, leading to cytotoxic cytokine overproduction.

NK Cell Development

Originate from CLPs in the bone marrow, sharing a lineage with T cells and other ILCs.
Development driven by:
- IL-15: Essential for development, proliferation, and survival.
- IL-2 and IL-12: Maturation and activation.
- Transcription factors: Eomes and T-bet regulate lineage commitment and specialization.
Mature NK cells circulate in the blood and are present in peripheral tissues.
Development stages:
- Pro-NK cells (stage 1) -> pre-NK cells (stage 2) -> immature NK cells (stage 3) -> CD56 bright (stage 4) -> CD56 dim (stage 5).

NK Cell Activation

Activated through a balance of activating and inhibitory receptors.
Recognize stress signals and changes on target cell surfaces.
Redundant system, making it difficult to determine activation/inhibition with receptor removal.

Inhibitory Receptors

Prevent NK cells from attacking healthy cells by recognizing self-molecules (MHC class I).
MHC I interaction with inhibitory receptors identifies cells as "self" and protects them from killing.
Includes:
- KIRs: Bind specific MHC class I molecules (HLA-A, HLA-B, HLA-C).
- CD94/NKG2A: Recognizes the non-classical MHC class I molecule (HLA-E).
Send inhibitory signals through ITIMs in their cytoplasmic domains, recruiting phosphates (SHP-1, SHP-2) to suppress activation signals.

Follicular DCs

Not derived from bone marrow precursors.
Do not present protein antigens to T cells.
Involved in B cell activation in germinal centers of secondary lymphoid organs.
Express TLRs and NLRs.
Important for T-cell activation.
Constantly express MHC-I (self-antigen expressed in healthy conditions).

Dendritic Cells

Diverse population with distinct functions.
Major players in immune responses.
Can be classified based on surface markers, TLR expression, transcription factors, cytokine production, and function.

Dendritic Cell Subtypes

cDC2s: Express CD11c, BCDA-1 (CD1c) and produce various cytokines. Source of inflammatory cytokines, involved in antigen presentation to CD4+ T cells.
cDC1s: Express CD11c, BDCA-3 (CD141), CLEC9A, XCR1+, and produce IL-12. Capture antigens and cross-present them to CD8+ T cells, inducing Th1 responses.
pDCs: Express BDCA-2 (CD303), BDCA-4 (CD304), CD123, and produce type I IFN. Play a role in antiviral immunity, early innate response, and priming antiviral T cells.
Langerhans Cells: Express CD11b, Langerin (CD207), EPCAM, BDCA1, and CD1a. Capture and present antigens to CD4+ T cells.
moDCs: Express CD11b, CCR2, CD14, and produce various cytokines. Involved in inflammatory cytokine production and other functions.

Dendritic Cell Development

Originate from hematopoietic stem cells in the bone marrow.
Develop from CMPs and CLPs.
- Conventional DCs: From myeloid precursors, specialize in antigen presentation and T cell activation.
- Plasmacytoid DCs: From lymphoid precursors, key producers of type I interferons during viral infections.

Immature Dendritic Cells

Located in peripheral tissues, specialized for antigen capture.
Express PRRs to detect pathogens.
Highly phagocytic, capturing pathogens, dead cells, and foreign particles.
Low expression of costimulatory molecules (CD80, CD86) necessary for T cell activation.

Antigen Uptake

Immature DCs efficiently capture various antigens, including pathogens, dead cells, and soluble molecules.

Antigen Presentation Pathways

Process whereby cells display antigenic peptides on MHC molecules for recognition by T cells.
Two types of antigen presentation based on antigen origin:
- Endogenous pathway: MHC class I
- Exogenous pathway: MHC class II

Endogenous Pathway (MHC class I)

Presents intracellular antigens (viral or tumor-derived proteins) on MHC class I.
Active on all nucleated cells.
Process:
1. Protein synthesis and ubiquitination - tagging for degradation.
2. Proteasomal degradation - breakdown into peptides by proteasomes.
3. Peptide transport into the endoplasmic reticulum - by TAP complex.
4. Peptide loading onto MHC-I - in the ER with chaperone proteins.
5. Transport to the cell surface - via the Golgi apparatus, displayed for recognition by CD8+ cytotoxic T cells.

Exogenous Pathway (MHC class II)

Presents extracellular antigens (bacteria, fungi, debris from dead cells) on MHC class II.
Occurs in professional APCs like dendritic cells, macrophages, and B cells.
Process:
1. Antigen uptake - through phagocytosis, pinocytosis, or receptor-mediated endocytosis.
2. Proteolytic processing - degradation in a lysosome after fusion with an endosome or phagosome.
3. [Process continues - check back for final steps]

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Explore the key aspects of innate and adaptive immune responses in this quiz. Understand the differences in speed and specificity, as well as the important roles of memory cells and pattern recognition receptors. Test your knowledge on how the immune system detects, responds to, and resolves infections.