Immunology

Question 1

What is the molecular basis of pattern recognition?

Answer 1

Pattern recognition involves the detection of microbial structures by specific receptors present on immune cells. Key words: pattern recognition, microbial structures, receptors.

Question 2

Name the three main stimulators of the complement system and its pathways.

Answer 2

The three main stimulators of the complement system are classical pathway, mannose binding lectin pathway, and alternative pathway. Key words: complement system, stimulators, pathways.

Question 3

What are the three main consequences of complement activation? specify which part of the complement system is responsible for which one.

Answer 3

the three main results of complement activation are opsonization (especially C3b and C4b), chemotaxis (especially C3a and C5a), and destruction through the membrane attack complex (MAC). Key words: complement activation, results.

Question 4

Define Toll-like receptors (TLRs) and list major intracellular and extracellular TLRs.

Answer 4

Toll-like receptors are molecules that recognize specific microbial patterns. Major TLRs include TLR 2, 3, 4, 5, 7, 8, and 9, each recognizing different microbial patterns. Key words: Toll-like receptors, microbial patterns, major TLRs.

Question 5

Discuss the significance of NOD receptors in the immune system.

Answer 5

NOD receptors detect peptidoglycan and play a crucial role in recognizing pathogenic invasive bacteria versus friendly commensal bacteria. Key words: NOD receptors, peptidoglycan, commensal bacteria.

Question 6

List three consequences of activation of Pattern Recognition Receptors (PRRs).

Answer 6

Activation of PRRs leads to cytokine secretion, anti-apoptotic gene expression, and leukocyte recruitment, contributing to the immune response. Key words: PRR activation, consequences.

Question 7

Explain the significance of complement regulation in immune function.

Answer 7

Complement regulation prevents excessive immune activation and tissue damage. Key regulators include Factor I, Factor H, DAF, and CD55. Key words: complement regulation, tissue damage, key regulators.

Question 8

Identify important disorders resulting from inappropriate complement activation.

Answer 8

Disorders include angioneurotic edema and paroxysmal nocturnal hemoglobinuria, caused by lack of inhibition or mutations in complement regulation. Key words: disorders, complement activation, mutations.

Question 9

What are the consequences of deficiency in early versus later complement components?

Answer 9

Deficiency in early complement components leads to significant immunodeficiency, while deficiency in later components makes individuals susceptible to Neisseria spp infections. Key words: complement deficiency, immunodeficiency, susceptibility.

Question 10

Explain the downstream effects of NFkB activation.

Answer 10

NFkB activation leads to gene transcription of pro-inflammatory genes, cytokine secretion, anti-apoptotic gene expression, and leukocyte recruitment. Key words: NFkB activation, downstream effects.

Question 11

What is opsonization?

Answer 11

Opsonization is the process by which entities, including pathogens, are tagged for phagocytosis. Key words: opsonization, tagging, phagocytosis.

Question 12

How does complement activation occur in the classical pathway?

Answer 12

Complement activation in the classical pathway requires an antibody. Key words: classical pathway, antibody.

Question 13

What are the consequences of continuous activation of pattern recognition receptors?

Answer 13

Continuous activation of pattern recognition receptors leads to ongoing inflammation, tissue damage, and eventually systemic inflammatory response syndrome and multiorgan dysfunction. Key words: continuous activation, inflammation, tissue damage.

Question 14

Explain the importance of complement regulation in immune function.

Answer 14

Complement regulation prevents excessive immune activation and tissue damage. Key regulators include Factor I, Factor H, DAF, and CD55. Key words: complement regulation, tissue damage, key regulators.

Question 15

What are the functions of phagocytes?

Answer 15

Phagocytes engulf and digest pathogens through a process called phagocytosis. They also participate in the respiratory burst, producing toxic molecules to kill pathogens.

Question 16

How do monocytes and neutrophils differ?

Answer 16

Monocytes are circulating cells that differentiate into tissue macrophages, whereas neutrophils are primarily involved in acute inflammatory responses and are short-lived.

Question 17

What is the significance of pattern recognition receptor expression by monocytes?

Answer 17

Pattern recognition receptors allow monocytes to recognize conserved molecular patterns present in pathogens, enabling them to initiate immune responses.

Question 18

What does the term “innate-like” imply in immunology?

Answer 18

“Innate-like” refers to cells that exhibit characteristics of both innate and adaptive immune responses but lack specificity and dependence on T cells.

Question 19

Discuss the functions of NK cells, B1 B cells, and NKT cells.

Answer 19

NK cells kill infected or tumor cells via the missing self-hypothesis. B1 B cells produce natural antibodies independently of T cells. NKT cells recognize non-peptide antigens and initiate inflammatory responses.

Question 20

How do eosinophils, basophils, and mast cells contribute to immunity?

Answer 20

Basophils and mast cells are associated with parasitic infections and release granules upon activation. Eosinophils arrive later and contribute to the late effects of basophil/mast cell activation.

Question 21

Question: What process leads to the formation of the T-cell receptor, involving VDJ recombination and junctional diversity?

Answer 21

T-cells undergo V(D)J recombination, which includes combinatorial diversity. Terminal deoxynucleotidyl transferase (TdT) adds random nucleotides, contributing to junctional diversity.

Question 22

What are the components of the T-cell receptor structure?

Answer 22

The T-cell receptor consists of alpha and beta chains, with exceptions in some cases.Italso consists of constant and variable regions.

Question 23

Where does the education of T-cells primarily occur, and what is its significance?

Answer 23

T-cells undergo complete VDJ recombination and junctional diversity in the thymus. Thymic education involves positive and negative selection, crucial for shaping the T-cell repertoire.

Question 24

What is AIRE, and what role does it play in the thymus?

Answer 24

AIRE stands for Autoimmune Regulatory Element. It facilitates the random expression of self-antigens by medullary epithelial cells, contributing to negative selection by eliminating autoreactive T-cells.

Question 25

What is peripheral tolerance, and how is it maintained in the immune system?

Answer 25

Peripheral tolerance refers to the immune system’s ability not to respond to self-antigens. It involves mechanisms such as regulatory T-cells (Tregs) that suppress autoreactive T-cells and prevent inappropriate immune responses.

Question 26

Cue Card Questions:

1. Learning Objective 1: Describe T-cell receptor formation
   
   • Question: What process leads to the formation of the T-cell receptor, involving VDJ recombination and junctional diversity?
   • Answer: T-cells undergo V(D)J recombination, which includes combinatorial diversity. Terminal deoxynucleotidyl transferase (TdT) adds random nucleotides, contributing to junctional diversity.
2. Learning Objective 2: Draw the T-cell receptor structure
   
   • Question: What are the components of the T-cell receptor structure?
   • Answer: The T-cell receptor consists of alpha and beta chains, with exceptions in some cases.
3. Learning Objective 3: Understand thymic education of T-cells
   
   • Question: Where does the education of T-cells primarily occur, and what is its significance?
   • Answer: T-cells undergo complete VDJ recombination and junctional diversity in the thymus. Thymic education involves positive and negative selection, crucial for shaping the T-cell repertoire.
4. Learning Objective 4: Define AIRE and its function
   
   • Question: What is AIRE, and what role does it play in the thymus?
   • Answer: AIRE stands for Autoimmune Regulatory Element. It facilitates the random expression of self-antigens by medullary epithelial cells, contributing to negative selection by eliminating autoreactive T-cells.
5. Learning Objective 5: Define peripheral tolerance and its mechanisms
   
   • Question: What is peripheral tolerance, and how is it maintained in the immune system?
   • Answer: Peripheral tolerance refers to the immune system’s ability not to respond to self-antigens. It involves mechanisms such as regulatory T-cells (Tregs) that suppress autoreactive T-cells and prevent inappropriate immune responses.

Important Words to Remember:
- V(D)J recombination
- Junctional diversity
- T-cell receptor
- Thymus
- Positive selection
- Negative selection
- AIRE (Autoimmune Regulatory Element)
- Peripheral tolerance
- Regulatory T-cells (Tregs)
- Autoreactive T-cells
- Immunological synapse

Answer 26

1. V(D)J Recombination: A genetic process that occurs during the development of lymphocytes, particularly B cells and T cells, where variable (V), diversity (D), and joining (J) gene segments are rearranged to generate a diverse repertoire of antigen receptors.
2. Junctional Diversity: The variability in the DNA sequences at the junctions where gene segments are joined during V(D)J recombination, leading to additional diversity in the antigen receptor repertoire.
3. T-cell Receptor: A protein complex found on the surface of T cells that recognizes antigens bound to major histocompatibility complex (MHC) molecules. It plays a crucial role in the activation of T cells in response to pathogens or abnormal cells.
4. Thymus: A primary lymphoid organ located in the upper chest, essential for the development and education of T cells. The thymus provides the microenvironment where immature T cells undergo maturation and selection processes.
5. Positive Selection: A process in the thymus where developing T cells that recognize self-MHC molecules with moderate affinity are allowed to survive and mature, ensuring compatibility with the body’s own MHC molecules.
6. Negative Selection: The process in the thymus where developing T cells that strongly recognize self-antigens presented by self-MHC molecules undergo apoptosis (cell death), preventing the development of T cells that could potentially cause autoimmune reactions.
7. AIRE (Autoimmune Regulatory Element): A transcription factor expressed in medullary thymic epithelial cells that regulates the expression of tissue-specific self-antigens in the thymus. AIRE helps in the deletion of autoreactive T cells through negative selection.
8. Peripheral Tolerance: The mechanisms by which the immune system maintains tolerance to self-antigens outside of the central lymphoid organs, such as the thymus. This includes regulatory T cells and other mechanisms that suppress autoimmune responses.
9. Regulatory T-cells (Tregs): Specialized CD4+ T cells that suppress the immune response and maintain peripheral tolerance. Tregs play a crucial role in preventing autoimmune reactions and maintaining immune homeostasis.
10. Autoreactive T-cells: T cells that recognize and respond to self-antigens, potentially leading to autoimmune diseases if not properly controlled by mechanisms of tolerance and regulation.

Question 27

How is antibody diversity generated in B-cells, including processes like VDJ recombination, junctional diversity, somatic hypermutation, and class switch?

Answer 27

Antibody diversity in B-cells is generated through VDJ recombination, junctional diversity involving terminal deoxyribonucleotidyl transferase (Tdt), somatic hypermutation, and class switch recombination.

Question 28

What are the components of the B-cell receptor structure, and how does it differ from the secreted antibody?

Answer 28

The B-cell receptor structure consists of variable, diversity, and joining gene segments. The Fab (fragment antigen-binding) region recognizes antigens, while the Fc (fragment crystallizable) region mediates effector functions. When secreted, the B-cell receptor becomes an antibody.

Question 29

Where do B-cells undergo education, and what processes ensure self-tolerance and survival?

Answer 29

B-cells undergo education in the bone marrow. Processes like negative selection eliminate self-reactive B-cells, while those incapable of binding antigens undergo apoptosis.

Question 30

What is the immunological synapse, and what are the two components of B-cell “help” provided by T-cells?

Answer 30

The immunological synapse is the interface between a B-cell and a T-cell during antigen presentation. B-cell “help” involves activation-induced cytidine deaminase (AID) for somatic hypermutation and class switch, and cytokines secreted by T-helper 2 cells.

Question 31

What are the five subclasses of antibodies, and what are their primary functions?

Answer 31

The five subclasses of antibodies are IgM, IgG, IgA, IgE, and IgD. They have distinct functions such as opsonization, neutralization, complement fixation, and antibody-dependent cellular cytotoxicity.

Question 32

Important Words to Remember:
B-cell
B-cell receptor
Antibody
VDJ recombination
Junctional diversity
Somatic hypermutation
Class switch recombination
Fab and Fc fragments
Immunological synapse
T-helper 2 cells
Antibody subclasses (IgM, IgG, IgA, IgE, IgD)
Opsonization
Neutralization
Complement fixation
Antibody-dependent cellular cytotoxicity

Answer 32

1. B-cell: A type of lymphocyte involved in the adaptive immune response. B-cells are responsible for producing antibodies and play a crucial role in humoral immunity.
2. B-cell receptor: A protein complex found on the surface of B-cells that recognizes specific antigens. Upon binding to antigens, the B-cell receptor initiates signaling cascades leading to B-cell activation and antibody production.
3. Antibody: Also known as immunoglobulin, antibodies are proteins produced by B-cells in response to specific antigens. Antibodies recognize and bind to antigens, marking them for destruction or neutralization by other components of the immune system.
4. VDJ recombination: A genetic process during B-cell development where variable (V), diversity (D), and joining (J) gene segments are rearranged to generate a diverse repertoire of antibody genes, leading to antigen specificity.
5. Junctional diversity: The variability in DNA sequences at the junctions where gene segments are joined during VDJ recombination, contributing to the diversity of antigen receptors.
6. Somatic hypermutation: A process occurring in activated B-cells where the DNA sequence of antibody genes undergoes mutations, leading to the generation of antibodies with increased affinity for antigens.
7. Class switch recombination: A genetic process in B-cells where the constant region of the antibody molecule is changed, resulting in the production of antibodies with different effector functions while retaining the same antigen specificity.
8. Fab and Fc fragments: The Fab (fragment antigen-binding) region of an antibody contains the antigen-binding sites responsible for antigen recognition, while the Fc (fragment crystallizable) region mediates effector functions such as complement activation and binding to immune cells.
9. Immunological synapse: A specialized structure formed between immune cells during antigen recognition and signaling. It facilitates the transfer of signals between cells, leading to immune activation or suppression.
10. T-helper 2 cells: A subset of CD4+ T-cells that secrete cytokines to help B-cells during the immune response. T-helper 2 cells promote antibody class switching, affinity maturation, and memory B-cell formation.
11. Antibody subclasses: Different forms of antibodies characterized by variations in their constant regions, leading to distinct effector functions. Common subclasses include IgM, IgG, IgA, IgE, and IgD.
12. Opsonization: The process by which antibodies bind to pathogens, marking them for phagocytosis by immune cells such as macrophages and neutrophils.
13. Neutralization: The ability of antibodies to block the activity of toxins or viruses by binding to their functional sites, preventing them from interacting with host cells.
14. Complement fixation: The activation of the complement system by antibodies bound to antigens, leading to the formation of membrane attack complexes that lyse target cells.
15. Antibody-dependent cellular cytotoxicity (ADCC): A mechanism where antibodies bound to target cells facilitate their destruction by immune cells, such as natural killer cells, through the recognition of Fc receptors.

Question 33

Define the term antigen

Answer 33

Literally: Antibody generator
* This is any molecule which can stimulate an
immunological response

Question 34

Define the terms polymorphic and polygenic and discuss these in the context of MHC and protection against disease

Answer 34

Polygenic- Encoded by more than one gene
Polymorphic- allelic/genetic variation in the population

Question 35

Compare and contrast MHC 1 and MHC 2 molecules with respect to:
Cellular expression
Structure
Protein Binding
Function

Answer 35

MHC 2 cells are only expressed by professional antigen presenting cells, and they present to CD4+ T cells.

Question 36

What is required for a good synapse

Answer 36

1) An MHC molecule which is bound to peptide(not antigen NB)
2)A T-cell receptor which fits the peptide
3)CD4 or CD8 to stabilise the TCR-MHC interaction
4)A second signal