Module 7 - Immunology

Question 1

Describe at least 4 physical or chemical barriers which prevent infection.

Answer 1

Skin: The skin is the body’s first line of defense, forming a tough physical barrier against pathogens. Its outermost layer, the epidermis, consists of tightly packed cells that prevent microorganisms from entering. Additionally, skin secretes antimicrobial substances like defensins that inhibit pathogen growth.
Mucus: Mucous membranes line the respiratory, gastrointestinal, and genitourinary tracts. Mucus traps pathogens and particles, preventing them from adhering to epithelial surfaces. In the respiratory tract, cilia help move mucus upwards, clearing debris and pathogens out of the lungs.
Acidic pH: The stomach’s highly acidic environment (pH 2) is crucial for killing many bacteria and pathogens ingested with food. Similarly, the skin has a slightly acidic pH (around 5), which discourages the growth of harmful microbes while supporting beneficial flora.
Antimicrobial peptides: These small proteins are secreted onto epithelial surfaces and have broad-spectrum activity against bacteria, fungi, and viruses. They disrupt microbial membranes, leading to cell lysis and death, thus providing an essential chemical defense against infection.

Question 2

What is humoral immunity?

Answer 2

Role of B Cells and Antibodies: Humoral immunity involves B cells that differentiate into plasma cells, which produce antibodies targeting specific antigens.

Neutralization and Pathogen Marking: Antibodies bind to pathogens or toxins, neutralizing them or marking them for destruction.

Effective Against Extracellular Pathogens: This type of immunity is particularly effective against pathogens outside of cells by neutralizing toxins, promoting phagocytosis, and activating the complement system.

Memory B Cells Formation: After initial exposure to an antigen, memory B cells form, allowing for a faster response upon re-exposure.

Basis for Vaccination: The formation of memory B cells underlies the principle of vaccination, providing long-term immunity against specific pathogens.

Question 3

Which is the most abundant cell in the blood? Which is the most abundant leukocyte in the blood?

Answer 3

The most abundant cell type in the blood is the red blood cell (RBC), which is responsible for transporting oxygen from the lungs to tissues and carbon dioxide from tissues back to the lungs. RBCs are highly abundant, with approximately 5 trillion cells per liter of blood, and have a lifespan of around 120 days.
The most abundant leukocyte in the blood is the neutrophil, comprising 60-70% of the total white blood cell count. Neutrophils play a critical role in the innate immune response by migrating to sites of infection, where they perform phagocytosis to engulf and destroy pathogens. Their short lifespan (10 hours to a few days) means they are quickly replenished from the bone marrow to maintain effective immune surveillance.

Question 4

Of the following cells, which are components of the innate immune system? Macrophage, monocyte, mast cell, T cell, NK cell, B cell,
neutrophil, eosinophil, endothelial cell, dendritic cell.

Answer 4

Components of the innate immune system include macrophages, which are versatile phagocytes that clear pathogens and debris; monocytes, which circulate in the blood and differentiate into macrophages or dendritic cells upon entering tissues; mast cells, which release histamine and other mediators during allergic responses; neutrophils, which are the first responders to infection; eosinophils, which target larger parasites; and dendritic cells, which act as antigen-presenting cells (APCs) to activate T cells.
These cells provide a rapid and non-specific response to pathogens, playing a crucial role in the initial defense against infections and in shaping the subsequent adaptive immune response.

Question 5

Discuss the role of the lymphatic system. Where does the fluid in the lymphatic system come from? What is its composition? How is it pumped? Where does it go to? What is the role of the lymphatic system in immune defense?

Answer 5

The lymphatic system is essential for maintaining fluid balance in the body by draining excess interstitial fluid from tissues, which originates from plasma that leaks out of blood capillaries. This fluid, now called lymph, contains water, electrolytes, proteins, cell debris, and pathogens.
Lymphatic fluid is not pumped but is propelled by the contraction of surrounding skeletal muscles during movement and aided by one-way valves that prevent backflow. This fluid ultimately returns to the bloodstream via the thoracic duct.
The lymphatic system plays a vital role in immune defense by filtering lymph through lymph nodes, where it captures pathogens and facilitates the activation of immune cells, such as T and B lymphocytes, leading to a targeted immune response.

Question 6

What is the role of secondary lymphoid organs? Name the secondary lymphoid organs. Which one is involved in filtering out particulate and foreign matter from the blood?

Answer 6

Secondary lymphoid organs serve as sites for the activation and proliferation of lymphocytes (B and T cells) in response to pathogens. They provide a structured environment for immune cells to interact with antigens and each other.
The primary secondary lymphoid organs include lymph nodes, spleen, and mucosa-associated lymphoid tissues (MALT), which collectively facilitate immune surveillance and response.
The spleen filters blood and removes old or damaged red blood cells while also capturing foreign particles and pathogens, activating B and T cells to mount an immune response.

Question 7

Which innate immune cells are phagocytic?

Answer 7

Phagocytic cells in the innate immune system include neutrophils, which rapidly respond to infections by engulfing and destroying bacteria; macrophages, which are larger phagocytes that can also process and present antigens to T cells; and dendritic cells, which act as professional antigen-presenting cells, capturing pathogens and migrating to lymph nodes to activate T cells.
These cells utilize mechanisms such as phagocytosis, where they surround and internalize pathogens, leading to their destruction through lysosomal enzymes and reactive oxygen species.

Question 8

What is meant by “opsonisation”? What kinds of molecules can opsonise targets, and what is the outcome of this?

Answer 8

Opsonisation refers to the process by which pathogens are marked for phagocytosis by being coated with specific molecules. This enhances the efficiency of phagocytosis by making the pathogen more recognizable to phagocytes.
Molecules that can opsonise targets include antibodies (especially IgG) and complement proteins. Antibodies bind to specific antigens on the pathogen, while complement proteins bind to pathogen surfaces.
The outcome of opsonisation is an increased likelihood that phagocytes will engulf and destroy the pathogen, as opsonised targets are recognized more easily through Fc receptors for antibodies and complement receptors.

Question 9

Dendritic cells have much in common with macrophages, but they are more specialised. For what role are they specialised?

Answer 9

Dendritic cells are specialized for the uptake, processing, and presentation of antigens to T cells. Unlike macrophages, which primarily engage in phagocytosis and cytokine production, dendritic cells are particularly effective at activating naïve T cells.
Upon encountering pathogens, dendritic cells undergo maturation and migrate to lymph nodes, where they present processed antigens on MHC Class II molecules to CD4 T helper cells.
This role is crucial for linking the innate immune response to the adaptive immune response, as dendritic cells help establish long-lasting immunological memory.

Question 10

The complement system consists of approximately 30 serum proteins which undergo a cascade of cleavage in response to detection of bacteria. Describe 4 outcomes mediated by the products of the cascade. What triggers are there for complement activation?

Answer 10

1. Opsonisation: Complement proteins coat pathogens, enhancing their recognition and uptake by phagocytes.
2. Formation of the membrane attack complex (MAC): This complex forms pores in the membranes of pathogens, leading to their lysis and death.
3. Inflammation: Complement fragments promote inflammation by attracting immune cells to the site of infection and increasing vascular permeability.
4. Clearance of immune complexes: The complement system helps clear immune complexes from circulation, preventing tissue damage.

Triggers for complement activation include the classical pathway (initiated by antibodies bound to pathogens), the alternative pathway (direct recognition of microbial surfaces), and the mannose-binding lectin pathway (binding of lectins to specific sugars on pathogen surfaces).

Question 11

What are the 4 signs of inflammation (i.e., observed non-invasively after an injury/infection)?

Answer 11

1. Redness (rubor): Caused by increased blood flow to the affected area due to vasodilation.
2. Swelling (tumor): Resulting from the accumulation of fluid and immune cells in the tissue.
3. Pain (dolor): Triggered by the release of inflammatory mediators and pressure from swelling, leading to sensitivity in the affected area.
4. Heat (calor): Also caused by increased blood flow and metabolic activity in the inflamed area, contributing to the warmth observed during inflammation.

Question 12

Pathogen recognition by receptors on the innate immune cells causes cytokine secretion, enhanced microbial killing, and dendritic cell maturation. Name the family of receptors best characterised in mediating these responses, and give an example of a foreign molecule which can be recognised by one of these receptors.

Answer 12

The Toll-like receptors (TLRs) are the best-characterized family of receptors in the innate immune response. They are crucial for recognizing pathogen-associated molecular patterns (PAMPs).
An example of a foreign molecule recognized by TLRs is lipopolysaccharide (LPS), a component of the outer membrane of Gram-negative bacteria, which is specifically detected by TLR4. This recognition leads to the activation of immune responses, including cytokine secretion and enhanced phagocytosis.

Question 13

Describe at least 3 key differences between the innate and acquired immune responses. What is the major characteristic which allows for effective vaccination or lifelong immunity to a particular infection?

Answer 13

1. Response Time: The innate immune response is immediate (within hours), whereas the acquired immune response takes several days to develop.
2. Specificity: The innate immune response is non-specific, recognizing general patterns shared by many pathogens, while the acquired immune response is highly specific to particular antigens.
3. Memory: The acquired immune response has immunological memory, allowing for a faster and more robust response upon re-exposure to the same pathogen, which is the principle behind effective vaccinations.

Question 14

Where do T cell precursors originate, and where do they differentiate into mature naïve T cells?

Answer 14

T cell precursors originate from hematopoietic stem cells in the bone marrow. These precursors then migrate to the thymus, where they undergo a maturation process that includes gene rearrangement to form T cell receptors (TCRs).
During their time in the thymus, T cells are subject to selection processes that ensure self-tolerance, meaning T cells that react strongly to self-antigens are eliminated, while those that can recognize foreign antigens are allowed to mature and enter circulation as naïve T cells.

Question 15

Where do B cells differentiate into mature naïve B cells?

Answer 15

B cells differentiate into mature naïve B cells within the bone marrow. The process involves the rearrangement of immunoglobulin genes, allowing each B cell to produce a unique B cell receptor (BCR) that can bind a specific antigen.
After this differentiation, mature naïve B cells migrate to secondary lymphoid organs, such as lymph nodes and the spleen, where they can encounter their specific antigens.

Question 16

What are the two major subtypes of T cells, and what is their function?

Answer 16

Cytotoxic T lymphocytes (CTL): These cells have the CD8 marker and are primarily responsible for directly killing infected cells, particularly those infected by viruses or transformed by cancer. They recognize antigens presented on MHC Class I molecules.
Helper T cells (Th): These cells have the CD4 marker and assist other immune cells, including B cells and macrophages. They are crucial for orchestrating the immune response by releasing cytokines that stimulate B cell antibody production and enhance macrophage activity.

Question 17

Discuss the processes used by phagocytes to kill the organisms they have ingested.

Answer 17

Phagocytes, such as neutrophils and macrophages, utilize several mechanisms to kill ingested organisms:

Phagocytosis: Phagocytes engulf pathogens into a phagosome, which then fuses with lysosomes to form a phagolysosome, where the pathogen is exposed to digestive enzymes and reactive oxygen species.
Degradative Enzymes: Enzymes like lysozyme degrade bacterial cell walls, while acid proteases break down proteins, contributing to the destruction of the pathogen.
Reactive Oxygen Species (ROS): Phagocytes produce superoxide and hydrogen peroxide within the phagolysosome, which are highly reactive and can damage and kill the ingested pathogens

Question 18

What does “MHC” stand for, and why are these molecules given this name?

Answer 18

“MHC” stands for Major Histocompatibility Complex. They are named so because these molecules play a critical role in distinguishing self from non-self, which is fundamental in the context of tissue compatibility during organ transplantation. The variation in MHC molecules among individuals is a significant factor in the success or failure of transplant procedures.

Question 19

Describe the structure of an antibody. How many chains does it have? What different domains are present? Where does antigen bind?

Answer 19

An antibody is structured with four polypeptide chains: two identical heavy chains and two identical light chains. The structure contains two main regions: the variable region, which binds to specific antigens, and the constant region, which determines the antibody’s class and function.
The antigen-binding sites are located at the tips of the variable regions, forming the Fab (fragment antigen-binding) portion of the antibody, while the remainder of the molecule forms the Fc (fragment crystallizable) region, which interacts with other components of the immune system.

Question 20

What are the major differences between the way that the BCR and TCR bind to antigen?

Answer 20

B cell receptors (BCRs) can bind directly to free antigens, including whole proteins, toxins, and other soluble molecules. In contrast, T cell receptors (TCRs) recognize only processed peptide fragments that are presented on MHC molecules by antigen-presenting cells.
Furthermore, BCRs can exist in both membrane-bound forms and secreted forms (as antibodies), while TCRs are exclusively membrane-bound and do not have a soluble form.

Question 21

Explain how B and T cells come to generate millions of antigen receptors of different sequence (BCR and TCR) when there are less than 30,000 genes in the human genome.

Answer 21

The diversity of BCRs and TCRs is generated through a process called V(D)J recombination, where specific gene segments (variable (V), diversity (D), and joining (J) segments) are randomly selected and recombined during the maturation of B and T cells.
This rearrangement occurs in the bone marrow for B cells and in the thymus for T cells, allowing each cell to express a unique receptor specific to a particular antigen. Additionally, further diversity is introduced through somatic hypermutation and class switching in B cells after activation

Question 22

Describe 3 ways in which antibodies can act to counter infection.

Answer 22

Neutralization: Antibodies can bind to pathogens or toxins, blocking their ability to interact with host cells. This is particularly important for viruses and bacterial toxins, preventing them from causing damage.

Opsonization: Antibodies coat pathogens, which enhances their recognition by phagocytes through Fc receptors. This process significantly increases the efficiency of phagocytosis, enabling immune cells to clear infections more effectively.

Complement Activation: Antibodies can activate the complement system, leading to the formation of the membrane attack complex (MAC), which creates pores in the membranes of pathogens, causing their lysis. This enhances the inflammatory response and recruits more immune cells to the site of infection

Question 23

What is meant by different antibody classes? What part of the antibody changes when it switches class during the progress of an immune response?

Answer 23

Different antibody classes refer to the various isotypes of antibodies, such as IgM, IgG, IgA, IgE, and IgD, each characterized by distinct heavy chain constant regions and functions.
When an antibody switches class (a process called class switching), it involves recombination of the heavy chain gene segments, bringing the variable region (that determines antigen specificity) closer to a different constant region. This allows the immune response to adapt to different types of pathogens or infection scenarios without changing the specificity for the antigen.

Question 24

CD4 and CD8 are expressed by different classes of T cells. Why does the possession of CD4 or CD8 determine whether the T cells will be activated by display on MHC Class I or Class II?

Answer 24

CD4 T cells express the CD4 co-receptor, which specifically binds to MHC Class II molecules, found on professional antigen-presenting cells (APCs). This interaction is critical for helper T cell activation, as it facilitates the recognition of peptide antigens presented by MHC Class II.
Conversely, CD8 T cells express the CD8 co-receptor, which binds to MHC Class I molecules present on all nucleated cells. This interaction allows cytotoxic T cells to recognize and respond to intracellular pathogens or cancerous cells presenting antigens on MHC Class I, leading to their activation and cytotoxic function.

Question 25

Describe the source of antigens which are displayed on MHC Class I. To which T cells are these displayed?

Answer 25

Antigens displayed on MHC Class I molecules are derived from endogenous proteins that are synthesized within the cell, including viral proteins produced during viral infections or abnormal proteins from cancer cells. These proteins are processed into short peptides by proteasomes and transported into the endoplasmic reticulum for loading onto MHC Class I.
MHC Class I molecules present these peptide antigens to CD8 T cells (cytotoxic T lymphocytes), which then recognize and kill infected or abnormal cells.

Question 26

Describe the source of antigens which are displayed on MHC Class II. To which T cells are these displayed?

Answer 26

Antigens displayed on MHC Class II molecules are derived from exogenous proteins that have been taken up by antigen-presenting cells (APCs) through processes like phagocytosis or receptor-mediated endocytosis. After internalization, these proteins are processed into peptides within endosomes or lysosomes before being presented on MHC Class II.
These peptide-MHC Class II complexes are presented to CD4 T cells (helper T cells), which play a crucial role in assisting B cells in antibody production and activating macrophages to enhance their pathogen-killing abilities.

Question 27

Describe two similarities and two differences between the BCR and the TCR.

Answer 27

Similarities:
Both B cell receptors (BCRs) and T cell receptors (TCRs) are responsible for recognizing specific antigens and are critical for initiating immune responses.
Both receptors undergo gene rearrangement during cell development, leading to a vast diversity of specificities that allows the immune system to respond to numerous pathogens.

Differences:
BCRs can recognize and bind to free antigens in their native form, including proteins, carbohydrates, and lipids, while TCRs only recognize processed peptide antigens presented on MHC molecules.
BCRs can be secreted as antibodies (immunoglobulins), whereas TCRs are solely membrane-bound and do not have a soluble form.

Question 28

How do costimulatory molecules on dendritic cells (DC) restrict responses of T cells to infectious situations? Discuss the molecular interactions between DCs and T cells necessary for activation of naïve T cells.

Answer 28

Costimulatory molecules such as B7 are upregulated on dendritic cells when they recognize pathogen-associated molecular patterns (PAMPs). This ensures that T cells receive the necessary second signal for activation only in the presence of an infection, reducing the likelihood of inappropriate immune responses.

For activation, naïve T cells require two signals:
1. The first signal is the binding of the T cell receptor (TCR) to the peptide-MHC complex on the dendritic cell.
2. The second signal is provided by the interaction of CD28 on T cells with B7 on dendritic cells. This dual signaling mechanism helps ensure T cell activation occurs only in response to pathogens

Question 29

True or False – Each MHC molecule binds a single peptide sequence.

Answer 29

False: Each MHC molecule can bind a diverse array of peptides, although it can present only one peptide at a time. The specificity of binding varies with the peptide’s length and sequence, allowing MHC molecules to present a range of potential antigens to T cells.

Question 30

What is a major way that natural killer cells recognize virally infected cells?

Answer 30

Natural killer (NK) cells recognize virally infected cells primarily by detecting reduced levels of MHC Class I molecules on the surface of infected cells. Many viruses employ strategies to downregulate MHC Class I to evade detection by cytotoxic T lymphocytes. NK cells, which can identify these abnormal cells, initiate apoptosis in those lacking adequate MHC Class I expression.

Question 31

How do cytotoxic T cells kill target cells?

Answer 31

Cytotoxic T cells kill target cells by recognizing specific antigens presented on MHC Class I molecules. Upon recognition, CTLs release cytotoxic granules containing perforin and granzymes. Perforin forms pores in the target cell membrane, allowing granzymes to enter and trigger apoptosis, effectively eliminating infected or abnormal cells.

Question 32

Which is more serious – deficiency of T cells, or deficiency of B cells? Why?

Answer 32

Deficiency of T cells is more serious than deficiency of B cells because T cells play a central role in regulating the immune response. They provide essential help for B cells to produce antibodies and activate other immune cells, such as macrophages. Without T cell help, B cells may be unable to mount an effective antibody response, leading to increased susceptibility to infections and certain cancers.

Question 33

A dendritic cell in the skin is infected with a virus. Describe the steps necessary for CTL to be activated and get back to the site of infection. Use a diagram to outline molecular interactions between cells.

Answer 33

1. Captures viral antigens and processes them for presentation on MHC Class I.
2. Matures in response to PAMP recognition and migrates to the nearest lymph node.
3. In the lymph node, the dendritic cell presents viral peptides on MHC Class I to naïve CD8 T cells (CTL precursors).
4. Costimulatory signals are provided through the interaction of B7 on dendritic cells with CD28 on T cells.
5. Activated CTLs proliferate and differentiate into effector cells, which then leave the lymph node and travel back to the site of infection to destroy virally infected cells

Question 34

Name two autoimmune diseases and the tissues affected.

Answer 34

Type 1 Diabetes: This autoimmune condition affects the pancreatic islet β-cells, leading to their destruction and resulting in insulin deficiency.
Multiple Sclerosis: In this disease, the immune system attacks the myelin sheath surrounding nerve axons in the central nervous system, causing neurological symptoms.

Question 35

Allergy involves a reaction against environmental antigens. Describe the role of B cells and mast cells in the generation of an allergic response.

Answer 35

B cells play a pivotal role in allergy by becoming activated upon first exposure to allergens, leading to the production of allergen-specific IgE antibodies. These IgE antibodies bind to mast cells, sensitizing them to future exposures to the same allergen.
Upon subsequent exposure, the allergen cross-links the IgE on the surface of mast cells, causing them to degranulate and release histamine and other inflammatory mediators. This release results in the characteristic symptoms of allergy, such as swelling, redness, and bronchoconstriction.

Question 36

Why does HIV infection lead to immunodeficiency?

Answer 36

HIV infects and depletes CD4 T cells, which are crucial for orchestrating the immune response. The loss of CD4 T cells results in a diminished ability to activate other immune cells, including B cells and cytotoxic T lymphocytes.
This compromised immune system makes individuals susceptible to opportunistic infections and certain cancers that a healthy immune system would typically control.

Question 37

Consider the case of a bacterially infected ingrown toenail. Explain how the lymphatic system contributes to the activation of T cells that recognize the bacterial antigens, and where this activation occurs. Refer to the positioning of dendritic cells, and describe the normal pattern of circulation of naïve T cells.

Answer 37

In the case of an infected ingrown toenail, dendritic cells located in the affected tissue capture bacterial antigens. These activated dendritic cells then migrate through the lymphatic vessels to the nearest lymph node.
Within the lymph node, dendritic cells present the processed bacterial antigens on MHC Class II molecules to naïve CD4 T cells, leading to their activation. Naïve T cells circulate between the bloodstream and secondary lymphoid organs, constantly surveying for their specific antigens

Question 38

An outbreak of a highly invasive and contagious skin disease was traced to a novel bacterium Hypotheticus itchii. An experimental vaccine was based on the heat-killed H. itchii and tested in mice. After vaccination of groups of mice of several different genotypes, the serum antibody levels specific for the bacterial surface protein FOMO were assessed, as shown in Figure 1.

Answer 38

For part (i), it appears that the pathways involved are the recognition of PAMPs by TLR2 and TLR5 in dendritic cells, as knocking them out affects antibody production, especially TLR2 while there is no effect of knocking out TLR 4. Therefore, these receptors are essential for an optimal immune response

For part (ii), because the antibody production is lower in TLR2 and TLR5 knockouts, we know that these receptors are important in the immune response to the bacteria. So, the response involves detection of lipoproteins and flagellin, but not lipopolysaccharide.
Lipopolysaccharide is only in gram negative cell walls, flagellin can be in either gram status, and lipoproteins are more abundant in gram negative cells (due to periplasmic space).
Due to the absence of lipopolysaccharide and presence of flagellin, the bacteria is probably a gram positive bacterium with a flagellum.

For part (iii), TLR signaling activates dendritic cells, promoting their maturation and ability to uptake antigens. The activation leads to increased expression of costimulatory molecules like B7.
For T cell activation, two signals are required: Signal 1 is provided by the T cell receptor (TCR) binding to the peptide-MHC complex on the dendritic cell, while Signal 2 is given by the interaction of CD28 on the T cell with B7 on the dendritic cell. TLR signaling ensures that B7 is only expressed when there is an active infection, thus restricting T cell activation to appropriate contexts