Vaccination and Immunity Notes

Immunity

Biology 2240 SP25 Lecture 19.2 by M. Iyengar discusses the concepts of immunity, focusing on the immune response, B-lymphocytes, T-lymphocytes, and clinical implications of immunity, including vaccinations.

The Immune Response

The immune response involves the body's defense against antigens or pathogens. There are two main lines of defense:

• Innate defenses: These prevent the entry of pathogens into the body.

• Adaptive defenses: These are activated if pathogens gain entry. Adaptive defenses include:

  • Humoral immunity: Involves B-lymphocytes that create antibodies.

  • Cellular immunity: Involves T-lymphocytes that seek and destroy antigens, infected body cells, or tumor cells.

Lymphocytes: B-cells and T-cells

B-Lymphocytes (B-cells)

• Mature in bone marrow.

• Migrate to lymphatic organs and tissues (via bloodstream and lymphatic circulation).

• Activation requires an antigen. Activation occurs in secondary lymphoid organs.

• Once activated, they differentiate into:

  • Plasma cells: Create and release antibodies.

  • Memory B-cells: Provide long-term immunity.

T-Lymphocytes (T-cells)

• Mature in the thymus.

• Migrate to lymphatic organs and tissues (via bloodstream and lymphatic circulation).

• Activation requires an antigen. Activation occurs in secondary lymphoid organs.

• Once activated, they differentiate into:

  • Cytotoxic T-cells (TC): Directly kill infected cells.

  • Helper T-cells (TH): Assist in activating other immune cells.

  • Regulatory T-cells (TR): Inhibit immune responses to prevent over-activation.

  • Memory T-cells: Provide long-term immunity.

The Humoral Response: B-lymphocytes

The humoral response involves the following steps:

1. A B-cell encounters an antigen, which binds to the IgD antibody on its surface (sensitization).

2. The antigen is brought into the B-cell and presented on the cell surface to a Helper T cell (TH).

3. The TH receptor (CD4) attaches to the antigen.

4. TH releases cytokines that stimulate B-cell activation, replication, and proliferation.

5. Cells divide and specialize into:

   • Plasma cells: make and release antibodies specific to the antigen encountered.

   • Memory B-cells: retained for future encounters with the same antigen, creating long-term immunity.

     • Memory B-cells create a faster and stronger secondary response by quickly making antibodies.

The Cellular Response: T-lymphocytes

• T-cells mature with either a CD4 or CD8 receptor.

• An antigen-presenting cell (APC) presents the antigen to mature but inactivated T-cells.

• Specific proteins on the APC recognize the CD4 or CD8 receptor.

• Specialized cells:

  • Helper T-cells (TH) help to initiate the specific immune response by activating TC, TR, B-cells, and others.

  • Cytotoxic T-cells (TC) recognize abnormal or infected cells and release perforins, adding holes to the cell’s membrane.

  • Memory T-cells respond to antigens that have been encountered previously.

    • Create a faster and stronger secondary response by immediately creating TC and TH cells.

  • Regulatory T-cells inhibit T- and B-cell activities to control the immune response.

Clinical Implications

Allergic reactions

Occur when allergens or antigens cause a hypersensitive reaction.

• B-cells are activated, creating a huge number of plasma cells to remove the allergens.

• Antibodies embed in mast cells, which release histamine upon a second exposure. Antihistamines block the effects of histamine.

• Anaphylactic shock: Massive release of histamine throughout the body by mast cells, causing a drop in Mean Arterial Pressure (MAP). The problem is a drastic reduction in blood pressure and difficulty breathing.

Immunological Memory

• Primary Response:

  • The first response to a foreign antigen.

  • Takes 10-17 days to create lymphocytes.

  • Memory cells are created.

• Secondary Response:

  • The body has already recognized an antigen.

  • Memory cells mount a response 2-7 days after exposure.

  • Antibodies and T-cells are created quickly to fight the infection quicker.

Active vs. Passive Immunity

Passive Immunity

Antibodies are transferred from one individual to another, for example:

• Pregnancy and breastfeeding.

• Injection of antibodies provides immediate but temporary protection.

Active Immunity

Creating antibodies and memory cells through:

• Getting the disease.

• Immunizations (Vaccinations): Dead or weakened pathogens are introduced into the body to stimulate an immune response without causing severe illness.

COVID-19 Vaccines

COVID-19 vaccines introduce a small piece of mRNA for the COVID-19 antigen into the body. Vaccinations are important for public health, but may not entirely prevent sickness, and boosters are needed to maintain immunity.

Immunity

Biology 2240 SP25 Lecture 19.2 by M. Iyengar discusses the concepts of immunity, focusing on the immune response, B-lymphocytes, T-lymphocytes, and clinical implications of immunity, including vaccinations. Immunity is the capability of multicellular organisms to resist harmful microorganisms. Immunity involves both specific and non-specific mechanisms to defend against pathogens, toxins, and other harmful substances.

The Immune Response

The immune response involves the body's defense against antigens or pathogens. There are two main lines of defense:

• Innate defenses: These prevent the entry of pathogens into the body. Innate immunity is the first line of defense and includes physical barriers like skin and mucous membranes, as well as internal defenses such as antimicrobial proteins, natural killer cells, phagocytes, and inflammation. These responses are rapid and non-specific, meaning they respond to a broad range of pathogens without prior exposure.

• Adaptive defenses: These are activated if pathogens gain entry. Adaptive defenses, also known as acquired immunity, are specific and develop over time. They involve lymphocytes (B-cells and T-cells) that recognize and respond to specific antigens. Adaptive defenses include:-

  • Humoral immunity: Involves B-lymphocytes that create antibodies. Humoral immunity is mediated by antibodies produced by B-cells, which recognize and bind to specific antigens in the blood and lymph, marking them for destruction.

  • Cellular immunity: Involves T-lymphocytes that seek and destroy antigens, infected body cells, or tumor cells. Cellular immunity involves T-cells that directly attack infected or abnormal cells. Cytotoxic T-cells (CD8+ T-cells) kill infected cells, while helper T-cells (CD4+ T-cells) coordinate the immune response by activating other immune cells.

Lymphocytes: B-cells and T-cells

B-Lymphocytes (B-cells)

• Mature in bone marrow. B-cells develop and mature in the bone marrow, where they undergo a process of selection to ensure they do not react to self-antigens.

• Migrate to lymphatic organs and tissues (via bloodstream and lymphatic circulation). Mature B-cells migrate to secondary lymphoid organs such as the spleen and lymph nodes, where they can encounter antigens and initiate an immune response.

• Activation requires an antigen. Activation occurs in secondary lymphoid organs. B-cells are activated when their B-cell receptor (BCR) binds to a specific antigen. This interaction triggers a cascade of intracellular signals that lead to B-cell proliferation and differentiation.

• Once activated, they differentiate into:-

  • Plasma cells: Create and release antibodies. Plasma cells are specialized B-cells that produce large quantities of antibodies. These antibodies are secreted into the blood and lymph, where they can bind to antigens and mediate their neutralization or destruction.

  • Memory B-cells: Provide long-term immunity. Memory B-cells are long-lived cells that remain in the body after an infection has been cleared. If the same antigen is encountered again, memory B-cells can quickly differentiate into plasma cells and mount a rapid and effective immune response.

T-Lymphocytes (T-cells)

• Mature in the thymus. T-cells develop and mature in the thymus, where they undergo a process of selection to ensure they do not react to self-antigens. T-cell maturation involves the expression of either CD4 or CD8 co-receptors, which determine their function.

• Migrate to lymphatic organs and tissues (via bloodstream and lymphatic circulation). Mature T-cells migrate to secondary lymphoid organs, where they can encounter antigens presented by antigen-presenting cells (APCs) and initiate an immune response.

• Activation requires an antigen. Activation occurs in secondary lymphoid organs. T-cells are activated when their T-cell receptor (TCR) binds to a specific antigen presented on an APC. This interaction, along with co-stimulatory signals, triggers T-cell proliferation and differentiation.

• Once activated, they differentiate into:-

  • Cytotoxic T-cells (TC): Directly kill infected cells. Cytotoxic T-cells (CD8+ T-cells) recognize and kill cells infected with viruses or other intracellular pathogens. They release cytotoxic granules containing perforin and granzymes, which induce apoptosis (programmed cell death) in the target cell.

  • Helper T-cells (TH): Assist in activating other immune cells. Helper T-cells (CD4+ T-cells) coordinate the immune response by activating B-cells, cytotoxic T-cells, and other immune cells. They secrete cytokines that promote cell growth, differentiation, and activation.

  • Regulatory T-cells (TR): Inhibit immune responses to prevent over-activation. Regulatory T-cells (Tregs) suppress the immune response to prevent excessive inflammation and autoimmunity. They play a critical role in maintaining immune homeostasis.

  • Memory T-cells: Provide long-term immunity. Memory T-cells are long-lived cells that remain in the body after an infection has been cleared. If the same antigen is encountered again, memory T-cells can quickly differentiate into effector T-cells and mount a rapid and effective immune response.

The Humoral Response: B-lymphocytes

The humoral response involves the following steps:

1. A B-cell encounters an antigen, which binds to the IgD antibody on its surface (sensitization). The B-cell receptor (BCR), which is a membrane-bound antibody molecule such as IgD or IgM, binds to a specific antigen. This binding initiates the process of B-cell activation.

2. The antigen is brought into the B-cell and presented on the cell surface to a Helper T cell (TH). The B-cell internalizes the antigen-BCR complex through receptor-mediated endocytosis. The antigen is then processed and presented on the B-cell surface in conjunction with MHC class II molecules.

3. The TH receptor (CD4) attaches to the antigen. Helper T-cells recognize the antigen-MHC class II complex on the B-cell surface through their T-cell receptor (TCR) and CD4 co-receptor. This interaction provides the necessary signals for B-cell activation.

4. TH releases cytokines that stimulate B-cell activation, replication, and proliferation. Activated Helper T-cells secrete cytokines such as IL-4, IL-5, and IL-6, which stimulate B-cell proliferation, differentiation, and antibody production. These cytokines act as growth factors for B-cells and promote their development into plasma cells.

5. Cells divide and specialize into:-

   • Plasma cells: make and release antibodies specific to the antigen encountered. Plasma cells are highly specialized cells that produce and secrete large quantities of antibodies. These antibodies circulate in the blood and lymph, where they can bind to antigens and mediate their neutralization or destruction.-

   • Memory B-cells: retained for future encounters with the same antigen, creating long-term immunity.-

   • Memory B-cells create a faster and stronger secondary response by quickly making antibodies. Memory B-cells are long-lived cells that remain in the body after an infection has been cleared. If the same antigen is encountered again, memory B-cells can quickly differentiate into plasma cells and mount a rapid and effective immune response. This secondary response is faster and more robust than the primary response due to the presence of memory cells.

The Cellular Response: T-lymphocytes

• T-cells mature with either a CD4 or CD8 receptor. T-cells develop and mature in the thymus, where they acquire either a CD4 or CD8 co-receptor. CD4+ T-cells become Helper T-cells, while CD8+ T-cells become Cytotoxic T-cells.

• An antigen-presenting cell (APC) presents the antigen to mature but inactivated T-cells. Antigen-presenting cells (APCs) such as dendritic cells, macrophages, and B-cells process and present antigens on their surface in conjunction with MHC class I or MHC class II molecules. This allows T-cells to recognize and respond to the antigen.

• Specific proteins on the APC recognize the CD4 or CD8 receptor. The MHC class I molecule presents antigens to CD8+ T-cells, while the MHC class II molecule presents antigens to CD4+ T-cells. The T-cell receptor (TCR) on the T-cell recognizes the antigen-MHC complex, while the CD4 or CD8 co-receptor stabilizes the interaction.

• Specialized cells:-

  • Helper T-cells (TH) help to initiate the specific immune response by activating TC, TR, B-cells, and others. Helper T-cells (CD4+ T-cells) play a central role in coordinating the immune response. They secrete cytokines that activate B-cells, cytotoxic T-cells, and other immune cells. They also help to regulate the immune response and prevent excessive inflammation.-

  • Cytotoxic T-cells (TC) recognize abnormal or infected cells and release perforins, adding holes to the cell’s membrane. Cytotoxic T-cells (CD8+ T-cells) recognize and kill cells infected with viruses or other intracellular pathogens. They release cytotoxic granules containing perforin and granzymes, which induce apoptosis (programmed cell death) in the target cell.-

  • Memory T-cells respond to antigens that have been encountered previously.-

  • Create a faster and stronger secondary response by immediately creating TC and TH cells. Memory T-cells are long-lived cells that remain in the body after an infection has been cleared. If the same antigen is encountered again, memory T-cells can quickly differentiate into effector T-cells and mount a rapid and effective immune response. This secondary response is faster and more robust than the primary response due to the presence of memory cells.-

  • Regulatory T-cells inhibit T- and B-cell activities to control the immune response. Regulatory T-cells (Tregs) suppress the immune response to prevent excessive inflammation and autoimmunity. They play a critical role in maintaining immune homeostasis.

Clinical Implications

Allergic reactions

Occur when allergens or antigens cause a hypersensitive reaction. Allergic reactions are exaggerated immune responses to harmless substances (allergens). These reactions can range from mild to severe and can involve various parts of the body.

• B-cells are activated, creating a huge number of plasma cells to remove the allergens. When an allergen enters the body, B-cells are activated and differentiate into plasma cells, which produce large quantities of IgE antibodies specific to the allergen. These IgE antibodies bind to mast cells and basophils.

• Antibodies embed in mast cells, which release histamine upon a second exposure. Antihistamines block the effects of histamine. Upon a second exposure to the allergen, the allergen binds to the IgE antibodies on mast cells, causing them to release histamine and other inflammatory mediators. Histamine causes vasodilation, increased vascular permeability, and bronchoconstriction. Antihistamines block the H1 histamine receptors, reducing the effects of histamine.

• Anaphylactic shock: Massive release of histamine throughout the body by mast cells, causing a drop in Mean Arterial Pressure (MAP). The problem is a drastic reduction in blood pressure and difficulty breathing. Anaphylactic shock is a severe, life-threatening allergic reaction that involves a massive release of histamine throughout the body. This causes vasodilation, increased vascular permeability, and bronchoconstriction, leading to a drop in blood pressure and difficulty breathing. Epinephrine (adrenaline) is the treatment of choice for anaphylactic shock, as it reverses these effects.

Immunological Memory

• Primary Response:-

  • The first response to a foreign antigen. The primary immune response occurs when the body encounters an antigen for the first time. During this response, naive B-cells and T-cells are activated, proliferate, and differentiate into effector and memory cells.

  • Takes 10-17 days to create lymphocytes. The primary immune response takes 10-17 days to develop fully, as it takes time for the immune cells to recognize the antigen, proliferate, and differentiate into effector cells.-

  • Memory cells are created. Memory cells are long-lived cells that remain in the body after the infection has been cleared. These cells can quickly respond to subsequent encounters with the same antigen, providing long-term immunity.

• Secondary Response:-

  • The body has already recognized an antigen. The secondary immune response occurs when the body encounters an antigen that it has previously encountered. This response is faster and more robust than the primary response due to the presence of memory cells.-

  • Memory cells mount a response 2-7 days after exposure. Memory cells can quickly differentiate into effector cells and mount a rapid and effective immune response within 2-7 days of exposure to the antigen.-

  • Antibodies and T-cells are created quickly to fight the infection quicker. During the secondary immune response, antibodies and T-cells are produced more quickly and in greater numbers than during the primary response, leading to a more effective clearance of the infection.

Active vs. Passive Immunity

Passive Immunity

Antibodies are transferred from one individual to another, for example:

• Pregnancy and breastfeeding. During pregnancy, antibodies are transferred from the mother to the fetus across the placenta. Breastfeeding also provides antibodies to the infant through breast milk. This passive immunity protects the infant from infection during the first few months of life.

• Injection of antibodies provides immediate but temporary protection. Injection of antibodies, such as immune globulin, provides immediate but temporary protection against infection. This is often used when there is a high risk of infection or when the individual is immunocompromised.

Active Immunity

Creating antibodies and memory cells through:

• Getting the disease. When an individual gets the disease, their immune system is exposed to the pathogen and mounts an immune response. This leads to the production of antibodies and memory cells, providing long-term immunity to the disease.

• Immunizations (Vaccinations): Dead or weakened pathogens are introduced into the body to stimulate an immune response without causing severe illness. Vaccinations introduce dead or weakened pathogens (or their components) into the body, stimulating an immune response without causing severe illness. This leads to the production of antibodies and memory cells, providing long-term immunity to the disease.

COVID-19 Vaccines

COVID-19 vaccines introduce a small piece of mRNA for the COVID-19 antigen into the body. Vaccinations are important for public health, but may not entirely prevent sickness, and boosters are needed to maintain immunity. The mRNA is translated into the viral spike protein, which triggers an immune response and leads to the production of antibodies and memory cells. While COVID-19 vaccines are highly effective at preventing severe illness, they