WEEK 5: DEFENSE AND VACCINATION AGAINST INFECTIONS Flashcards
State the two types of adaptive immunity.
Humoral immunity
Cell-mediated immunity
Differentiate between humoral and cell-mediated adaptive immunity.
Humoral Immunity:
*Mediated by Antibodies:
Humoral immunity primarily involves the production of antibodies, also known as immunoglobulins. Antibodies are produced by B cells (B lymphocytes).
*Targets Extracellular Pathogens:
It is effective against extracellular pathogens, such as bacteria and viruses that are outside of host cells.
Cell-Mediated Immunity:
*Mediated by T Cells: Cell-mediated immunity primarily involves the activation and functions of T cells (T lymphocytes), specifically cytotoxic T cells (CD8+ T cells) and helper T cells (CD4+ T cells).
*Targets Intracellular Pathogens: It is effective against intracellular pathogens, such as viruses that infect host cells, as well as some types of cancer cells.
Route of activation depends on the nature of the antigen.
State the 2 ways in which B-cell activation can be triggered.
What are the two signals required?
Can be triggered in two ways:
T-dependent or T-independent
Requires two signals -cross-linking of surface immunoglobulin and signals from the B-cell co-receptor.
Define T-dependent and T independent antigens?
- T Cell Dependence:
T-dependent antigens require the involvement of T helper (CD4+) cells to activate B cells and initiate a robust immune response.
EXAMPLES: Proteins
- T-independent antigens can activate B cells without the direct help of T cells. They can stimulate B cell responses independently.
EXAMPLES: Polysaccharides and Lipopolysaccharides
Compare T-dependent antigens and T-independent antigens.
T-DEPENDENT ANTIGENS
*T-helper cells involved
*Memory cells
*High affinity antibodies
*Antibody class switching
*Response by B Cells: B cells recognize T-dependent antigens and process them for presentation to T helper cells. This interaction activates the T helper cells.
T-INDEPENDENT ANTIGENS
*No T-helper cells involved
*Weak IgM response
*No memory cells
*B cells in young children react poorly to Type 2 independent antigens
*Response by B Cells: B cells can directly recognize and respond to T-independent antigens. This direct activation is often mediated by repetitive epitopes on the antigen’s surface.
State the 2 types of the T-independent antigens.
Give examples.
- Type 1 T-independent antigens: Lipopolysaccharides
- Type 2 T-independent antigens: Polysaccharides
State the effector functions of antibodies.
- Neutralization:
Antibodies can bind to viruses, bacteria, or toxins and neutralize their activity. This prevents these pathogens from infecting or damaging host cells.
- Opsonization:
Antibodies can mark pathogens, such as bacteria, for phagocytosis (engulfing and destruction) by white blood cells like macrophages and neutrophils. This enhances the clearance of pathogens.
- Complement Activation:
Some antibody isotypes, particularly IgM and certain subclasses of IgG, can activate the complement system. This cascade of proteins helps destroy pathogens by creating pores in their membranes, promoting inflammation, and facilitating phagocytosis.
- Antibody-Dependent Cellular Cytotoxicity (ADCC):
Antibodies, primarily IgG, can recruit natural killer (NK) cells to recognize and destroy target cells, such as infected or cancerous cells, by binding to Fc receptors on the NK cells.
- Mucosal Immunity:
IgA antibodies are prevalent in mucosal surfaces, such as the respiratory and gastrointestinal tracts. They help prevent pathogens from adhering to and infecting mucosal epithelial cells.
- Allergic Reactions:
IgE antibodies are involved in allergic responses. They bind to mast cells and basophils, leading to the release of histamine and other mediators, resulting in allergy symptoms.
- Regulation of Immune Responses:
Antibodies, especially IgG, can help regulate immune responses by binding to antigens and forming immune complexes. This can impact the activation of various immune cells.
- Transport of Nutrients and Immunity to Newborns:
IgG antibodies can cross the placenta from the mother to the fetus, providing passive immunity to the newborn. Additionally, IgA antibodies are present in breast milk, offering protection to infants.
- Long-Term Immune Memory:
Antibodies play a role in immune memory. After an initial exposure to an antigen, memory B cells are generated, leading to a faster and stronger antibody response upon re-exposure.
The cell mediated immunity involves the activation of naive T cells.
Describe how the CD4 + T cells are activated.
- Antigen Presentation:
CD4+ T cell activation begins with the presentation of antigens by antigen-presenting cells (APCs), such as dendritic cells, macrophages, and B cells. These APCs have the ability to capture, process, and display antigens, which are typically derived from pathogens, on their cell surface.
- Antigen Uptake and Processing:
APCs capture antigens from the surrounding environment. In the case of dendritic cells, they are highly efficient at phagocytosing pathogens and processing their antigens. Once inside the APC, antigens are broken down into smaller fragments.
- Major Histocompatibility Complex (MHC) Class II Presentation:
APCs present the processed antigens on their cell surface in association with MHC class II molecules. These MHC class II-antigen complexes serve as a molecular platform for CD4+ T cell recognition.
- T Cell Receptor (TCR) Recognition:
Naïve CD4+ T cells, which have not encountered their specific antigen before, circulate in the bloodstream and lymphoid tissues. When a naïve CD4+ T cell encounters an APC displaying the relevant antigen, the T cell’s TCR binds to the MHC class II-antigen complex with high specificity. This interaction is known as TCR recognition.
- Co-stimulation:
In addition to TCR recognition, co-stimulatory signals are required for full CD4+ T cell activation.
These co-stimulatory signals are typically provided by molecules on the surface of the APC and their receptors on the T cell, such as CD28 on the T cell and CD80/CD86 on the APC.
Co-stimulation ensures that the T cell response is appropriate and prevents the activation of T cells by irrelevant antigens.
- Activation and Differentiation:
Upon TCR recognition and co-stimulation, the CD4+ T cell becomes activated.
This activation triggers the differentiation of the T cell into various subsets, including T helper 1 (Th1), T helper 2 (Th2), T helper 17 (Th17), regulatory T cells (Tregs), and others. Each subset has specific functions in immune responses.
Activated CD4+ T cells secrete cytokines that modulate the immune response.
State the cytokines released by the 3 main CD4+ T cells.
- Th1: Interferon Gamma cells, IL12
- Th2: IL-4, IL5
*Th17: IL17, IL6cells
*TFH: IL21
*Treg: TGF beta, IL 10
State the cytokines released by the different Th cells and their function.
Th1: IL12, INF-gamma: Activate macrophages.
Th17: IL17 & IL6: Enhance neutrophil response.
Th2: IL4, IL5: Activate cellular and antibody response to parasites.
TFH: IL21, Activate B cell maturation and antibody response.
Treg: TGF beta, IL10: Suppress other effector T-cells.
State the cytokines and the CD4+ T cells responsible for the following functions.
- Activate macrophages.
- Enhance neutrophil response.
- Activate cellular and antibody response to parasites.
- Activate B cell maturation and antibody response.
- Suppress other effector T-cells.
- Th1: Interferon Gamma cells, IL12
- Th17: IL17, IL6
- Th2: IL-4, IL5
- FH: IL21
- Treg: TGF beta, IL 10
Describe the mechanisms of CTL-mediated killing.
- Antigen Recognition:
CTLs are activated when they recognize specific antigens presented on the surface of target cells. These antigens are typically peptides derived from intracellular pathogens or proteins associated with malignancies.
- T Cell Receptor (TCR) Engagement:
The TCR on the CTL’s surface binds to the antigen-MHC class I complex presented by the target cell. This interaction provides specificity for recognizing infected or abnormal cells.
- Co-stimulation:
Co-stimulatory signals, such as interactions between CD8 molecules on the CTL and MHC class I on the target cell, are required to fully activate the CTL. Co-stimulation ensures that the immune response is appropriate and prevents CTL activation by irrelevant antigens.
- Granule Exocytosis:
CTLs contain specialized granules known as cytotoxic granules or lytic granules. These granules are rich in proteins, including perforin and granzymes.
Upon activation, CTLs release the contents of these granules toward the target cell. Perforin forms pores in the target cell’s membrane, facilitating the entry of granzymes.
- Granzyme-Mediated Apoptosis:
Granzymes are serine proteases that induce apoptosis (programmed cell death) in the target cell.
They can enter the target cell through the perforin-created pores and activate various intracellular pathways leading to apoptosis ( caspases).
- Fas Ligand (FasL)-Mediated Apoptosis:
In addition to granule exocytosis, CTLs can express Fas ligand (FasL) on their surface. FasL binds to Fas receptors on the target cell, triggering apoptosis through the extrinsic pathway.
Release of Proinflammatory Cytokines:
- Activated CTLs can produce proinflammatory cytokines, such as interferon-gamma (IFN-γ), which can enhance the immune response and assist in the clearance of infections.
Describe the principle of adaptive immunity in the terms of primary immune response and secondary immune response.
PRIMARY IMMUNE RESPONSE
Antigen Encounter: The primary immune response occurs when the immune system first encounters a new and unfamiliar antigen (e.g., a pathogen or a vaccine). The antigen is recognized as foreign by the immune system.
Activation of Naïve Lymphocytes: Naïve B cells and T cells, which have not previously encountered the antigen, are activated. B cells recognize the antigen directly, while T cells may require antigen presentation by antigen-presenting cells (APCs).
Clonal Expansion: Once activated, B and T cells undergo clonal expansion, multiplying to form a population of effector cells that specifically target the antigen.
Antibody Production: B cells differentiate into plasma cells, which produce antibodies (immunoglobulins) specific to the antigen. This leads to the release of antibodies into the bloodstream.
T Cell-Mediated Immunity: Activated T cells (CD4+ helper T cells and CD8+ cytotoxic T cells) contribute to immune responses, helping B cells produce antibodies and assisting in the killing of infected cells.
Immune Memory: Memory B cells and memory T cells are generated as a result of the primary immune response. These memory cells “remember” the encountered antigen and provide long-term immunity.
Time Frame: The primary immune response takes several days to develop, and the peak of the response may occur 7-10 days after initial antigen exposure.
Secondary Immune Response:
Antigen Re-Encounter: If the same antigen is encountered again, the secondary immune response is triggered. This can occur upon re-infection with the same pathogen or re-exposure to the antigen in a vaccine.
Rapid Activation: Memory B cells and memory T cells specific to the antigen are already present in the body. When the antigen is encountered, these memory cells are rapidly activated.
Quicker and Stronger Response: The secondary immune response is much faster and more robust than the primary response. Antibody levels rise rapidly, and the immune system can effectively control the infection.
Memory Cells Play a Central Role: Memory B cells can quickly differentiate into plasma cells, leading to the rapid production of antibodies. Memory T cells can rapidly exert their effector functions, such as cytotoxicity or cytokine secretion.
Long-Lasting Protection: The secondary immune response provides long-lasting protection against the antigen. Memory cells can persist for years or even decades.
Immune Memory at Work: The secondary response is responsible for the effectiveness of vaccines. Vaccination primes the immune system, generating memory cells that ensure rapid and efficient immune responses upon exposure to the targeted pathogen.
State the 2 types of naturally acquired immunity.
-Naturally acquired active
-Naturally acquired passive immunity
What is naturally acquired passive immunity?
Results when a person receives someone else’s.
antibodies.
