SPECIFIC HOST DEFENSE MECHANISMS

Immunology Terms Defined

1. Immunology: Immunology is the branch of biomedical science that focuses on the study of the immune system, which is responsible for defending the body against foreign substances and infectious diseases.
2. Immunity: Immunity refers to the ability of an organism to resist and protect itself from harmful pathogens or foreign substances. It involves the immune system’s ability to recognize and respond to specific antigens.
3. Antigenic determinant: An antigenic determinant, also known as an epitope, is a specific region on an antigen molecule that is recognized by the immune system. It is the part of the antigen that triggers an immune response by interacting with specific receptors on immune cells.
4. Immunoglobulins: Immunoglobulins, also called antibodies, are proteins produced by plasma cells (a type of immune cell) in response to the presence of antigens. They play a critical role in recognizing and neutralizing foreign substances, such as bacteria, viruses, and toxins, by binding to specific antigens.
5. Primary response: The primary response refers to the initial immune response that occurs when the immune system first encounters an antigen. It takes time for the immune system to mount an effective response during the primary response, as it involves the activation and proliferation of specific immune cells.
6. Secondary response: The secondary response, also known as the memory response, occurs when the immune system encounters the same antigen again after the primary response. It is a faster and more robust immune response due to the presence of memory cells that “remember” the antigen from the previous encounter. The secondary response leads to a more rapid production of antibodies and provides long-lasting immunity.
7. Agammaglobulinemia: Agammaglobulinemia is a rare genetic disorder characterized by the absence or extremely low levels of immunoglobulins (antibodies) in the blood. It results in a weakened immune system and increased susceptibility to infections.
8. Hypogammaglobulinemia: Hypogammaglobulinemia is a condition characterized by reduced levels of immunoglobulins, specifically the gamma globulins (antibodies), in the blood. It can be acquired or inherited, and it can lead to an increased risk of infections.
9. T cell: T cells, also known as T lymphocytes, are a type of white blood cell that plays a crucial role in the immune response. They are responsible for recognizing and destroying infected cells, coordinating the immune response, and regulating other immune cells.
10. B cell: B cells, also known as B lymphocytes, are a type of white blood cell involved in the immune response. They produce antibodies (immunoglobulins) in response to antigens, and they play a vital role in humoral immunity by recognizing and neutralizing foreign substances.
11. Plasma cell: Plasma cells are mature B cells that have been activated by an antigen. They are responsible for producing and secreting large amounts of antibodies (immunoglobulins) into the bloodstream, providing a specific immune response against the antigen.
12. Immunosuppression: Immunosuppression refers to the deliberate or unintentional suppression or weakening of the immune system. It can be achieved through various means, such as medications, diseases, or certain medical procedures. Immunosuppression is often used in the context of organ transplantation to prevent rejection, or in the treatment of autoimmune diseases and certain cancers.

 

Immune Responses: Humoral vs. Cellular

 

Active vs Passive Immunity

 

Immunity: Natural vs Artificial

Natural active acquired immunity refers to the immune response generated by an individual’s own immune system after encountering and responding to a pathogen naturally. It occurs when the body is exposed to an infectious agent, such as a virus or bacteria, through infection or direct exposure. The immune system recognizes the pathogen, mounts an immune response, and develops immunological memory for future protection. Examples of natural active acquired immunity include:

1. Infection and recovery: When an individual contracts a disease, such as chickenpox or measles, their immune system responds by producing specific antibodies and immune cells to fight off the infection. After recovery, the immune system retains memory cells that can recognize and respond rapidly if the person encounters the same pathogen again, providing long-lasting protection.
2. Exposure to antigens in the environment: Certain encounters with pathogens or antigens in the environment can lead to the development of immunity. For example, individuals who live in areas with high malaria prevalence may develop immunity to the disease over time due to repeated exposure to the malaria parasite.

On the other hand, artificial active acquired immunity refers to the deliberate induction of an immune response through vaccination. Vaccines contain weakened or inactivated forms of pathogens or specific components (antigens) that stimulate the immune system to recognize and remember the pathogen without causing severe illness. Examples of artificial active acquired immunity include:

1. Vaccination against diseases: Vaccines are designed to trigger an immune response by introducing specific antigens of pathogens into the body. The immune system responds by producing antibodies and memory cells to provide future protection against the actual pathogen. Examples include vaccines for diseases like polio, measles, influenza, and hepatitis.
2. Booster shots: Some vaccines require multiple doses or periodic booster shots to ensure long-term protection. For instance, tetanus and diphtheria vaccines often require booster shots every 10 years to maintain immunity.

Artificial active acquired immunity through vaccination offers the advantage of preventing diseases without the individual having to experience the illness, reducing the risk of complications and promoting community-wide protection through herd immunity.

 

Passive Immunity Differences

Natural passive acquired immunity and artificial passive acquired immunity are two types of immunity that can be acquired through different means. Here’s how they differ:

1. Natural Passive Acquired Immunity: Natural passive acquired immunity refers to the immunity that is obtained naturally without any intentional intervention. It is typically transferred from a mother to her offspring through the placenta or breast milk. This type of immunity provides temporary protection to the newborn until their own immune system develops. Example: Maternal antibodies passed to a baby through the placenta during pregnancy or through breastfeeding. For instance, a newborn receives antibodies against various diseases such as measles, mumps, rubella, and pertussis from the mother’s immune system, which provide protection during the early months of life.
2. Artificial Passive Acquired Immunity: Artificial passive acquired immunity is immunity that is intentionally acquired through medical interventions. It involves the administration of pre-formed antibodies or immune cells from an external source to provide immediate, temporary protection against specific diseases or toxins. This type of immunity does not result in the long-term production of antibodies by the recipient’s immune system. Example: Administration of immune globulins or antitoxins. For instance, if an individual is exposed to a particular infectious disease and there is a high risk of severe illness or complications, they may receive an injection of specific antibodies (immune globulins) obtained from individuals who have already developed immunity to that disease. This provides immediate protection until the person’s immune system can mount its own response.

In summary, natural passive acquired immunity is obtained naturally through maternal transfer, while artificial passive acquired immunity is intentionally acquired through medical interventions such as administration of specific antibodies.

 

T-Independent & T-Dependent Antigen Processing

The processing of T-independent antigens and T-dependent antigens involves distinct mechanisms and steps. Here’s an outline of the general processes involved in the processing of each type of antigen:

Processing of T-Independent Antigens:

1. Recognition: T-independent antigens, such as certain polysaccharides or lipopolysaccharides, can directly bind to B cell receptors (BCRs) on the surface of B cells without requiring assistance from T cells.
2. Internalization: The BCR-bound antigen is internalized through receptor-mediated endocytosis, leading to the formation of antigen-containing endosomes within the B cell.
3. Antigen Processing: Within the endosomes, the antigen is broken down into smaller peptide fragments by lysosomal enzymes. However, T-independent antigens usually do not require extensive processing, as they can often activate B cells directly.
4. Presentation: The processed antigen peptides are then presented on the surface of the B cell in association with major histocompatibility complex class II (MHC II) molecules. This allows the B cell to act as an antigen-presenting cell (APC).
5. B Cell Activation: The presentation of antigen-MHC II complexes on the B cell surface triggers signaling events, leading to B cell activation. Activated B cells undergo clonal expansion and differentiate into plasma cells, which produce and secrete antibodies specific to the antigen.

Processing of T-Dependent Antigens:

1. Recognition: T-dependent antigens, such as proteins or protein fragments, require the assistance of T cells for their processing and presentation. Initially, antigen fragments may be recognized by BCRs, but this interaction alone is insufficient for full activation.
2. Antigen Uptake and Processing: The antigen is internalized by B cells through receptor-mediated endocytosis or phagocytosis. The internalized antigen is then broken down into smaller peptide fragments within endosomes or phagolysosomes by lysosomal enzymes.
3. Presentation: Similar to T-independent antigens, the processed antigen peptides are presented on the surface of the B cell in association with MHC II molecules.
4. T Cell Interaction: The B cell-antigen-MHC II complex interacts with a helper T cell (CD4+ T cell) that recognizes the specific antigen fragment presented on the B cell surface. This interaction occurs through the binding of the T cell receptor (TCR) on the T cell to the antigen-MHC II complex.
5. Co-stimulation: Co-stimulatory signals, such as interaction between CD40 on the B cell and CD40L on the T cell, and secretion of cytokines, are exchanged between the B cell and the T cell. These signals promote further activation of the B cell.
6. B Cell Activation: The interaction with the helper T cell and receipt of co-stimulatory signals result in full activation of the B cell. Activated B cells undergo clonal expansion and differentiation. Some B cells differentiate into plasma cells that secrete antibodies, while others become memory B cells, providing long-term immunological memory.

Overall, while T-independent antigens can directly activate B cells, T-dependent antigens require the involvement of T cells to fully activate B cells, leading to a robust and coordinated immune response.

 

Immune System Functions

Monomeric Antibody Molecule Structure

A monomeric antibody molecule, also known as an immunoglobulin, is a Y-shaped protein molecule produced by the immune system. It plays a crucial role in the immune response by recognizing and binding to specific antigens, such as foreign substances or pathogens.

The basic structure of a monomeric antibody molecule consists of four polypeptide chains: two identical heavy chains (H chains) and two identical light chains (L chains). These chains are held together by disulfide bonds and non-covalent interactions.

The H chains are larger and consist of a variable region (VH) and a constant region (CH). The VH region is responsible for antigen binding and is highly diverse among different antibodies, allowing them to recognize a wide range of antigens. The CH region, on the other hand, determines the class or isotype of the antibody, such as IgG, IgM, IgA, IgD, or IgE.

The L chains are smaller and consist of a variable region (VL) and a constant region (CL). The VL region is also involved in antigen binding and exhibits variability similar to the VH region. The CL region of the light chain interacts with the CH region of the heavy chain.

The antibody molecule has two antigen-binding sites, one at the tip of each arm of the Y-shaped structure. These sites are formed by the complementary pairing of the variable regions of the heavy and light chains. The antigen-binding sites are highly specific, allowing antibodies to recognize and bind to a particular antigen.

Additionally, the constant regions of the antibody molecule can interact with various immune cells and molecules, thereby initiating or modulating immune responses.

It’s important to note that while the general structure of a monomeric antibody molecule is described here, there can be variations and modifications in different antibody classes and subclasses, leading to differences in their functions and properties.

 

Immunoglobulin Isotypes Description

The five immunoglobulin classes, also known as isotypes, are IgG, IgM, IgA, IgD, and IgE. Each class of immunoglobulin has unique structural and functional properties, allowing them to perform different roles in the immune system. Here’s a description of each class:

1. IgG (Immunoglobulin G): IgG is the most abundant class of antibodies in the bloodstream, accounting for approximately 75-80% of all immunoglobulins. It is the only class that can cross the placenta, providing passive immunity to newborns. IgG plays a crucial role in long-term immunity, as it can neutralize toxins, opsonize pathogens for phagocytosis, and activate complement proteins.
2. IgM (Immunoglobulin M): IgM is the first antibody produced during an initial immune response to an infection. It is the largest antibody molecule and primarily exists as a pentamer, consisting of five antibody subunits joined together. IgM is efficient at activating the complement system and is involved in agglutination and neutralization of pathogens. It is commonly found on the surface of B cells as a receptor for antigen recognition.
3. IgA (Immunoglobulin A): IgA is primarily found in mucosal secretions, such as saliva, tears, respiratory and gastrointestinal tracts, as well as in milk. It exists in two forms: secretory IgA (sIgA) and serum IgA. sIgA plays a crucial role in preventing pathogens from attaching to mucosal surfaces, while serum IgA is involved in systemic immune responses. IgA can neutralize toxins, inhibit bacterial and viral adhesion, and activate complement proteins.
4. IgD (Immunoglobulin D): IgD is present in low concentrations in the bloodstream and is primarily found on the surface of mature B cells, acting as a B cell receptor. Its precise role is not entirely understood, but it is thought to be involved in the activation and differentiation of B cells.
5. IgE (Immunoglobulin E): IgE is present in trace amounts in the bloodstream but plays a crucial role in allergic reactions and defense against parasitic infections. It binds to specific receptors on mast cells and basophils, triggering the release of inflammatory mediators when exposed to allergens. IgE is involved in the immediate hypersensitivity response, leading to symptoms like asthma, hay fever, and hives.

Each immunoglobulin class has distinct properties that contribute to the overall effectiveness of the immune response against various pathogens and antigens.

 

The types of cells that are killed by natural killer (NK) cells

Natural killer (NK) cells are a type of cytotoxic lymphocyte that plays a crucial role in the immune system’s innate response against infected or cancerous cells. While NK cells primarily target abnormal cells, such as virus-infected or tumor cells, they also have the ability to recognize and eliminate certain healthy cells under specific circumstances. Here are the types of cells that can be targeted by NK cells:

1. Virus-infected cells: NK cells can detect cells that have been infected by certain viruses and induce their destruction. They recognize virus-infected cells by detecting changes in the expression of surface molecules, such as MHC class I molecules.
2. Tumor cells: NK cells play a critical role in immune surveillance against cancer. They can identify and kill tumor cells, particularly those that have reduced or altered expression of MHC class I molecules. This ability allows NK cells to target cancer cells that may evade recognition by other immune cells.
3. Abnormal cells: NK cells can eliminate cells that display signs of abnormality or stress, such as cells undergoing transformation, cellular stress responses, or DNA damage. These cells may exhibit altered surface markers or release signals that activate NK cell responses.
4. Cells lacking self-MHC molecules: NK cells have the unique ability to recognize cells lacking or displaying reduced levels of MHC class I molecules, a condition known as “missing self.” This mechanism prevents the escape of virus-infected or tumor cells that downregulate MHC class I molecules to evade detection by other immune cells.
5. Transplanted cells: In the context of organ or tissue transplantation, NK cells can target and eliminate foreign cells that express non-self MHC molecules, leading to rejection of the transplant. This is particularly relevant during the early stages of transplantation before the adaptive immune system becomes fully activated.

It is important to note that NK cells possess mechanisms to distinguish between healthy cells and those that pose a threat. They utilize a balance of activating and inhibitory receptors to regulate their cytotoxic responses, ensuring that they target only abnormal or dangerous cells while sparing healthy cells.

 

Types of hypersensitivity reaction

 

Allergy Reactions: Sensitization to Symptoms

Here are the steps involved in allergic reactions, starting from the initial sensitization to an allergen and ending with the typical symptoms of an allergic reaction:

1. Sensitization: The first step in an allergic reaction is sensitization. During this process, the immune system of an individual is exposed to an allergen for the first time. The allergen can be a substance such as pollen, pet dander, dust mites, certain foods, or insect venom.
2. Recognition: Upon exposure to the allergen, the immune system recognizes it as foreign and potentially harmful. This recognition triggers the production of specific antibodies called immunoglobulin E (IgE) antibodies.
3. Production of IgE antibodies: The immune system produces IgE antibodies that are specific to the particular allergen encountered. These antibodies bind to specialized immune cells called mast cells and basophils.
4. Sensitized immune response: Upon subsequent exposure to the same allergen, the allergen binds to the IgE antibodies already attached to mast cells and basophils.
5. Activation of mast cells and basophils: The binding of the allergen to the IgE antibodies on mast cells and basophils triggers the release of inflammatory substances, such as histamine, leukotrienes, and cytokines.
6. Inflammatory response: The released inflammatory substances cause various effects in the body, leading to the typical symptoms of an allergic reaction. These substances cause blood vessels to dilate, smooth muscle contraction, increased mucus production, and increased vascular permeability.
7. Allergic reaction symptoms: The inflammatory response affects different organs and tissues, resulting in a range of symptoms. Common symptoms of allergic reactions include: a. Skin reactions: Itching, hives (urticaria), redness, swelling, and rashes. b. Respiratory symptoms: Sneezing, coughing, wheezing, shortness of breath, nasal congestion, runny nose, and watery eyes. c. Gastrointestinal symptoms: Nausea, vomiting, abdominal pain, and diarrhea. d. Cardiovascular symptoms: Drop in blood pressure (hypotension), increased heart rate, and fainting. e. Systemic symptoms: In severe cases, an allergic reaction can progress to anaphylaxis, a potentially life-threatening condition characterized by widespread and severe symptoms, including difficulty breathing, throat tightness, swelling of the face and tongue, dizziness, and loss of consciousness.

It’s important to note that the severity and specific symptoms of an allergic reaction can vary widely from person to person. The above steps provide a general outline, but individual responses to allergens can differ. It’s always best to consult a healthcare professional for proper diagnosis, management, and treatment of allergies.

 

Examples of allergens

 

Positive PPD Explanations

A positive purified protein derivative (PPD) skin test, also known as a tuberculin skin test, indicates exposure to Mycobacterium tuberculosis, the bacterium that causes tuberculosis (TB). There can be several reasons for a positive PPD skin test result. Here are five possible explanations:

1. Prior exposure to TB: A positive PPD test can occur if you have been exposed to TB bacteria at some point in your life. This exposure may or may not have resulted in active TB disease. The PPD test detects the presence of an immune response to the bacteria, indicating prior exposure.
2. Latent tuberculosis infection (LTBI): A positive PPD test may indicate the presence of latent TB infection. In this case, the person carries the TB bacteria in their body, but the bacteria are in a dormant state and not causing active disease. Latent TB can progress to active TB if the immune system weakens, so further evaluation and possibly treatment may be necessary.
3. BCG vaccination: The Bacillus Calmette-Guérin (BCG) vaccine is used in many countries to protect against TB. This vaccine can cause a positive PPD test because it contains a weakened form of Mycobacterium bovis, a closely related bacterium to Mycobacterium tuberculosis. If a person has received the BCG vaccine, their PPD test may be positive, even if they have not been exposed to TB.
4. Cross-reactivity with nontuberculous mycobacteria (NTM): Some individuals may have a positive PPD test due to exposure to nontuberculous mycobacteria, which are related but different species of bacteria from Mycobacterium tuberculosis. These bacteria can cause infections similar to TB but are not the same as the TB-causing bacteria.
5. False-positive result: Although rare, false-positive PPD test results can occur due to various reasons. These may include errors in administering or interpreting the test, incorrect storage or handling of the tuberculin solution, or other factors that can lead to an inaccurate result.

It’s important to note that a positive PPD test alone does not diagnose active TB disease. Further evaluation, such as chest X-rays, sputum tests, and clinical assessment, is typically required to determine if active TB is present.