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BIO15 Exam5 Chapter 17: Adaptive Immune System Quick Recap of Innate vs. Adaptive Immunity In chapter 16 , we discussed innate immunity – these are generic responses your body uses to fight off pathogens that bypass the skin and outer barriers. Today, we're focusing on the adaptive immune system – this response is specific to a particular pathogen. Key Features of the Adaptive (Acquired) Immune System (Part 1 of 6)
- Tolerance of Self o The immune system must differentiate between self and non-self. o It must recognize your own cells and not attack them.
- Specificity o The response is activated against a specific antigen on a specific microbe. o It will only attack that particular antigen for the rest of your life.
- Minimal Self-Damage o The ideal immune response attacks the pathogen without damaging your own tissue. o We’ve talked about superantigens before—when the immune system overreacts to a small amount of pathogen, excessive cytokine release causes tissue damage.
- Immunological Memory o Once you've seen a pathogen, you can mount a defense against it in the future. o This leads to lifelong protection , in most cases.
Self-Tolerance and MHC Complexes Normally, your immune system does not attack your own cells. This is called tolerance of self. This tolerance is regulated by MHCs (Major Histocompatibility Complexes) : o Proteins bound to the plasma membrane of all cells (except red blood cells). o Help your cells determine what belongs and what doesn’t. MHC Classes:
- MHC Class I o Found on all nucleated cells in your body. o Note: Red blood cells are not nucleated – they do not have MHC-I. o This is why blood transfusions are possible without immune rejection.
- MHC Class II o Found only on antigen-presenting cells (APCs) : Neutrophils Macrophages
Dendritic cells B cells (not mentioned in Chapter 16 but included here) Sometimes eosinophils o These cells can phagocytose pathogens and present antigens to activate the adaptive response. ⚠️ When your immune system fails to recognize your own MHCs correctly, autoimmune diseases can occur. These are not typically microbial-related , so we won’t focus on them in this class.
Three Lines of Immune Defense:
- First Line – Physical and chemical barriers
- Second Line – Innate immunity o Phagocytosis, fever, complement, etc.
- Third Line – Adaptive immunity (today’s focus) o Divided into: Humoral Response Cellular Response
Humoral vs. Cellular Immunity Humoral Response: Involves blood, lymph, and extracellular fluid. Targets antigens outside cells (e.g., bacteria). Includes: o Antibodies o Macrophages o Proteins in blood/lymph Cellular Response: Targets pathogens inside your cells (e.g., viruses). Carried out primarily by T cells. ✅ It’s important to understand the difference between humoral and cellular responses.
Immune System Cells: T Cells and B Cells These are the prominent cells in adaptive immunity. Origin and Development: Both B and T cells begin as stem cells in the bone marrow. From there:
Cellular Immunity : o Based on various T cell types. o T cells begin in bone marrow → mature in thymus → differentiate based on activation signals.
Understanding Antigens and Antibodies We’ve talked a lot about antigens —let’s define them more clearly. What is an Antigen? A foreign substance that causes your body to produce a specific antibody or sensitized T cells. Typically, a protein , but can also be a: o Carbohydrate o Lipid Usually associated with a microbe or pathogen. The antibody does not bind to the whole microbe , but to a specific part of it. Epitope / Antigenic Determinant: The specific part of the antigen that the antibody binds to. Also called: o Epitope o Antigenic determinant For simplicity, in this class, we’ll use the terms antigen , epitope , and antigenic determinant interchangeably. Haptens: Very small antigens that cannot be recognized by the immune system on their own. Must be attached to a larger molecule to be immunogenic.
Key Points about Antigens: Named "antigen" because they generate antibodies. Antigens are like microbial fingerprints —each microbe has unique antigens : o E. coli vs. Staphylococcus aureus have different antigens. Proteins make the best antigens: o Made from 20+ amino acids , can be arranged into unique patterns. Carbohydrates and lipids are less effective antigens due to limited diversity in their structure. Nucleic acids are rarely antigens because all organisms share the same basic nucleotide structure.
Antibody Diversity: Humans can respond to over 1 million epitopes.
You are born with the capacity to make all antibodies you will ever need—even if you haven’t been exposed yet.
Diagram Summary: Antigen and Epitope The antigen is the entire structure. The epitope is the small region on the antigen that antibodies bind to. Again, in this course, we will refer to antigen = epitope for simplicity. ✅ Remember: Antigen = foreign substance Antibody = protein made by your body in response to antigen ======= Chapter 17 Part 2/6 Antibodies (Immunoglobulins) ======= So now we're going to talk a little bit about antibodies. Antibodies are proteins made by your body in reaction to a foreign substance , such as an antigen. Antibodies are also called immunoglobulins. o You may see a patient’s chart requesting a differential count of immunoglobulins —this is essentially a look at what antibodies the individual is producing at that time. o The presence or variation in antibodies gives a good idea of what infection the person may have or what is going on in their body. ✅ Each antibody binds only one antigen very specifically.
Structure of an Antibody Antibodies are made of four protein chains : o 2 Heavy chains (identical in composition; often shown in green/light green) o 2 Light chains (identical; often shown in blue) All antibodies in a given class share the same constant region (C region). The variable region is what differs among antibodies and is responsible for antigen specificity. o This is the region that binds to the antigen. ✅ Unless two antibodies come from the same plasma cell, their variable regions will differ even if they’re in the same class.
Five Classes of Antibodies Now let’s talk about the five classes of antibodies. Each has unique functions and structural features.
1. IgM – Immunoglobulin M (Macroglobulin) Largest antibody class (referred to as a macroglobulin). Structure: Pentamer (five Y-shaped antibody units joined by disulfide bonds).
Half-life: ~2 days (presence ~4 days).
5. IgD – Immunoglobulin D Least understood of all. Functions primarily as a B cell receptor (BCR). Important in the activation of B cells —though exact mechanisms are still under investigation.
Antibody Functions (Mechanisms of Action) Antibodies don’t just bind—they also perform critical immune functions. There are five main mechanisms by which antibodies work in the immune system.
1. Agglutination Antibody binds multiple antigens on different microbes. Causes microbes to clump together , making them easier for: o Phagocytosis o Complement activation IgM is especially efficient here due to its 10 binding sites. 2. Opsonization Antibodies coat a bacterium , and their Fc region binds to macrophage receptors. Enhances the macrophage’s ability to phagocytose the pathogen. Essentially, it tags pathogens for destruction. 3. Neutralization Some pathogens must bind to a host cell to infect it. o All viruses , for instance. Antibodies bind to: o The binding sites on the virus or bacteria. o Exotoxins (not endotoxins), neutralizing them. This blocks pathogen entry and inactivates toxins. 4. Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC) Involves eosinophils (discussed in Chapter 15). Used especially for parasitic worms or large eukaryotic pathogens (too big to be phagocytosed).
Process:
- B cells produce antibodies to the parasite.
- Antibodies bind to antigens on the parasite.
- Eosinophils bind to the Fc region of those antibodies.
- Eosinophils release: o Cytokines o Granules o Perforins
- This causes the parasite cells to undergo apoptosis (programmed cell death). ✅ This is similar to natural killer (NK) cell activity, though the activation pathways differ. 5. Complement Activation Antibodies bind to the surface of bacteria. This triggers a cascade of complement proteins → leads to: o Cell lysis o Inflammation o Phagocytosis Only IgM and IgG can initiate this classical complement pathway.
When to Use This Information If asked to describe the different classes of antibodies , you should explain: Physical characteristics (e.g., monomer, dimer, pentamer) Lifespan Where they are found What kind of immune event they respond to If asked to explain how antibodies work , you should discuss: The five mechanisms :
- Agglutination
- Opsonization
- Neutralization
- ADCC
- Complement activation ======= Chapter 17 Part 3/6: B Cell Activation and Clonal Selection Theory ======= All right, so, so far we've talked about antibodies , and we've talked about antigens.
MHC Checkpoint The adaptive immune system relies on recognizing self via major histocompatibility complexes (MHCs). If a B cell’s receptor binds to self MHC markers , it is destroyed. o ✅ You do not want antibodies against your own cells. If the B cell does not recognize self MHC , it’s allowed to leave the bone marrow and circulate in the blood and lymph.
Clonal Selection and Activation Now we have B cells floating in circulation , most of which will be destroyed before activation. But if a B cell happens to find its exact match —an antigen that fits its receptor—it becomes activated. Clonal Selection The activated B cell undergoes clonal selection. It creates a whole bunch of clones —identical copies of itself, each with the same receptor for that antigen. Some of these clones will: Simply circulate , remaining on standby. Others will internalize the microbe via phagocytosis.
Phagocytosis and Antigen Presentation by B Cells Let’s walk through what happens when one of these clones phagocytizes a microbe:
- The B cell receptor binds to the specific antigen on the microbe.
- The B cell engulfs the entire bacterium through phagocytosis.
- Inside the cell: o A phagosome forms and merges with a lysosome. o The lysosomal enzymes destroy the microbe.
- The B cell retains a copy of the original antigen —the one that its receptor bound to.
- That antigen is then loaded into an MHC class II molecule.
- The B cell displays the antigen-MHC complex on its plasma membrane. ✅ These MHC markers (shown in red in the diagram) are either MHC-II (primarily) or MHC-I.
Signal Required from T Cells At this stage, the B cell has done all it can on its own. It has presented the antigen using MHC-II. But it cannot yet produce antibodies. ✅ It now waits for a signal from a helper T cell (CD4+) to complete activation and begin antibody production.
======= Chapter 17 Part 4/6 T Cell Activation and Its Role in B Cell Differentiation ======= T Cell Development Overview Okay, so before we can continue our discussion with the B cells and see how they ultimately end up making plasma cells, we need to switch over and talk a little bit about T cells. T cells start their development in the bone marrow , just like B cells. But then, T cells migrate to the thymus. In the thymus, they go through further differentiation and checks and balances before they’re allowed to enter the lymphatic and blood systems.
What T Cells Do (Functions) T cells do not secrete antibodies. T cells have two key roles :
- Activate B cells → So they can differentiate into plasma cells and release antibodies.
- Directly attack infected cells → Leading to destruction of the infected cell.
Two Main Types of T Cells
- Cytotoxic T Cells o Have the CD8 receptor.
- Helper T Cells (Naïve T Cells) o Have the CD4 receptor.
T Cell Receptor Development and MHC Recognition T cells, like B cells, undergo somatic gene rearrangement : o Polymerases transcribe and translate different gene segments. o This creates unique T cell receptors (TCRs) with specific binding sites. Once receptors are made, T cells are screened for proper MHC recognition : o If a T cell does not recognize your MHC , it is destroyed. o ✅ T cells must be able to recognize your body’s MHC in order to function properly. ✅ This is opposite of B cells : B cells that recognize your MHCs are destroyed to prevent autoimmunity. T cells that recognize your MHCs appropriately are allowed to circulate.
Helper T Cells and Antigen Presentation Let’s continue with the naïve (helper) T cells and how they interact with an antigen:
o The T cell releases cytokines , which stimulate the B cell.
B Cell Differentiation and Antibody Production Once stimulated by the helper T cell, the B cell does two things:
- Differentiates into plasma cells : o These clone themselves and begin releasing antibodies. o The antibodies have antigen-binding sites specific for that original microbe.
- Differentiates into memory B cells : o These remain in the body long-term. o Upon re-exposure to the same antigen , memory cells: Skip clonal selection. Go directly to plasma cell production. This results in rapid antibody production within hours , preventing illness.
Antibody Production Timing and Class Switching The first antibodies produced are IgM. The second wave is IgG. After 2–3 days , class switching may occur depending on the pathogen: o IgA for mucosal surfaces. o IgE if it's a eukaryotic pathogen or allergen.
Antibody Functions (Quick Reminder) Once produced, antibodies can carry out five immune mechanisms :
- Opsonization
- Agglutination
- Neutralization
- Antibody-dependent cell-mediated cytotoxicity (ADCC)
- Activation of complement system ✅ The specific mechanism depends on the type of pathogen and the number of microbes involved. ======= Chapter 17 Part 5/6: Cellular Immunity and Cytotoxic T Cells (CD8+) ======= Transition from Humoral to Cellular Response So what we've talked about so far is the humoral response. The humoral response involves microbes that are in: o The blood
o The lymph o The skin o The extracellular space around your cells This is where B cell and T cell interaction occurs, leading to antibody production. ❓ But what if the microbe is inside your cell? If a microbe is intracellular , antibodies can’t reach it. That’s where cellular immunity comes into play.
Role of Cellular Immunity Cellular immunity primarily involves cytotoxic T cells (CD8+ cells). There’s more to the story, but we’re only focusing on CD8 cells as presented in the textbook.
Cytotoxic T Cell Basics Just like helper T cells have the CD4 receptor , cytotoxic T cells have the CD8 receptor. These T cells target abnormal or infected cells , including: o Cells that aren’t yours o Cells invaded by a virus o Cells that have mutated and need to be removed (e.g. cancerous cells)
Outcome of CD8 Activation Activation of cytotoxic T cells leads to apoptosis (programmed cell death) of the target cell. This is achieved by the release of: o Perforins o Gran enzymes (granzymes)
Activation of Cytotoxic T Cells: Step-by-Step Let’s take a look at what happens:
- Dendritic Cell Activation o Back when we discussed T cell activation: A dendritic cell recognized a microbe and phagocytosed it. It became an antigen-presenting cell (APC). It displayed the antigen on MHC-II to activate helper T cells (CD4+). Helper T cells then activated B cells, leading to antibody production.
- Eosinophils o Look for a foreign antigen bound by IgE. o Eosinophils bind to the Fc region of IgE and release perforins and granzymes.
- Cytotoxic T Cells (CD8+) o Look for altered MHC-I markers on your own cells. o Release perforins and granzymes. ✅ Different activation mechanisms , but same end result : target cell death.
Understanding Cytokines I've been talking a lot about cytokines, so here’s what you need to know: In general , you can just say cytokines are released. You don’t need to memorize every type or action. But you do need to know the main categories of cytokines:
Types of Cytokines (You Should Know)
- Interleukins o Function: Communicate between leukocytes (T cells and B cells).
- Chemokines o Special type of cytokine. o Function: Induce movement of leukocytes. o Example: During inflammation , macrophages release chemokines to attract more leukocytes.
- Interferons o We discussed these in the innate immune system (Chapter 16). o Function: Protect against viral infections. o Many types—just remember their general antiviral role.
- Tumor Necrosis Factor (TNF) o Released during inflammatory reactions. o Important in cell signaling during inflammation. ======= (Part 6 of 6) Immunological Memory and Types of Adaptive Immunity ======= Immunological Memory and Secondary Response So during the adaptive immune response , when you get: Plasma cell production Activation of:
o Helper T cells (CD4+) o Cytotoxic T cells (CD8+) o B cells Not only do you get antibody production , but you're also going to get memory cells. ✅These memory cells are what make sure you don’t get sick from the same pathogen the next time it comes in.
What Is Immunological Memory? It has to do with the antibody titer – how much antibody is present in your serum at any given time. Over time, the IgG antibodies will be removed from circulation. But those memory cells remain. They can quickly reactivate into plasma cells and start producing antibodies again when needed.
Primary vs. Secondary Immune Response The primary response is everything we talked about in Chapter 17: o Initial exposure to pathogen o Activation of immune cells o Creation of memory cells The secondary response occurs after a second exposure to the same pathogen. Example: A pathogen enters the body for the first time : o Antibody production begins around day 7 o IgM is produced first o Followed by a rise in IgG After the pathogen is cleared, antibody levels settle down. The next time the same pathogen enters: o There is immediate IgM o Followed by a huge spike in IgG o Response is much faster and stronger , often preventing any symptoms. ✅ This forms the basis of how vaccines work.
Types of Adaptive Immunity The adaptive immune system is classified into four main types based on how the immunity is acquired :
1. Naturally Acquired Active Immunity
Antiserum : A generic term for serum containing antibodies. Globulins / Immunoglobulins : o These are the serum proteins that make up antibodies (e.g., IgA, IgG, IgM ). o Gamma globulin is the serum fraction that contains the antibodies.
