Helper T Cells
What two signals are required to fully activate a naïve T cell?
→ Antigen binding (via TCR to MHC) and co-stimulation
What is the primary role of cytotoxic T cells (CD8+)?
→ To directly kill virus-infected or abnormal cells
What is meant by the “secret handshake” in T cell activation?
→ The costimulatory interaction between T cells and antigen-presenting cells (APCs)
Why are organ transplants often rejected by the recipient’s immune system?
→ The recipient’s immune system recognizes donor MHC proteins as foreign and attacks them
What is the general definition of a hypersensitivity reaction?
→ An exaggerated or inappropriate immune response to an antigen
What key molecule do helper T cells release to coordinate immune responses?
→ Cytokines
What molecules do cytotoxic T cells release to trigger apoptosis in target cells?
→ Perforins and granzymes
Why is co-stimulation required in addition to antigen binding?
→ To prevent inappropriate activation of T cells against harmless or self-antigens
What type of drugs are given to transplant patients to reduce the risk of rejection?
→ Immunosuppressive drugs
What type of hypersensitivity is commonly called an “allergy”?
→ Type I hypersensitivity
How do helper T cells activate B cells?
→ By releasing cytokines that stimulate B cell proliferation and antibody production
Why are cytotoxic T cells sometimes compared to “serial killers” of the immune system?
→ They can destroy multiple infected cells, one after another, without harming themselves
What happens to a T cell that recognizes antigen but does not receive co-stimulation?
→ It becomes anergic (functionally inactive)
Why does immunosuppressive therapy increase infection risk in transplant patients?
→ It weakens the immune response against pathogens
Which antibody class is involved in allergic reactions?
→ IgE
Why do cytotoxic T cells depend on helper T cells for effective function?
→ Helper T cells provide cytokines that enhance cytotoxic T cell activation and killing ability
How do cytotoxic T cells differ from natural killer (NK) cells in their method of identifying targets?
→ Cytotoxic T cells require antigen presentation on MHC I, while NK cells act without antigen specificity
Which cells provide the costimulatory signals that activate naïve T cells?
→ Antigen-presenting cells (APCs) such as dendritic cells
What is an autoimmune disease?
→ A condition where the immune system attacks the body’s own tissues
What happens during the sensitization phase of an allergy?
→ The immune system first encounters the allergen, produces IgE, and attaches it to mast cells and basophils
How do helper T cells enhance the activity of innate immune cells like macrophages?
→ Cytokines from helper T cells boost macrophage activity, improving pathogen destruction
What is the function of regulatory T cells (Tregs)?
→ To suppress immune responses and maintain self-tolerance
How does the “two-signal” requirement of T cell activation increase immune system safety?
→ It reduces the risk of autoimmunity by ensuring multiple checkpoints before activation
Name one example of an autoimmune disease from the lecture.
→ Examples: Multiple sclerosis, Type 1 diabetes, Rheumatoid arthritis
What triggers the secondary (subsequent) allergic response?
→ Allergen binding to IgE on mast cells/basophils, causing histamine release
What is the advantage of helper T cells activating both B cells and cytotoxic T cells?
→ It links humoral and cellular immunity, ensuring a coordinated and comprehensive defense
Why are regulatory T cells important for preventing autoimmunity?
→ They shut down self-reactive lymphocytes that escaped earlier tolerance checks
What is the role of helper T cells in enhancing co-stimulation for cytotoxic T cells?
→ Helper T cells release cytokines that strengthen activation signals
Why is loss of self-tolerance dangerous for the body?
→ It allows self-reactive lymphocytes to attack normal tissues
What is the most severe form of allergic reaction, which can be life-threatening?
→ Anaphylaxis
Why would an immune response be weaker if helper T cells only stimulated B cells and not cytotoxic T cells?
→ Pathogens hiding inside host cells would escape detection, since only cytotoxic T cells can destroy infected cells
Compare the killing mechanisms of cytotoxic T cells with the suppression mechanisms of regulatory T cells.
→ Cytotoxic: induce apoptosis via perforins/granzymes. Regulatory: release inhibitory cytokines to dampen immune activity
Compare the outcomes of T cell–APC interactions with and without proper co-stimulation.
→ With co-stimulation: full activation and proliferation. Without co-stimulation: anergy or tolerance
Compare immunodeficiency and autoimmunity in terms of immune system function.
→ Immunodeficiency = too weak a response; autoimmunity = inappropriate attack against self
Compare the timing of Type I hypersensitivity to other types.
→ Type I is immediate (minutes), while Types II–IV are delayed (hours to days)
Compare the role of helper T cells in activating adaptive immunity with their role in enhancing innate immunity.
→ Adaptive: activate B and cytotoxic T cells. Innate: stimulate macrophages and NK cells
Why must cytotoxic T cells be tightly regulated by the immune system?
→ Overactive cytotoxic T cells could damage healthy tissue and cause immunopathology
Why might pathogens attempt to interfere with co-stimulatory pathways in host cells?
→ Blocking co-stimulation could prevent T cell activation, allowing infection to persist
What is SCID (severe combined immunodeficiency), and why is it so dangerous?
→ A genetic defect causing failure of both B and T cells, leaving patients defenseless
What is Type II hypersensitivity, and give an example.
→ Antibody-mediated destruction of cells; e.g., mismatched blood transfusion
Case: A patient has normal B cells and cytotoxic T cells, but no helper T cells. What is the likely outcome of infection?
→ Both humoral and cellular responses are severely impaired, leaving the body vulnerable
Case: A patient recovers poorly from viral infections despite having normal helper T cells. Which T cell type may be deficient, and why?
→ Cytotoxic T cells, because they are needed to directly eliminate infected cells
Case: A patient’s APCs fail to express costimulatory molecules. What impact does this have on their adaptive immunity?
→ T cells cannot be properly activated, leading to weak or absent immune responses
Case: A patient has frequent infections and no antibody production, but normal T cells. Which type of immunodeficiency is most likely?
→ A B cell immunodeficiency
Case: A patient develops a rash days after taking medication, not immediately. Which type of hypersensitivity is this?
→ Type IV (delayed-type, T cell–mediated)
How does the ability of helper T cells to activate multiple immune cell types illustrate the concept of immune system “amplification”?
→ A single helper T cell can trigger large-scale activation, multiplying the immune system’s power against pathogens
Case: A patient develops autoimmune symptoms due to loss of immune “brakes.” Which T cell type is likely impaired?
→ Regulatory T cells
Why is co-stimulation especially important in preventing autoimmunity compared to pathogen defense?
→ It provides a safeguard to stop self-reactive T cells that escaped central tolerance from becoming activated
Why does HIV specifically lead to immunodeficiency?
→ It destroys helper T cells, crippling both humoral and cellular immunity
How does Type III hypersensitivity cause tissue damage?
→ Immune complexes deposit in tissues, triggering inflammation
Case: HIV targets and destroys helper T cells. Why does this eventually lead to immunodeficiency?
→ Without helper T cells, both arms of adaptive immunity (B cells and cytotoxic T cells) cannot function effectively
Why might an imbalance between cytotoxic T cells and regulatory T cells contribute to chronic inflammation?
→ Excess cytotoxic activity increases tissue damage, while insufficient regulation fails to limit response
Case: In organ transplantation, blocking co-stimulation is sometimes used as therapy. Why?
→ It prevents donor-specific T cells from being activated, reducing graft rejection
Case: A transplant patient is given strong immunosuppressants and later develops a fungal infection. Which part of their immune defense was weakened, and why?
→ T cell–mediated defenses, because suppression prevents rejection but also blocks normal pathogen defense
Case: A patient has chronic joint pain due to immune complex deposition. Which type of hypersensitivity best explains this?
→ Type III (immune-complex–mediated)
Explain how helper T cells act as a “communication hub” between the innate and adaptive immune systems.
→ They release cytokines that both activate adaptive cells (B, cytotoxic T) and strengthen innate cells (macrophages, NK), coordinating all defenses
Explain how cytotoxic and regulatory T cells represent opposite but complementary forces in adaptive immunity.
→ Cytotoxic T cells eliminate infected or abnormal cells, while regulatory T cells prevent overreaction, together ensuring effective yet balanced immunity
Explain how the “secret handshake” illustrates the immune system’s balance between sensitivity and safety.
→ Co-stimulation ensures T cells activate only when antigen recognition is paired with danger signals, preventing autoimmunity while enabling strong pathogen defense
Explain how the three categories of immune disorders (transplant rejection, autoimmunity, immunodeficiency) reflect failures in the immune system’s balance between recognizing self and non-self.
→ Rejection = overreacts to non-self; autoimmunity = fails to tolerate self; immunodeficiency = fails to react to true pathogens
Explain how the four types of hypersensitivity differ in mechanism (antibody- vs. T cell–mediated) and timing, and why this distinction is clinically important.
→ Type I = IgE, immediate; Type II = IgG/IgM, cell destruction; Type III = immune complexes, inflammation; Type IV = T cells, delayed. Recognizing the type guides diagnosis and treatment