Innate Immune System
How do innate immune cells recognize pathogens and why is this recognition is considered non-specific?
Innate immune cells recognize pathogens using pattern recognition receptors (PRRs) that bind to pathogen-associated molecular patterns (PAMPs), which are common structures found on many microbes. This recognition is considered non-specific because PRRs detect general features shared by groups of pathogens, not unique antigens specific to individual microbes.
CD8+ cells would assist in the elimination of…
Viruses. CD8+ T cells act with MHC Class 1 cells to recognise virally infected cells and their destruction.
Why are individuals with HIV at higher risk for opportunistic infections, and which part of the immune system is primarily affected?
Individuals with HIV are at higher risk for opportunistic infections because the virus attacks and destroys CD4+ T cells, which are essential for coordinating the immune response. This weakens the adaptive immune system, making it harder to fight off infections that a healthy immune system would normally control.
A 23-year-old patient presents with recurrent bacterial infections despite normal lymphocyte counts. Genetic testing reveals a defect in the Toll-like receptor (TLR) signaling pathway. How does this defect contribute to impaired coordination between the innate and acquired immune responses?
TLRs are critical pattern recognition receptors in the innate immune system. A defect in TLR signaling compromises the ability of innate immune cells (like dendritic cells and macrophages) to recognize pathogens, release pro-inflammatory cytokines, and present antigens effectively. This impairs the activation of T and B cells, weakening the adaptive immune response.
A 28-year-old woman presents to the clinic with a history of recurrent viral infections, including herpes simplex virus (HSV) and cytomegalovirus (CMV), despite receiving appropriate antiviral therapy. Laboratory studies reveal a low CD4+ T cell count and a low percentage of memory T cells. Her CD8+ T cell count is normal, and her B cell count is also within the normal range.
What is the most likely underlying mechanism for her recurrent infections?
This patient’s clinical presentation is most consistent with defective CD4+ T cell function, which plays a pivotal role in adaptive immunity. CD4+ T cells are crucial for helper functions, including:
Activation of B cells for antibody production, Stimulation of CD8+ cytotoxic T cells (CTLs) for killing infected cells
Macrophage activation for effective phagocytosis
In this case, the patient's low CD4+ T cell count and impaired memory T cells suggest a T-helper dysfunction, which leaves the body vulnerable to recurrent viral infections such as HSV and CMV. CD4+ T cells are essential for initiating the immune response to viruses, and their loss or dysfunction can lead to poor control of viral infections, even when CD8+ T cells (which are responsible for cytotoxic killing) are normal.
A 6-month-old infant is brought to the clinic with failure to thrive, chronic diarrhea, and recurrent thrush. On examination, there is absent lymphoid tissue, including tonsils and palpable lymph nodes. Laboratory studies show profound lymphopenia, undetectable serum immunoglobulins, and absence of CD3+ T cells and CD19+ B cells on flow cytometry. Genetic analysis reveals a mutation in the RAG1 (Recombination Activating Gene 1) gene. What is the immunological basis of this patient’s condition?
RAG1 (Recombination Activating Gene 1) is essential for V(D)J recombination, the process by which B and T cells generate diverse antigen receptors. A mutation in RAG1 leads to T−, B− NK+ SCID, a form of severe combined immunodeficiency where both T and B cells are absent due to failure in receptor gene rearrangement. NK cells remain unaffected because they do not rely on V(D)J recombination.
A 9-month-old boy is brought to the GP with recurrent bacterial infections, including Staphylococcus aureus skin abscesses and Streptococcus pneumoniae otitis media. Flow cytometry reveals markedly reduced expression of CD18 on neutrophils. What innate immune function is most directly impaired in this patient?
This patient likely has Leukocyte Adhesion Deficiency type 1 (LAD-1), an autosomal recessive disorder characterized by defective CD18, a component of β2 integrins (e.g., LFA-1, Mac-1). These integrins are essential for neutrophil adhesion to the endothelium and subsequent migration (diapedesis) into infected tissues
A 10-year-old child receives the seasonal influenza vaccine. Two weeks later, they are exposed to the influenza virus but remain asymptomatic.
Explain how the adaptive immune system responds to the vaccine and protects the child upon later exposure to the virus. Include the roles of B cells, T cells, and immunological memory.
The seasonal influenza vaccine introduces viral antigens that are recognized by antigen-presenting cells (APCs), which present them to helper T cells (CD4⁺). These T cells activate B cells that are specific to the influenza antigens. Activated B cells undergo clonal expansion and differentiate into plasma cells, which produce influenza-specific antibodies, and memory B cells, which persist long-term.
Upon later exposure to the influenza virus, memory B cells rapidly produce high-affinity antibodies, neutralizing the virus before it can establish infection. Cytotoxic T cells (CD8⁺), also primed during vaccination, can recognize and destroy infected cells. This coordinated adaptive response prevents symptomatic illness and provides long-term protection.
62-year-old man with relapsed multiple myeloma undergoes treatment with chimeric antigen receptor (CAR) T-cell therapy targeting B-cell maturation antigen (BCMA). Two weeks after the infusion, he develops a fever of 39.2°C, hypotension, and tachycardia. Laboratory studies reveal elevated ferritin and C-reactive protein levels. Blood cultures are negative.
Which of the following best explains the pathophysiology of this patient’s most likely complication?
This patient is showing signs of cytokine release syndrome (CRS), the most common acute toxicity of CAR-T cell therapy, particularly those targeting BCMA in multiple myeloma.
CRS is driven by:
Massive activation of CAR-T cells upon binding to tumor antigen.
This leads to release of proinflammatory cytokines (e.g., IL-6, IFN-γ, TNF-α)
Monocytes and macrophages are also activated and contribute to the cytokine surge
Clinical features include fever, hypotension, tachycardia, hypoxia, and elevated inflammatory markers
Severe cases may require treatment with IL-6 receptor antagonists (e.g., tocilizumab) and steroids
A 55-year-old man presents with high fever and hypotension following urosepsis. Lab studies show elevated TNF-α, IL-1, and IL-6. What cell primarily releases these cytokines after recognition of LPS via TLR4.
Macrophages are key innate immune cells that recognize bacterial lipopolysaccharide (LPS) via Toll-like receptor 4 (TLR4), triggering the release of proinflammatory cytokines like TNF-α, IL-1, and IL-6 — major mediators of septic shock.
A 21-year-old man with infectious mononucleosis demonstrates activated CD8+ T cells targeting EBV-infected B cells. These cytotoxic lymphocytes recognize viral peptides in the context of what MHC molecule?
MHC class I molecules present endogenous peptides (e.g., viral proteins) to CD8+ cytotoxic T cells. In EBV infection, infected B cells display viral antigens via MHC I, which activates CD8+ T cells to kill them.
What is the immunopathogenesis of systemic lupus erythematosus (SLE), including the role of autoantibodies and immune complexes in tissue damage?
SLE involves a breakdown in central and peripheral tolerance, resulting in autoantibody production by B cells. The anti-dsDNA antibodies are a hallmark of the disease and form immune complexes that circulate and deposit in organs. These complexes trigger complement activation (especially via the classical pathway) and attract neutrophils and macrophages, which release enzymes and reactive oxygen species, causing tissue inflammation and damage—a classic type III hypersensitivity reaction. This mechanism explains clinical features like glomerulonephritis, arthritis, and cutaneous rashes.
A 6-month-old infant presents with recurrent infections caused by catalase-positive organisms, including Staphylococcus aureus and Serratia marcescens. Neutrophil count is normal, but the dihydrorhodamine (DHR) flow cytometry test shows absent oxidative burst. This innate immune defect is due to a mutation affecting what enzyme complex?
This is chronic granulomatous disease (CGD), an inherited defect in the NADPH oxidase complex required for the respiratory burst in neutrophils. Without it, phagocytes cannot generate reactive oxygen species to kill engulfed pathogens. Catalase-positive organisms are particularly problematic because they degrade their own hydrogen peroxide, depriving host cells of a compensatory ROS source.
A 5-year-old boy presents with recurrent bacterial infections, particularly from encapsulated organisms. Laboratory studies show normal neutrophil and NK cell counts but very low IgG and IgM levels. Which of the components of the immune system is most likely defective?
B cell antibody production
This patient has recurrent infections with encapsulated bacteria and markedly low IgG and IgM levels, indicating a defect in B-cell antibody production, which is a central component of adaptive immunity. B cells are responsible for producing antibodies that opsonize pathogens, neutralize toxins, and activate complement to facilitate pathogen clearance. The normal neutrophil and NK cell counts suggest that innate immunity is intact, and the problem lies specifically within the humoral arm of the adaptive immune system. Defects in T-cell receptor signaling, complement proteins, or phagocytosis would present differently: T-cell defects often cause viral or opportunistic infections, complement deficiencies lead to recurrent pyogenic infections but with normal antibody levels, and phagocyte defects impair bacterial clearance regardless of antibody levels. Therefore, the underlying issue is a primary B-cell immunodeficiency impairing antibody-mediated protection
A 52-year-old woman presents with symmetric swelling and pain in her hands and wrists for several months. Laboratory studies reveal positive rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies. What immune mechanisms primarily contributes to the pathogenesis of her disease?
T-cell–mediated activation of macrophages and synovial fibroblasts.
This patient’s symmetric joint inflammation and positive rheumatoid factor (RF) and anti-CCP antibodies indicate rheumatoid arthritis (RA), an autoimmune disease. The primary pathogenic mechanism involves T-cell–mediated activation of macrophages and synovial fibroblasts, leading to the release of pro-inflammatory cytokines (e.g., TNF-α, IL-1, IL-6) that drive synovial inflammation, pannus formation, and joint destruction. B cells contribute by producing autoantibodies like RF and anti-CCP, but the initiating and sustaining tissue damage is largely T-cell–driven.
Complement deficiencies, NK cell dysfunction, and impaired neutrophil chemotaxis are not central to RA pathogenesis.