Immune System

What is a pathogen?

A biological agent that causes disease or illness to its host

What is pathogenesis?

The biological mechanism and step-by-step development through which a disease progresses in the body

What are the 5 main types of pathogens?

Bacteria, viruses, fungi, protozoa, and helminths

How are the 5 types of pathogens categorized into microorganisms versus parasites?

Microorganisms: Bacteria, viruses, fungi, and protozoa

Parasites: Helminths (multicellular parasitic worms) and protozoa (unicellular parasites)

What are the two fundamental strategies the immune system uses to defend the body?

Preventing entry: Physical, chemical, and biological barriers that block pathogens from penetrating body surfaces

Destroying invaders: Cellular and molecular responses that target, neutralize, and clear pathogens that cross barriers

How does the immune system differentiate between self cells and foreign cells?

Self cells display specific surface marker proteins (MHC Class I) recognized by host immune cells

Foreign cells lack self-markers or display non-self antigens and Pathogen-Associated Molecular Patterns (PAMPs)

What protein complexes on cell surfaces serve as the primary markers for self-recognition?

Major Histocompatibility Complex (MHC) class I proteins present on all nucleated cells

What is the definition of an autoimmune disease?

A illness resulting from a breakdown in self-tolerance, causing the immune system to attack the host's own healthy tissues

What are the primary differences between nonspecific (innate) and specific (adaptive) immunity?

Nonspecific (innate): Present at birth, responds immediately to generic threats, lacks immunological memory

Specific (adaptive): Acquired over time, targets specific individual antigens, forms long-term immunological memory

How does the specific immune system adapt with age through antigen exposure?

Encounters with novel antigens and vaccinations trigger clonal expansion, building an expanded library of long-lived memory B and T cells

What is immunosenescence and how does thymic involution affect the aging adaptive immune system?

Immunosenescence: The gradual decline of immune function associated with aging

Thymic Involution: The progressive shrinking of the thymus gland with age, which reduces production of new naive T cells

Why are viruses classified as non-living obligate intracellular parasites?

They lack cellular machinery for metabolic processes or self-replication and must hijack host cell machinery to reproduce

What structural characteristic distinguishes bacteria from eukaryotic pathogens like fungi and protozoa?

Bacteria are prokaryotes lacking a membrane-bound nucleus and membrane-bound organelles, whereas fungi and protozoa are eukaryotes with distinct nuclei

How does the skin act as a mechanical first line of defense?

The outer epidermal layer consists of tightly packed, dead keratinized cells that form a tough physical barrier that continuously sloughs off bound microbes

How do oily and acidic sweat secretions protect the skin?

Sweat creates a low-pH (pH 3-5) surface environment and contains antimicrobial peptides that inhibit bacterial and fungal growth

What is sebum and how does it contribute to chemical defense?

An oily substance secreted by sebaceous glands that contains unsaturated fatty acids, which inhibit pathogenic bacterial and fungal species

What are mucous membrane secretions and where do they function as barriers?

Secretions like mucus, tears, and saliva found in the respiratory, digestive, and urogenital tracts that trap microbes and wash away debris

What is lysozyme and what specific bacterial structure does it target?

An antimicrobial enzyme present in saliva, tears, and sweat that breaks down bacterial cell walls by cleaving peptidoglycan bonds

What are vibrissae and what is their protective role in the nose?

Coarse hairs lining the nasal passages that trap large airborne particles and microbes upon inhalation

What are cilia and how does the mucociliary escalator protect the lungs?

Microscopic, hair-like projections on respiratory epithelial cells that beat rhythmically to sweep mucus-trapped pathogens upward toward the pharynx to be swallowed or expelled

How does gastric juice acidity function as a chemical barrier?

Strong stomach acid (pH 1.5-3.5) destroys ingested bacteria, viruses, and microbial toxins while denaturing foreign proteins

How do symbiotic bacteria in the digestive tract and vagina protect host surfaces?

Competitive exclusion: Outcompete pathogens for binding sites and nutrients

Chemical inhibition: Produce antimicrobial substances (bacteriocins) and maintain acidic conditions (e.g., vaginal lactobacilli producing lactic acid)

How does urine flushing act as an expulsion mechanism?

The periodic downward flow of urine physically flushes microbes out of the urethral tract, preventing ascending urinary tract infections

How does defecation serve as a gastrointestinal expulsion mechanism?

Peristaltic movement moves waste through the colon, ejecting undigested materials, unattached pathogens, and bacterial toxins from the body

How does vomiting act as a rapid expulsion mechanism?

Reverse peristalsis forcefully ejects toxic substances or harmful pathogens from the stomach and upper gastrointestinal tract before systemic absorption

What is hematopoiesis and where does it occur?

The formation and differentiation of all cellular blood components from pluripotent hematopoietic stem cells inside the red bone marrow

What is phagocytosis and how do phagocytes move toward pathogens?

Phagocytosis: The engulfment, ingestion, and destruction of foreign cells or cellular debris

Movement: Phagocytes extend temporary cytoplasmic extensions called pseudopods, crawling toward targets guided by chemical gradients (chemotaxis)

What are macrophages, what cell type do they mature from, and what is their lifespan?

Large, highly active phagocytes that mature from circulating monocytes after migrating into body tissues; they are long-living cells

What are the primary functions of macrophages in tissue defense?

Removal of foreign pathogens and apoptotic cell debris

Antigen presentation to adaptive immune cells

Secretion of cytokines that coordinate acute and chronic inflammatory responses

What are neutrophils and what is their abundance relative to other white blood cells?

Granulocytic phagocytes that represent the most abundant type of leukocyte in human blood circulation (50-70%)

What is the primary role of neutrophils during an infection?

Serving as rapid first responders to sites of acute inflammation to engulf bacteria and form Neutrophil Extracellular Traps (NETs)

What are mast cells and where are they located in the body?

Tissue-resident granulocytes located in connective tissue near epithelial boundaries and vascularized spaces

What primary chemical mediators do mast cells secrete during a wound response?

Histamine and serotonin, which trigger vasodilation and increase vascular permeability

What are dendritic cells and what is their role as messengers?

Professional antigen-presenting cells residing in outer tissues that ingest pathogens and travel to lymph nodes to activate naive T cells, bridging innate and adaptive immunity

What are basophils and what chemical do they release during allergic responses?

Non-phagocytic circulating granulocytes that secrete histamine and heparin to promote vasodilation and mediate allergic reactions

What are eosinophils and what is their primary target of defense?

Non-phagocytic granulocytes that release cytotoxic granule proteins (like major basic protein) to destroy large multicellular parasites (helminths) and participate in allergic reactions

Are basophils and eosinophils classified as primary phagocytes?

No, both are non-phagocytic granulocytes that function primarily via degranulation and extracellular chemical release

What are Natural Killer (NK) cells and what target cells do they attack?

Lymphocytes of the innate immune system that detect and destroy virus-infected cells and abnormal tumor cells that lack normal surface MHC Class I expression

What toxic granules do Natural Killer cells release to induce cell death?

Perforin (creates pores in the target cell membrane) and Granzymes (enter pores to initiate programmed cell death / apoptosis)

What is the complement system and where are its proteins synthesized?

A cascade system of approximately 30 plasma proteins synthesized by the liver that circulate in an inactive state until triggered by classical, lectin, or alternative pathways

What three main actions does the complement system perform upon activation?

Opsonization: Coating pathogens to enhance phagocytosis

Chemotaxis: Recruiting inflammatory white blood cells

Cell Lysis: Forming the Membrane Attack Complex (MAC) to punch holes in bacterial membranes

What are interferons and how do they defend against viral spreading?

Cytokines released by virus-infected cells that bind to receptors on neighboring uninfected cells, signaling them to synthesize antiviral proteins that block viral replication

What are chemokines and how do they guide leukocyte movement?

Specialized signaling cytokines that create a chemical concentration gradient, guiding phagocytes and white blood cells directly to sites of tissue damage or infection

How are fevers induced by pyrogens and how do elevated temperatures aid defense?

Pyrogens stimulate the hypothalamus to raise the body's temperature setpoint

High temperature inhibits heat-sensitive bacterial enzyme function and speeds up host cellular metabolism and tissue repair

What is the biological purpose of the inflammatory response?

A localized protective tissue response designed to isolate invaders, neutralize harmful agents, clear dead tissue, and initiate structural repair

What are the 5 cardinal signs of inflammation in Latin and English?

Tumor (swelling)

Dolor (pain)

Rubor (redness)

Calor (heat)

Functio laesa (loss of function)

In the 6-step inflammatory cascade, what occurs immediately upon tissue damage (Step 1)?

Damaged tissue cells and resident macrophages release chemokines and chemical signals into surrounding fluid

What action do local mast cells take during Step 2 of the inflammatory cascade?

Mast cells degranulate and release histamine into neighboring tissue and capillaries

What physical mechanics occur during vasodilation in Step 3 of inflammation?

Capillaries dilate and become porous/leaky, local blood flow increases, and endothelial cells express selectin adhesion molecules on their inner walls

What are selectins and integrins and how do they facilitate neutrophil movement during Step 4?

Selectins bind lightly to passing neutrophils to slow them down along capillary walls

Integrins bind firmly to endothelial adhesion molecules to stop neutrophils completely

What is margination (pavementing) during the inflammatory cascade?

The process where rolling white blood cells slow down and adhere along the inner endothelial surface of blood vessel walls

What is diapedesis (extravasation)?

The active squeezing of leukocytes through narrow gaps between endothelial cells in capillary walls to enter damaged tissue

What is exudation and how does it lead to edema?

The leakage of protein-rich fluid and blood plasma out of porous capillaries into interstitial spaces, resulting in localized swelling (edema)

What secondary cascade systems are activated in Step 6 of the inflammatory cascade, and how is the response resolved?

Secondary Systems: Complement system (cell destruction/opsonization), Kinin system (bradykinin pain/vasodilation), Coagulation system (blood clotting), and Fibrinolysis (clot breakdown)

Resolution: Phagocytes clean up dead pathogens and debris, allowing growth factors to induce tissue repair

What is an antigen?

Any foreign molecule (typically a protein or large polysaccharide) that is recognized by the immune system and triggers an adaptive immune response

What is an epitope?

The specific small surface region or determinant on an antigen molecule that binds directly to antibody antigen-binding sites or T-cell receptors

What is MHC Class I and where is it located in the body?

A surface glycoprotein present on all nucleated body cells (absent on non-nucleated erythrocytes/red blood cells) that displays internally generated peptides to the immune system

Which T-cell coreceptor pairs with MHC Class I and what cell response occurs?

Pairs with CD8 receptors on Cytotoxic T-cells, triggering targeted cell lysis or apoptosis if foreign/abnormal peptides are displayed

What is MHC Class II and where is it expressed?

A surface glycoprotein expressed exclusively on professional Antigen-Presenting Cells (APCs) that displays engulfed exogenous peptides

Which cell types are classified as professional Antigen-Presenting Cells (APCs)?

B cells, Macrophages, and Dendritic cells

Which T-cell coreceptor pairs with MHC Class II and what cell response occurs?

Pairs with CD4 receptors on Helper T-cells, activating the Helper T-cell to release interleukins and coordinate adaptive responses

Where do B cells originate and mature?

B cells originate in the bone marrow and complete their maturation within the bone marrow

What are plasma cells and what is their function?

Fully differentiated B-cell lineages that actively synthesize and secrete large quantities of soluble antibodies into the blood and lymph

What are memory B cells and what is their role in long-term immunity?

Quiescent, long-lived lymphocytes produced during a primary infection that remain in lymphoid tissues to mount a rapid antibody response upon secondary re-exposure

What is the general structural layout of an antibody (immunoglobulin)?

A Y-shaped glycoprotein made of two identical heavy chains and two identical light chains, featuring constant (Fc) regions and variable (Fab) antigen-binding regions

What is the specific function and location of IgA antibodies?

A dimeric antibody class found in mucosal secretions (saliva, tears, mucus, breast milk) that prevents pathogen attachment to mucosal surfaces

What is the primary role of IgD antibodies?

Monomeric antibodies that function primarily as antigen receptors on the surface membranes of naive B cells

What is the function of IgE antibodies and what cells do they bind to?

Monomeric antibodies that bind to receptors on mast cells and basophils, triggering degranulation and histamine release during allergic reactions and parasite defense

What are the key characteristics of IgG antibodies?

The most abundant antibody class in serum; functions as an opsonin, activates complement, and is the only antibody class capable of crossing the placenta to protect a fetus

What is unique about IgM antibodies regarding structure, synthesis, and function?

Large pentamer structure; the first antibody class synthesized by a fetus and during initial primary antigen exposure; highly effective at agglutination (clumping antigens)

Where do T cells originate and where do they mature?

Originate in the bone marrow and migrate to the thymus gland for maturation and immunocompetence selection

What are Cytotoxic T-cells versus Helper T-cells?

Cytotoxic T-cells (CD8+): Target and destroy virus-infected cells, tumor cells, and foreign tissue grafts via perforins and granzymes

Helper T-cells (CD4+): Secrete cytokines (interleukins) that stimulate B-cell proliferation, activate Cytotoxic T-cells, and recruit macrophages

What is clonal selection in adaptive immunity?

The process where binding of a specific antigen selectively stimulates matching lymphocyte clones to multiply rapidly into functional effector and long-lived memory cells

What drives the Cell-Mediated Immune Response and what role do interleukins play?

Driven by T-cells targeting intracellular pathogens and foreign host cells

APCs present antigen-MHC II to CD4+ Helper T-cells, which release interleukins in a positive-feedback loop to activate CD8+ Cytotoxic T-cells

What drives the Humoral Immune Response and where are targets located?

Driven by B cells and secreted antibodies targeting extracellular pathogens, viruses, and free toxins circulating in blood or lymph

What is the overall primary purpose of the lymphatic system?

Drains excess interstitial fluid from tissues to return it to blood circulation, and transports white blood cells and absorbed dietary lipids

Where is the spleen located and what are its blood-filtering functions?

Location: Upper left quadrant of the abdomen, behind the stomach

Functions: Red pulp filters blood, recycles old red blood cells, and breakdown products; white pulp mounts immune responses against blood-borne antigens

What cellular components are stored inside the spleen?

Red blood cells, white blood cells (lymphocytes and macrophages), and blood platelets

Where is the thymus located and what is its primary role?

Location: Superior mediastinum, anterior to the heart

Role: Site of T-lymphocyte differentiation and selection; active in early life and shrinks (involutes) post-puberty

Where are the tonsils located and what is their function?

Location: Ring of lymphoid tissue in the pharynx (palatine, lingual, pharyngeal/adenoid)

Function: Acts as a first line of lymphoid defense against ingested or inhaled pathogens, aiding T-cell and B-cell exposure

What are lymph nodes and how does lymph fluid flow through them?

Lymph Nodes: Small, bean-shaped organ filters along lymphatic vessels

Pathway: Afferent lymphatic vessels -> subcapsular sinus -> cortex and medulla (node filter containing macrophages/lymphocytes) -> efferent lymphatic vessels

What is the overview, cause, symptoms, and treatment for Asthma?

Overview: Chronic inflammatory respiratory airway disease

Cause: Hyper-responsiveness triggered by allergens, exercise, or environmental pollutants

Symptoms: Airway inflammation, bronchospasms, excessive mucus, wheezing, dyspnea, and coughing

Treatments: Inhaled corticosteroids, short-acting bronchodilators (albuterol), and long-acting bronchodilators/anticholinergics (formoterol, salmeterol, tiotropium)

What is the overview, cause, symptoms, and treatment for Ataxia Telangiectasia (AT)?

Overview: Rare neurodegenerative autosomal recessive immunodeficiency disease

Cause: Mutations in the ATM gene on chromosome 11 (locus 11q22.3), disrupting DNA break repair

Symptoms: Cerebellar ataxia, skeletal muscle incoordination, dilated blood vessels in eyes/skin (telangiectasias), immunodeficiency, and elevated cancer risk

Treatments: Intravenous gammaglobulins, physical therapy, and antispasmodic medications like Diazepam

What are Autoimmune Polyglandular Syndromes (APS) and how do Type 1, Type 2, and IPEX differ?

Overview: Autoimmune disorders causing multi-organ endocrine gland failure

Type 1 APS: Autosomal recessive mutation in the AIRE gene on chromosome 21; features candidiasis, hypoparathyroidism, and Addison's disease

Type 2 (Schmidt's Syndrome): Polygenic disorder linked to HLA-DQ2/DQ8; features Addison's disease plus thyroid autoimmunity or Type 1 Diabetes

IPEX Syndrome: X-linked recessive mutation in the FOXP3 gene; causes regulatory T-cell dysfunction leading to polyendocrinopathy and enteropathy

What is the overview, cause, symptoms, and treatment for Burkitt Lymphoma?

Overview: Fast-growing B-cell Non-Hodgkin Lymphoma

Cause: Translocation dysregulating the c-myc gene on chromosome 8 (t(8;14)); strongly associated with Epstein-Barr Virus (EBV), malaria, and HIV

Symptoms: Rapidly enlarging tumor masses in jaw/facial bones (endemic form) or abdomen (sporadic form)

Treatments: Intensive intravenous and intrathecal chemotherapy protocols

What is the overview, cause, symptoms, and treatment for Type 1 Diabetes?

Overview: Autoimmune metabolic disease causing absolute insulin deficiency

Cause: Autoreactive T-cell destruction of insulin-producing beta cells in pancreatic Islets of Langerhans; linked to HLA-DQB1 genes

Symptoms: Polydipsia, polyuria, polyphagia, unexplained weight loss, and risk of Diabetic Ketoacidosis (DKA)

Treatments: Lifelong exogenous insulin replacement via daily injections or insulin pump therapy

What is the overview, cause, symptoms, and treatment for DiGeorge Syndrome?

Overview: Congenital immunodeficiency and developmental disorder

Cause: Autosomal dominant microdeletion on chromosome 22 at locus 22q11.2; best diagnosed using Fluorescence In Situ Hybridization (FISH)

Symptoms: Thymic hypoplasia leading to T-cell deficits, congenital heart defects, hypocalcemia from parathyroid hypoplasia, and facial clefting

Treatments: Calcium/Vitamin D supplements, cardiac surgery, prophylactic antibiotics, and thymus tissue or stem cell transplantation

What is Familial Mediterranean Fever (FMF)?

Overview: Hereditary autoinflammatory disorder of the innate immune system (occurs without autoantibodies or antigen-specific T cells)

Cause: Mutations in the MEFV gene encoding pyrin, causing uncontrolled interleukin-1 beta production

Symptoms: Recurrent unprovoked episodes of high fever and painful serositis (peritonitis, pleuritis, joint pain)

Treatments: Daily oral colchicine to prevent attacks and amyloidosis; IL-1 receptor antagonists (anakinra)

What is the overview, cause, symptoms, and treatment for Graves' Disease?

Overview: Autoimmune disorder resulting in hyperthyroidism

Cause: Thyroid-Stimulating Immunoglobulins (TSI) bind and continuously activate TSH receptors, triggering excessive thyroid hormone synthesis

Symptoms: Diffuse goiter, thyrotoxicosis, heat intolerance, weight loss, rapid heart rate, and bulging eyes (exophthalmos)

Treatments: Antithyroid drugs (methimazole, propylthiouracil), beta-blockers, radioactive iodine ablation, or thyroidectomy

What is Immunodeficiency with Hyper-IgM and what are its four main variants?

Overview: Primary immunodeficiencies where B cells fail to undergo class-switch recombination, leading to low IgG/IgA/IgE and normal or elevated IgM

HIGM1: X-linked recessive, caused by CD40LG gene mutation on T cells

HIGM2: Autosomal recessive, caused by AICDA gene mutation (lack of AID enzyme)

HIGM3: Autosomal recessive, caused by CD40 receptor gene defect on B cells

UNG Deficiency: Autosomal recessive, caused by Uracil-DNA Glycosylase gene defect impairing DNA repair

What is Chronic Myeloid Leukemia (CML), its genetic cause, phases, and targeted treatment?

Overview: Myeloproliferative cancer causing overproduction of granulocytes

Cause: Translocation between chromosomes 9 and 22, t(9;22), forming the Philadelphia Chromosome and BCR-ABL1 fusion oncogene

Phases: Chronic phase, Accelerated phase, and Blast crisis phase

Treatments: Targeted Tyrosine Kinase Inhibitors (TKIs) like imatinib and dasatinib

What is the overview, cause, symptoms, and treatment for Multiple Sclerosis (MS)?

Overview: Autoimmune inflammatory demyelinating disease of the Central Nervous System (CNS)

Cause: Helper and Cytotoxic T-cells cross the blood-brain barrier and attack myelin sheaths on CNS nerve fibers, forming scar tissue (sclerosis)

Symptoms: Optic neuritis, sensory disturbances, loss of motor coordination, muscle weakness, and fatigue

Treatments: Corticosteroids for acute relapses; disease-modifying therapies (interferon-beta, glatiramer acetate, monoclonal antibodies)

What is the overview, cause, symptoms, and treatment for Rheumatoid Arthritis (RA)?

Overview: Chronic systemic autoimmune arthritis

Cause: Autoimmune attack against joint synovial linings (synovium) mediated by autoantibodies like Rheumatoid Factor and anti-CCP

Symptoms: Symmetric joint pain and swelling, prolonged morning stiffness, joint cartilage destruction, bone erosion, and deformities

Treatments: Disease-Modifying Antirheumatic Drugs (DMARDs like methotrexate), TNF-alpha inhibitors, and NSAIDs

What is Severe Combined Immunodeficiency (SCID)?

Overview: Life-threatening primary immunodeficiency marked by complete absence of functional T cells and secondary B-cell dysfunction

Causes: X-linked SCID caused by IL2RG gene mutations; autosomal recessive forms caused by Adenosine Deaminase (ADA) deficiency

Symptoms: Severe, recurrent opportunistic infections in early infancy, failure to thrive, persistent diarrhea, and chronic candidiasis

Treatments: Hematopoietic stem cell transplantation (HSCT), gene therapy, and enzyme replacement therapy for ADA-SCID

What is Systemic Lupus Erythematosus (SLE)?

Overview: Systemic autoimmune connective tissue disease

Cause: Antinuclear Antibodies (ANA) and anti-dsDNA form circulating immune complexes that deposit in blood vessels and tissues

Symptoms: Severe fatigue, joint pain, photosensitivity, kidney damage (lupus nephritis), and a classic "butterfly" rash across the cheeks and bridge of the nose

Treatments: Hydroxychloroquine, corticosteroids, immunosuppressants (mycophenolate, azathioprine), and targeted biologics (belimumab)

What are the primary mechanisms and features of the 4 Types of Hypersensitivity?

Type I (Immediate): IgE-mediated cross-linking on mast cells/basophils triggering immediate histamine release (e.g., anaphylaxis, asthma)

Type II (Cytotoxic): IgG or IgM antibodies bind directly to target host cell surface antigens, triggering complement lysis or cell destruction (e.g., transfusion reactions)

Type III (Immune Complex): Circulating antibody-antigen complexes deposit in blood vessels, kidney glomeruli, or joints, causing inflammatory damage (e.g., SLE, serum sickness)

Type IV (Delayed-Type): Cell-mediated response where sensitized Th1 T-cells release cytokines to activate macrophages 24-72 hours post-exposure, independent of antibodies (e.g., contact dermatitis, tuberculin test)

What is Hyperacute Organ Rejection regarding timing, cause, and mechanism?

Timing: Occurs within minutes to hours post-transplant

Cause: Pre-existing recipient donor-specific antibodies binding graft endothelium

Mechanism: Triggers immediate complement activation, widespread thrombosis, and graft necrosis (e.g., mismatched blood type)

What is Acute Organ Rejection regarding timing and mechanism?

Timing: Occurs within 1 week to 3 months post-transplant

Mechanism: Mediated primarily by host T-cells recognizing foreign donor MHC antigens, leading to cell-mediated damage to graft tissue

What is Chronic Organ Rejection regarding timing and mechanism?

Timing: Occurs gradually over months to years post-transplant

Mechanism: Continuous low-grade cell-mediated and antibody responses cause progressive smooth muscle proliferation, vascular occlusion, fibrosis, and eventual organ failure

How do Allografts and Autografts compare regarding donor source, rejection risk, surgical sites, healing time, and expense?

Allograft: Tissue transplanted from a non-genetically identical donor of the same species. Carries higher rejection risk, requires 1 surgical site on the recipient, and has lower recipient healing time and surgical expense

Autograft: Tissue transplanted from one part of a person's body to another location on the same individual. Carries zero rejection risk, but requires 2 surgical sites, resulting in longer total healing time and higher overall expense