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What are the three lines of host defense?
First line: physical/chemical barriers. Second line: innate internal defenses (inflammation, phagocytosis, fever, antimicrobial proteins). Third line: adaptive/acquired immunity.
What characterizes the first line of defense?
Any barrier that blocks invasion at the portal of entry; nonspecific and very general in action.
What characterizes the second line of defense?
An internalized system of protective cells and fluids (inflammation, phagocytosis) that acts rapidly, locally and systemically, once the first line is overcome.
What characterizes the third line of defense?
Acquired individually as lymphocytes encounter each foreign substance; produces unique protective substances and provides long-term immunity.
Define immunology.
The study of the body's second and third lines of defense, its response to infectious agents, and the study of allergies and cancer.
What is the mandate of a healthy immune system?
Surveillance of the body, recognition of foreign material, and destruction of entities deemed foreign.
What is an antigen (marker)?
A surface molecule (protein and/or sugar) that lets immune cells evaluate a cell as self and mark it for destruction if needed.
What are PAMPs?
Pathogen-associated molecular patterns — markers shared by many different kinds of microbes.
What are PRRs?
Pattern recognition receptors — used by host cells of the innate (2nd line) immune system to recognize PAMPs.
What is the mononuclear phagocyte system (MPS)?
A network of phagocytic cells enmeshed in connective tissue reticulum, in direct contact with tissue cells and extracellular fluid.
Name the primary lymphatic organs.
Red bone marrow and the thymus — sites of immune cell birth and maturation.
Name the secondary lymphatic organs.
Lymph nodes, spleen, and associated lymphoid tissues — sites of immune cell activation, residence, and function.
Where do B cells mature? Where do T cells mature?
B cells mature in the bone marrow; T cells mature in the thymus.
What is the function of the spleen?
Filters blood (not lymph); removes worn-out red blood cells; filters pathogens for phagocytosis by macrophages; stores blood.
What are SALT and MALT?
Skin-associated lymphoid tissue and mucosa-associated lymphoid tissue — diffuse bundles of lymphocytes beneath the skin/mucosa.
What is GALT and what does it include?
Gut-associated lymphoid tissue; includes the appendix, lacteals, and Peyer's patches.
Differentiate plasma and serum.
Plasma is the clear, yellowish fluid portion of whole blood; serum is the same fluid minus clotting factors (obtained from clotted blood).
What are cytokines?
Small active molecules secreted by immune and other cells to regulate, stimulate, suppress, or otherwise control cell development, inflammation, and immunity.
Give an example of a pro-inflammatory and an anti-inflammatory cytokine.
Pro-inflammatory: IL-1 or TNF-β. Anti-inflammatory: IL-10.
Name the three types of phagocytes.
Neutrophils, monocytes, and macrophages.
How do neutrophils differ from macrophages?
Neutrophils are general-purpose, early-responding phagocytes and the main component of pus; monocytes migrate into tissue and transform into long-lived macrophages.
List the steps of phagocytosis in order.
Chemotaxis → adhesion → engulfment/phagosome formation → phagolysosome formation & killing → elimination (excretion of debris).
What are histiocytes? Give 3 examples.
Tissue-resident macrophages that stay in one tissue for life: alveolar (lung) macrophages, Kupffer cells (liver), dendritic cells (skin).
List the five classic signs of inflammation.
Rubor (redness), calor (heat), tumor (swelling), dolor (pain), and loss of function.
List the stages of inflammation.
Injury/immediate reactions → vascular reactions (dilate–constrict–dilate) → edema and pus formation → resolution/scar formation.
Define diapedesis.
The migration of white blood cells out of blood vessels into tissues.
Define chemotaxis
Migration of cells toward a specific chemical stimulus gradient (e.g., toward a site of infection).
Differentiate exudate and edema.
Exudate is fluid that escapes from blood vessels; edema is the local swelling caused by accumulation of that fluid in tissue.
What is pus composed of?
White blood cells (mainly neutrophils) plus liquefied cellular debris and bacteria.
What does 'pyogenic' mean? Give examples.
Pus-producing; e.g., streptococci, staphylococci, gonococci, and meningococci are pyogenic bacteria.
What is a fever and what controls body temperature?
An abnormally elevated body temperature; set-point is maintained by the hypothalamus (normally ~37°C/98.6°F).
Differentiate exogenous and endogenous pyrogens.
Exogenous pyrogens come from outside the body (microbial products, toxins, vaccines); endogenous pyrogens are released by host cells (e.g., IL-1, TNF from monocytes/macrophages/neutrophils).
List three benefits of fever.
Inhibits multiplication of temperature-sensitive microbes; reduces bacterial access to iron; increases metabolism and stimulates immune reactions (e.g., speeds phagocytosis).
What are interferons and their three main types?
Small antiviral/immune-regulatory proteins; IFN-alpha and beta (from lymphocytes, fibroblasts, macrophages) and IFN-gamma (from T cells).
How does interferon protect neighboring cells?
t's secreted and binds receptors on nearby host cells, inducing proteins that degrade viral RNA and block viral protein synthesis; it is not microbe-specific.
What is complement?
A system of over 30 blood proteins that work in a cascade to destroy bacteria, certain viruses, parasites, and other cells.
List the 4 stages of the complement cascade.
1) Initiation: C3 → C3a + C3b.
2) Activation/cascade: C3b cleaves C5 → C5a + C5b.
3) Polymerization: C5b + C6-C8 form the membrane attack complex (MAC).
4) Membrane attack: MAC forms pores → cell lysis.
Differentiate the classical and alternative complement pathways.
Classical requires antibody already bound to the microbe to initiate; alternative doesn't require antibody, is triggered by foreign antigens directly, and is faster.
What are antimicrobial peptides? Give an example family.
Short proteins (12–50 amino acids), e.g., defensins, that insert into bacterial membranes and form pores, causing lysis.
What are the four major categories of the second line of defense?
Phagocytosis, inflammation, fever, and antimicrobial products (interferon, complement, antimicrobial peptides).
What does lysozyme do and where is it found?
An enzyme in tears and saliva that hydrolyzes peptidoglycan in bacterial cell walls.
How does the normal microbiome contribute to the first line of defense?
It forms a structural barrier blocking pathogen access to epithelial surfaces, competes for nutrients, and alters local pH.
Name the four body systems that participate in the first line of defense.
Integumentary (skin), digestive, respiratory, and genitourinary systems (mucous membranes throughout).
What makes the third line of defense different from the other two?
It is acquired individually after exposure to a specific antigen (infection or vaccination), is highly specific, and has memory — unlike the general, nonspecific first two lines.
Differentiate antigen, immunogen, and epitope
Antigen = any molecule the immune system can recognize; immunogen = an antigen that actually provokes an immune response; epitope = the specific site on an antigen recognized by an antibody/receptor.
Define immunocompetence.
The ability of the body to react against countless different foreign substances
List the four stages of an adaptive immune response.
1) Lymphocyte development & clonal deletion.
2) Antigen presentation & clonal selection.
3) Challenge of B and T lymphocytes by antigen.
4) T-cell response (cell-mediated) and B-cell response (antibody production).
What is the MHC?
The major histocompatibility complex — a set of genes coding for human cell surface markers (also called the HLA system); central to self-recognition and antigen presentation
Differentiate MHC Class I, II, and III genes.
Class I: markers on all nucleated cells (self ID). Class II: on macrophages, dendritic cells, B cells; present antigen to T cells. Class III: encode complement proteins.
What are CD molecules?
'Cluster of differentiation' — a naming system for cell-surface markers; CD3, CD4, and CD8 are the most important in immunity.
What do CD4 and CD8 do?
CD4 is a coreceptor on T helper cells that binds MHC class II; CD8 is a coreceptor on cytotoxic T cells that binds MHC class I.
Where do B and T cells mature, and where do they migrate afterward?
B cells mature in bone marrow, T cells mature in the thymus; both then migrate to and recirculate through lymph nodes, spleen, and other lymphoid tissue.
How do B-cell and T-cell antigen receptors differ?
B cells bind free/unprocessed antigen directly; T cells only bind antigen that has been processed and is complexed with MHC on a presenting cell.
List the three functional types of T cells.
Helper T cells, regulatory T cells, and cytotoxic T cells.
What do helper T cells do?
Activate macrophages, assist B-cell processes, and help activate cytotoxic T cells — they secrete cytokines but do NOT produce antibodies.
What do cytotoxic T cells do?
Destroy infected host cells, cancer cells, and foreign (grafted) cells via direct lysis; require MHC class I recognition.
What happens when B cells are activated by antigen?
They divide and differentiate into plasma cells (secrete antibodies) and memory cells.
Compare B cells and T cells: site of maturation, surface marker, and MHC requirement.
B cells: bone marrow, immunoglobulin receptor, no MHC required, produce antibodies. T cells: thymus, T-cell receptor + CD markers, MHC required, cell-mediated functions.
What is clonal selection?
The mechanism by which the one pre-programmed B or T cell whose receptor exactly fits an incoming antigen is activated.
What is clonal deletion?
The process by which self-reactive lymphocyte clones are destroyed during development, producing immune tolerance.
What is clonal expansion?
Mitotic proliferation of an activated lymphocyte clone into a larger population, all sharing the same antigen specificity.
How is immunologic diversity generated?
By extensive rearrangement of gene segments coding for antigen receptors during B- and T-cell development (an estimated 10 trillion possible antibody specificities).
Describe the basic structure of an immunoglobulin (antibody).
A Y-shaped molecule with two heavy and two light chains; the two Fab arms bind antigen (variable regions), the Fc stem is constant and mediates effector functions.
How do T-cell receptors differ from B-cell receptors (immunoglobulins)?
TCRs are relatively small, are never secreted, and bind antigen only when complexed with MHC; B-cell receptors can be secreted as free antibody.
What features make a 'good' immunogen?
Foreignness, larger size, and chemical complexity (proteins are usually more immunogenic than repetitive polysaccharides); context/cytokines present also matter.
What is a hapten?
A small foreign molecule too small alone to trigger an immune response; becomes immunogenic when bound to a larger carrier molecule, serving as the epitope.
What are alloantigens?
Cell-surface markers/molecules that differ among members of the same species — the basis of blood groups and MHC incompatibility in transfusions/transplants.
What are superantigens?
Bacterial toxins that are potent, nonspecific stimulators of T cells (activating them ~100x normal), causing overwhelming cytokine release; linked to toxic shock syndrome.
Name the main antigen-presenting cells (APCs).
Macrophages, B cells, and dendritic cells.
What are T-cell-independent antigens?
Antigens (e.g., repetitive polysaccharides like LPS or pneumococcal capsule) that can activate B cells directly, without APCs or T helper cells.
Compare TH1, TH2, TH17, and Treg cells.
TH1: drives cell-mediated immunity/activates macrophages. TH2: helps B cells/antibody response, involved in allergy. TH17: promotes inflammation. Treg: suppresses/controls immune response, prevents autoimmunity.
What do perforins and granzymes do?
Released by cytotoxic T cells: perforins punch pores in the target cell membrane; granzymes are enzymes that enter through the pores and trigger apoptosis.
Differentiate NK cells and NKT cells.
NK cells are innate lymphocytes that kill abnormal cells nonspecifically; NKT cells are hybrid cells with both T-cell receptors and NK-like killing activity.
What are innate lymphoid cells (ILCs)?
Innate immune cells (ILC1, ILC2, ILC3, and NK cells) that mirror T helper/cytotoxic T cell functions but lack antigen receptors and do not undergo clonal expansion
List the five main antibody functions.
Opsonization, neutralization, agglutination, lysis (via complement), and antitoxin activity.
List the five immunoglobulin classes and one key fact for each.
IgG: most abundant, crosses placenta. IgA: mucosal secretions, dimer form. IgM: first antibody made, pentamer, B-cell receptor early on. IgD: B-cell receptor. IgE: mediates allergy and anti-parasite response.
Which immunoglobulin crosses the placenta?
IgG.
Which immunoglobulin is produced first in a primary immune response?
IgM.
Compare the primary and secondary immune responses.
Primary: first exposure, slower onset, lower titer (IgM then IgG). Secondary: faster and stronger due to memory cells, mostly IgG, occurs on re-exposure.
Differentiate natural and artificial immunity.
Natural immunity is acquired through normal biological experiences (infection, mother-to-infant transfer); artificial immunity is acquired via medical procedures (vaccines, immune serum).
Differentiate active and passive immunity.
Active: body produces its own antibodies/memory, slow onset, long-lasting. Passive: receives preformed antibodies, no memory, immediate but short-term protection.
Give an example of natural passive immunity.
Antibodies passed from mother to fetus/infant via the placenta or breast milk (colostrum).
What are gamma globulins?
Immunoglobulins extracted and concentrated from the pooled blood of many human donors, used for passive immunization.
Who developed the first vaccine, and how?
Edward Jenner (1796); he used material from cowpox lesions to protect a boy against smallpox
List the qualities of an ideal vaccine.
Protects against the natural pathogen, low toxicity/side effects, stimulates both antibody (B-cell) and cell-mediated (T-cell) responses, produces long-term memory, needs few doses, and is inexpensive, stable, and easy to give.
List the major types of vaccine preparations.
Live attenuated, killed/inactivated, subunit, conjugate, mRNA, and viral vector vaccines.
Give an example each of an mRNA vaccine and a viral vector vaccine.
mRNA: Pfizer and Moderna COVID-19 vaccines. Viral vector: Johnson & Johnson COVID-19 vaccine.
What are adjuvants?
Substances added to vaccines that enhance immunogenicity, prolong antigen retention at the injection site, and help engage the innate immune system.
What is herd immunity?
A phenomenon where a sufficient percentage of a population is immune, making it difficult for a pathogen to circulate and protecting the unvaccinated.
What is a booster shot? Give two examples of schedules.
A repeat vaccine dose to maintain long-term protection; e.g., tetanus every 10 years, measles booster at age 5–6.
Describe the three phases of vaccine clinical trials.
Phase 1: 20–100 volunteers, tests safety. Phase 2: several hundred volunteers, tests short-term side effects/immune response. Phase 3: hundreds to thousands, compares vaccinated vs. unvaccinated for safety and effectiveness.
What is VAERS?
The Vaccine Adverse Event Reporting System — collects and analyzes reports of adverse events following vaccination, submitted by anyone including patients and providers.
What are the three major categories of microbial identification techniques?
Phenotypic, immunologic, and genotypic.
Define phenotypic identification.
Identification based on observing a microbe's macroscopic/microscopic morphology, physiology, and biochemical properties.
Define immunologic (serologic) identification.
Identification using antibodies — either known antibodies to identify an unknown microbe, or known antigens to detect a patient's antibodies.
Define genotypic identification.
Identification based on analysis of a microbe's DNA or RNA.
Why is rapid identification critical in bloodstream infections (sepsis)?
Sepsis is a medical emergency; standard culture-based identification takes too long, increasing mortality risk, so broad-spectrum antibiotics are started immediately and narrowed once the organism is known.
Why is aseptic technique important in specimen collection?
It prevents contamination of the sample from the environment or the patient's own normal microbiota, which could lead to misidentification.
Differentiate 'clean catch' and 'dirty catch' urine samples.
Clean catch: midstream urine collected after washing the external urethra, minimizing normal flora contamination. Dirty catch: first-voided urine, needed for certain diagnostic tests.
Which stains are used for immediate direct examination of specimens?
Gram stain (bacteria), acid-fast stain (Mycobacterium), and KOH stain (fungi).