Immunology

Pathogens

Types of Pathogens

A pathogen is any organism or agent that can cause disease. The DSE specification requires knowledge of four main types of pathogen.

Pathogen Type	Structure	Examples of Diseases	Key Features
Bacteria	Prokaryotic cells; no nucleus; cell wall (peptidoglycan); single circular chromosome; 70S ribosomes; plasmids	Cholera, tuberculosis, gonorrhoea, tetanus, syphilis	Reproduce by binary fission (rapid, every 20 min); produce toxins (endotoxins and exotoxins); most are free-living; treated with antibiotics
Viruses	Non-cellular; protein coat (capsid) surrounding nucleic acid (DNA or RNA); no ribosomes; no metabolism; no cell membrane	Influenza, HIV/AIDS, COVID-19, measles, polio, HPV	Obligate intracellular parasites; replicate inside host cells using host machinery; not affected by antibiotics
Fungi	Eukaryotic; chitin cell wall; true nucleus; 80S ribosomes; can be unicellular (yeasts) or multicellular (moulds)	Athlete's foot, ringworm, thrush (Candida)	Reproduce by spores; saprotrophic nutrition; treated with antifungal drugs
Protozoa	Eukaryotic; unicellular; no cell wall; true nucleus; some have flagella or cilia	Malaria (Plasmodium), amoebic dysentery, sleeping sickness	Often have complex life cycles involving multiple hosts; transmitted by vectors (e.g., mosquitoes for malaria)

How Pathogens Cause Disease

Pathogens cause disease through several mechanisms:

1. Production of toxins:

Toxin Type	Description	Example
Exotoxins	Secreted by living bacteria into the surrounding environment; highly potent; specific targets (nerves, cells, etc.)	Tetanus toxin (Clostridium tetani); cholera toxin (Vibrio cholerae)
Endotoxins	Components of the outer membrane of Gram-negative bacteria; released when bacteria die; less potent but cause fever and inflammation	Lipopolysaccharide (LPS) from Salmonella, E. coli

2. Cell damage:

• Viruses replicate inside host cells, causing cell lysis and tissue damage
• Some bacteria produce enzymes that damage host tissues (e.g., hyaluronidase, which breaks down connective tissue, facilitating spread)
• Protozoa such as Plasmodium destroy red blood cells during their life cycle

3. Host immune response:

• The symptoms of many diseases (fever, inflammation, tissue damage) are caused by the body's own immune response, not directly by the pathogen
• For example, the severe lung damage in severe influenza is largely caused by an overactive immune response (cytokine storm)

Transmission of Pathogens

Transmission Route	Description	Example
Direct contact	Physical contact with an infected person (skin, bodily fluids)	Herpes simplex, HIV, HPV
Droplet infection	Coughing, sneezing, talking expels droplets containing pathogens	Influenza, common cold, COVID-19, tuberculosis
Water-borne	Ingestion of contaminated water	Cholera, typhoid, amoebic dysentery
Food-borne	Ingestion of contaminated food (undercooked meat, unwashed vegetables)	Salmonella, E. coli O157, botulism
Vector-borne	Transmission by an insect or other animal vector	Malaria (mosquito), dengue fever (mosquito), Lyme disease (tick)
Fomite transmission	Transfer via contaminated objects (door handles, towels, medical equipment)	Common cold viruses, MRSA
Blood-borne	Transfer through blood or blood products	HIV, Hepatitis B and C

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Innate (Non-Specific) Immunity

First Line of Defence: Physical and Chemical Barriers

The body's first line of defence prevents pathogens from entering the body.

Barrier	Mechanism
Skin	Physical barrier; keratinised outer layer (epidermis) is tough and waterproof; sebaceous glands secrete sebum (antimicrobial lipids)
Mucous membranes	Line respiratory, digestive, and reproductive tracts; trap pathogens in sticky mucus
Cilia	Microscopic hair-like structures in the respiratory tract; move mucus (with trapped pathogens) upwards and out of the airways
Stomach acid	Hydrochloric acid (HCl) in the stomach (pH ~2) denatures proteins in pathogens and destroys most ingested bacteria
Tears and saliva	Contain lysozyme, an enzyme that breaks down peptidoglycan in bacterial cell walls, causing lysis
Ear wax (cerumen)	Traps pathogens and insects; contains antimicrobial properties
Vaginal secretions	Slightly acidic (pH ~4) due to lactic acid production by Lactobacillus; inhibits growth of many pathogens
Normal flora (microbiome)	Commensal bacteria on the skin and in the gut compete with pathogens for nutrients and space; some produce antimicrobial substances

Second Line of Defence: Internal Defences

If pathogens breach the first line of defence, the second line provides a rapid, non-specific response.

1. Phagocytosis:

Phagocytes (neutrophils and macrophages) are white blood cells that engulf and destroy pathogens.

Phagocyte Type	Source	Location	Characteristics
Neutrophils	Bone marrow; short-lived (hours)	Blood; recruited to infection sites	Most abundant phagocyte; first to arrive at infection; multi-lobed nucleus; granules contain digestive enzymes
Macrophages	Derived from monocytes	Tissues (liver, lungs, lymph nodes, spleen)	Larger and longer-lived than neutrophils; can present antigens to T cells (antigen-presenting cells); important in adaptive immunity

Stages of phagocytosis:

1. Chemotaxis: Phagocytes are attracted to the site of infection by chemical signals released by pathogens and damaged cells (e.g., cytokines, bacterial products)
2. Recognition: Phagocyte receptors bind to molecules on the pathogen surface. Non-self molecules that trigger an immune response are called antigens. Phagocytes can also bind to pathogens that have been opsonised (coated with antibodies or complement proteins)
3. Engulfment: The phagocyte extends pseudopodia around the pathogen, enclosing it in a membrane-bound vesicle called a phagosome
4. Digestion: The phagosome fuses with a lysosome (containing digestive enzymes: lysozyme, proteases, lipases) to form a phagolysosome. Enzymes break down the pathogen
5. Exocytosis: Indigestible material is expelled from the cell by exocytosis

2. Inflammation:

Inflammation is a localised response to tissue damage or infection. Its purpose is to isolate and destroy pathogens, remove damaged tissue, and initiate tissue repair.

The four cardinal signs of inflammation:

Sign	Mechanism
Redness	Vasodilation increases blood flow to the area
Heat	Increased blood flow brings warm blood from the body core to the surface
Swelling	Increased permeability of capillary walls allows plasma proteins and fluid to leak into the tissue (oedema)
Pain	Swelling compresses nerve endings; inflammatory chemicals (prostaglandins, bradykinin) stimulate pain receptors

Sequence of events:

1. Tissue damage releases chemical mediators (histamine from mast cells, prostaglandins, cytokines)
2. Histamine causes vasodilation and increased capillary permeability
3. More blood flows to the area, bringing phagocytes (neutrophils first, then macrophages)
4. Fluid and proteins leak into the tissue, causing swelling and helping to dilute toxins
5. Phagocytes engulf and destroy pathogens
6. Fibrin forms a clot around the area, walling off the infection

3. Fever (pyrexia):

• Macrophages release cytokines called pyrogens that travel to the hypothalamus
• Pyrogens raise the hypothalamic set point, causing body temperature to increase
• Higher temperature inhibits pathogen growth (many pathogens grow best at 37 degrees C)
• Higher temperature increases metabolic rate, speeding up immune responses and tissue repair
• Extremely high fever (above 41 degrees C) is dangerous because it denatures human enzymes

4. Interferons:

• Proteins produced by virus-infected cells
• They diffuse to neighbouring cells and stimulate them to produce antiviral proteins
• These antiviral proteins inhibit viral replication by degrading viral mRNA and blocking translation
• Interferons are NOT virus-specific -- they provide broad-spectrum antiviral defence

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Adaptive (Specific) Immunity

Overview

Adaptive immunity is a specific response to a particular pathogen. It is slower than innate immunity (takes several days to develop) but provides long-lasting protection through immunological memory.

Two types of adaptive immunity:

Type	Cells Involved	Target	Mechanism
Cell-mediated immunity	T lymphocytes (T cells)	Body's own cells that are infected, cancerous, or transplanted	Cytotoxic T cells directly destroy abnormal cells; T helper cells coordinate the immune response
Humoral immunity	B lymphocytes (B cells)	Extracellular pathogens (bacteria, viruses outside cells, toxins)	B cells differentiate into plasma cells that secrete antibodies specific to the pathogen's antigens

Antigens

An antigen is any molecule that can trigger an immune response. Most antigens are proteins or glycoproteins on the surface of pathogens.

• Self-antigens: Molecules on the surface of the body's own cells that are recognised as "self." These do NOT normally trigger an immune response.
• Non-self antigens: Molecules on the surface of pathogens or foreign cells that are recognised as "non-self." These DO trigger an immune response.
• Allergens: Harmless antigens (e.g., pollen, dust mite faeces, peanut proteins) that trigger an exaggerated immune response in sensitised individuals.

T Lymphocytes (T Cells)

T cells originate in the bone marrow but mature in the thymus gland.

T Cell Type	Function	Surface Marker
T helper cells ($\mathrm{CD4}^+$)	Release cytokines that stimulate B cells to differentiate into plasma cells and memory cells; activate cytotoxic T cells and macrophages	CD4
Cytotoxic T cells ($\mathrm{CD8}^+$)	Directly destroy virus-infected cells and cancer cells by inducing apoptosis (programmed cell death); recognise antigens presented on MHC class I	CD8
Memory T cells	Long-lived; provide rapid secondary response upon re-exposure to the same antigen	--
Regulatory T cells (Tregs)	Suppress immune responses; prevent autoimmune reactions; maintain tolerance to self-antigens	CD4, CD25

T cell activation:

1. Antigen presentation: Antigen-presenting cells (macrophages, dendritic cells, B cells) engulf pathogens, process their antigens, and display the antigens on their cell surface using MHC class II molecules
2. Recognition: A T helper cell with the specific receptor for that antigen binds to the antigen-MHC complex
3. Co-stimulation: A second signal (from co-stimulatory molecules on the APC) is required to fully activate the T helper cell
4. Clonal expansion: The activated T helper cell divides by mitosis, producing many identical copies (clones) with the same antigen-specific receptor
5. Effector function: The cloned T helper cells release cytokines that activate B cells and cytotoxic T cells

Cytotoxic T cell action against virus-infected cells:

1. Virus-infected cells display viral antigens on their surface using MHC class I molecules
2. A cytotoxic T cell with the matching receptor binds to the antigen-MHC I complex
3. The cytotoxic T cell releases perforin, which forms pores in the target cell membrane
4. Granzymes (enzymes) enter through the pores and activate caspases, which trigger apoptosis (programmed cell death)
5. The virus inside the cell is destroyed along with the cell

B Lymphocytes (B Cells)

B cells originate and mature in the bone marrow.

B cell activation and antibody production:

1. Antigen recognition: A B cell with the specific surface receptor (membrane-bound antibody) binds to a free antigen
2. Antigen internalisation: The B cell internalises the antigen and displays it on its surface using MHC class II
3. T helper cell interaction: An activated T helper cell with the matching receptor binds to the B cell's antigen-MHC complex and releases cytokines
4. Clonal expansion: The B cell divides by mitosis, producing many identical clones
5. Differentiation: Most clones differentiate into plasma cells (short-lived, secrete large quantities of antibodies); some differentiate into memory B cells (long-lived, provide immunological memory)

Antibodies (Immunoglobulins)

Structure of an antibody:

An antibody is a Y-shaped protein (immunoglobulin) composed of:

• Two identical heavy chains (longer polypeptide chains)
• Two identical light chains (shorter polypeptide chains)
• Variable regions (at the tips of the Y): unique to each antibody type; determine which antigen the antibody can bind to (complementary shape)
• Constant regions (stem and base of the Y): the same for all antibodies of the same class; determine the antibody's effector function
• Hinge region: allows flexibility, enabling the antibody to bind to antigens at different distances

How antibodies work:

Mechanism	Description
Neutralisation	Antibodies bind to the surface antigens of pathogens or toxins, blocking their ability to bind to host cells or enter tissues
Agglutination	Antibodies bind to multiple pathogens, clumping them together. This prevents them from spreading and makes it easier for phagocytes to engulf multiple pathogens at once
Opsonisation	Antibodies coat the surface of pathogens, marking them for phagocytosis. Phagocytes have receptors for the constant region of antibodies
Complement activation	Antibodies bound to pathogens trigger the complement system -- a cascade of proteins that: (a) form membrane attack complexes (MAC) that lyse pathogens, (b) enhance inflammation, (c) promote opsonisation
Precipitation	Antibodies bind to soluble antigens (toxins), forming insoluble complexes that precipitate out of solution and are cleared by phagocytes

Primary and Secondary Immune Responses

Feature	Primary Response	Secondary Response
Trigger	First exposure to an antigen	Subsequent exposure to the SAME antigen
Speed	Slow: 5-10 days before antibody production peaks	Fast: 1-3 days before antibody production peaks
Antibody level	Lower peak	Much higher peak (10-100 times primary)
Antibody class	Mainly IgM initially, then IgG	Mainly IgG (rapid, large-scale production)
Duration	Short-lived (weeks)	Long-lived (months to years)
Cells involved	Naive B cells and T cells	Memory B cells and memory T cells
Result	Symptoms of disease may develop before immunity is established	Usually no symptoms; pathogen destroyed rapidly

Immunological memory: After the primary response, memory B cells and memory T cells persist in the body for years or even a lifetime. Upon re-exposure to the same antigen, memory cells rapidly divide and differentiate into effector cells, producing a faster, stronger, and longer-lasting secondary response.

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Vaccination

Principles of Vaccination

Vaccination exploits the immune system's ability to develop immunological memory. By exposing the body to a harmless form of a pathogen (or its antigens), vaccination stimulates a primary immune response, producing memory cells without causing the disease.

Types of vaccine:

Vaccine Type	Description	Examples
Live attenuated	Weakened (attenuated) form of the pathogen; can replicate but does not cause disease in healthy individuals	MMR (measles, mumps, rubella); BCG (tuberculosis)
Inactivated (killed)	Dead pathogen; cannot replicate; generally requires booster doses	Influenza; polio (Salk vaccine); rabies
Toxoid	Inactivated toxin; stimulates antibody production against the toxin	Tetanus; diphtheria
Subunit (recombinant)	Specific antigenic proteins from the pathogen	HPV vaccine; Hepatitis B; COVID-19 (subunit)
mRNA	Messenger RNA that instructs cells to produce the pathogen's antigen	COVID-19 (Pfizer-BioNTech, Moderna)
Viral vector	Harmless virus engineered to carry genes for the pathogen's antigen	COVID-19 (Oxford-AstraZeneca, Janssen)

Herd Immunity

If a large proportion of a population is immune to a disease (through vaccination or previous infection), the spread of the pathogen is significantly reduced because there are fewer susceptible hosts. This provides indirect protection to individuals who are not immune (e.g., newborns, immunocompromised individuals).

Herd immunity threshold:

$\text{Threshold} = \left(1 - \frac{1}{R_0}\right) \times 100\%$

Where $R_0$ is the basic reproduction number (average number of secondary infections produced by one infected individual in a fully susceptible population).

Disease	$R_0$	Herd Immunity Threshold
Measles	12-18	92-94%
Polio	5-7	80-86%
COVID-19 (Omicron)	8-12	87-92%
Seasonal flu	1.5-3	33-67%

Advantages and Risks of Vaccination

Advantages	Risks and Limitations
Provides individual immunity	Rare adverse reactions (allergic reactions, fever)
Protects vulnerable individuals (herd immunity)	Some vaccines require multiple doses (boosters)
Eliminates or eradicates diseases	Not 100% effective in all individuals
Cost-effective compared to treating disease	Vaccine hesitancy and misinformation can reduce uptake
Reduces antibiotic resistance	Antigenic variation (mutations) in pathogens may require updated vaccines (e.g., annual flu vaccine)

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Immune System Disorders

Autoimmune Diseases

In autoimmune diseases, the immune system mistakenly attacks the body's own tissues (self-antigens), failing to distinguish between self and non-self.

Disease	Target Tissue/Cells	Symptoms
Type 1 diabetes	$\beta$ cells of the islets of Langerhans	Destruction of $\beta$ cells; no insulin production; hyperglycaemia
Rheumatoid arthritis	Synovial membranes of joints	Joint inflammation, pain, swelling, cartilage destruction, deformity
Multiple sclerosis (MS)	Myelin sheath of neurons in the CNS	Demyelination; impaired nerve conduction; muscle weakness, vision problems
Lupus (SLE)	Connective tissue, skin, kidneys, joints	Butterfly rash, joint pain, kidney damage, fatigue
Myasthenia gravis	Acetylcholine receptors at neuromuscular junctions	Muscle weakness that worsens with activity; drooping eyelids, difficulty swallowing
Coeliac disease	Villi of the small intestine (triggered by gluten)	Damage to intestinal villi; malabsorption; diarrhoea, weight loss

Possible causes of autoimmune disease:

• Genetic predisposition (certain HLA genes are associated with autoimmune conditions)
• Environmental triggers (infections, stress, hormones)
• Molecular mimicry: some pathogens have antigens similar to self-antigens; antibodies produced against the pathogen cross-react with the body's own tissues

Allergies (Hypersensitivity)

An allergy is an exaggerated immune response to a harmless antigen (allergen). The most common type is Type I hypersensitivity (IgE-mediated).

Mechanism of an allergic response:

1. Sensitisation (first exposure): The allergen enters the body for the first time. B cells produce IgE antibodies against the allergen. IgE binds to the surface of mast cells (in connective tissue) and basophils (in blood).
2. Re-exposure: Upon subsequent exposure, the allergen binds to the IgE antibodies on mast cells, cross-linking them.
3. Degranulation: The mast cells release histamine and other inflammatory mediators (degranulation).
4. Symptoms: Histamine causes vasodilation, increased capillary permeability (swelling), mucus production, and smooth muscle contraction (bronchoconstriction).

Allergic Condition	Symptoms
Hay fever (allergic rhinitis)	Sneezing, runny nose, itchy eyes, nasal congestion (pollen allergen)
Asthma	Wheezing, difficulty breathing, bronchoconstriction (dust mites, pollen, pet dander)
Anaphylaxis	Life-threatening: airway constriction, drop in blood pressure, swelling of tongue/throat
Eczema (atopic dermatitis)	Red, itchy, inflamed skin
Food allergy	Hives, swelling, gastrointestinal symptoms, anaphylaxis (peanuts, shellfish, eggs)

Treatment of allergies:

• Antihistamines: Block histamine receptors, reducing symptoms
• Adrenaline (epinephrine): Used for anaphylaxis -- constricts blood vessels, opens airways, increases heart rate
• Corticosteroids: Reduce inflammation
• Desensitisation (immunotherapy): Gradual exposure to increasing doses of the allergen to induce tolerance (shifts immune response from IgE to IgG)

HIV/AIDS

Human Immunodeficiency Virus (HIV):

Feature	Description
Pathogen type	Retrovirus (RNA virus) that carries reverse transcriptase
Target cells	T helper cells ($\mathrm{CD4}^+$ T cells) -- the cells that coordinate the immune response
Transmission	Unprotected sexual contact; contaminated blood products; sharing needles; mother-to-child (during birth or breastfeeding)
Not transmitted by	Casual contact, hugging, sharing utensils, mosquito bites

HIV lifecycle:

1. HIV binds to CD4 receptors and co-receptors (CCR5 or CXCR4) on T helper cells
2. The viral envelope fuses with the host cell membrane
3. Viral RNA and reverse transcriptase enter the cell
4. Reverse transcriptase converts viral RNA into viral DNA
5. Viral DNA is integrated into the host cell's genome by integrase
6. The host cell uses its own machinery to transcribe and translate the viral genes, producing new viral proteins
7. New viral particles are assembled and bud from the cell membrane, acquiring an envelope
8. The new viruses infect other T helper cells

Stages of HIV infection:

Stage	Description
Acute infection	2-4 weeks after exposure; flu-like symptoms; high viral load; T helper cell count drops briefly then partially recovers
Clinical latency	May last 8-10 years; no symptoms; virus replicates slowly; T helper cell count gradually declines
AIDS	T helper cell count drops below 200 cells/mm$^3$; immune system severely compromised; opportunistic infections (infections that a healthy immune system would normally control) develop

Opportunistic infections in AIDS:

• Pneumocystis jirovecii pneumonia (fungal lung infection)
• Mycobacterium tuberculosis (tuberculosis)
• Kaposi's sarcoma (cancer caused by human herpesvirus 8)
• Candidiasis (thrush)
• Cytomegalovirus (CMV) infections

Treatment and prevention:

• Antiretroviral therapy (ART): Combination of drugs targeting different stages of the HIV lifecycle: reverse transcriptase inhibitors, protease inhibitors, integrase inhibitors, fusion inhibitors. ART does not cure HIV but can reduce viral load to undetectable levels, preventing AIDS and transmission.
• Prevention: Safe sex (condoms); needle exchange programmes; pre-exposure prophylaxis (PrEP); screening of blood products; avoiding sharing needles; mother-to-child transmission prevention (ART during pregnancy and delivery)

Monoclonal Antibodies

Monoclonal antibodies are identical antibodies produced by a single clone of B cells (plasma cells). They are all specific to the same antigen.

Production (using hybridoma technology):

1. A mouse is injected with the target antigen, stimulating B cells to produce antibodies
2. B cells are extracted from the mouse's spleen
3. B cells are fused with myeloma cells (cancerous B cells that divide indefinitely) using polyethylene glycol
4. The resulting hybridoma cells have the antibody-producing ability of B cells and the immortality of cancer cells
5. Hybridoma cells are cultured; each clone produces one specific antibody
6. The desired clone is selected and grown in large-scale culture
7. Antibodies are extracted and purified

Applications:

Application	Description
Medical diagnosis	Pregnancy tests (detect hCG); detection of specific pathogens or disease markers in blood samples
Cancer treatment	Monoclonal antibodies designed to bind to specific cancer cell antigens, marking them for destruction by the immune system
Autoimmune disease	Infliximab (binds to and neutralises TNF-alpha, reducing inflammation in rheumatoid arthritis and Crohn's disease)
COVID-19 treatment	Monoclonal antibody cocktails that bind to the SARS-CoV-2 spike protein, neutralising the virus

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ELISA and Diagnostic Immunology

Enzyme-Linked Immunosorbent Assay (ELISA)

ELISA is a widely used biochemical technique that uses antibodies and colour change to detect and quantify specific antigens (or antibodies) in a sample.

Direct ELISA (detecting antigen):

1. The specific antibody is attached to the bottom of a well in a microtitre plate
2. The patient's sample (potentially containing the target antigen) is added to the well
3. If the antigen is present, it binds to the antibody on the plate
4. The well is washed to remove unbound material
5. A second antibody, linked to an enzyme, is added. This antibody binds to a different epitope on the antigen (forming a "sandwich")
6. The well is washed again
7. A substrate is added that the enzyme converts to a coloured product
8. The intensity of the colour is measured with a spectrophotometer and is proportional to the amount of antigen in the sample

Indirect ELISA (detecting antibodies -- used in HIV testing):

1. The specific antigen is attached to the bottom of a well
2. The patient's blood serum (potentially containing antibodies against the antigen) is added
3. If the target antibody is present, it binds to the antigen
4. The well is washed to remove unbound antibodies
5. A secondary antibody (anti-human immunoglobulin) linked to an enzyme is added; it binds to the patient's antibody
6. The well is washed again
7. Substrate is added; enzyme converts it to a coloured product
8. Colour intensity indicates the amount of antibody in the sample

Applications of ELISA

Application	Target	Description
Disease diagnosis	HIV antibodies; hepatitis B surface antigen; SARS-CoV-2 antibodies	Detects exposure to specific pathogens
Pregnancy testing	hCG (human chorionic gonadotropin)	Detects the hormone produced during early pregnancy in urine or blood
Allergy testing	IgE antibodies specific to allergens	Measures the level of allergen-specific IgE in blood
Drug testing	Specific drug molecules	Detects drugs or their metabolites in blood or urine
Food safety	Food allergens, pathogens	Detects traces of allergens (peanut protein) or bacteria (Salmonella, E. coli) in food samples
Environmental monitoring	Toxins, pollutants	Measures levels of environmental contaminants in water or soil samples

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Types of Immunity

Classification of Immunity

Category	Type	Description	Example
Active	Natural	The body produces its own antibodies after natural exposure to a pathogen	Recovering from chickenpox provides immunity to future infection
Active	Artificial	The body produces its own antibodies after vaccination	MMR vaccine provides immunity to measles, mumps, and rubella
Passive	Natural	Pre-formed antibodies are transferred from mother to baby across the placenta (IgG) or in breast milk (IgA/sIgA)	Newborn immunity to diseases the mother has had
Passive	Artificial	Pre-formed antibodies are injected into the body (from an immune animal or human donor)	Antivenom for snake bite; rabies immunoglobulin; tetanus antitoxin

Feature	Active Immunity	Passive Immunity
Antibody source	Body's own plasma cells	Pre-formed antibodies from another source
Memory cells	Produced (long-lasting protection)	NOT produced (short-lived protection)
Onset	Slow (days to weeks)	Immediate (instant protection)
Duration	Long-lasting (years to lifetime)	Short-lived (weeks to months)
Boosters	Booster doses extend immunity	Cannot be boosted (no memory cells)

warning

A common DSE question asks students to distinguish between active and passive immunity and between natural and artificial immunity. Remember: "active" means the body MAKES its own antibodies; "passive" means the body RECEIVES pre-made antibodies. "Natural" means the exposure occurred naturally (infection or maternal transfer); "artificial" means the exposure was deliberate (vaccination or antibody injection).

1. Confusing antigens and antibodies: Antigens are molecules on the surface of pathogens (or other foreign substances) that trigger an immune response. Antibodies are proteins produced by plasma cells that bind to specific antigens. Antigens are the "target"; antibodies are the "weapon."

2. Writing that phagocytes are specific: Phagocytosis is a NON-SPECIFIC (innate) response. Phagocytes engulf any foreign material, not just a specific pathogen. Specificity is the feature of adaptive immunity (B cells and T cells).

3. Confusing T cells and B cells: T cells mature in the THYMUS; B cells mature in the BONE MARROW. T cells are involved in cell-mediated immunity (directly killing infected cells); B cells are involved in humoral immunity (producing antibodies). T helper cells HELP B cells; they do not produce antibodies themselves.

4. Writing that antibodies directly kill pathogens: Antibodies do NOT kill pathogens directly. They work by neutralising, agglutinating, opsonising (marking for phagocytosis), activating complement, or precipitating. The actual killing is done by phagocytes, complement proteins, or cytotoxic T cells.

5. Confusing memory cells with plasma cells: Plasma cells are short-lived (days to weeks) and secrete large quantities of antibodies during the primary response. Memory cells are long-lived (years) and do NOT secrete antibodies until re-exposure triggers a secondary response.

6. Writing that antibiotics treat viral infections: Antibiotics target bacterial structures (cell wall, ribosomes) that viruses do not have. Antibiotics are ineffective against viruses. Antiviral drugs (e.g., reverse transcriptase inhibitors for HIV) are used to treat viral infections.

7. Confusing IgM and IgG: IgM is the FIRST antibody produced in the primary response; it is a large pentamer (5 antibody units) that is effective at agglutination. IgG is the MAIN antibody in the secondary response; it is smaller (monomer), crosses the placenta, and provides long-term immunity.

8. Writing that HIV directly kills the host: HIV does not directly cause death. It destroys T helper cells, which are essential for coordinating the immune response. Without T helper cells, the immune system collapses, and the person becomes susceptible to opportunistic infections that ultimately cause death.

9. Confusing the roles of perforin and antibodies: Perforin is released by CYTOTOXIC T CELLS and forms pores in the membrane of infected cells. Antibodies are produced by PLASMA CELLS and bind to free pathogens. They are different components of the immune response.

10. Writing that vaccination provides passive immunity: Vaccination provides ACTIVE artificial immunity (the person's own immune system produces antibodies and memory cells). Passive immunity involves receiving pre-formed antibodies from another source (e.g., maternal antibodies crossing the placenta, antivenom injections).

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Problem Set

Problem 1: Describe the stages of phagocytosis. Explain how the innate immune system and the adaptive immune system work together to eliminate a bacterial infection.

If you get this wrong, revise: Innate Immunity -- Phagocytosis; Adaptive Immunity -- T Cells and B Cells

Solution

Stages of phagocytosis:

1. Chemotaxis: Phagocytes are attracted to chemical signals (cytokines, bacterial products) released at the infection site.
2. Recognition: Phagocyte receptors bind to antigens on the bacterial surface (or to antibodies/complement coating the bacteria -- opsonisation).
3. Engulfment: Pseudopodia extend around the bacterium, enclosing it in a phagosome.
4. Digestion: The phagosome fuses with a lysosome to form a phagolysosome. Enzymes (lysozyme, proteases) break down the bacterium.
5. Exocytosis: Indigestible material is expelled from the cell.

Cooperation between innate and adaptive immunity:

Macrophages (innate) phagocytose bacteria and become antigen-presenting cells. They display bacterial antigens on their surface using MHC class II molecules. A T helper cell (adaptive) with the matching receptor recognises the antigen-MHC complex and is activated. The activated T helper cell releases cytokines that stimulate B cells to produce antibodies specific to the bacteria. These antibodies (adaptive) then opsonise more bacteria, making them easier for phagocytes (innate) to engulf. This cooperation enhances the overall effectiveness of the immune response.

Problem 2: Explain the difference between the primary and secondary immune responses. Why does the secondary response provide better protection against disease?

If you get this wrong, revise: Adaptive Immunity -- Primary and Secondary Immune Responses

Solution

The primary response occurs on first exposure to an antigen. It is slow (5-10 days to peak antibody production), produces a lower peak of antibodies (mainly IgM initially), and the person may experience symptoms of disease before immunity is established. Clonal expansion of naive B and T cells takes time.

The secondary response occurs on subsequent exposure to the SAME antigen. It is fast (1-3 days to peak), produces a much higher peak of antibodies (mainly IgG, 10-100 times more than primary), and provides rapid protection before symptoms develop. This is because memory B cells and memory T cells produced during the primary response persist in the body. Upon re-exposure, memory cells rapidly divide and differentiate into effector cells (plasma cells and cytotoxic T cells) without needing to go through the slow initial activation process. The pathogen is destroyed before it can multiply enough to cause disease.

Problem 3: A person is bitten by a snake and requires antivenom. Explain why the antivenom provides only temporary protection and does not provide long-term immunity. Contrast this with the protection provided by a tetanus vaccine.

If you get this wrong, revise: Antibodies -- Types of Immunity; Vaccination

Solution

Antivenom contains pre-formed antibodies against the snake venom. This is passive artificial immunity -- the person receives antibodies produced by another organism (typically a horse or sheep that has been injected with snake venom). These antibodies circulate in the blood, neutralising the venom. However, the antibodies are NOT produced by the person's own immune system, so no memory B cells are generated. The antibodies are gradually broken down by the body (within weeks), and the person is not protected against future snake bites. If bitten again, they would need another dose of antivenom.

In contrast, a tetanus vaccine contains a toxoid (inactivated tetanus toxin). This stimulates the person's own immune system to produce a primary response, generating memory B cells and memory T cells. If the person is later exposed to tetanus toxin (from a wound contaminated with Clostridium tetani), memory cells mount a rapid secondary response, producing large quantities of antibodies that neutralise the toxin before it causes symptoms. This is active artificial immunity and provides long-lasting protection (booster doses every 10 years).

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HIV/AIDS in Detail

Structure and Lifecycle of HIV

Human Immunodeficiency Virus (HIV) is a retrovirus -- an RNA virus that carries reverse transcriptase, enabling it to convert its RNA genome into DNA, which integrates into the host cell's chromosomes.

Feature	Description
Pathogen type	Retrovirus (RNA virus with reverse transcriptase)
Target cells	T helper cells ($\mathrm{CD4}^+$ T cells), macrophages, dendritic cells
Genetic material	Two copies of single-stranded RNA; nine genes (gag, pol, env, tat, rev, nef, vif, vpr, vpu)
Viral envelope	Stolen from host cell membrane during budding; contains viral glycoproteins gp120 (binds CD4 receptor) and gp41 (mediates fusion)
Transmission	Unprotected sexual contact; contaminated blood products; sharing needles; mother-to-child (during birth or breastfeeding)
Not transmitted by	Casual contact, hugging, sharing utensils, mosquito bites, swimming pools

HIV lifecycle:

1. Attachment: gp120 on the viral envelope binds to CD4 receptors and a co-receptor (CCR5 or CXCR4) on the target cell surface
2. Fusion: gp41 mediates fusion of the viral envelope with the host cell membrane, and the viral capsid enters the cell
3. Reverse transcription: Reverse transcriptase converts the viral RNA genome into double-stranded viral DNA
4. Integration: Viral integrase inserts the viral DNA into the host cell's chromosomes at a random location (provirus)
5. Latency: The proviral DNA may remain dormant (latent) for years, producing no new viral particles. During latency, the person is HIV-positive but may show no symptoms
6. Activation: When the T cell is activated, transcription of the proviral DNA begins, producing viral mRNA and genomic RNA
7. Translation: Host ribosomes translate viral mRNA into viral proteins (gag, pol, env)
8. Assembly: New viral particles assemble at the cell membrane
9. Budding: New viruses bud from the host cell membrane, acquiring an envelope, and go on to infect other cells

Stages of HIV Infection

Stage	Description	CD4 count (/mm$^3$)
Acute infection	Flu-like symptoms 2-4 weeks after exposure; high viral load; CD4 count drops briefly then partially recovers	500-1000 (may drop below 200)
Clinical latency	May last 8-10 years; no symptoms; virus replicates slowly; CD4 gradually declines	200-500
AIDS	CD4 falls below 200; immune system severely compromised; opportunistic infections develop	Below 200

Opportunistic infections in AIDS:

Infection	Pathogen Type	Description
Pneumocystis jirovecii pneumonia	Fungus	Fatal without treatment; causes coughing, fever, shortness of breath
Tuberculosis	Mycobacterium tuberculosis	Reactivation of latent TB is common in HIV/AIDS patients
Kaposi's sarcoma	Human herpesvirus 8 (HHV-8)	Cancer of blood vessel cells; causes purple skin lesions
Candidiasis (thrush)	Candida albicans	Fungal infection of mouth, oesophagus, vagina
Cytomegalovirus (CMV)	Cytomegalovirus (HHV-5)	Can cause retinitis (blindness), colitis, pneumonia

Treatment and Prevention

Antiretroviral therapy (ART):

Drug class	Example	Mechanism
NRTIs	AZT, lamivudine (3TC)	Competitive inhibitors of reverse transcriptase; cause chain termination during DNA synthesis
NNRTIs	Efavirenz, nevirapine	Bind to and inhibit reverse transcriptase at an allosteric site
PIs	Ritonavir, indinavir	Inhibit HIV protease; prevent processing of viral polyproteins into functional proteins
Integrase inhibitors	Raltegravir	Block integrase; prevent integration of viral DNA into host chromosomes
Entry inhibitors	Maraviroc	Block CCR5 co-receptor; prevent HIV from entering T cells

ART does not cure HIV but can reduce viral load to undetectable levels, preventing AIDS and allowing near-normal life expectancy. Combination therapy (3 or more drugs from at least 2 classes) is standard practice to prevent resistance.

Prevention: Condoms; needle exchange programmes; pre-exposure prophylaxis (PrEP); screening blood products; avoiding sharing needles; mother-to-child transmission prevention with ART during pregnancy and delivery.

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Autoimmune Diseases

Mechanism of Autoimmunity

In autoimmune diseases, the immune system fails to distinguish between self-antigens and non-self antigens, attacking the body's own tissues.

Possible causes:

1. Molecular mimicry: Pathogens have antigens similar to self-antigens; antibodies produced against the pathogen cross-react with self-tissues
2. Genetic predisposition: Certain HLA genes are associated with autoimmune conditions
3. Environmental triggers: Infections, stress, hormones may trigger onset in genetically susceptible individuals
4. Epigenetic factors: Environmental exposures may alter gene expression in immune cells

Major Autoimmune Diseases

Disease	Target Tissue/Cells	Symptoms
Type 1 diabetes	$\beta$ cells of islets of Langerhans	Destruction of $\beta$ cells; no insulin production; hyperglycaemia
Rheumatoid arthritis	Synovial membranes of joints	Joint inflammation, pain, swelling, cartilage destruction, deformity
Multiple sclerosis (MS)	Myelin sheath of neurons in the CNS	Demyelination; impaired nerve conduction; muscle weakness, vision problems
Systemic lupus erythematosus (SLE)	Connective tissue, skin, kidneys, joints	Butterfly rash, joint pain, kidney damage, fatigue
Myasthenia gravis	Acetylcholine receptors at neuromuscular junctions	Muscle weakness that worsens with activity; drooping eyelids, difficulty swallowing
Coeliac disease	Villi of the small intestine (triggered by gluten)	Damage to intestinal villi; malabsorption; diarrhoea, weight loss
Hashimoto's thyroiditis	Thyroid gland	Hypothyroidism; weight gain, fatigue, cold intolerance, goitre

Treatment Approaches for Autoimmune Diseases

Approach	Description
Immunosuppressants	Drugs that suppress immune system activity (e.g., corticosteroids, methotrexate, cyclosporine)
Anti-inflammatory drugs	NSAIDs (e.g., ibuprofen) for pain and inflammation
Replacement therapy	Insulin for Type 1 diabetes; thyroxine for Hashimoto's thyroiditis
Monoclonal antibodies	Targeted antibodies that block specific immune pathways (e.g., anti-TNF-alpha for rheumatoid arthritis)
Plasmapheresis	Filtering blood to remove autoantibodies and immune complexes

tip

tip Ready to test your understanding of Immunology? Review the Cell Biology and Biochemistry diagnostic test which covers immune system topics within the DSE specification.

See Diagnostic Guide for instructions on self-marking and building a personal test matrix.

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Hypersensitivity (Allergic Reactions)

Mechanism of Type I Hypersensitivity

Type I hypersensitivity (immediate hypersensitivity) is the mechanism underlying allergic reactions:

1. Sensitisation: On first exposure to an allergen (e.g., pollen, dust mite faeces, peanut protein), the allergen is taken up by antigen-presenting cells (APCs) and presented to T helper cells
2. Th2 response: T helper cells differentiate into Th2 cells, which release cytokines (IL-4, IL-5, IL-13) that stimulate B cells to produce IgE antibodies specific to the allergen
3. IgE binding: The IgE antibodies bind to Fc receptors on the surface of mast cells (in connective tissue) and basophils (in blood). The person is now "sensitised" -- no symptoms occur on this first exposure
4. Re-exposure: On subsequent exposure to the same allergen, the allergen cross-links the IgE antibodies on mast cells/basophils
5. Degranulation: Cross-linking triggers mast cells to degranulate -- releasing pre-formed mediators stored in granules:
   • Histamine: Causes vasodilation, increased capillary permeability (leading to swelling, redness, heat), mucus secretion, smooth muscle contraction (bronchoconstriction in the airways), itching
   • Heparin: Prevents blood clotting at the site of inflammation
   • Serotonin (5-HT): Contributes to inflammation and smooth muscle contraction
6. Late-phase response: Hours later, newly synthesised mediators are released (leukotrienes, prostaglandins, cytokines), causing sustained inflammation

Allergic Symptoms and Treatments

Symptom	Cause	Treatment
Hay fever (allergic rhinitis)	Histamine causes vasodilation and mucus secretion in nasal passages	Antihistamines; corticosteroid nasal sprays
Asthma	Histamine and leukotrienes cause bronchoconstriction and mucus secretion in airways	Bronchodilators (salbutamol); inhaled corticosteroids; leukotriene receptor antagonists
Eczema (atopic dermatitis)	Inflammatory response in the skin; dry, itchy, red patches	Moisturisers; topical corticosteroids; antihistamines
Anaphylaxis	Systemic release of histamine; massive vasodilation causing drop in blood pressure; airway constriction; swelling of throat	Adrenaline (epinephrine) auto-injector (EpiPen); call emergency services

Antihistamines

• Competitive antagonists of histamine at H1 receptors
• They bind to H1 receptors on target cells (blood vessels, smooth muscle, nerve endings) without activating them
• This prevents histamine from binding and exerting its effects
• First-generation antihistamines (e.g., diphenhydramine): cross the blood-brain barrier, cause drowsiness
• Second-generation antihistamines (e.g., cetirizine, loratadine): do not readily cross the blood-brain barrier, minimal sedation

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Blood Groups and Transfusion

ABO Blood Group System

Blood Group	Antigens on RBC Surface	Antibodies in Plasma	Can Donate To	Can Receive From
A	A	Anti-B	A, AB	A, O
B	B	Anti-A	B, AB	B, O
AB	A and B	Neither	AB	A, B, AB, O (universal recipient)
O	Neither	Anti-A and Anti-B	A, B, AB, O (universal donor)	O

Agglutination: If incompatible blood is transfused, antibodies in the recipient's plasma bind to antigens on the donor's red blood cells, causing them to clump (agglutinate). This blocks blood vessels and triggers complement-mediated lysis of the RBCs, which can be fatal.

Rhesus (Rh) Factor

• The RhD antigen is another antigen on the surface of red blood cells
• Individuals who have the RhD antigen are Rh-positive (Rh+); those who do not are Rh-negative (Rh-)
• Rh-negative individuals can produce anti-Rh antibodies if exposed to Rh-positive blood (e.g., during pregnancy or transfusion)

Haemolytic disease of the newborn (HDN):

1. An Rh-negative mother carries an Rh-positive foetus (inherited from the father)
2. During the first pregnancy, foetal Rh-positive red blood cells may cross into the maternal circulation (usually during delivery)
3. The mother's immune system produces anti-Rh antibodies
4. In a subsequent pregnancy with another Rh-positive foetus, maternal anti-Rh antibodies (IgG) can cross the placenta
5. These antibodies bind to foetal Rh-positive RBCs, causing agglutination and complement-mediated lysis (haemolysis)
6. This leads to haemolytic disease of the newborn (erythroblastosis fetalis): anaemia, jaundice, brain damage, or death of the foetus
7. Prevention: Administration of anti-RhD immunoglobulin (RhoGAM) to the Rh-negative mother within 72 hours of delivery. This antibody binds to and destroys any foetal Rh-positive RBCs in the maternal circulation before the mother's immune system can produce its own antibodies

Tissue Transplantation

For a tissue or organ transplant to be successful, the donor and recipient must be as genetically similar as possible to minimise immune rejection.

Type of Match	Description	Rejection Risk
Autograft	Tissue transplanted from one part of a person's body to another	None
Isograft	Tissue transplanted between genetically identical individuals (identical twins)	None
Allograft	Tissue transplanted between genetically non-identical individuals of the same species	High
Xenograft	Tissue transplanted from a different species	Very high

Types of rejection:

Type	Timing	Mechanism
Hyperacute rejection	Minutes to hours	Pre-existing antibodies in the recipient immediately attack the donor tissue; caused by ABO or HLA incompatibility
Acute rejection	Days to weeks	T cells recognise foreign HLA antigens on donor cells and mount a cell-mediated immune response
Chronic rejection	Months to years	Gradual T cell and antibody-mediated damage; fibrosis and scarring of the transplanted tissue

Immunosuppressive drugs (e.g., ciclosporin, tacrolimus, corticosteroids) are given to transplant recipients to suppress the immune response and prevent rejection. However, these drugs also increase susceptibility to infections.

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Lymphatic System

Structure and Function

The lymphatic system is a network of vessels, tissues, and organs that:

1. Returns excess interstitial fluid to the blood (prevents tissue swelling/oedema)
2. Transports dietary lipids from the small intestine to the blood (via lacteals in villi)
3. Provides a pathway for immune cells (lymphocytes, macrophages) to travel throughout the body
4. Filters lymph at lymph nodes, trapping pathogens, dead cells, and cellular debris

Lymphatic Vessels

Feature	Description
Structure	Thin-walled vessels with valves (similar to veins); carry lymph (a clear fluid similar to blood plasma but without RBCs and platelets)
Flow direction	One-way: from tissues towards the heart; lymph drains into the subclavian veins via the thoracic duct (left) and right lymphatic duct
Pumping mechanism	Lymph is moved by contraction of surrounding skeletal muscles, breathing movements, and valves that prevent backflow
Capillaries	Lymphatic capillaries are blind-ended and more permeable than blood capillaries; they allow larger molecules (proteins, cell debris) to enter

Lymph Nodes

• Small, bean-shaped structures distributed along lymphatic vessels
• Filter lymph as it passes through
• Contain lymphocytes (B cells and T cells) and macrophages
• During an infection, lymph nodes become swollen and tender (e.g., swollen glands in the neck during a throat infection)
• Major lymph node groups: cervical (neck), axillary (armpits), inguinal (groin), mesenteric (abdomen)

Other Lymphatic Organs

Organ	Location	Function
Spleen	Upper left abdomen	Filters blood; removes old/damaged RBCs; stores platelets; contains lymphocytes; responds to blood-borne pathogens
Thymus	Upper chest (behind sternum)	Site of T cell maturation; T cells migrate from bone marrow to thymus where they undergo selection (positive and negative); atrophies after puberty
Tonsils	Throat (pharynx)	Trap pathogens entering through the mouth and nose; contain lymphocytes; often removed if chronically infected
Peyer's patches	Small intestine	Aggregates of lymphoid tissue in the intestinal wall; monitor intestinal bacteria and pathogens; part of GALT (gut-associated lymphoid tissue)

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Vaccination in Detail

Types of Vaccines

Vaccine Type	Description	Examples	Advantages	Disadvantages
Live attenuated	Weakened form of the pathogen; can replicate but cannot cause disease in healthy individuals	MMR (measles, mumps, rubella); BCG (tuberculosis); oral polio	Strong immune response; often lifelong immunity with 1-2 doses	Cannot be given to immunocompromised individuals; risk of reversion to virulence
Inactivated (killed)	Pathogen is killed by heat or chemicals; cannot replicate	Influenza (injectable); hepatitis A; cholera	Safer than live vaccines; no risk of reversion	Weaker immune response; requires booster doses; often requires adjuvant
Toxoid	Inactivated toxin produced by the pathogen; immune response targets the toxin, not the pathogen	Tetanus; diphtheria	Effective against toxin-mediated diseases	Requires booster doses (every 10 years for tetanus)
Subunit (recombinant)	Purified antigenic components of the pathogen (specific proteins)	Hepatitis B; HPV; acellular pertussis	Very safe; well-defined composition	Weaker immune response; more expensive to produce
Conjugate	Polysaccharide antigens linked to a carrier protein; improves immune response in young children	Hib (Haemophilus influenzae type b); pneumococcal; meningococcal	Effective in infants and young children	More complex to manufacture
mRNA	Synthetic mRNA encoding a pathogen antigen; host cells translate the mRNA to produce the antigen, triggering an immune response	COVID-19 (Pfizer, Moderna)	Rapid development; strong immune response; no live pathogen used	Requires cold storage; relatively new technology
Viral vector	Harmless virus engineered to carry genes encoding a pathogen antigen; the vector delivers the gene to host cells, which produce the antigen	COVID-19 (AstraZeneca, Janssen); Ebola	Strong immune response; no live pathogen	Pre-existing immunity to the vector may reduce effectiveness

Herd Immunity

• When a sufficiently high proportion of a population is immune to a disease (through vaccination or previous infection), the spread of the disease is significantly reduced, providing indirect protection to those who are not immune
• The herd immunity threshold depends on the basic reproduction number ($R_0$) of the disease:

$\text{Herd immunity threshold} = 1 - \frac{1}{R_0}$

Disease	$R_0$	Herd Immunity Threshold
Measles	12-18	92-94%
Polio	5-7	80-86%
COVID-19 (Omicron)	8-10	87-90%
Influenza	1.5-3	33-67%
Diphtheria	4-6	75-83%

Common Pitfalls

• IgE is involved in allergic reactions, NOT IgG or IgM. IgE binds to mast cells and basophils; cross-linking triggers degranulation
• Histamine causes vasodilation and increased permeability, NOT vasoconstriction. The result is swelling, redness, and heat
• Rh-negative mothers are given anti-RhD immunoglobulin AFTER delivery, not before. This prevents sensitisation to Rh-positive foetal RBCs that entered maternal circulation during delivery
• Universal donor = O negative (not just O). The donor must be negative for both ABO and Rh antigens
• Vaccines contain antigens, NOT antibodies. Vaccines stimulate the body to produce its own antibodies and memory cells

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Comparison of Immune Responses

Innate vs Adaptive Immunity

Feature	Innate Immunity	Adaptive (Acquired) Immunity
Speed of response	Immediate (minutes to hours)	Slower (days to weeks); requires clonal selection and expansion
Specificity	Non-specific; responds to a broad range of pathogens in the same way	Highly specific; produces antibodies and T cells targeted to specific antigens
Memory	No immunological memory; responds identically on each exposure	Immunological memory; second exposure produces a faster, stronger response
Components	Physical barriers (skin, mucous membranes); phagocytes (neutrophils, macrophages); complement system; natural killer cells; inflammation	B lymphocytes (antibodies); T lymphocytes (helper T cells, cytotoxic T cells, memory cells)
Types of molecules involved	Pattern recognition receptors (PRRs) that recognise pathogen-associated molecular patterns (PAMPs) -- broad molecular patterns shared by many pathogens	B cell receptors (BCRs) and T cell receptors (TCRs) that recognise specific antigen epitopes -- unique molecular shapes
Effectiveness	Effective against a wide range of pathogens but can be overwhelmed; does not improve with repeated exposure	Highly effective; improves with each exposure (affinity maturation, memory cells)

Primary vs Secondary Immune Response

Feature	Primary Response	Secondary Response
Trigger	First exposure to a specific antigen	Subsequent exposure to the SAME antigen
Lag phase	Longer (5-10 days); time needed for clonal selection, expansion, and differentiation of B and T cells	Shorter (1-3 days); memory cells already exist and respond quickly
Antibody concentration	Lower peak; IgM produced first, then IgG	Higher peak; mainly IgG (due to class switching); peak antibody level is much higher (10-100x primary response)
Antibody affinity	Lower affinity (antibodies bind less tightly to the antigen)	Higher affinity (antibodies bind more tightly; affinity maturation has occurred during primary response via somatic hypermutation)
Duration	Shorter; antibody levels decline relatively quickly after the peak	Longer; antibody levels remain elevated for weeks to months
Memory cells	Memory B and T cells are produced during the primary response	Memory cells from the primary response are immediately activated; no need for clonal selection
Clinical significance	The person may experience symptoms of the disease while the immune system is mounting its response	The person is usually protected from the disease; may have mild or no symptoms (immunity)

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Infectious Diseases

Malaria

Feature	Description
Pathogen	Plasmodium falciparum (most severe), P. vivax, P. ovale, P. malariae (protozoan parasite)
Vector	Female Anopheles mosquito (transmits the parasite when it takes a blood meal)
Lifecycle	(1) Infected mosquito injects Plasmodium sporozoites into the human bloodstream $\rightarrow$ (2) Sporozoites travel to the liver and infect liver cells $\rightarrow$ (3) They multiply in the liver (asexual reproduction), then burst out and infect red blood cells $\rightarrow$ (4) Inside RBCs, they multiply again (asexual), causing RBCs to burst (causing the characteristic fever cycles) $\rightarrow$ (5) Some parasites develop into gametocytes in the blood $\rightarrow$ (6) Another mosquito bites and ingests the gametocytes $\rightarrow$ (7) Sexual reproduction occurs in the mosquito $\rightarrow$ (8) New sporozoites develop and the cycle repeats
Symptoms	Recurring fever (every 48-72 hours, corresponding to RBC bursting cycles), chills, sweating, headache, nausea, anaemia, splenomegaly (enlarged spleen)
Prevention	Mosquito nets (insecticide-treated); antimalarial drugs (prophylaxis); mosquito control (draining breeding sites, insecticide spraying); vaccine (RTS,S -- partially effective)
Treatment	Artemisinin-based combination therapies (ACTs); quinine (for severe cases)
Global impact	~240 million cases per year; ~600,000 deaths per year (mostly children under 5 in sub-Saharan Africa)

Tuberculosis (TB)

Feature	Description
Pathogen	Mycobacterium tuberculosis (bacterium)
Transmission	Airborne droplets (coughing, sneezing); close and prolonged contact with an infected person
Primary infection	Bacteria are inhaled and engulfed by macrophages in the alveoli; the bacteria can survive and multiply INSIDE the macrophages (they resist destruction by inhibiting phagosome-lysosome fusion)
Latent TB	In most healthy individuals, the immune system walls off the infection in a granuloma (a collection of immune cells surrounding the bacteria); the person has no symptoms and is not infectious; the bacteria can remain dormant for years
Active TB	If the immune system weakens, the bacteria reactivate and multiply; symptoms include persistent cough (sometimes blood-tinged sputum), weight loss, night sweats, fever, fatigue
Treatment	Combination antibiotic therapy (isoniazid, rifampicin, pyrazinamide, ethambutol) for at least 6 months; drug resistance is a growing problem (MDR-TB, XDR-TB)
Prevention	BCG vaccine (provides partial protection, especially against severe TB in children); improved living conditions; infection control
DOTS programme	Directly Observed Treatment, Short-course -- WHO strategy to ensure patients complete their full course of treatment

Cholera

Feature	Description
Pathogen	Vibrio cholerae (bacterium; curved, rod-shaped, flagellated)
Transmission	Faecal-oral route; contaminated water and food (especially in areas with poor sanitation)
Mechanism	V. cholerae attaches to the intestinal wall and produces cholera toxin; the toxin causes chloride ion channels in the intestinal epithelial cells to remain open; chloride ions are secreted into the intestinal lumen; sodium ions and water follow by osmosis; massive volumes of watery diarrhoea result (up to 20 litres per day)
Symptoms	Profuse, painless, watery diarrhoea ("rice-water stools"); vomiting; rapid dehydration; electrolyte imbalance; can be fatal within hours if untreated
Treatment	Oral rehydration therapy (ORT): a solution of clean water, glucose, sodium chloride, and potassium chloride is given orally; the glucose facilitates the co-transport of sodium ions back into the epithelial cells (using SGLT1 transporters), and water follows by osmosis; antibiotics (tetracycline) reduce the duration and severity
Prevention	Clean water supply; proper sanitation; hand hygiene; vaccination (oral cholera vaccine)

HIV/AIDS (Extended Detail)

Feature	Description
Why HIV is hard to cure	(1) High mutation rate: reverse transcriptase has no proofreading function, so many mutations occur; this creates viral variants that can evade the immune system and develop drug resistance. (2) Latency: HIV integrates into the host genome as a provirus and can remain dormant for years, invisible to the immune system and unaffected by antiretroviral drugs that target active viral replication. (3) Reservoirs: HIV persists in reservoirs such as lymph nodes, the brain, and the gut-associated lymphoid tissue (GALT), where drugs may not reach effective concentrations. (4) Destruction of CD4+ T cells: HIV specifically targets and destroys the immune cells needed to fight it, progressively weakening the immune system
"Berlin Patient"	Timothy Ray Brown, the first person cured of HIV (2011). He received a bone marrow transplant from a donor with a CCR5-delta32 mutation (a natural genetic mutation that makes cells resistant to HIV because the CCR5 co-receptor is non-functional). This demonstrated that a cure is theoretically possible, but bone marrow transplantation is too risky and expensive for widespread use
"London Patient"	Adam Castillejo, the second person cured of HIV (2019). Similar approach: bone marrow transplant from a CCR5-delta32 donor for Hodgkin's lymphoma treatment

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Practical Techniques

Using Aseptic Technique to Investigate Antibiotic Effectiveness

1. Prepare a bacterial lawn on an agar plate (spread a known volume of bacterial culture evenly across the surface)
2. Using sterile forceps, place antibiotic discs (or discs soaked in different concentrations of an antibiotic) onto the agar surface
3. Incubate the plate at an appropriate temperature (e.g., 30 degrees C for environmental bacteria, 37 degrees C for human pathogens) for 24-48 hours
4. Measure the zone of inhibition (the clear area around each disc where bacteria have been killed or their growth has been inhibited)
5. A larger zone of inhibition indicates greater effectiveness of the antibiotic against that bacterium
6. Compare zones of inhibition between different antibiotics to determine which is most effective

Controls:

• Positive control: an antibiotic disc with a known effective antibiotic (confirms the bacteria are susceptible to some antibiotics)
• Negative control: a disc with no antibiotic (confirms that the bacteria can grow on the agar and that the clear zone is caused by the antibiotic, not by the disc itself)