- Microbial Antagonism

o Competition for nutrients and colonization sites.

o Production of bacteriocins (proteins produced by bacteria which is
toxic to other bacteria).
Microbiology
Second Line of Defense:
Host Defense Mechanisms 1) Transferrin: Glycoprotein synthesized in liver à high affinity for iron.
à The body protects itself from pathogens through three lines of defense: 2) Fever: Stimulating WBC & Reducing free plasma iron
§ Nonspecific: First & Second Line o Exogenous Pyrogens: Originating outside the body (endotoxins).
§ Specific: Third Line of Defense o Endogenous Pyrogen: Produced in the body (IL-1) LC activation.
3) Acute-Phase Proteins : resistance to infection & promote tissue repair
Non specific HDM o C-reactive protein (inflammation marker), Amyloid A protein,
§ Innate or inborn general defense mechanism 4) Cytokines: Chemical mediators that enable intercellular communication.
5) Interferons: Small, antiviral proteins produced by virus-infected cells
First Line of Defense: o Not virus-specific but Species-specific
o Activate NK cells to kill virus-infected cells.
Details
Skin § Intact, skin prevents pathogen penetrationà Physical barriers. Alpha (α): Produced by B cells, monocytes, & macrophages
§ Dryness acidity (<37°C) inhibits microbial growth. Beta (β): Produced by fibroblasts &virus-infected cells
§ Sebum contains fatty acids toxic to certain pathogens. Gamma (γ): Produced by T lymphocytes & NK cells
MM § Sticky mucus traps pathogens & contains substances like:
6) The Complement System
o Lysozyme: Degrades bacterial cell walls (G+ Mostly).
o Lactoferrin: Protein binds to iron, depriving pathogens. o C1 to C9 proteins in normal blood plasma.
o Complement cascade: classical, or lectin or alternative pathways.
RS § Cilia sweep pathogens upward for expulsion by coughing
§ Initiation and amplification of inflammation.
§ Lysozymes destroy & lyse bacteria. § Attraction of phagocytes to sites of infection (chemotaxis).
GIT § Digestive enzymes & stomach acidity kill pathogens. § Opsonization.
§ Small intestine is relatively free of bacteria because of stomach § MAC formationà cell lysis.
acid, bile, salts, and rapid content flow. § Mast cell degranulation & Activation of leukocytes .
UGT § Sterile in healthy persons except distal urethra normal flora.
§ Urine flow flushes pathogens. à Complement Fragments function:
§ Urination after sexual intercourse reduces infection risk. o C3b: opsonin, promoting phagocytosis.
§ Obstructed urine flow in BPH can lead to cystitis. o C3a, C4a, and C5a: Induce mast cell degranulation
§ Low vaginal pH (acidity) inhibits pathogen colonization. o C5a: Acts as a chemoattractant for neutrophils & macrophages.
o C3 (classical & alternative) & Properdin Deficiency (alternative)
7) Inflammation à Disorders Affecting Phagocytic Function:
à Sequence of events: injury à vasodilation à increased permeability à 1) Leukocyte Motility and Chemotaxis Disorders:
leukocyte migration à chemotaxis. o Chediak-Higashi Syndrome (CHS):
à Inflammatory Response Aims: § Decreased neutrophil chemotaxis.
o Localizing infections. § Abnormal lysosomes in PMNs fail to fuse with
o Preventing the spread of microbial invaders. phagosomes, reducing bactericidal activity.
o Neutralizing toxins at the injury site. § Symptoms: Albinism, CNS abnormalities, RBI
o Facilitating tissue repair. 2) Intracellular Killing Disorders:
à Signs: Redness (rubor), Heat (calor), Swelling (tumor) & Pain (dolor). o Chronic Granulomatous Disease (CGD):
§ Fatal Genetic disorder.
8) Phagocytes § Repeated catalase + bacterial infections.
§ PMNs can ingest bacteria but fail to kill it.
o Neutrophils (PMNs): Phagocytic granulocyte.
§ PMNs Lack of hydrogen peroxide & myeloperoxidase in.
§ More effective than eosinophils (phagocyte).
§ Play a major role in acute inflammation.
o Eosinophils: Involved in allergies and parasitic infections.
o Macrophages: Monocytes in blood → in tissue → macrophage. Specific Host Defense mechanism
§ Extremely efficient phagocyte à Functions of the Immune System
§ Liver (Kupffer cells), Lungs (Alveolar or dust cells)
§ Differentiates between "self" and "nonself" (foreign).
§ Brain (Microglia), Histocytes: (Fixed macrophages)
§ Destroys "nonself" entities & has memory cells.

à Arms of the Immune System

à Steps in Phagocytosis
1) Humoral Immunity:
Step Details o Involves antibody production by plasma cells.
Chemotaxis Phagocytes attracted to site of inf.à By chemotactic o Antibodies circulate in blood to protect against pathogens.
agents (chemoattractant) o Known as antibody-mediated immunity (AMI).
Attachment Phagocyte attaches to object, aided by opsonization:
particle is coated with antibodies or complement proteins. 2) Cell-Mediated Immunity (CMI):
Ingestion By Phagocyte pseudopodiaàEngulfing it into o Involves various cell types (macrophages, T helper cells,
phagosome cytotoxic T cells , NK cells).
Digestion Phagolysosome: Phagosome fuses with a lysosome. o Antibodies play a minor or no role.
Killing Mechanisms
Reactive Oxygen Species & Myeloperoxidase (HOCl) Types of immunity

à Pathogens That Evade Phagocytosis: 1) Natural/Innate Immunity:

o MTB : waxes in CW resist digestion within phagocytes. o Humans are naturally resistant to certain pathogens (inborn)
o Bacterial capsule: prevent phagocytosis (antiphagocytic) o Reasons include lack of appropriate cell surface receptors.
 2) Acquired Immunity: Antibodies (gamma globulin)
§ Glycoproteins produced by plasma cells in response to antigens.
Category Natural Artificial
§ Specificity:
Active § Infection § Vaccines o Bind only to antigenic determinant that stimulated their production.
Passive § In uterus trans § Antibody formation takes 2 weeks o Rarely, cross-react with similar determinants (not identical).
placental IgG § Person receives Abs in antisera or
gamma globulin to bridge this gap.
à Antibody Structure: Resembles the letter "Y."
à Specific Immune Globulin
§ In colostrum o Hyperimmune Serum Globulin o Two identical light & heavy polypeptide chains.
(IgA) o Ig for Hepatitis B ,Tetanus o Chains are connected by disulfide bonds.
o Rabies Ig o Fc region: Binds to cell receptor.
o Fab region most flexible part: bivalent: 2 antigen binding sites.

à Classes of Immunoglobulins:
Antigens o MW: IgM>IgA dimer>IgE>IgD>IgG.
o Valency: Number of fab region: Ags binding site
§ Immunogenic: Foreign organic substances large enough to stimulate
antibody production. § Monomer: Bivalent (2) : IgA , IgE, IgD & IgG.
§ Examples: Proteins (>10,000 Da)à the best, § Dimer: Secretory IgA = 4.
§ Pentamer: IgM = 10.
§ Antigenic Determinants (Epitopes): Molecules on a bacterial cell's
surface that stimulate antibody production. Class Features Functions
§ Hapten: small molecule coupled with carrier protein act as Ag (penicillin) IgA § Two forms: § Secretory IgA predominant in
o Non-secretory (monomer) secretions (saliva, tears,
§ APC ingest Ags & Display it on surface as Ag-MHC complex mucus , semen).
o Secretory IgA:
§ Dendritic cells: most professional. § Protects newborns via
§ Dimer by J chain.
§ Macrophages. colostrum (breastfeeding)
§ Has secretory part
§ B cells: least professional §
§ 10-20% of total Abs in serum.
IgD § <1% of total Abs in serum § Act as an antigen receptor
à Processing of Antigens § Found on B-cell surface. § Determine which Ags will
activate B cells.
T-dependent T-independent IgE § <1% of Abs in serum (lowest) § In basophils & mast cells.
Majority of antigens Minority of antigens § AKA: Prausnitz-Küstner
Depends on T helper cells Independent of T helper cells IgG § 70-85% Abs in serum (most) § Activates complement,
Need APC NO APC § Only Abs to cross placenta. § Promotes cytotoxicity,
§ Lowest MW but long lived. § High amount in 2nd R.
Ags type: proteins Ags : lipopolysaccharides
IgM § Pentamer (by J chain) § Antibody in primary response
§ 10% of total Abs in serum § Most efficient in complement
§ Largest MW but short lived. activation.
 Natural Killer (NK) Cells
à Primary and Secondary IR
§ Subpopulation of lymphocytes called granular lymphocytes.
o Primary Response:
§ Differ from T and B cells (innate immunity):
§ Initial immune response (10-14 days for antibody production). o They lack typical T- and B-cell surface markers.
§ Predominant Abs IgM. o They do not proliferate in response to antigens.
o Secondary Response (Anamnestic or Memory Response): o They are not involved in antigen-specific recognition.
§ Rapid production of antibodies upon subsequent exposure. § Antibody-dependent cellular cytotoxicity:
§ Memory Cells: T & B cells (rapid production of IgG ) o NK cell activity is not dependent on Abs but can enhanced by them.
o Have receptors for the Fc region of antibodies.
à Sites of immune response o Enabling them to attack and kill antibody-coated targets.
o Spleen: IR to antigens in the blood. o Release perforin & granzymes à kill cancer cells.
o Mucosa-associated lymphoid tissues (MALT):
§ Peyer patches: intestinal mucosa; activated by ingested Ags
transported by specialized epithelial cell :microfold (M) Cell-Mediated Immunity (CMI)
§ Control chronic infections caused by intracellular pathogens.
à Monoclonal Antibodies § AMI: Control infections caused by extracellular pathogens.
o Purified Abs directed against specific Ags are produced in lab. § Complex system of interactions B/ W: macrophages, DCs, Tₕ, Tc, NK
o Created using hybridomas: à Steps of a Cell-Mediated Cytotoxic Response: Video
§ Fusion of plasma cells producing a single type of antibody.
§ With myeloma cells (tumor cells).
Hypersensitivity Reactions

Type I Hypersensitivity Reactions

CELLS OF THE IMMUNE SYSTEM
§ AKA immediate or anaphylactic reactions.
§ Immune cells originate in bone marrow. § Allergic responses such as hay fever, asthma, hives, and food allergies.
§ Lymphoid stem cells in BM give rise to three lymphocyte types § Other examples : allergy to insect stings, drugs, and anaphylactic shock.
§ Histamine from mast cells & basophils, triggered by IgE antibodies.
T Cells § People prone to allergies (atopic individuals)
1) Helper T cells (T-helper, TH, CD4+ cells): Subcategories:
à Allergic Response
o TH1 cells: Secrete type 1 cytokines à CMI à (macrophages, o Initial exposure:
cytotoxic T cells, NK cells).
§ IgE (reagin) Abs are produced in response to the allergen.
o TH2 cells: Secrete type 2 cytokinesà AMI à B-cell activation & § Abs bind to the surface of basophils & mast cellsà convert
differentiation into plasma cells. them into sensitized cells
2) Cytotoxic T cells (Tc, CD8+): Destroy virally infected, & tumor cells. o Subsequent exposure:
3) Regulatory T cells (Treg): brake on the immune response. § Allergen binds to cell-bound IgE antibodies.
§ Sensitized cells undergo degranulation
à Localized vs. Systemic Anaphylaxis Type IV Hypersensitivity Reactions
1) Localized Reactions: § AKA: delayed-type hypersensitivity (DTH) or CM immune reactions.
§ Mast cell degranulation at the allergen site Common § Observed 24–48 hours or longer after exposure to an allergen.
§ Examples include hay fever, asthma, and hives. § Involves T cells, macrophages, dendritic cells, and NK cells.
2) Systemic Reactions: § Antibodies are not involved.
§ Widespread basophil degranulationà anaphylactic shock. à Examples:
§ Triggers are drugs (penicillin) and insect venom.
o Positive TB skin tests (Mantoux test)
§ Symptoms : flushing, itching, difficulty breathing, & LBP
o Contact dermatitis (reactions to poison ivy or latex)
§ Rx: epinephrine and antihistamines is crucial.
o Transplantation rejection.
à Immunotherapy à Interpretation of a Positive TB Skin Test:
o Small allergy shots for HS 1 treatment, which induce IgG production o Active TB
o Reduce sensitivity: IgG prevent allergens from binding to IgE. o Past TB infection with recovery.
à Latex Allergy o Previous exposure with no active disease.
o Current latent TB infection
o Irritant Contact Dermatitis: Non-allergic dry, itchy skin. o Previous (BCG) vaccination
o Allergic Contact Dermatitis: DTH by chemicals in latex (poision ivy)
o Latex Allergy: severe type I, IgE-mediated reaction, AUTOIMMUNE DISEASES
§ IS mistakenly attacks the body’s own tissues, perceiving them as foreign.
Type II Hypersensitivity Reactions à Classification:
§ AKA: cytotoxic reactions, involve the destruction of body cells. o Organ-specific:
§ Reactions involve IgG or IgM antibodies & activation of complement. §Thyroid: Hashimoto thyroiditis, Graves disease, primary
§ Examples: myxedema, thyrotoxicosis.
o Incompatible blood transfusions § Gastric mucosa: Pernicious anemia.
o Rh incompatibility reactions § Adrenal glands: Addison disease.
o Drug induced § Pancreas: Type 1 diabetes.
o Myasthenia gravis o Non-organ-specific:
§ Myasthenia gravis (muscles): Type II HS.
Type III Hypersensitivity Reactions § Dermatomyositis (skin).
§ SLE (multiple organs): Type III HS.
§ AKA: immune complex reactions.
§ Scleroderma (skin, internal organs).
§ Occur when immune complexes form à inflammation & tissue damage.
§ Rheumatoid arthritis (joints): Type III HS.
à Examples:
Immune privilege area
o Serum sickness
o Autoimmune diseases : SLE & RA § Lens of the eye, brain, spinal cord, sperm remain unrecognized by the im-
o S. pyogenes: rheumatic heart, arthritis, & glomerulonephritis. mune system.
§ Exposure later via injury lead to autoimmune responses.
IMMUNOSUPPRESSION Radio allegro sorbent Test (RAST)
§ Immune system is impaired § Detects IgE Abs produced against allergens (alternative to skin test)
§ Leading to increased vulnerability to infections. § Used as an alternative or supplement to traditional skin testing to identify
à Causes: allergens causing allergic reactions.
1) Acquired: Malnutrition (most common )Drugs & Infections
Skin Testing
2) Inherited: § In vivo rather than in vitro
o SCID: Severe recurrent infections due to absent B/T cells. § Examples:
o DiGeorge syndrome: o Tuberculosis (TB) skin test (most used)
§ Thymus & Para thyroid gland absence. o Schick Test, Dick Test Schultz-Charlton Test
,

§ Causes Pure T cells deficiency & developmental issues. Vaccines

o Wiskott-Aldrich syndrome: § Come from words vacca (cows)
§ Deficiencies in B cells, T cells, monocytes, platelets. § Edward jenner is the father of vaccination.
§ Leads to bleeding, eczema. à Ideal Vaccine Characteristics:
o Agammaglobulinemia: No gamma globulins. § Sufficient antigenic determinants to stimulate protective antibodies
o Hypogammaglobulinemia: Insufficient Abs (Bruton disease). § Covers all strains causing the disease
§ Minimal or no side effects, does not cause disease.
Immunodiagnostic Procedures
à Types of Vaccines:
à Types of Detection in IDPs
Type of Vaccine &Definition Examples
Antibody Detection Antigen Detection §

§ Past or present inf. or § Indicates of a specific pathogen 1) Attenuated Vaccines § Viral: chicken pox (varicella) ,MMR,
vaccination. § Direct evidence of infection. § Live weakened pathogens polio (oral ,Sabin), rotavirus,
§ Test for IgM (Acute Inf.) § Best proof of current infection. smallpox, yellow fever
§ C/I immunosuppressed
§ Test for IgG convalescent § Not available for many § Gold standard vaccine is § Bacterial: BCG (TB), cholera,
o 4 fold increase in IgG 2W infection the whole pathogen. tularemia, typhoid fever (oral)
later
2) Inactivated Vaccines § Viral: Hepatitis A, influenza,
§ killed pathogens. polio (SC, Salk), rabies.
à Tests for Antigen-Antibody Reactions
§ Easier to produce but less § Bacterial: typhoid fever (SC),
1) Agglutination: Insoluble Ags : Clumping of RBC or latex effective. Anthrax, cholera, pertussis, Q fever.
2) Precipitin Line/Band Formation: 3) Conjugate Vaccines: Capsular § H. influenzae type b,
o Soluble Ags : Produces a visible precipitate line. Ags with immune-stimulating § Meningococcal meningitis,
3) Fluorescence: Observed under a microscope. molecules. § Pneumococcus
4) Color Production: Enzyme Immunoassays (ELISAs). 4) Toxoid : inactivated toxins. § Tetanus, diphtheria.
5) Capsular Swelling (Quellung R): Detect encapsulated bacteria. 5) Subunit Vaccines : Ags parts § Anthrax,hepatitis B, whooping cough