MICROBIO MODULE THREE

Physical Barriers

Epithelial tissues like the skin (tough, stratified, and keratinized with hair as a filter) and mucosa (protected by mucus) prevent microbial entry.

Mechanical Barriers

Muscular contractions and fluid secretions expel microbes.

Chemical Barriers

Acidity in the stomach, skin, vagina, and urethra creates an inhospitable environment for microbial growth.

Biological Barriers (Normal Flora)

Microbial antagonism from approximately 38 trillion normal microflora bacteria limits the growth of pathogens.

Erythrocytes (RBCs)

Transport blood gases.

Thrombocytes (Platelets)

Limit blood loss during injury through coagulation.

Leukocytes (WBCs)

General term for cells that fight infection.

Neutrophils

Most abundant WBC; early responders to inflammation that leave the blood to eliminate microbes via phagocytosis.

Basophils

Release chemical mediators of inflammation, such as histamine.

Mast Cells

Similar to basophils but more abundant and localized to tissues; play a critical role in inflammation.

Eosinophils

Attach to and destroy large eukaryotic parasites (helminths) using toxic chemicals.

Monocytes

Secondary responders to inflammation that leave the blood and mature into Macrophages in tissues for phagocytosis.

Dendritic Cells (DC)

Tissue-resident phagocytes that act as professional Antigen Presenting Cells (pAPCs) to activate T cell responses.

Natural Killer (NK) Cells

Innate lymphocytes that kill infected host cells.

B Lymphocytes

Mediate adaptive immunity; differentiate into Plasma Cells (which secrete antibodies) and Memory B Cells.

Helper T Cells (CD4)

Produce cytokines to activate other immune cells (TH1, TH2, TH17).

Cytotoxic T Cells (CD8)

Kill infected host cells via perforins and granzymes.

Regulatory T Cells (Treg)

Inhibit immune responses to maintain tolerance.

Interferon

Signaling molecules produced by virus-infected cells to induce antiviral responses in nearby cells.

Complement

30+ plasma proteins that form a cascade resulting in inflammation, opsonization, and the Membrane Attack Complex (MAC) that lyses cells.

Defensin

Host defense peptides that destabilize microbial membranes to cause lysis.

Innate vs. Adaptive Immunity

Innate immunity is quick, systemic, and nonspecific (recognizes PAMPs), whereas adaptive immunity is slow initially, specific (recognizes antigens), and creates memory.

Innate immunity

Quick, systemic, and nonspecific (recognizes PAMPs)

Adaptive immunity

Slow initially, specific (recognizes antigens), and creates memory

Clonal Diversity

Created by receptor gene rearrangement, shuffling over 500 gene segments to generate billions of unique TCR and BCR specificities

Immune Tolerance

Established via clonal deletion, where any clone recognizing "self" antigens is forced into apoptosis during development

Primary Response

Involves clonal selection (antigen binds specific receptor), expansion (proliferation), and differentiation into effector and memory cells

MHC I

Found on all nucleated cells; presents endogenous (intracellular) antigens to CD8 Cytotoxic T cells

MHC II

Found only on pAPCs (macrophages, dendritic cells, B cells); presents exogenous (extracellular) antigens to CD4 Helper T cells

T-cell receptor

2 polypeptide chains; only recognizes processed peptides presented with MHC

B-cell receptor

4 polypeptide chains; recognizes native (unprocessed) antigens

IgG

Most prevalent in blood; crosses the placenta; main antibody of secondary responses

IgM

Pentamer; first Ig produced in a primary response; excellent at complement initiation

IgA

Dimer in secretions (mucus, saliva) providing mucosal immunity

IgD

Monomer used as a BCR on B cells

IgE

Binds to mast cells and basophils; mediates parasite defense and allergies

Neutralization

Blocks microbes or toxins from binding to host cells

Opsonization

Coats microbes to enhance phagocytosis

Agglutination

Cross-links microbes into immobile clumps

Complement Activation

Initiates the classical pathway leading to MACs

Natural/Active Immunity

Immunity from infection

Artificial/Active Immunity

Immunity from vaccination

Natural/Passive Immunity

Maternal antibodies (placenta/breast milk)

Artificial/Passive Immunity

Immunotherapy (transfer of antibodies/antiserum)

Herd Immunity

Protecting a population from outbreaks by ensuring a high percentage of individuals are immune through vaccination

Type I (Immediate) Hypersensitivity

IgE-mediated. Mast cells and basophils release histamine and other mediators

Type II (Cytotoxic) Hypersensitivity

IgG/IgM-mediated cell lysis (e.g., blood transfusion rejection)

Type III (Immune Complex) Hypersensitivity

Deposition of antigen-antibody complexes in tissues

Type IV (Delayed) Hypersensitivity

T-cell mediated (e.g., Tuberculin skin test, poison ivy)

Biological Barriers

Normal microflora (e.g., Staphylococcus on skin, Lactobacillus in the vagina) that limit pathogen growth through microbial antagonism.

Innate Immunity (2nd Line)

Systemic, nonspecific response that occurs quickly after a barrier is breached.

PAMPs

Pathogen-Associated Molecular Patterns; conserved microbial molecules recognized by PRRs.

PRRs

Pattern Recognition Receptors; receptors used to recognize PAMPs.

Acquired/Adaptive Immunity (3rd Line)

Specific response acquired after exposure to nonself antigens.

Professional Antigen Presenting Cells (pAPCs)

Cells like macrophages that phagocytose pathogens and present their antigens to activate T cells.

Inflammatory Response

Activated by PAMPs or tissue injury; involves mast cells releasing histamine causing vasodilation and increased vascular permeability.

Fever Response

Triggered by pyrogens (like LPS) stimulating leukocytes to produce fever-stimulating cytokines (IL-1, TNF-α).

Phagolysosome

A structure formed when a phagosome fuses with a lysosome, where lysozyme and an oxidative burst destroy the microbe.

Erythrocytes

Transport blood gases.

B Cells

Recognize native antigens via BCR; differentiate into Plasma Cells (antibody secretors) and Memory B cells.

Regulatory Lymphocytes (Treg)

Inhibit/terminate immune responses to maintain tolerance.

Edward Jenner

Developed the first vaccine in 1798 by using cowpox (harmless) to protect against smallpox (deadly).

Atopy

Local, chronic allergy (e.g., hay fever).

Anaphylaxis

Systemic, severe, life-threatening reaction.

Phenotypic Diagnosis

Physical or biochemical observations (e.g., Gram stain, selective/differential media, biochemical multitests like API 20E).

Genotypic Diagnosis

Analysis of DNA/RNA (e.g., PCR to amplify DNA, FISH using fluorescent probes).