Basic Principles in Immunology Flashcards
Immune Response
Ability of the body to defend and recognize itself. Vertebrates have different mechanisms and memory.
Inoculation idea
Came from Onesimus, a slave owned by Collen Mather. Proposed Idea during Boston Outbreak in 1721. Wrote to Zabdiel Boylston, a physician that tried and worked. Was not well received.
Von Behring and Kitasato
Antitoxic activity in serum from animals immune to diphtheria or tetanus.
Robert Koch
German physician and bacteriologist, lived 1843-1910. Developed a criteria for determining whether a given bacteria is the cause of a given disease
Koch’s Postulates
- The microorganism must be found in all organisms suffering from the disease, but not in healthy organisms
- The microorganism must be isolated from a diseased organism and grown in pure culture
- The cultured microorganism should cause disease when introduced into a healthy organism
- The microorganism must be again isolated from the inoculated, diseased experimental host and identified as identical to the original specific causative agent.
Metchnikoff
Discovered Phagocytosis
Bordet
Discovered complements
Innate Immunity
Response is the same whether or not the pathogen has been previously encountered
External barriers
Skin/exoskeleton, secretions, mucous membranes
Internal defenses
Phagocyte cells, NK cells, defensive proteins, inflammatory response
Acquired immunity
Found only in invertebrates, previous exposure to pathogen enhances immune response. Involves antibodies and lymphocytes.
Antigens
Not usually part of the host, most are proteins or large polysaccharides on the surfaces of viruses and foreign cells
Epitopes
Specific regions on an antigen to which antibodies bind. Linear or conformational
Influenza growth cycle
- Virus attaches to receptors on respiratory epithelial cell and is endocytosed
- Viral membrane fuses with vesicle membrane and its genome is released into the cytoplasm
- Cell synthesizes viral capsid and glycoproteins, and replicates the viral genome
- Virus particles are assembled by viral genomes binding to coat protein. Particles bud off from the cell membrane
1-1: Commensal organisms cause little damage
Microbiome and virome within humans
Four categories of pathogens
Viruses, intracellular bacteria, extracellular bacteria (Archaea, Protozoa), fungi, and parasites
All pathogens must accomplish the following to be successful
Entry, adherence, avoidance, growth, and exit
Innate response barriers
*Anatomic barriers (skin, oral mucosa, respiratory epithelium, intestine)
*Complement/antimicrobial proteins (C3, defensins, regallly)
*Innate immune cells (macrophages, granulocytes, natural killer cells, epithelial cells)
Adaptive immunity cells
B cells/antibodies, T cells
Inflammatory inducers
Bacterial lipopolysaccharides, ATP, urate crystals
Innate Recognition Receptors
Recognize when something’s wrong, make cytokines or chemokines
Sensor cells
Macrophages, neutrophils, dendritic cells
Mediators
Cytokines, cytotoxicity
Target tissues
Production of antimicrobial proteins, induction of intracellular antiviral proteins, killing of infected cells
PAMP
Pathogen associated molecular patterns, found in white blood cells
Where do immune cells originate from?
The hematopoietic stem cells in bone marrow. When mature they populate tissues (including specialized lymphoid tissues) and circulate through blood and lymph fluid
1° lymphoid tissue
Thymus and bone marrow (sites of development)
2° lymphoid tissue
Serves to collect pathogens from lymph and other fluids, and act as a point immune cell activation. Adenoid tonsil, lymph node, spleen, and Peyer’s patch in small intestine
Lymph nodes
Filter lymph. Lymphatics collect extracellular fluid and return it to the blood.
Peyer’s patch
Samples intestinal lumen
Myeloid cells
Innate immune cells
Lymphoid cells
Adaptive immune cells (except NK and ILCs)
Cells of innate immune system
Phagocytic cells, granulocytes, innate lymphoid cell (ILC)
Natural Killer (NK) cell
Releases lytic granules that kill some virus-infected cells
Phagocytic cells
Directly ingest and kill pathogens
Macrophage
Use phagocytosis and activation of bactericidal mechanisms, antigen presentation, inflammation
Dendritic cell
Antigen uptake in peripheral sites, antigen presentation, mediators to activate other cells
Neutrophils
Phagocytosis and activation of bactericidal mechanisms
Granulocytes
Release multiple mediators stored in granules that promote pathogen removal due to toxic effects, induced clearance mechanisms, and recruitment of other immune effector cells
Eosinophil
Kill antibody-coated parasites
Basophil
Promotion of allergic responses and augmentation of anti-parasitic immunity
Mast cell
Release of granules containing histamine and active agents
Natural Killer cells
Limit intracellular pathogen growth indirectly by killing infected host cells; Use cytotoxic granule release to kill infected cells, similar mechanism to cytotoxic T cells. Lack Antigen-specific receptor, important in viral infections
Innate Lymphoid Cells (ILCs)
Derived from common lymphoid progenitor cell, but don’t express an antigen receptor. Recruited to sites of infection, they produce cytokines similar to T cells that modulate the functions of other immune cells (enhancing innate immunity and regulating function of lymphoid cells)
ILC1
intracellular immunity
ILC2
Barrier immunity
ILC3
extracellular immunity
Pattern recognition receptors (PPRs)
Recognize specific structures found on groups of microbes. Used by innate immune cells.
Inflammatory response steps
- Bacteria trigger macrophages to release cytokines and chemokines
- Vasodilation and increased vascular permeability cause redness, heat, and swelling
- Inflammatory cells migrate into tissue, releasing inflammatory mediators that cause pain
What does pathogen recognition lead to?
An alarm sent out and the release of cytokines that lead to the recruitment of additional immune cells
Innate immune cells present pathogen structures (antigens) to stimulate the adaptive immune system
- Immature dendritic cells reside in peripheral tissues
- Dendritic cells migrate via lymphatic vessels to regional lymph nodes
- Mature dendritic cells activate naive T cells in lymphoid organs such as lymph nodes
Types of lymphocytes
B and T cells. Have highly variable antigen receptors on their surface, immunological memory
Antibodies and T-cell receptors recognize antigens by fundamentally different mechanisms
- The epitopes recognized by T-cell receptors are often buried
- The antigen must first be broken down into peptide fragments
- The epitope peptide binds to a self molecule, an MHC molecule
- The T-cell receptor binds to a complex of MHC molecule and epitope peptide
Antigen-receptor genes are assembled by somatic gene rearrangements of incomplete gene segments
Antibodies produced by B lymphocytes (B cells) bind pathogens directly to inactivate them and promote their removal.
Cytotoxic T cells
Kill infected cells
MHC
Major Histocompatibility complex
Helper T cells
Stimulate innate immune cells and B cells
Initial site of interaction between innate and adaptive immune cells, and where lymphocytes are first activated
Secondary lymphoid tissue.
Naive lymphocytes enter lymph nodes from ____
Blood
Antigen presentation
Display of peptides from pathogen proteins is required for recognition by T cells.
Antigen presentation process
Virus infects cell –> Viral proteins synthesized in cytosol –> Peptide fragments of viral proteins bound by MHC class I in ER –> Bound peptides transported by MHC class I of the cell surface –> Cytotoxic T cell recognizes complex of viral peptide with MHC class I and kills infected cell
Clonal selection
- A single progenitor cell gives rise to a large amount of lymphocytes, each with a different specificity
- Removal of potentially self-reactive immature lymphocytes by clonal deletion
- Pool of mature naive lymphocytes
- Proliferation and differentiation of activated specific lymphocytes to form a clone of effector cells
Postulates of the clonal selection hypothesis
*Each lymphocyte bears a single type of receptor with a unique specificity
*Interaction between a foreign molecule and a lymphocyte receptor capable of binding that molecule with high affinity leads to lymphocyte activation
*The differentiated effector cells derived from an activated lymphocyte will bear receptors of identical specificity to those of the parental cell
*Lymphocytes bearing receptors specific for ubiquitous self molecules are deleted at an early stage in lymphoid cell development and are therefore absent from the repertoire of mature lymphocytes
Steps in B-cell proliferation
- Antigen recognition induces expression of effector molecules by T cell, which activates B cell
- B-cell proliferation, then differentiation to resting memory cells and antibody-secreting plasma cells
Type 3
Extracellular, interstitial spaces, blood, lymph
Type 2
Extracellular, epithelial surfaces
Type 1, cytotoxicity
Cytoplasmic and vesicular
