Immune system protects from disease - Answers Including heritable disorders (genetic ex. SCID),
acquired disorders (infections ex HIV), aging
How does Immune system participate in disease? - Answers Allergy, Autoimmunity,
Immunopathology, Graft rejection, Graft vs host disease (GVHD)
Observed that those exposed to cowpox were protected against smallpox, however, did not know the
cause of disease, prompted the term vaccination - Answers Edward Jenner (late 18th century)
Vaccination - Answers The deliberate inoculation of individuals with weakened or attenuated strains
of disease-causing agents to provide protection
Discovered that individual microorganisms are responsible for particular diseases - Answers Robert
Koch (19th century)
4 categories of pathogens - Answers Viruses, Bacteria, Fungi, Parasites
How rabies vaccine was developed by Louis Pasteur (he also developed vaccine for chicken cholera) -
Answers Passaging virus through rabbits and injecting dried spinal cord from these infected rabbits, as
passaging of viruses through many animals weakened or attenuated the pathogenicity of the virus
Innate response - Answers Immediately availible to fight any infection, broad, does not have memory,
first line of defense
Innate immunity - Answers Intrinsic mechanisms that protect host from infections, inherited in the
genome
Mechanisms of innate immunity - Answers Basic physiology (temp), anatomical barriers (skin,
mucous), chemical (pH, anti-microbial proteins), Biological (commensal flora), Specialized cells that
respond to microbes
Adaptive response - Answers Occur as an adaptation to particular pathogen, lead to memory
formation whihc confers life-long protection, very specific (only recognizes particular microbes)
Adaptive immunity - Answers Encoded in multiple gene segments, requires gene rearrangement, has
clonal distribution
How do vaccinations work - Answers Induces memory formation in lymphocytes
Antigen - Answers Any substance that can be induce adaptive immunity, ex. peptide, pathogen,
allergen, food protein, commensal microbe
Cells of immune system - Answers Leukocytes (WBC), ex. PMN, Monocytes
PMN - Answers These granulocytes have multi-lobed nuclei and cytoplasmic granules, ex.
neutrophils, esinophils, basophils
Monocytes - Answers Precursors of tissue macrophages (type of phagocyte)
Small lymphocyte - Answers Produces antibodies (b cells) or cytotoxic and helper functions (T cells)
Plasma cell - Answers Fully differentiated form of B cell that secretes antibodies (has large ER area for
antibody production)
Dendritic cell - Answers Activates T cells and initiates adaptive response
Lymphocytes - Answers Subset of leukocytes, include T (thymus) and B (bone marrow) cells
Innate immune system cells - Answers Macrophage (phagocytosis, antigen presentation), Dendritic
(antigen uptake and presentation), Neutrophil (phagocytosis, bactericidal mechs), Eosinophil (kills
antibody coated parasites), Basophil (promotes allergic responses and augmentation of anti-parasite
immunity
Cytokines - Answers Any secreted protein that affects behavior of cells bearing receptors, include
interleukins, help develop cellular and humoral receptors, induced inflammation, wound healing,
regulation of hematopoiesis
Chemokines - Answers Small secreted cytokines responsible for chemotaxis (cell movement in
response to cytokines), typical structure w/ cysteines, ex. CCR7 (chemokine receptor 7), CCL19 (C-C
motif ligand 19) *****did he ever mention what exactly we needed to know about these example???
*****
Cytokine chemokine functions - Answers Any cells can produce cytokines, they initiate inflammation,
recruit innate immune cells from blood into tissue, increase flow of lymph, can recruit effectors of
adaptive immune system, part of both innate and adaptive systems
Lymph - Answers Fluid that circulates within lymphatic system
Interstitial space and fluid - Answers area between cells, fluid in interstitial space
Edema - Answers Swelling due to excess fluid in interstitial spaces due to lymph flow blockage
Elaphantiasis - Answers nematode caused parasitic disease lymphatic filariasis
, Naïve - Answers B and T cells that have not met their specific antigen, not "activated"
B cells - Answers Part of humoral, secretes antibodies after stimulation with antigen (differentiates to
plasma cell), recognizes specific antigens at epitope of antigen binding site
T cell - Answers Part of cellular, includes helper CD4 and cytotoxic CD8, recognize broken peptide
fragments of antigens bound to MHC molecule on infected cells with TCR
Innate recognition of pathogens - Answers Pattern recognition is key, common features are
recognized like flagella, dsRNA, unmethylated DNA that are not usually present in body, foreign/non-
self triggers danger alarm
PAMPs - Answers Pathogen associated molecular patterns ex. repettitive arraus of protein, carbs,
lipids on pathogens, recognized by PRR (pattern recognition receptors) found on innate immune cells
(macro, neutro, dendritic)
4 main groups of PRR - Answers free receptors in serum (Mannose binding lectin - MBL) part of
complement, membrane bound phagocytic receptors, membrane bound signaling receptors,
cytoplasmic signaling receptors
TLR4 recognizes ___ and is located on ___
A. LPS; cell surface
B. Flagellin; cytoplasm
C. Flagellin; cell surface
D. Viral RNA; cytoplasm
E. DNA; nucleus - Answers LPS, cell surface
Examples of barriers to infection - Answers Cilia and mucus
Takeaways for pattern recognition receptors - Answers -Nod sees bacterial peptidoglycan in the
cytoplasm
-TLRs know location and ligand for TLR3, 4, 5, 7, and 9
-RIG sees viral RNA in the cytoplasm -> interferon
-cGAS sees viral DNA in the cytoplasm -> inferferon
Membrane bound signaling receptors - Answers -TLRs
-Very ancient pathway
-Originally discovered during a genetic screen in Drosophila, which had uncontrolled fungal growth
-These induce the secretion of cytokines, chemokines, and antimicrobial proteins and molecules
-Between 10-13 TLR in mouse and human
-Each has a distant ligand
TLR3 - Answers recognizes dsRNA in viruses
TLR4 - Answers recognizes LPS
TLR5 - Answers recognizes flagellin
TLR7 - Answers recognizes ssRNA in viruses
TLR9 - Answers recognizes unmethylated CPG (bacteria and herpesvirus)
Where can TLR be found? - Answers On cell surfaces or intracellular membranes
NOD-like receptors (NLR) - Answers -A cytoplasmic receptor for PAMPs
-Recognize bacterial wall peptidoglycans
-Induce secretion of inflammatory cytokines, antimicrobial products
-Mutations in NOD2 are associated with Crohn's disease (IBD). These mutations impair downstream
signaling of NOD, causing decreased production of anti-microbials.
RIG-I-like helicases (RLH) - Answers -A cytoplasmic receptor for PAMPs
-Recognizes cytoplasmic viral RNA
-Viral replication in cytoplasm produces a modified, uncapped RNA
-This binds to RIG-I, which in turn binds another protein, leading to the production of inflammatory
cytokines and interferons. Interferons are cytokines, which have anti-viral activity.
cGAS - Answers -cyclic GMP-AMP synthase
-recognizes viral DNA
-activates er protein STING to trigger type-1 interferon secretion
NK cells - Answers -Leukocytes in the innate immune system
-Lack antigen-specific receptors
-Are cytotoxic: can kill other cells by secreting cytokines and other molecules
TNF-α - Answers -Secreted by macrophages
-Activates vascular endothelium and increases vascular permeability
-Increased entry of IgG, complement, cells to tissues, and fluid drainage to lymph nodes