Ch 6: Immunopathies (Part 1 - immunity) Flashcards
What is innate immunity? Cells and proteins involved?
Pre-existing defense against pathogens
Barrier defense = skin, epithelia
Cells = neutrophils, dendritic cells, NKs
Proteions = complement
What is adaptive immunity? Cells involved?
Specific programmed defense in response to Ag presence
Cells = lymphocytes + antibodies
Name some physical/chemical barriers of innate immunity.
Skin Ciliated lining of tracheobronchial tree Saliva Tears pH of stomach
What are Pattern Recognition Receptors? Types?
Recognize aspects of microbes
Types = TLRs, NOD-like receptors, C-type lectin receptors
What is signaled when TLRs are activated?
Synthesis and secretion of NF-kB and interferon regulatory factors (IRF)
NF-kB stimulates synthesis and secretion of cytokines and adhesion molecules that are critical for recruitment of neutrophils
IRFs stim production of Type-1 IFN (antiviral cytokine)
If TLRs are lost from germline mutation, what class of disease can you get?
Immunodeficiency diseases
What do NOD-like receptors recognize?
Products of necrotic cells = uric acid, ATP
ion disturbances = loss of K
microbial products
What is the pathway signaled by NLRs?
Signal via inflammasome –> activates caspase-1 (cleaves IL-1 precursor to active form
If there is gain-of-function of NLRs, what class of disease can you get?
autoinflammatory disease (will respond well to IL-1 antagonists)
autoimmune diseases (gout, atherosclerosis)
What are characteristic of CLRs, RIG-lie, GPCRs, and Mannose receptors?
CLRs = fungal glycan recognition
RIG-like = intracellular nucleic acids (viral RNA) recognition
GPCRs = N-formylmethionyl recognition (prokaryotes, mitochondria)
Mannose = recognize mannose - bacterial cell wall constituent
What are the generative organs involved in adaptive immunity? What occurs there?
Bone marrow
Thymus
What are peripheral organs involved in adaptive immunity? What occurs there?
Lymph nodes = can interact with APCs and Ags in circulating lymph
Spleen = Lymphocytes can interact with blood-borne Ags
MALT (tonsils, adenoids, peyers patches) = allow lymphocytes and plasma cells to be in vicinity of Ags within mouth and intestinal tract
What is occurring in the bone marrow in regards to immunity?
Primary site of hematopoiesis
Generation of lymphocyte stem cells
B-lymphocyte maturation
What is occurring in the thymus in regards to immunity?
Maturation of T-lymphocytes (naive cells migrate from cortex to medulla)
Medulla contains:
maturing T-cells
dendritic APCs with high levels of MHC 1 and 2
Hassall corpuscles = squamous cell nests
What mediates gene recombination involved in receptor encoding? What happens if it is mutated?
RAG-1 and RAG-2
No mature lymphocytes is RAG mutated
How can a molecular assay using PCR determine if lymphocyte proliferation is polyclonal or monoclonal?
B/c T and B cells and their clonal progeny have unique DNA rearrangements and receptors
Analysis of Ag receptor gene rearrangements is valuable assay to erect tumors derived from lymphocytes (lymphoma)
What are the types of T-lymphocytes?
Helper T-cells (CD4+) = stimulates B-cells to make Ab and activate other leukocytes to kill microbes
CTLs (CD8+) = kill infected cells
Regulatory (tregs) = limit immune response and prevent reaction against self-ag
Describe MHC class 1.
All nucleated cells
+ platelets
Typically recognize intracell Ags (viral, tumor)
Ags processed into peptides by proteosome –> transport to ER, load into groove of MHC –> complex travels to surface
Presentation to CTLs
Describe MHC class 2.
Ag presenting cells
Typically recognize extracellular Ags (bacterial, allergens)
Ags process into peptides by endolysosomal enzymes –> vesicles form MHC complex
Presentation to Helper Ts
What chromosome encodes HLA molecular structure?
Chromosome 6
Thousands of alleles
What type of immunity are B-lymphocytes responsible for?
Humoral immunity - Ab production
Describe the characteristics of Ab classes.
IgM - first Ig produced, pentamer
IgG - long half life, fetal protection
IgA - mucosal defense, colostrum
IgE - short half life, regulate hypersensitivity reactions
What activated and inhibits NK cells?
Activated by damaged cells - recognized by NKG2D receptors
Inhibited by self MHC and class 1 MHC
What is clonal selection? clonal deletion?
When an Ag is introduced, particular lymphocyte targeted against Ag is preferentially activated and produces identical cells
Clonal deletion is when lymphocytes are killed if they recognize self-ag
Describe TH1 cells. What cytokines? Stimulated by? Triggers what? Implicated in?
Cytokines produced: IFN-Y
Stim by: IFN-y, IL-12
Triggers macrophage activation, IgG production
Good for killing intracellular microbes
Implicated in: autoimmune diseases, chronic inflammatory disease, granulomatous inflammation
Describe TH2 cells. What cytokines? Stimulated by? Triggers what? Implicated in?
Major cytokines produced: IL-4, IL-5, IL-13
Stim by: IL-4
Triggers stim of IgE production, activation of mast cells and eosinophils
Implicated in: allergies
Describe TH17 What cytokines? Stimulated by? Triggers what? Implicated in?
Major cytokines produced: IL-17, IL-22
Stim by: TGF-B, IL-6, IL-1, IL-23
Triggers recruitment of neutrophils and monocytes
Good for killing extra cell bacteria and fungi
Implicated in: autoimmune, chronic inflammation dz, psoriasis, MS
