Immunology Flashcards
What phagocytes cells circulate
Neutrophils and monocytes
What phagocytes are in tissues
Macrophages and langerhans
What are the dominant cells of destruction of microbes and other offending agents
Macrophages
Dendrite
In epithelial, lymphoid organs and most tissues
Capture protein antigens and display peptides for T cells
*stimulate secretion of cytokines and involved in the initiation of innate immune responses
Nk cell
Early protections gainst viruses and intracellular bacteria
Plasma proteins
Complement
Mannose binding lectin CRP that coat microbes OPSONINS
Lung surfactant to provide protection against inhaled microbes
PRR (pattern recognition receptor)
Recognize aspects of microbes or DAMP
Damp
Damage associated molecular pattern released by dying or damaged cells
Danger signals/alarmin
Where are PRR
Plasma membrane for extracellular
Endosomes for digested
Cytosolic for cytoplasm
What are the four innate immune receptors
TLR(plasma membrane and endosomes vesicles), NOD like(cytosolic), C type lectin receptors, and RIG like receptors
TLR activation from microbial products
Activate transcription factors-
NF-KB and interferon regulatory factors
NFKB-stimulates synthesis and secretion of cytokines and adhesion molecules for recruitment and activation of leukocytes.
IRF-antiviral cytokines -type 1 interferons
If TLR lost
Serious immunodeficiency problems
NOD-like receptors (NLRs) when bind products of necrotic cells like uric acid and ATP, ion disturbances like k loss and some microbial products
Inflammasome which activates caspase 1 that cleaves a precursor form of il1 into its active form
Gain of function NLR
Periodic fever syndrome called autoinflammatory syndrome which is treated by an il1 antagnoist
NLR in gout
NLR inflammasome pathway plays a role int he innate immune system recognition of urate crystals and promoting the inflammation associated with gout.
Inflammasome pathway
Protein complex that recognizes products of dead cells and some microbes and induces the secreiton of biologically activated IL-1
NLR activates inflammasome which activates caspase 1 which cleaves pro-I1b into il-1B for it to be secreted from the cell
NLPR3
Sensor protein leucine rich
C type lectin receptors
Expressed not he plasma membrane of macrophages and dendritic cells
Detect fungal glucan and elicit inflammatory reactions to fungi
Rig like receptors
Cytosolic detect nuclei acids of viruses that replicate int he cytosolic of infected cells
Stimulate production of antiviral cytokines
Intracellular nuclei acids (viral RNA)
Gpcr
Neutrophils, macrophages, and msot leukocytes
Recognize bacterial peptides containing n-formylmethionyl (prokaryotes and mitochondria)
Mannose receptors
Recognize microbial sugars with terminal mannose residues and induce microbial phagocytes
Mannose is bacterial cell well constituent)
Type 1 interferons
Activate enzymes that degrade viral nuclei acids and inhibit viral replication to induce antiviral state
When does lymphocyte become not naive
When find antigen
How get lymphocyte diversity
Somatic recombination of genes hat encode the receptor proteins in thymus for T cells and bone marrow for B cells
For lymphocyte diversity how are gene segments recombined randomly
RAG1 and RAG2
RAG mutated
No mature lymphocytes
How tell if lymphocyte proliferation is polyclonal )non neoplastic) or monoclonal (neoplastic)
molecular assays using PCR
Bc each t or B cell and its colonial progeny have a unique DNA rearrangement (unique antigen receptor)
For lymphoma
TCR ab
Ab
Recognize MHC
CD3 and zeta chain-invariant, identical in all cells
TCR gamma delta
Peptides, lipids, small molecules, without assistance from MHC proteins
On epithelial surfaces (skin, GI and urogenital tracts)
NKT cell
Some have TCR that recognize MHC like molecule CD1
But this is adaptive immunity
T cell coactivator
CD28 on T cell interacts with cd80/86 (b7)
B cell receptor
IgM or igd
Activated B cell
Turns into plasma cells
Co receptors B cells
Iga and IgB (CD79a and CD79b)
0invariant for transduction
T cell and. Cell interaction
CD40L Cd40
HyperIgM syndrome
CR2 or CD21
This receptor can also be used by EBV to enter and infect B cells
Dendritic cells
APC for T cell responses
Located at the right place to capture antigens-under epithelial (langerhans in skin)-interstitial of all tissues where antigens may be produced
TLR and lectins
Recruited to T cell zones of lymphoid organs in response to microbes
Dendrites MHC
Lots of them needed for presenting antigens to and activating T cells
Dendritic follicular cells
Found in germinal centers of of lymphoid follicles in spleen and lymph nodes
Fc receptors for IgG and Receptors for c3b to trap antigens bound to antibodies or complement proteins
Present and select the highest addnity B cells
_ cells can activate macrophages and enhance their ability to kill ingested microbes
T
How macrophages phagocytes and destroy microbes
Opsonized by igg or c3b
NK cells what kill
Kill virus infected cells and tumor cells
How do nk cells kill
Azurophilic granules without prior exposure
Surface molecules of NK
CD16: an Fc receptor for IgG, lyse IgG coated cells in antibody dependent cell mediated cytotoxicity
Secrete ifny for macrophage activation
Antibody dependent cell mediated cytotoxicity
Nk cell kids and lyse IgG coated target cels
When nk cell kill
No MHC
What cytokines regulate nk cells
Il2, il15, stimulate proliferation
Il2 and il15->NK cells->il12->TH1->ifny->macrophage (classical activation)
Il12 activates killing and secretion of ifny
Innate lymphoid cells
New
Nk cells are first defined ILC
Early defense
HLA chromosome
6
MHC1 antigen binding
A1, a2 binding groove
A3 is nonpolymorphc and has a binding sitefor cd8
B2 microglobulin
Cytoplasm like viral and tumor antigens
Mhc2 binding (macrophages B cells dendritic cell)
A1, b1 binding groove
B2 binding site for cd4
Extracellular bacteria and soluble proteins
HLA inheritance
Codominantly from each parent
Everyone has different HLA HaplotypE
Transplant hard
Except identical twin
Cytokines that limit and terminate immune response
Tgfb and il10 and antiinflammatory
What cytokines stimulate hematopoietic
CSF
GM CSF and IL7
Treat RA
Tnf antagonists
Primary lymphoid organs
Thymus and bone marrow
Secondary lymphoid organs
Lymph nods, spleen, mucosal and cutaneous lymphoid tissues
Lymph nodes vs spleen
Nodes-lymph dendrites
Spleen-blood macrophages and dendrites
How does blood enter spleen
Sinusoids trapped in macrophages and dendrites
Mucosal lymphoid systems
Under epithelial of skin, GI and respiratory tracts
Antigens through breach of epithelium
Immmunization with a protein antigen
Microbial mimics called adjuvants are given with the antigen and these stimulate the innate immune response
TH1
Ifny is 12 —-> il2 ifny
Macrophage activation and stimulate IgG production
Intracellular microbes
Autoimmune disease, IBD< psoriasis, granulomatous inflammation
TH2
Il4->4, 5, 13
5-IgA class switch, eosinophils 4->igE class switching Il13-alternate macrophage activation (tissue repair and fibrosis)
Stimulates igE, activation of mast cells and eosinophils
Helminthis parasites
Allergies
TH17
TGFB, il6, 1, 23->IL17, 22
Recruits neutrophils and monocytes
Extracellular bacteria and fungi
Autoimmune disease, chronic inflammation, psoriasis, ms
T dependent humoral immunity-protein antigens
Require T cell help
B cell ingest protein display on mhc2
Helper T cell use cd40L to help class switch and affinity maturation
Ifny and il4->isotype switching
IgA
Mucosal epithelial
IgG
Transported across the placenta and immunity to newborn
IgE and eosinophils
Parasites
T independent humoral immunity
Non protein antigens
Polysaccharide and lipid antigens cant be recognized by T cells but have multiple identical antigenic determinants (epitomes) that are able to engage many antigen receptor molecules on each B cell and initiate process of B cell activation
NO IMMUNOGLOBULIN ISOTYPE SWITCHING AND AFFINITY MATURATION
Mainly igM
Type I hypersensitivity
IgE, TH2, mast, and other leukocytes
Il4-IgE and TH2
Il5-eosinophils
Il13-enhance IgE and stimulate mucus
Who gets immediate hypersensitivity type I
Presensitized
Immediate reaction type I
Vasodilation, vascular leakage, congestion, edema
Minutes after exposure and subsides in a few hours
Treat immediate type I
Epinephrine
Late phase type I
2-24 hours lasts for days
Allergic rhinitis and bronchial asthma
Eosinophils, neutrophils, basophils, monocytes, and cd4, tissue destruction
What cell dominates late phase type I
Eosinophils
Mast cells and basophils
Mast-tissue
Basophils-circulating counterpart
Stain mast cells
Blue
Activation mast cell
Cross link igE FceR1 receptors
C2a and c5a
IgE coated mast cells
Sensitized
MOA type I hypersensitivityq
Cd4 activated by a DC and release Il4, get TH2 and il4, 5, 13
4-IgE and TH2
50development and activation eosinophils
13-igE enhance and mucus,
TH2, mast, and epithelial cells make chemokine attract th2 and other leukocytes which sensitize mast cells so the next time mast cells exposed to antigen get IgE crosslinks and activation
Treat anaphylaxis
Epinephrine
What are preformed mast cell mediators
Vasoactive amine: histamine
Enzymes:neutral proteases (Chumash trypatase) and acid hydrolase)
Histamine
Sm contraction, vascular permeability, and increased secretion
Epinephrine counteracts histamine
A1 agonist, beta 1 agonist, beta 2 agonist
Proteoglycans
Heparin; anticoagulant
Chondriotin sulfate
Lipid mast cell mediator
Arachidonic acid derived
Reactions in mast cell membranes lead to activation of phospholipase a2, converts membrane phospholipids to aa which is converted to leukotrienes and prostaglandins
Leukotriene c4 and d4
Most potent vasoactive and spasmogenic agents
Leukotriene b4
Highly chemotactic for neutrophils, eosinophils, and monocytes
Prostagladin D2
Abundant, causes intense bronchospasm and increased mucus secretion
PAF
Platelet aggregation, release of histamine, bronchospasm, increased vascular permeability and vasodilation.
Not derived from aa
What does mast cell secrete
Tnf il1 and chemokine
Leukocyte recruitment , epithelial damag,
Il4-amplifies th2 Response
What mediators are responsible for immediate hypersensitivity
Preformed0histamine, neutral proteases, proteoglycans
Secondary mediators-leukotrienes, prostagladin D2, PAF
Cytokines-tnf il1, il4 chemokine
What mediators and responsible for the intense immediate reactions characterized by edema , mucus secretions and smooth muscle spasm
Histamine and leukotrienes
Which mediators set the stage for the late phase response by recruiting additional leukocytes
Cytokines and chemokines
Late phase type I
Leukocytes (eosinophils) don need additional triggering antigen
Major cause of symptoms
Eosinophils release what
Proeolytic enzymes, major basic protein, eosinophil cationic protein
Treat late phase
Anti inflammatory
When use antihistamine
Only intermediate reaction
Most potent eosinophil activating factor
Il5
Chemotactic for eosinophils
Eotaxin
Atopy genetic
More IgE and IL4 producing TH2 cells
Why allergies more in developed countries
Exposure to pollutants trigger
Non atopic allergy
No th2 or ige
Mast cells abnormally sensitive to activation by nonimmune stimuli
Systemic anaphylaxis
Minutes, vascular shock, widespread edema, and difficulty in breathing
Sensitized individuals
Type II
IgM and IgG promote lysis or phagocytosis and injure tissue
Complement activation
Antibody dependent cellular cytotoxicity
Antibody dependent cellular cytotoxicity
cells coated with IgG antibody are killed by a variety of effector cells, mainly NK cells and macrophages, and cell lysis occurs without phagocytosis
MOA: When antibody is directed at a parasitic infection, there if Fc receptor-mediate inflammation and phagocytosis, characteristic of ADCC. IgG and IgE antibodies bearing Fc receptors coat the parasite. Macrophages, natural killer cells, and neutrophils can then recognize the Fc receptor and destroy the antibody-coated target cells.
contribution of ADCC to hypersensitivity diseases is uncertain