Immunology Flashcards
lymph node paracortex
T cells (this is between follices and medulla). contain High Endothelial venules where T and B cells enter blood. This is maldeveloped in DiGeorge syndrome
lymph drainage: upper limb and lateral breast
axilla
lymph drainage: stomach
celiac
lymph drainage: sigmoid colon
colic to inferior mesenteric
lymph drainage: rectum above pectinate line
internal iliac
lymph drainage: anal canal below pectinate line
superficial inguinal
lymph drainage: testes
para aortic
lymph drainage: scrotum
superficial inguinal
lymph drainage: thigh
superficial inguinal
lymph drainage: lateral side of dorsum of foot
popliteal
right lympatic duct vs thoracic duct
right drains right arm/chest/half of head. thoracic duct drains everything else
T cell located in spleen
PALS (periarterial lymphatic sheath) within white pulp
what in the spleen removes encapsulated bacteria?
macrophages
heme changes in asplenia
Howell-Jolly bodies (nuclear remnants), Target Cells, thrombocytosis
thymus origin
3rd branchial pouch
thymus maturation axis
deeper is more mature
selection order in thymus
positive then negative
MHC I is composed of which HLA genes and binds what?
HLA-A/B/C. binds TCR and CD8
MHC II expresses which HLA genes and binds what?
Expresses HLA-DR/DP/DQ. binds TCR and CD4
MHC I is expressed on what?
all nucleated cells (not RBCs)
MHC I is loaded with antigens how
loaded with peptide antigen in RER. it pairs with Beta2 microglobulin to aid in transport to cell surface
MHC I provides coverage for what infxn?
viral. it will load anything inside of cell to be checked by CD8s.
MHC II is expressed where and how does it load?
expressed on antigen presenting cells. antigen loading follows release of invariant chain in an acidified endosome
only lymphocytic member of the innate immune system
natural killer cells
HLA A3 association
hemochromatosis
HLA B27
PAIR: Psoriasis, Ankylosing Spondylitis, Inflammatory Bowel Disease, Reiters syndrome
HLA DQ2/8
Celiacs
HLA DR2
MS, hayfever, sle, goodpastures
HLA DR3
Graves and type I diabetes
HLA DR4
Rheumatoid arthritis and Diabetes TYpe I
HLA DR5
pernicious anemia secondary to B12 def. Hashimoto’s thyroiditis
natural killer cell function
kills virally infected and neoplastic cells which have stopped presenting antigen on MHC I. So they bridge innate to adaptive.
B cell functions
make antibody to opsonize bacteria, neutralize virus (IgG); activate compliment (IgM and IgG); sensitize mast cells (IgE)
when B cells fuck up
- Allergy (type I hypersen via IgE)
- Cytotoxic (type II) and immunocomplex (type III) hypersen (IgG)
- hyperacute and humorally mediated acute and chronic organ rejection
Lymph node follicle functions
B Cells proliferate. primary follices are dense and dormant, secondary are pale and proliferative
T cell major functions
CD4 help B cells make antibodies and make cytokines to direct others
CD 8 kill viral cells
what happens when T cells fuck up?
delayed cell mediated hypersensitivity (type IV)
acute and chronic cellular organ rejection
IL-12 causes helper to to become?
Th1 cell
IL-4 directs helper T cells to become
Th2 cell
only cell that can activate naive T cell
dendritic cell
all APCs
dendritic, marcophage, B cell
naive T cell activation
1: dendritic cell uptakes and presents on MHC I and II which is recognized by TCR
2: signal 2 costimulates with B7 and CD 28
3: T cell activates
B cell activation and class switching
1: Helper T cell activation
2: B cell receptor endocytosis of antigen which then presents on MHC II to Th cell which was activated in step 1.
3: CD40 receptors on B cells bind to CD40L on Th (signal 2)
4: Th cell secrretes cytokines that cause Ig class switching/affinity maturation/antibody production
how do Th1 and Macrophages interplay
Th1 secrete IFN-gamma which stims macro.
Marco secretes IL-1 and TNF-alpha which stim Th1
Th1 secretes, activates, is inhibited by
secretes IFN-gamma
activates macrophages for viral immunity
inhibited by IL-4 and IL-10 (from Th2)
Th2 secretes, activates, inhibited by
Th2 secretes IL-4, IL-5, IL-10, IL-13
activates eosinophils (parasites) and IgE production from B cells
inhibted by IFN-gamma(from Th1)
Cytotoxic T cells target what?
virus, neoplastic, graft
how do cytotoxic T’s kill?
cytotoxic granules containing perforin, granzyme, granulysin
what do T Regs express on their surface?
CD3, CD4, CD25 (which is IL-2 alpha chain)
What do T Regs secrete?
IL-10 and TGF-Beta
recombination of heavy vs light chain have how many parts?
three for heavy (VDJ) vs two for light (VJ)
What does the Fab portion of the immunoglobulin do?
antigen specificity
What makes Fc portion of Ig and what are its components?
the cterminal half of heavy chain. hinge (disulfides) - Ch2 (complement binding) - Ch3 (macrophage binding)
In addition to recombination of chains how else is antibody diversity created? (3)
- random combo of heavy and light chains
- somatic hypermutation following antigen stim
- addition of nucleotides after recombination
B-cell immunoglobulin switching
mature B cells express IgM and IgD on their surfaces. Following cytokine and CD40-L stimulation they becomes plasma cells which secrete IgA, IgE, or IgG
IgG
Main antibody in delayed reaction. Most abundant Ig. Fixes complement. Crosses placenta. Opsonizes bacteria, neutralizes bacterial toxins and viruses
IgA
prevents virus and bacteria to mucus membranes. doesn’t fix complement. Monomeric in circulation and dimer when secreted. transcytosis into secretions and colostrum
name of process of IgA crossing epithelial cells?
transcytosis
IgM
produced as the immediate antigen response. fixes complement but can’t cross placenta. Monomer on B cell, pentamer in circulation (better to trap stuff)
IgD
found on B cells, but no idea what it does
IgE
binds mast cell and basophils, crosslink when exposed to allergen. mediates type I hypersensitivity by causing histamine release. immunity against worms by activating eosinophils
classical complement activation pathway begins with
IgG or IgM
alternative complement pathway activation triggered by
microbial surface molecules
lecthin complement pathway triggered by
mannose or other sugar on microbe
C3b function
opsonization
C3a and C5a function
anaphylaxis
C5a function
neutrophil chemotaxis
C5b-9 function
cytolysis by MAC
Decay-accelerating factor and C1 esterase inhibitor
prevent complement activation on self cells (like RBCs)
C1 esterase inhibitor deficency
hereditary angioedema. ace inhibs contraindicated
C3 deficency
severe recurrent pyogenic sinus and resp tract infxn. more susceptible to type 3 hypersen rxn
C5-9 deficiencies
recurrant Neisseria infxn
lymph node medulla
medullary chords packed with lymphocytes and plasma cells. sinuses comunicate with efferent lymphatics and contain reticular cells and macrophages
IL8 mnemonic
clean up on aisle 8 (neutrophils are the clean up crew)
IL-12 vs IL-4
12 - Th1
4 - Th2
DAF (decay accelerating factor) deficiency
complement mediated lysis of RBCs and paroxysmal nocturnal hemoglobinuria
IL mnemonic 1-5
Hot T-Bone stEAk:
IL1: fever (hot), IL2 (T all), IL3 (bone marrow growth), IL4 (IgE and G via Th2), IL5 (IgA via B cells and eosinophils)
IL-1
macrophage. pyrogen, inflam, endothelial adhesion molecules, chemokine secretion inducer
IL-6
macrophage and Th2. pyrogen, acute-phase proteins
IL-8
macrophage. chemotactic factor for neutrophils
IL-12
macrophage and B cells . induces diff of T cells into Th1. activates NK.
TNF-alpha
macrophage. mediates septic shock. activates endothelium. leukocyte recruitment, vascular leak
IL-2
all T cells (secretion). stimulates growth of helper,cytotoxic,and reg T cells
IL-3
secreted by all T cells. functions like GM-CSF (supports the growth and diff of bone marrow stem cells
Interferon-gamma
from Th1. activates Th1 and macrophages. Suppresses Th2. Antiviral and antitumor
IL-4
from Th2 cells. induces diff into Th2. promotes B cell growth. causes class switching to IgE and IgG
IL-5
from Th2. promotes diff of B cells. class switching to IgA. stimulates growth and diff of eosinophils
IL-10
from Th2 and T regs. dampens down inflammation. inhibits T cells and Th1.
TGF-beta acts like _____ cause _____
IL-10 cause it also inhibits inflammation
Interferon mechanism
activates antiviral state. alpha/beta inhibit viral protein synth (via viral specific ribonuclease). gamma upregulates MHCI/II and antigen presentation globally. activates NK cells/macrophages.
classic antigen variation examples: bacteria (3), virus, parasites
Bacteria: salmonella (2 flagella), Borrelia (replasping fever), Neisseria (pilus)
VIrus (influ)
Parasites (trypanosomes)
antibody in milk?
IgA
preformed antibodies are available for
To Be Healed Rapidly: Tetanus toxin, Botulism toxin, HBV, Rabies
Type of immunity achieved by live attenuated vs inactivated/killed vaccine
Live: cellular response
Killed: humoral immunity
live attenuated vaccines
measles, mumps, rubella, polio (Sabin), varicella, yellow fever
killed/inactivated vaccines available for
cholera, hepatits A, polio (Salk), rabies
which hypersensitiveity rxn are antibody mediated?
type 1,2,3
type I hypersensitivity
Anaphylactic/atopic. IgE on Mast cell or basophil binds antigen causing degranulation (histamines, vasodialators). Very fast.
Type II hypersensitivity
cytotoxic (antibody mediated). IgG/M bind antigen/cell causing opsonization, complement activation (MAC), Antibody-dependent cell-mediated cytotoxicity due to NK cells
how to test for type II hypersensitivity?
direct and indirect coombs test
receptor for EBV?
CD21 on B cells
Type III hyper sensitivity
Immune complex mediated. ANtibody-antigen complexes activate complement (type III has those three) which recruits neutrophils which release lysosomal enzymes. Serum sickness and Arthus reaction
serum sickness
after administration of serum antibodies form 5 days later then immune complexes deposit causing tissue damage . TYpe III hypersen
arthus reaction
type III hypersen. local subacute antibody. injection of antigens intradermally
type IV hypersensitivity
very slow. T cells bind antigen then release lymphokines to recruit macrophages which cause hell.
pneumonic of hypersensitivities
ACID: I: anaphylactic II: Cytotoxic III: Immune complex IV: delayed (cell mediated)
what are all of the type I hypersensitivities
anaphylactic and allergic.
anaphylactic: bee stang, food/drug allergies
allergic: rhinitis, hay fever, eczema, hives, asthma
what are the type II hypersensitivities
they are generally tissue specific/where antigen is. Heme, derm, plus some.
Autoimmune hemolytic anemia, pernicious anemia, idiopathic thrombocytopenic purpura, erythroblastosis fetalis, acute hemolytic transfusions, Rheumatic fever, goodpastures, Bullous pemphigoid, pemphigus vulgaris
what are the type III hypersensitivities?
typically vasculitities and systemic: SLE, polyarteritis nodosa, poststreptococcal glomer, serum sickness, arthus reaction (following tetanus vaccine)
what are the type IV hypersensitivities?
delayed non-antibody mediated: multiple sclerosis, Guillain-barre, Graft v host, PPD test, contact dermatitis (poison ivy ect)
Blood transfusion allergic reaction
type I hyper (immediate) due to plasma proteins. give antihistamines
Blood transfusion anaphylactic reaction
due to IgA blood given to IgA defiecent patient. causes shock/really bad
Blood transfusion: febrile nonhemolytic transfusion reaction
type II hypersen. antibodies against HLA
Blood transfusion: Acute hemolytic transfusion reaction
type II hypersen due to ABO incompatibillity (intravascular hemolysis) and other RBC antigens (extravascular hemolysis)
B cell def leads to what?
bacteria more than virus/fungi (encasulated bacteria)
T cell def lead to what?
virus and fungi more than bacteria (CMV, EBV, VZV, and chronic viral infxns) (candida, PCP)
which parasites infect people with no B cells?
GI giardia cause they lack IgA
which bacteria infects people without complement system?
Neisseria
Hyperacute rejection
within minutes. preformed antibodies (type II). occludes graft vessels
Acute rejection
weeks. CD8 Ts react against foreign MHC. vasculitis of graft vessels with dense intersitial lymph infiltrates. reversible with immunosupp
Chronic rejection
months to years. CD8T/NK think that foreign MHC I is self but presenting nonself peptides. Irreversible. t and antibody mediated vascular damage, fibrosis, obliterative
Graft vs host disease
variable time line. T cells of graft take on the recipient. maculopapular rash, jaundice, hepatosplenomegally, diarrhea. from Bone Marrow and Liver Transplant
