Immunology Flashcards
Peyer’s patches
unencapsulated
in lamina propria and submucosa of ileum
Overlying epithelium - follicule associated epithelium
- flattened w/ M (microfold) cells interspersed
- take up antigens to basal side
Germinal center w/ B cells - IgA
Innate immune system
non specific
rapid response
no memory
macrophages dendritic cells -APC - activate Th cells neutrophils mast cells eosinophils basophils NK cells complement proteins skin and other barriers
adaptive immune system
very specific
memory
takes longer to get activated
T and B lymphocytes
circulating Abs
T cell markers
TCR - antigen specific
CD3
CD4 - Th –> MHCII
CD8- Tc –> MCHI
MHCI
all nucleated cells (Not on RBCs since no nucleus)
HLA-A, -B, -C
MHCII
APCs
HLA-DR, -DP, -DQ
Dendritic cells surface markers
MHC I, MHC II
B7 (CD 80/86) - costimulatory
CD40 - interact w/ T cells to further activate the APC
Dendritic cell function
Peripheral sentinel - immature or Ag capturing state
- Phagocytosis
- receptor-mediated endocytosis via clathrin coated pits
- pinocytosis
migrate to LN via circulation to present to Th cells
Langerhans cells
in epidermal layers of skin
cutaneous associated lymphoid tissue - CALT
Interstitial dendritic cells
in interstitial spaces of all organs except brain
Langerhans cell histiocytosis
Excessive proliferation of Langerhans Cells
not good at APC
S100+
CD1a
Birbeck granules - tennis racket shape
Thymus organization
Outer - cortex - immature T cells
Middle - medulla - mature T cells
T cell positive and negative selection
Positive selection:
Cortex has MHC to test binding strength
Too strong or weak –> cell death
-survival signal keeps T cell alive –> specificity. Become only CD4 or CD8, lose the other marker
Negative selection:
Corticomedullary junction
-bind to self antigen –> apoptosis
–> naive T cell
Th0 cytokines to Th1 cells vs Th2 cells
Th0 release IL12 –> Th1
Th0 release IL4 –> Th2
Th0 release IL10 inhibits Th1
Th1 cells
stimulate macrophages and Tc
IL2 –> stimulate Tc and Th1, T reg prolif
IL3 - stimulate bone marrow stem cells (GM-CSF like)
IFN gamma –> activated Macrophages, suppresses Th2
Th2 cells
stimulate plasma cells to make Ab
IL4 - “BEG 4” - stimulates B cell prolif, IgE and IgG; induces Th0 –> Th2
IL5 - promote B cell growth, IgA production, stimulates eosinophils
IL 10 - inhibit Th1 cells and macrophages
B cell activation
- Th2 activated
- B cell endocytoses antigen bound to Ig presents to Th2
- Costimulatory signal CD40 on B binds to CD40L on Th2
- Th2 secretes IL4, IL5 –> proliferation of B cells and Ig class switching
Th cell activation
naive Th0 binds antigen from APC MHCII on TCR w/ CD4
costimulatory signal from B7 protein (CD80/86) bind CD 28
starts T cell producing cytokines
Tc activation
Tc binds antigen from APC/virus infected cell MCHI on TCR w/ CD8
CD28-B7 costimulatory
- -> kills infected cells
- -> clonal expansion
Cytokines produced by macrophages and dendritic cells
IL12
Function of Tc - CD8+ cells
bind MHCI on “self” cells
kills virus infected cells
kill cancer cells
kill transplant cells
release perforin and granzyme –> aopotosis
Fas-L activates Fas receptor –> apoptosis
Memory T cells
spleen and LN
inactive state
activated against pathogen
Allow live virus vaccines to induce life long immunity
T reg cells
inhibit B cells from producing Ab
inhibit Th and Tc cells
produce IL10
produce anti-inflammatory cytokines
If not working properly –> autoimmunity - atopic dz
FOXP3
- on X Chr
- transcription factor - controls development and function of Treg cells
mutations –> cant control immune system
IPEX syndrome
- Immune dysreg: eczema
- Polyendocrinopathy: T1DM, thyroiditis
- Enteropathy - severe D, failure to thrive
- X-linked
NK cell
innate immune
induce apoptosis in cells not expressing MHCI - down reg in virus infected and cancer cells
activity enhanced by:
IL12
IL2
IFN alpha and beta - secreted by virus infected cells
Secrete IFN-gamma –> macrophage activation
NK cell surface markers
CD56
CD16 –> Ab dependent cell mediated cytotoxicity (ADCC)
MHC I
CD16
NK cells
- binds AB at constant region
- -> ADCC
also found on macrophages, neutrophils, monocytes
B cell surface markers
CD19 CD20 CD21 IgM IgD MHCI, MHC II B7 (CD80/86) CD40 --> activate B cell
B cell stimulation
stimulated by IL4, IL5
activated B cells
- plasma cells –> Ab
- memory B cell –> dormant
Macrophage surface markers
CD14 - binds LPS endotoxin on gram - (--> activation) CD16 MHC I, MHC II B7 CD40 --> more sensitive to IFN gamma
Passive immunity
preformed Abs - immediate immunity
IgA in breast milk
21 day t1/2
-RSV - Palivizumab - Ab against RSV
Rabies - rabies Ig shots
Active immunity
exposure to foreign Ag
takes weeks to develop
–> memory T/B cells
Tetanus
influenza
MMR
pneumococcal
Live vaccine
weak, attenuated
infect cells to present to Tc
- -> cellular immunity
- -> memory Tc cells
Inactivated (Killed) vaccine
Ag to be presented
- -> humoral immunity
- -> memory Th cells
- need booster doses
Attenuated virus vaccines
“ATTENtion! Please Vaccinate Young Infants w/ MMR Regularly”
Attenuated virus vaccines (live) Polio vaccine (sabin - oral) Varicella Yellow fever Intranasal Influenza MMR Rotavirus
avoid in immunocompromised or those close to them
CD4>200 can give MMR, varicella, yellow fever
Inactivated virus vaccines
IM influenza
HAV
Rabies
Salk polio -inected form
Egg based vaccines
influenza
yellow fever
(MMR - very small amount)
Thymus-dependent Ag
present peptides via MHC to T cells in thymus –> B cell activation
better immune response and immunologic memory
Thymus independent Ag
LPS -non peptide Ag -cannot present to T cells in thymus no T cell response B cell response weaker --> weaker immune memory boosters needed
Bacterial vaccines
Toxins - tetanus toxoid
Capsular polysaccharides
-S pneumo, H flu
killed bacteria - vibrio cholerae
Live attenuated bacteria
- Typhoid vaccine
- BCG vaccine
–> humoral response to T cell response since not infecting cells
C1 inhibitor
aka C1 esterase inhibitor
inhibits cleavage of C1 starting point of classical pathway
Classic pathway of compliment activation
IgG or IgM bind Ag then binds C1 complement protein
Alternate pathway of compliment activation
molecules on surface microbe or spontaneously
Lectin pathway of compliment activation
mannose binding lectin binds mannose on surface of microbe
Membrane attack complex
C5b, C6-C9
Oposonizing proteins
C3b
IgG
Anaphylaxis complement
C3a, C5a
Complement stimulating mast cells and basophils
C3a
Complement responsible for neutrophil chemotaxis
C5a
Paroxysmal nocturnal hemoglobinuria (PNH)
Complement mediated damage of RBCs by MAC complex
- deficient in Glycosylphosphotidylinositol (GPI) which anchors decay accelerating factor (DAF) (CD55) to plasma membrane
- deficient MAC-inhibitory protein (CD59)
Present with:
- chronic intravascular hemolysis
- hemosiderinuria - red urine
- thrombosis
Dx: Ham’s test - RBC in acid lyse in low pH - diagnostic
-Flow cytometry - CD55/CD59 not present
Tx:
transfusion
warfarin
Eculizumab - inhibits complement
Deficiency of C1 esterase inhibitor
Hereditary angioendema
increased bradykinin
never take ACEI with these –> higher bradykinin
Deficiency of C3
recurrent pyogenic sinus infections and respiratory tract infections
-S. pneumo, H. flu
increased susceptibility to type III hypersensitivity
-esp glomerular nephritis - can’t clear out immune complexes
Deficiency in any of the MAC complement components
susceptible to Neisseria bacteremia
Deficiency in Decay accelerating factor (DAF) - CD55
protects self from spontaneous activated complement
–> Paroxysmal nocturnal hemoglobinuria (PNH)
Function of spleen
Macrophages remove damaged RBCs and encapsulated bacteria
sequesters and stores platelets and RBCs
-Thrombocytopenia in splenomegaly - more platelets sequestered in larger spleen
Asplenia
risk recurrent infections
sickle cell - autoinfarct
Trauma
hereditary spherocytosis - splenectomy to tx hemolytic anemia
Macrophage secreted cytokines
IL1, IL6, TNF alpha - acute phase reactants
- mediate fever, ramp up immune system
- TNFa - septic shock, recruit leukocytes
IL12: Th0 –> Th1; activate NK cells
IL8: neutrophil chemotaxis
Macrophage function
present Ag to T cells secrete cytokines Phagocytosis of bacteria opsonized w/ IgG or C3b -digests in lysosome -NADPH oxidase --> free radicals
Kill w/o phagocytosis via Ab-dependent cell mediated cytotoxicity (ADCC)
Form granulomas - combine to form multinucleated giant cells
-secrete Vit D
Mast cells
mucosa o fskin
granules: histamine –> type I HSR
Cromoyn blocks mast cell degranulation
- asthma tx- inhaled
- allergy nasal spray
Monocytes
Leave bone marrow for blood –> circulate 8-12 hours to mature –> migrate into tissues
Skin, connective tissue: dendritic cells (histiocytes) –> LN
Alveoli, intestines, spleen: macrophages - stay put
Liver - kupffer cells
Brain - microglia
Bone - osteoclasts
Joints - type A synoviocytes - clean synovial fluid
(type B similar to fibroblasts, secrete hyaluronic acid)
Differential diagnosis for eosinophila
“CANADA-P”
Collagen vascular disease (PAN, dermatomyositis)
Atopic dz (allergies, asthma, Churg-Strauss, allergic bronchopulmonary aspergillosis)
Neoplasm
Adrenal insufficiency (addison dz)
Drugs (NSAIDs, PCN, cephalosporins)
Acute interstitial nephritis
Parasites (Strongyloides, Ascaris –> Loeffler eosinophilic pneumonitis)
Other causes: HIV, hyper IgE syndrome, coccidioidomycosis
IL1-IL5 function
“Hot T-Bone stEAk”
IL1: fever IL2: stimulates T cells IL3: stimulates Bone marrow IL4: stimulates switch to IgE and IgG IL5: stimulates switch to IgA, eosinophils
IFNa and IFNb as antiviral
help neighboring cells avoid virus infeciton
inhibit cell protein synthesis
encourage activation of ribonuclease that degrades viral mRNA
activates NK cells
IFN gamma as antiviral
stimulate macrophages
Hyperacute rejection
within minutes to hours
type II HSR
-preformed Ab in host to donor Ag
Acute rejection
within 3 mo
cell mediated
Tc recognize foreign MHCI
give immunosuppressants to block IL2
Chronic rejection
months to years
T cell and Ab mediated
Th cells generate inflammation via interleukins –> vascular damage and fibrosis
Irreversible
Graft vs host disease
transplanted immune cells via bone marrow graft
graft T cells proliferate and attack host as foreign
maculopapular rash on neck, shoulders, ears, hands, trunk
-can blister
hemolysis, jaundice
HSM
Abd pain, N/V/D
