Immunology Flashcards
B-cells
Develop & Mature in bone marrow, differentiate in Lymph nodes germinal centers.
- Development: CD9, CD10 (Bone marrow)
- Maturation:
CD19 , CD20 (Bone marrow), IgM on the surface. - Differentiation:
CD21, CD19, CD20 (LN germinal centers),
IgM & IgD on the surface.
T-cells
Developed in Bone marrow, matured in Thymus, Differentiation in Lymph node Paracortex.
- Development:
CD8+ , CD4+ , CD3 (T-cell receptor) Bone marrow. - Maturation:
CD3 , CD8+ (T-cell) , CD4+ (Helper T-cell) Thymus. - Differentiation:
Cytotoxic CD8+
CD8+, IL-12 → Th-1
CD3 , IL-4 → Th-2
CD4+ (Helper T-cell) , IL-6 → T-inflamatory
CD4+ (Helper T-cell) , IL-6+ 3GF → T-cell (regulatory)
Lymph Node (Paracortex).
IL-1
Fever , Vasodilation
IL-2
T-cell proliferation, NK-cells, ↑MAC migration.
IL-3
B-cell proliferation.
IL-4
Class switching IgG → IgE, Upregulation of mast cells.
IL-5
Class switching IgG → IgA, Upregulates Eosinophills.
IL-6
Acute phase reactant, CRP, Cytochrome-C, ↑ESR,
↑Hepcidin, ↑Feratin (Inflamatory markers).
IL-8
Chemotaxis (production of pus) , C5a, LTB4, 5HETE, n-formulated peptides.
IL-10
↑ Humoral immunity.
↓ Cell mediated immunity (CMI)
IL-12
↓ Humoral immunity.
↑ Cell mediated immunity (CMI).
Stages of B-cell development
- PRE-B : CD9, CD10, µ-chain (bone marrow)
- IMMATURE : CD19, CD20, IgM (bone marrow)
- MATURE : CD19, CD20, CD21, IgM, IgD (lymph node germinal center)
NK-Cells
- Develop with T-cells in Thymus.
- Express MHC-I complex.
- Express CD16 & CD56.
- Responsible for Immunesurvillence.
- Can detect cancer at one cell stage.
CD8 T-cells
CD4 T-cells
Helper T-cells
C5a and IL-8
Chemotatic molecules that promote leukocytes migration to site of inflamation, Both are generated through normal inflamatory process.
Absolute neutrophil count
e.g if 700 WBCs/ leukocytes [20%Neutrophils + 10% bands]
Absolute neutrophil count= 700 x 30/100
Absolute neutrophil count= 210 neutrophils/mm3
IL-1
Fever
IL-2
T cell activation
IL-3
Bone marrow production
IL-4
Stimulate B-cells to make IgE
IL-5
Stimulate B-cells to make IgA
also used to make IgE and is a Eosinophil Chemotactic factor
IL-6
Stimulate B-cells to make IgG.
Also acts on liver to secrete acute phase reactants
IL-8
Clean up on Neutrophils
IL-10
Differentiates Th-2 cells and inhibits Th-1 cells.
IL-12
Differentiates Th-1 cells and inhibits Th-2 cells.
IFN-γ
Released by T-cells & Co-stimulate Macrophages
TNF-α
Released by Macrophages & Co-stimulate T-cells
Cell Marker CD56
NK-Cells
Cell Marker CD19 & CD20
B-Cells
Cell Marker CD3
T-Lymphocytes
Cell Marker CD4
T-Helper cells
Cell Marker CD8
Cytotoxic T-cells
Cell Marker CD68
Macrophages
Cell Marker CD45
Leukocytes
Cell Marker CD33
Myeloid cells
Cell Marker CD4+ & CD25+
T-regulatory Cells
Hypersensitivity Type-1
- Allergic
- Ig-E mediated
- Involves Basophils & Mast cells
- i.e. Bee Sting, Peanut allergy etc.
Hypersensitivity Type-2
- Cell mediated
- Cytotoxic
- IgG & IgM autoantibodies
- Complement activation
- Mediated by NK cells, Eosinophils, Neutrophils, Macrophages
- i.e. S. pyogenes M-protein, Localized autoimmune reactions, Graves disease, Autoimmune hemolytic anemia, Goodpasture syndrome etc.
Hypersensitivity Type-3
Immune Complex
- Deposition of antibody-antigen complexes
- Complement activation
- Seen in systemic autoimmune diseases
i.e. SLE, RA, Serum sickness, PSGN, Lupus nephritis etc.
Hypersensitivity Type-4
- Delayed type hypersensitivity
- Mediated by T cells & Macrophages
- i.e. Poison IV, Contact dermatitis, Transplant rejection, Organ failure, Hashimoto’s thyroiditis etc.
Cell Marker CD-14
Macrophages
CD 30+ & CD 15+
Reed Sternberg Cells (Owl’s Eye cells)
Hodgkin’s Lymphoma
PNH
(Proximal Nocturnal Hemoglobinuria)
Triad of hemolytic anemia, hypercoagulability, and pancytopenia
acquired mutation in the PIGA gene
associated deficiency of CD55 and CD59 complement inhibitor proteins
PNH results in impaired synthesis of Glycosylphospatidylinositol (GPI), resulting in inability to anchor DAF (CD55) & CD59 to the cell membrane and loss of inhibition of complement-mediated lysis of erythrocytes, leukocytes & platelets.
Hyper IgE Syndrome
Defective JAK-STAT signaling → impaired Th17
↓ Neutrophil proliferation/chemotaxis
Eczema
Abscesses (ie, cold) (eg, Staphylococcus, Candida)
Recur sinopulmonary infections
Dysmorphic facies (eg, broad nose, prominent forehead)
Retained primary teeth
↑ IgE
Eosinophilia
“ F A T E D “
Facies (dysmorphic), Abcesses(cold), Teeth(retained primary teeth), Eosinophila & inc IgE, Dermatological findings(Eczema).
SLE
Positive ANA, anti–double-stranded DNA, anti-Smith Antibodies
Skin & Joints:
Malar rash.
Arthritis
Cardiovascular manifestations of SLE:
accelerated atherosclerosis.
verrucous (Libman-Sacks) endocarditis.
Renal involvement in SLE:
(Nephritis or nephrotic Syndrome)
diffuse proliferative glomerulonephritis (characterized by proliferative and necrotizing lesions with crescent formation during active disease).
Light microscopy also classically shows diffuse thickening of the glomerular capillary walls with “wire-loop” structures due to subendothelial immune complex deposition
Rheumatoid arthritis
Onset 40-60; often younger
MCP, PIP, Wrists
Prolonged Morning Stiffness
Systemic Symptoms: Fever, Fatigue, Weight loss
Soft/spongy, warm joints
Hyper-IgE syndrome (Job syndrome)
(neutrophil chemotaxis abnormality)
Recurrent cold (noninflamed) abscesses, eczema, high serum IgE, High eosinophils
“ F A T E D”
F = Facial features (coarse)
A = Abcesses (cold)
T = Teeth (retained primary teeth)
E = Inc IgE, Eosinophilia
D = Dermatological finding (Eczema)
Bruton disease
(X-linked agammaglobulinemia)
Male child, recurrent bacterial infections (sepsis, meningitis, skin inf) , no mature B cells, all Immunoglobins are low, paucity of immune structures (i.e tonsils & lymph nodes)
T-cell response normal (normal immune response to viruses)
Present by 6 months of age when maternal antibodies wane off.
Wiskott-Aldrich
syndrome
Mutation in WAS gene
“WATER”
Wiskott-Aldrich:
Thrombocytopenia,
Eczema,
Recurrent (pyogenic) infections
Increase IgE, IgA
Acute Graft Vs Host Disease
- Damage to the Host cells (i.e Body)
- Common following stem cell transplantation
- Fever , Rash (maculopapular rash), Diarrhea and Tranaminitis.
- Result of HLA mismatch
- Donor T-Lymphocyte response against host cells
- Involves Apoptosis
In comparison Host vs Graft Disease
Damage is by the body to the graft (i.e transplanted organ)
Multiple Myeloma
- Most common primary bone tumor in elderly
- Over production of IgG (55% cases) > IgA.
- M-spike with IgG on electrophoresis.
“ C R A B “ C = hyperCalcemia R = Renal Involvement , Reaulux formation A = Anemia B = Bone lesions/ Back pain (lytic lesions, punched out lesions on x-ray)
- Rouleaux formation RBC stacked like poker chips (↑ESR)
- Urinanalysis show Ig light chains
( Bence-jones protienuira ), —ive urine dipstick
Complications:
-↑ risk of infections, - 1° Amyloidosis
- Multiple Myeloma is tumor of plasma cells.
Waldenstorm Macroglobulenemia
- Overproduction of IgM
- M-spike with IgM
- Peripheral Neuropathy
- No CRAB findings
HYPER VISCOSITY SYNDROME:
- Headache
- Blurry vision
- Raynaud phenomenon
- Retinal hemorrhages
- Complications: Thrombosis
Monoclonal Gammaopathy of Undetermined Significance
( M G U S )
- Over production of any type of Immunoglobin
- Usually Asymptomatic
- 1-2% per year risk of transitioning to Multiple Myeloma
Scleroderma/ Systemic Sclerosis
It can be localized called as localized scleroderma or diffuse/systemic scleroderma called as systemic sclerosis.
AKA “ C R E S T syndrome ”
C = Calcinosis (Ca+2 deposit in skin)
R = Raynauds Phenomenon
E = Esophageal dysfunction(acid reflux,↓motility)
S = Sclarodactyly (thickening & tightening of
skin on fingers & hands)
T = Telangectasias
– Anti-Centromere Antibodies are classic for CREST syndrome.
– Anti-Topoisomerase (Anti-Scl-70) are seen in diffuse systemic sclerosis.
Pulmonary fibrosis can be caused secondary to CREST syndrome, both limited and diffuse systemic sclerosis can lead to pulmonary fibrosis.
IgA Nephropathy
- Aka Bergers disease
- IgA deposition in Renal mesangium
- Red urine 1-3days after sore throat, in contrast PSGN is red urine 1-3 wks after sore throat
- IgA nephropathy is caused by viral infection not group-A strep.
Etiology includes Henoch-Scholen purpura;
- Palpable purpura (buttocks/ thigh)
- IgA nephropathy (red urine)
- Arthralgias
- Abdominal pain
CVID
(Common variable immune deficiency)
- Seen in Adults (3rd or 4th decade of life)
- Associated with increase Autoimmune disease and Lymphomas.
- Decrease plasma cells & Immunoglobins.
- Defective B-cells maturation
Note: B-cells number are normal but they are immature B-cells (lack IgM & IgD) thus can attack the body to cause autoimmune diseases or result in lymphomas.
Myasthenia gravis
- Autoantibodies against nicotinic acetylcholine receptors on the (post) synaptic membrane of the neuromuscular junction
- Associated with Thymoma
Lambert-Eaton syndrome
- Autoantibodies against voltage-gated calcium channels on the (pre) synaptic membrane of the neuromuscular junction
- Associated with Small cell lung cancer (SCLC)
Give the classic tetrad of IgA vasculitis (Henoch-Schonlein purpura).
- Palpable purpura without thrombocytopenia or coagulopathy (typically over the posterior lower extremities and buttocks)
- Arthritis/arthralgia
- Abdominal pain (due to localized bowel wall inflammation; patients are at risk of intussusception)
- Kidney disease (hematuria +/- proteinuria)
IgA deficiency
- Anaphylaxis following blood transfusion
- Recurrent Infections of Mucosal sites (i.e Respiratory, GI) which are protected by IgA.
- Patients blood lacks IgA but transfusion product contains IgA which leads to Anaphylaxis when body recogonizes IgA in transfusion product.
Leukocyte adhesion deficiency
(type 1; defective LFA-1 integrin)
Late separation (>30 days) of umbilical cord, No pus, Recurrent skin and mucosal bacterial infections.
Chronic granulomatous disease
- (defect of NADPH oxidase)
- Neutrophils lack respiratory burst
- Recurrent infections and granulomas with catalase ⊕ organisms (Staph Aureus, Burkholderia cepacia, serratia marceanes, Nocardia)
- Fungi: Aspergillus
Dx: DHR (Dihydrorhodamine test)
NBT (Nitroblue tetrazolium)
Hyper IgE Syndrome
Defective JAK-STAT signaling → impaired Th17
↓ Neutrophil proliferation/chemotaxis
Eczema
Abscesses (ie, cold) (eg, Staphylococcus, Candida)
Recur sinopulmonary infections
Dysmorphic facies (eg, broad nose, prominent forehead)
Retained primary teeth
↑ IgE
Eosinophilia
“ F A T E D “
Facies (dysmorphic), Abcesses(cold), Teeth(retained primary teeth), Eosinophila & inc IgE, Dermatological findings(Eczema).
SLE
Positive ANA, anti–double-stranded DNA, anti-Smith Antibodies
Skin & Joints:
Malar rash.
Arthritis
Cardiovascular manifestations of SLE:
accelerated atherosclerosis.
verrucous (Libman-Sacks) endocarditis.
Renal involvement in SLE:
(Nephritis or nephrotic Syndrome)
diffuse proliferative glomerulonephritis (characterized by proliferative and necrotizing lesions with crescent formation during active disease).
Light microscopy also classically shows diffuse thickening of the glomerular capillary walls with “wire-loop” structures due to subendothelial immune complex deposition
EBV Mononucleosis
Fever + Tonsillar exudates + Cervical lymphadenopathy + Cough + Hepatomegaly
IgA Nephropathy
Aka Bergers disease
IgA deposition in Renal mesangium
Red urine 1-3days after sore throat, in contrast PSGN is red urine 1-3 wks after sore throat
IgA nephropathy is caused by viral infection not groupA strep.
Etiology includes Henoch-Scholen purpura;
- Palpable purpura (buttocks/ thigh)
- IgA nephropathy (red urine)
- Arthralgias
- Abdominal pain
Serum Sickness
Serum sickness generally presents 1-2 weeks after exposure to nonhuman proteins in antivenom, antitoxins, monoclonal antibodies, or vaccinations
Presents as:
- Fever
- Urticarial Rash
- Arthralgias
Its a type-III hypersensitivity reaction, leads to immune complex deposition in tissues and complement activation
