Immune System Flashcards
Natural Killer cells
Carry marker CD 16
Kill cells with downregulated MHC class 1 and stress related Fc fragments-virus infected cells and tumour related cells
Release perforins which lyse cells
Respond to IFN and IL-2
MHC Class 1, 2 and 3 locations
MHC 1: All nucleated and platelet cells
Coded by HLA A, B and C
MHC 2: Macrophages, activated T cells, B cells and dendritic cells
MHC 3: Complement
Antigen presentation
MHC Class 1: Endogenous protein such as viral protein is presented by MHC class 1 and detected by CD 8+ T Cells
MHC Class 2: Exogenous protein such as phagocytosed material is presented by MHC class 2 and detected by CD 4+ T helper Cells
T cells, TCR and MHC
T cells recognise MHC via their own TCR
CD 4 T helper cells recognise MHC 2 and CD8 T cells recognise MHC 1
CD8 T cells
MHC Class 1 –> CD 8 T cells
Kill cells and leave memory cells behind
CD4 T Helper Cells
Recognise MHC Class 2:
IFN g—>macrophages
IL-2—>T cell and B cell proliferation
IL-4—>promotes CD4 T cells and B cell proliferation
IL-5—>activation of eosinophils
IL-6—>T cell and B cell differentiation
IL-10—>Suppresses macrophage cytokine production
IL-12—>Promotes cytotoxic action of T and B cells
B cells
B cells detect antigen via B cell receptor and then morph into plasma cells which secrete immunoglobulins
CD4 T helper cells (activated by MHC class II) promote Ig production
All Ig have similar structure except IgM
Hypersensitivity reactions Type I-V
Type 1: Immediate/Anaphylaxic Ig E
Asthma, anaphylaxis
Type 2: Ig to ag Cytotoxic
Drug reaction, autoimmune thrombocytopenia, transfusion reaction
Type 3: Ig/Ag Immune complexes
SLE, glomerulonephritis
Type 4: CD 8 T Cells
TB mantoux, transplant rejection
Type 5: Anti-receptor ab’s
Grave’s myasthenia gravis
Autoantibodies
ANA ---> SLE, Sjogrens Anti-Ro ---> Sjogrens Anti-La ---> Sjogrens Anti-centromere ---> CREST Anti-Scl70 ---> Scleroderma
MHC Class 1 and 2 diseases
MHC 1: More in men
- HLA b27 (Ankylosing spondylitis and Reiter’s syndrome)
- HLA Cw6 (Psoriasis)
MHC Class II: More in women
- HLA-DR5 (Pernicious anaemia and Hashimoto’s)
- Rheumatoid Arthritis (HLA-DR4)
Immune deficiency (6)
IgA Deficiency Common variable immunodeficiency Brutons' x-linked agammaglobulinaemia Subacute combined immunodeficency Di-George's syndrome Complement factor deficiency
IgA Deficiency
Congenital or acquired (post virus)
Recurrent pulmonary/Gi infections
Usually asymptomatic
Common variable immunodeficiency
Congenital
Hypogammaglobulinaemia particularly IgG
Recurrent pyogenic infections after first decade
Autoimmune disease and lymphoid malignancy
Brutons’ x-linked agammaglobulinaemia
X-linked
No B cells therefore no Ig
T cells function normal
Recurrent bacterial infections, viral and fungal infection normal
Di-Goerge Syndrome
Congenital-damage to 3rd and 4th pharyngeal pouches due to 22q11 (CATCH 22)
- CARDIAC (Aortic arch-heart failure)
- ATRESIA (Oesophageal)
- THYMIC (Hypoplasia)
- CLEFT palate (Dysmorphic facies)
- HYPOCALCAEMIA (parathyroid hypoplasia)
T cell deficiency=Viral and parasitic disease
B cells normal
Severe Combined immunodeficiency
Autosomal or x-linked recessive disease
T cell, B cell and lymphopenia
Death <1 year unless bone marrow transplant
Complement factor deficiency
C2-Autoimmune connective tissue disorder
C3-bacterial infections
C5-8 Recurrent Neisseria infections
Infections usually killed by spleen
Encapsulated organisms:
Strep. pneumoniae
Neisseria Meningitidis
Haemophilus influenzae
Post splenectomy vaccination
HiB vaccine and meningococcus vaccine prior to or after surgery
Pen V or erythromycin life long
Complement and B cell deficiency causes
pyogenic bacteria:
Staphy
Strep
Haemophilus
Neisseria
Phagocyte deficiency
Staph
Gram negative
Fungal
T cells
Opportunistic infections
Kostmann’s syndrome
Congential neutrophilia
Leukocyte adhesion deficiency
No ability for chemotaxis
Chronic granulomatous disease
X linked
NADPH oxidase deficiency
Classical pathway
Antigen and antibody complex
activates C1 into C1s
C1s signals C4 and C2 into C4b and C2b
these combine into C4bC2b (C3 convertase)
MBL pathway
MBL is lectin like molecule
MBL binds to mannose on foreign cell
activates MASP-2—>C4/C2 into C3 convertase
Alternative pathway
Stimulated by bacterial cell wall components e.g. teichoic acid, LPS
spontaneously form C3b
C3 converatse
C3 becomes:
C3a-Anaphylatoxin
C3b-Opsonin (Cr1 from neut binds to C3b-phagocytosis)
C3b-Forms C5 convertase
C5 Converstase
C5a-anaphylatoxin and chemokine for neut.
C5b-actuvates C6, 7, 8 and 9 to form MAC
Complement deficiencies
Classical pathway deficiency
- SLE
- Immune complexes not cleared
MBL pathway deficiency
- Common
- Only problematic in immunosuppression
Alternative pathway
-Encapsulated bacteria
C3 deficiency
Bacterial infections
Membranoproliferative glomerulonephritis
Terminal common pathway
C5-9
Encapsulated bacteria
(Neisseria Meningitis, N. gonorrhoa, strep pneumonia, haemophilus)
Meningitis
T cell defects affect B cells
Because CD 4 helper cells cause B cell class switching So IgM is normal but low IgG and IgA
ANA detects
SLE, Sjogrens, Scleroderma
Polymyositis,Dermatomyositis
Sensitive=No ANA no SLE
not specific=Positive-can be other things
Autoabs
dsDNA-normal SLE
Histones-drug induced SLE
Speckled RNP-SLE, MCTD
Speckled Smith-SLE
Speckled Ro/LA- SLE and Sjogrens
Speckled Jo-1POly/dermatomyositis
Centromere LC Scleroderma
Nucleolar scl-70 DC scleroderma
Nucleolar RNA-pol DC Scleroderma
ANCA
C-ANCA binds PR3
Wegener’s granulomatosis
P-ANCA binds Myeloperoxidase
Microscopic polyarteritis
Churg Strauss disease
Antiphospholipid Antibodies (Anticardiolipin, Lupus)
SLE
Syphilis
Antiphospholipid syndorme
Rheumatoid factor
IgM that targets IgG
- Rheumatoid arthritis (50%)
- Sjogrens
- Primary Biliary Cirrhosis
- SLE
- Subacute Infective Endocarditis
HLA disease states
DR4 Rheumatoid
DR3 Graves, Diabetes, Dermatitis herpetiformis
DR2 Goodpastures
B27 Ank Spondylitis
Type 2 reactions
Ab mediated
Ab binds to cell
-Opsonisation
-Classical complement activation
Haem anaemia BLood transfusion, ITP Good pastures Pernicious anaemia Myasthenia gravis Graves Pemphigus
Type 3
Immune complex deposition
- SLE
- Post strep glomerulonephritis
- Reactive arthritis
- Serum sickness
- Arthus reacion
- Rh arthritis if Rh factor +ve
Type 4
MS T1DM Rheumatoid arthritis Mantoux test Contact dermatitis
Transplantation rejection
Hyperacute-preformed abs
Acute cellular rejection-Type 4 hypersensitivity. Foreign HLA presented. Multicellular response
Acute vascular-Pure antibody reaction-pre-existing antibody or new Ab-intiates complement
Chronic allograft-reaction that causes fibrosis of lumens, scarring and fibrosis
