Diseases Flashcards
Hereditary angioedema
This is a complement disease when you are deficient in C1 INH which inhibits C1 cleaving C2 and C4 (start of the classical complement pathway)
Chronic granulomatous disease
you have a mutation in phagocyte oxidase which creates ROI needed for macrophage peptide degradation
Allergic Rhinitis
also known as hay fever
type one hypersensitivity reaction caused by EARLY PHASE MEDIATORS (histamine). Upper respiratory tract (nose) inflammation, mucosal edema,
treated with antihistamines
Bronchial asthma
hypersensitivity type one reaction
lower respiratory tract inflammation and bronchoconstriction due to LATE PHASE MEDIATORS
primary cells = eosinophils and Th2
key inflammatory molecule = LCT4
What is MIP1-alpha?
a late phase mediator that attracts neutrophils
what do cromolyn and corticosteroids do?
used to treat bronchial asthma
cromolyn - satbilises mast cell membrane
corticosteroids - block production of inflammatory cytokines
what are Urticaria and atopic eczema?`
Urticaria –> acute hives
atopic eczema –> chronic hives
typically caused by food allergies
type one HS
The transfusion reaction
hypersensitivity two deals with membrane-bound antibodies (typically IgG).
Type O = universal donor –> expresses no membrane anitgen
Type AB = universal acceptor –> expresses both A and B antigens (i.e. does not contain any antibodies)
Hemolytic disease of the newborn
- Rh - mom has a kid who is Rh+
- blood mixes and mom makes anti-D antibodies (D refers to antigen expressed by Rh+ people)
- if the next kid is Rh+ -> IgG antibodies that are anti-D can cross the placenta and attack the child’s blood
Farmers lung
type 3 hypersensitivity rxn
antigens in hay dust enter alveoli and cause inflammation (not the same as broncho asthma)
Arthus reaction
Serum Sickenss
both are type 3 HS rxns
arthus rxn –> vaccinate someone who already has Ab’s to vaccine = local inflammation / redness
serum sickness –> systemic inflammation / redness
cutanous vasulitis = vasodilation leading to skin redness
Tuberculin reactions
TD tests –> type 4 HS rxn
cell mediated HS
often involves metals and haptens
EPSTEIN-BARR Virus (EBV)
molecular mimicry
release of sequestered anitgen
these are different ways tolerance can be broken
EPSTEIN-BARR Virus (EBV) –> gives rise to polyclonal antibodies some of which may recognise self antigen
molecular mimicry –> by chance a antigen has the same peptide seuqence as a self peptide
release of sequestered anitgen –> injury can release hidden Ag which T cells have never seen and therefore think is foriegn (eyes, brain, testes)
Type 2 Auto immune disease
Streptococcos infection
Streptococcos infection is a type 2 AI disease –> therefore antigen is cell surface bound
in this case, the antigen from Streptococcos infection iis very similar to a heart protein leading to cardititis (molecular mimicry)
rhematic fever can also occur –> inflammatory disease that develops after a streptococcos infection
Type 2 AI
Graves disease
Graves disease is a type two AI –> antigen is cell surface bound.
antibodies recognise TSH receptor on the theyroid and bind with efficacy causing constant production of thyroid hormone
fatigue, weight loss, etc.
Type 2 AI
Myasthenia Gravis
Myasthenia Gravis is a type two AI –> antigen is cell surface bound.
self antigen is acetlycholine receptors at neuromuscualr junctions –> antibodies bind this and cause Ach receptor internalization
muscles become weak, droopy eyelids (ptosis)
Type 3 AI
Rhemaoid arthritis
Rhemaoid arthritis is a type 3 AI –> soluble antigen is detected and an immune complex forms.
TNF-alpha cytokine is detected as a foreign antigen. Antibodies bind this and form a complex that is too large for macrophages to engulf –> gets deposited into joints (a lot in hands) and causes destrcution.
what is Rheumatoid factor?
this is a gene that 80% of people with RA express.
RF is an IgG or IgM antibody that binds other antibodies
However, not everyone expresses this with RA so its not a given that you can’t develop it if you lack the RF.
Type 3 AI
Systemic Lupus Erythenatosus
Systemic Lupus Erythenatosus is a type 3 AI –> soluble antigen is detected and an immune complex forms.
antbody detects your own DNA!
when a cell lyses due to apoptosis sometimes DNA is let out –> antibody (usually IgG in all these cases) binds it and forms an immune complex that can be deposited in many different tissues
vasculititis --> vessel inflammation cardititis --> heart inflammation synvotitis --> joint inflammation dermatitis --> butterfy face glomerulophritis --> kidney inflammation
butterfly rash in face and kidney inf –> characteristic of lupus
Type 4 AI diseases
a. insulin dependent daibetes
b. rheumatoid arthritis (again)
c. multiple sclerosis
these three are type 4 AI –> cell mediated AI
a. insulin dependent daibetes
- pancreatic beta cell Ag –> destroys pancreas
b. rheumatoid arthritis (again)
- sinonovial joint Ag –> joint destruction
c. multiple sclerosis
- myelin is the anitgen
- demyelination of neurons leads to retardation
Primary immunodeficiency
chronic granulomatous disease
Innate immunity defect
when you are deficient in phagocyte oxidase which means you cannot form ROI which are essential in macrophage degradation of peptides (along with nitric oxide and elastase)
Primary ID
Complement ID
Innate immunity defect
macrophages lack C3b receptor (which is the opsonin often used for opsonization)
Primary ID
Bruton’s Disease
specific immunity defect
mutation in Bruton tyrosine kinase which is important in B cell development
person with Bruton’s disease will have very few B cells and antibodies
X linked disease
Why do children with Bruton’s disease only get infections after 3 months of living?
first three months the IgG placental antibodies given by the mother via passive immunity are still functional. Also, IgA antibodies in breast milk are given to the kid.
Primary ID
DiGoerge Syndrome
specific immunity defect
lack of proper thymus development leads to an inability to mature T cells –> lack CD4 CD8 NKT cells and lack B cells too since Th cells are needed for B cell activation.
live vaccine can be life-threatening
Primary ID
Hyper IgM syndrome
specific immunity defect
Mutation of the CD40L on CD4 Th cells
no CD40L-CD40 interaction with B cells inhibits T cell-dependent activation of B cells. Recall that Th2 produces Il-4 (and IL-5 and Il-13) which interacts with STAT 6 to produce an IgE class switch.
in Hyper IgM syndrome, there is no class switching
prone to infection in area’s IgM cannot go
What is Pneumocystis carinii?
Pneumocystis carinii is a fungal infection often developed by people with hyper IgM syndrome
Primary ID
Common Variable Id (CVID)
specific immunity defect
randomly cannot mature B cells perfectly causing a reduction in IgA or IgG or both depending on severity.
hypogammaglobulinaemia –> refers to a reduction in gamma globulins
treatment: IVIG aka IVGG
Primary ID
Adenosine deaminase deficiency (ADA)
specific immunity defect
Adenosine deaminase deficiency (ADA)
this is also called combined B and T cell immunodeficiency.
lack of the AD enzyme causes accumulation of deoxyadenosine which is toxic to lymphocytes leading to their death
must be homozygous recessive to get this disease
Primary ID
Sever combined ID (SCID)
specific immunity defect
lack of RAG 1 and 2 enzymes due to mutation meaning you cannot perform gene rearrangements at RSS sequences for either B or T cells. = no lymphocytes
treatment = bone marrow transplant
Primary ID
MHC 2 deficiency
specific immunity defect
bare lymphocyte syndrome is aka MHC 2 deficiency
mutation leading to no MHC2 –> no CD4 positive selection and no T cell-dependent B cell activation and no CD8 cell activation via Th1
treatment = bone marrow transplant
rather than primary ID (which are congenital/inherited) what is the main acquired ID?
HIV / AIDS
Explain HIV
a virus that infects macrophages and CD4 Th cells.
They target CD4 as their receptor to enter our cells
typically infects macrophages first then Th cells in the second wave.
HIV
explain
CD4
CCR5
GP120
GP41
CD4 –> main HIV receptor for infection
CCR5 –> co-receptor, also binds MIP (recall MIP is a late phase mediator in type 1 HS)
GP120 –> glycoprotein binds CD4 and other molecules
GP41 –> required for endocytosis of HIV
allograft rejections
hyperacute
acute
chronic
hyperacute –> preformed antibodies to graft –> rejection takes 24 hours
acute –> CMI (t cells) –> takes 10 days - 2 weeks
chronic –> constant battle to keep graft in (2-10 years)
minor H antigen such as H-Y antigen
or battle with therapy
cancer arises from
abnormal activity of a proto-oncogene –>
failure of a tumor supressor –>
defects in apoptosis –>
abnormal activity of a proto-oncogene –> RAS gene
failure of a tumor supressor –> P53 gene
defects in apoptosis –> BAD gene
what are tumor infiltrating lymphocytes
adaptive immunity lymphocytes that fight cancer
also b cells produce anti-tumor Ab’s to try cause NK ADCC
what are myeloid-derived suppressor cells (MDSC’s)?
myeloid-derived suppressor cells (MDSC’s) are recruited by T reg cells and they produce more Anti-inflammatory cytokines
