Immunology Flashcards
What is the difference between primary and secondary immunodeficiency?
Primary - mutations in genes required for normal development of immune system (e.g. congenital defect in thymus or bone marrow); basically congenitally
Secondary - follows treatment with IS drugs or in an IS disease like AIDS; basically acquired
What is SCID?
Severe Combined Immunodeficiency Disease
What are the signs of SCID?
- lymphopenia of T and B cells
- absent thymic shadow on xray
- small tonsils
- mitogen responses low
- serum Ig low
What happens in SCID-X1?
SCID-X1
- defect in the gene for gamma chain that forms part of IL-2 receptors and other cytokines needed for lymphoid development
- block from SCH to SCL
- lymphocytes don’t mature
- X-linked recessive
What happens in
Adenosine Deaminase Deficiency?
- autosomal recessive type of SCID
- lack adenosine deaminase –> adenosine accumulates in cells and impairs lymphocyte development
- can give blood transfusion, but must irradiate first to kill any T cells
What is Bruton’s disease?
- X-linked Agammaglobulinemia
- normal T cells, but low B cells
- due to a developmental block between pre-B cell and B cell formation
- protein tyrosine kinase in pre-B cells is defective
- see lots of bacterial infections –> pneumonia and diarrhea
- enteroviruses can go through mucous membranes since no IgA to protect
- viral infections not a problem since have T cells
What happens in X-linked hyperIgM syndrome?
- have high IgM and low IgG and IgA
- defect in IgM to IgG switching
- Tfh has CD154 or CD40-ligand that interacts with CD40 on B cells to activate them and switch to IgG
- if CD40 or CD40-ligand is defective, then don’t make IgG
What happens in Common Variable Immunodeficiency?
- normal pre-B cells and B cells (and T cells), but lack maturation to plasma cell
- low IgG
- recurrent bacterial infections since low antibodies
- treat with IVIG or SCIG
What happens in DiGeorge syndrome?
- thymus develops from 3rd and 4th pharyngeal pouches; if defective, then T cells are absent
- 45 gene deletion on chromosome 22
- parathyroid also affected, so can see hypocalcemic seizures
- abnormal development of heart as well
- see viral and fungal infections
- T cells low, meaning B cells fail to get activated as well
CATCH-22
Calcium: low due to parathyroid defect
Appearance: head and face deformities
Thymus: no thymus
Clefts palate
Heart: abnormalities
on chromosome 22
What kinds of infections are seen in T cell and B cell deficiencies?
T cell def: viral, yeasts, fungal (Candida albicans, P. jirovecii)
B cell def: high grade (extracellular, pus) bacteria like S aureus, H influenzae, S. pneumoniae
What happens in transient hypogammaglobulinemia of infancy?
- 6mo-18mo after birth
- slow to produce IgG after stop receiving from mom
- have lots of bacterial infections
What is selective IgA deficiency?
- most common ID disease (200/100000)
- usually asymptomatic, but can have diarrhea and sinopulmonary infections and allergies
- some familial tendency
- more common in people with celiac disease
What is ataxia telangiectasia?
- AR inheritance
- sinus infetions, pneumonia, ataxia, and telangiectasia
- T and B cell def
- IgA def
- also defect in DNA repair –> tumors
What is wiskott-aldrich syndrome?
- platelet and b cell def
- eczema
- bacterial infections
- X-linked
How do you treat immunodeficiency?
1) Isolation - not practical for long time
2) Prophylactic antibiotics - change regularly to avoid resistance
3) IVIg (when B cell def) - mostly IgG
4) Transplant - thymus in DiGeorge; bone marrow or purified stem cells for SCID; ADA with PEG for ADA def
Briefly describe Type I immunopathology
- due to IgE
- Th2 mediated events
Briefly describe Type II immunopathology
- due to IgG, IgM, and IgA causing harm to self (autoantibodies)
Briefly describe Type III immunopathology
- formation of immune complexes trapped in basement membrane of blood vessels that activate complement –> vasculitis
- in chronic type III, T cells are important
Briefly describe Type IV immunopathology
- pathologies due to T cell responses, both helper and cytotoxic
Briefly describe CFIR immunopathology
- chronic frustrated immune response
- body is using adaptive immunity to get rid of antigens that it never can
- e.g. gut flora (Crohn disease), skin flora (psoriasis), chemicals (Be disease), foods (celiac disease)
- can’t dispose or effectively wall of antigen
What are the 3 ways that antibodies can damage self tissue?
1) Neutralization
2) Complement-mediated damage
3) Stimulatory hypersensitivity
What is neutralization?
- human protein inactivated by an antibody
- IFNgamma antibodies exist for example
How does complement-mediated antibody tissue damage work?
- antibodies made against tissue
- activate complement and cells damaged by lysis, phagocytosis, or release of lysosomal enzymes and ROS from phagocytes
What is stimulatory hypersensitivity?
- if auto antibody against a cell surface receptor, can act as an agonist and activate it
What happens in Graves disease?
- IgG antibody to thyroid stimulating hormone receptor –> mimics TSH and secretes thyroid hormones and bypasses normal neg feedback from pituitary –> hyperthyroidism/Graves disease
- example of stimulatory hypersensitivity
What happens in myasthenia gravis?
- progressive muscle weakness
- antibody to acetylcholine receptor –> activates complement and and attracts neutrophils and have inflammation
- AIRE usually expresses CHRNA1, but there is an allele to CHRNA1 that doesn’t interact with AIRE –> Th clones that react with achr are not deleted by neg selection –> Tfh can help B cells make antibody to achr
- hyperplastic thymus
- treat with thymectomy, immunosuppression, IVIg
- destruction of ACHRs
What happens in goodpasture syndrome?
- auto Abs to lung and kidney basement membrane
- epitope on type IV collagen in BM of lung and kidneys
- persistent glomerulonephritis, pulmonary hemorrhages
- sharp and linear immunofluorescence because Abs line up literally on basement membrane
What is dressler syndrome?
- after an MI, people make an auto Ab against pericardial or myocardial antigens
- presents with cardiac pain, fever, malaise, pericardial effuson
- treat with anti-inflammatory agents
What happens in rheumatic heart disease/rheumatic fever?
- after a strep infection, cross reaction between Group A Strep M protein antigen and a structure on heart endothelial lining, probably laminin in valves (Abs made to fight bug, but also binds to antigens in heart)
- followed by complement and neutrophil-mediated tissue destruction
- rheumatic fever is more widespread affecting skin and CNS
What happens in autoimmune thrombocytopenic purpura (ATP)?
- bleeding due to destruction of platelets by auto Abs
- treat with IS or removal of spleen
- seen usually weeks after a viral infection in young people
What happens in autoimmune hemolytic anemia (AIHA)?
- usually follows a viral infection
- penicillin and other drugs can cause AIHA
- auto Abs against RBCs
What happens in Hashimoto disease?
- leading cause of hypothyroidism
- antigen is thyroglobulin (where iodine is stored) and thyroid peroxidase
- inflammatory and destructive due to antibodies and T cells)
What is tolerance?
When the body does not create an immune response to an antigen (important especially to self antigens)
What happens with hybrid antigen formation?
- say you have a B cell that attacks self
- normally you would be fine if T dependent and did not have Tfh cells to help
- but if B cells binds to epitope that has self and foreign parts (specifically binding to the self part)
- it then ingest the antigen
- the FOREIGN epitope is presented on the surface to a Th2 cell on MHC Class II
- Tfh releasese cytokines and activates B cell, which secretes more antibodies to self
What is the forbidden clone?
- when T cells against self bypass selection in the thymus and encounter self antigen
- seen in myasthenia gravis
How do you diagnose type II immunopathologies?
- immunofluorescence
- direct test: looking for Abs in the patient’s tissues; add anti-Ab that binds to antibodies on patients tissues if present and light up; need patients tissues
- indirect: only with serum and normal tissue; (e.g. normal kidney tissue with no Ab, patients serum has anti kidney Abs, labeled anti-Ab bind to anti kidney Abs and light up)
What is type IV hypersensitivity?
- t-cell mediated
- do not require Ab or B cells
- delayed hypersensitivity
Briefly describe the initiation and elicitation phases of a reaction
Initiation: response to first exposure of an antigen
Elicitation: reaction after already being immunized
Describe what happens during initiation in contact dermatitis with poison ivy
- urushiol goes through skin and MHC on dendritic cells presents to T cells in lymph nodes
- produce Th1 and Th17 and divide but by the time they are in circulation, the urushiol is usually gone
Describe what happens during elicitation during contact dermatitis with poison ivy
- urushiol rubs onto skin again and goes onto APC
- memory T cells from previous are throughout body and get activated in local area
- secrete IFNgamma to bring in macrophages
- not immediate, take a while
Explain the tuberculin skin test
- inject TB antigens intradermally
- if there are memory cells for TB present (indicating a prior immunization or infection), then you see a large bump (15mm)
- the bump is mainly macrophages
- the injected dose is enough to evoke an elicitation reaction but not an immune reaction
How does the QunatiFERON-TB Gold test work?
- helps distinguish between previous immunization and infection
- only human specific epitopes of TB proteins added to blood sample and IFNgamma measured
How does abacavir hypersensitivity work?
- if patient has HLA-B*5701, not recognized by Th1, then structure of that is changed by abacavir so that it binds self-peptides that are not usually presented –> drug induced AI
Explain multiple sclerosis
- brain is antigenic but not immunogenic because activated T cells will never get past blood brain barrier because APCs do not pick up antigen
- fi you make brain antigens presented to APCS in a normal way, then can make activated T cells that can get through BBB
What is CFIR?
Chronic frustrated immune response
- immune system is trying to get rid of a foreign antigen that it can’t eliminate or encapsulate
How is IBD related to CFIR?
- have abscesses in wall of intestine and inflammation
- patient activates Th1, Th17, and Th2 against gut bacteria but can’t get rid of them so continuous inflammation
Describe the immune activity of the gut
- lot of TGFbeta in peyer patches and IL-10 production by dendritic cells –> turns Th0 to Treg
- lots of Treg cells
- Tfh in PPs that drive B cells towards making IgA
- however combining TGFbeta and IL-6 (produced by epithelial cells in response to damage) can downreg Treg and upreg Th1, Th2, and Th17
What happens in celiac disease?
- antibody to gut endomysium, specifically TG2
- turns into a B cell autoantigen
- T cell immunity to gliadin peptides that cause inflammation
What happens in chronic Be disease?
- pulmonary inflammation and fibrosis
- Be inhaled covalently links to peptides and creates new epitopes that Th1 responds to and Th2 scarring
What happens in psoriasis?
- unregulated T cell response to normal skin flora
What happens in periodontal disease?
- bacteria can get stuck in gingival crevice where saliva can’t really reach well and T cells definitely can’t because it is outside of the body
- have shift from TBFbeta to adding IL-6 –> inflammation
What is the hygiene hypothesis?
- exposure to environmental dirt and infections helped the immune system mature normally, while lack of it leaves the child in an infantile state
- thought that you would keep a Th2 dominated system like in babies, but saw also an increased risk in Th1 diseases
What is the old friends hypothesis?
- certain microorganisms have been in us so long that they tell our immune systems to not overreact against them
- if you have adequate exposure to these guys, you have a balance between activation and regulation by Tregs
- otherwise, might not have enough Tregs and make a too strong Th1 or Th2 response
What do whipworms do?
- apparently help increase Treg in gut and suppress Th1,17,2
