Immunology Flashcards
(55 cards)
1
Q
What is the difference between primary and secondary immunodeficiency?
A
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
2
Q
What is SCID?
A
Severe Combined Immunodeficiency Disease
3
Q
What are the signs of SCID?
A
- lymphopenia of T and B cells
- absent thymic shadow on xray
- small tonsils
- mitogen responses low
- serum Ig low
4
Q
What happens in SCID-X1?
A
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
5
Q
What happens in
Adenosine Deaminase Deficiency?
A
- 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
6
Q
What is Bruton’s disease?
A
- 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
7
Q
What happens in X-linked hyperIgM syndrome?
A
- 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
8
Q
What happens in Common Variable Immunodeficiency?
A
- 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
9
Q
What happens in DiGeorge syndrome?
A
- 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
10
Q
CATCH-22
A
Calcium: low due to parathyroid defect
Appearance: head and face deformities
Thymus: no thymus
Clefts palate
Heart: abnormalities
on chromosome 22
11
Q
What kinds of infections are seen in T cell and B cell deficiencies?
A
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
12
Q
What happens in transient hypogammaglobulinemia of infancy?
A
- 6mo-18mo after birth
- slow to produce IgG after stop receiving from mom
- have lots of bacterial infections
13
Q
What is selective IgA deficiency?
A
- 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
14
Q
What is ataxia telangiectasia?
A
- AR inheritance
- sinus infetions, pneumonia, ataxia, and telangiectasia
- T and B cell def
- IgA def
- also defect in DNA repair –> tumors
15
Q
What is wiskott-aldrich syndrome?
A
- platelet and b cell def
- eczema
- bacterial infections
- X-linked
16
Q
How do you treat immunodeficiency?
A
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
17
Q
Briefly describe Type I immunopathology
A
- due to IgE
- Th2 mediated events
18
Q
Briefly describe Type II immunopathology
A
- due to IgG, IgM, and IgA causing harm to self (autoantibodies)
19
Q
Briefly describe Type III immunopathology
A
- formation of immune complexes trapped in basement membrane of blood vessels that activate complement –> vasculitis
- in chronic type III, T cells are important
20
Q
Briefly describe Type IV immunopathology
A
- pathologies due to T cell responses, both helper and cytotoxic
21
Q
Briefly describe CFIR immunopathology
A
- 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
22
Q
What are the 3 ways that antibodies can damage self tissue?
A
1) Neutralization
2) Complement-mediated damage
3) Stimulatory hypersensitivity
23
Q
What is neutralization?
A
- human protein inactivated by an antibody
- IFNgamma antibodies exist for example
24
Q
How does complement-mediated antibody tissue damage work?
A
- antibodies made against tissue
- activate complement and cells damaged by lysis, phagocytosis, or release of lysosomal enzymes and ROS from phagocytes
25
What is stimulatory hypersensitivity?
- if auto antibody against a cell surface receptor, can act as an agonist and activate it
26
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
27
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
28
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
29
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
30
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
31
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
32
What happens in autoimmune hemolytic anemia (AIHA)?
- usually follows a viral infection
- penicillin and other drugs can cause AIHA
- auto Abs against RBCs
33
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)
34
What is tolerance?
When the body does not create an immune response to an antigen (important especially to self antigens)
35
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
36
What is the forbidden clone?
- when T cells against self bypass selection in the thymus and encounter self antigen
- seen in myasthenia gravis
37
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)
38
What is type IV hypersensitivity?
- t-cell mediated
- do not require Ab or B cells
- delayed hypersensitivity
39
Briefly describe the initiation and elicitation phases of a reaction
Initiation: response to first exposure of an antigen
Elicitation: reaction after already being immunized
40
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
41
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
42
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
43
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
44
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
45
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
46
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
47
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
48
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
49
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
50
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
51
What happens in psoriasis?
- unregulated T cell response to normal skin flora
52
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
53
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
54
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
55
What do whipworms do?
- apparently help increase Treg in gut and suppress Th1,17,2
