1
Q
What is Immunodeficiency
A
Disorder or condition where the immune system has reduced function or is absent an can be traced to the failure of one or more parts of the immune system
2
Q
What are the 2 main types of immunodeficiency?
A
Primary
Secondary
3
Q
Describe primary immunodeficiencies
A
- Congenital
- Derive from a genetic or developmental defect leading to abnormal maturation of the immune system
- can be in either innate or adaptive immunity
- Most common kind is B-cell deficiencies
- rare because foetus rarely survives the defect
4
Q
Why are primary immunodeficiencies so rare%
A
In most cases, foetus does not survive the defect
5
Q
What are the 5 classifications of Primary immunodeficiencies?
A
1- B-cell deficiencies 2- T-cell deficiencies 3- Complement deficiencies 4- Phagocytic deficiencies 5- Combined T-cell and B-cell deficiencies
6
Q
Describe B-cell deficiencies
A
- Characterized by dysfunctional B Lymphocytes or a decrease in their prevalence
- First symptoms generally appear around the age of 7-9 months old (when Mother’s antibody pool from mother decreases)
- Increased susceptibility to infection especially by encapsulated bacteria
- Example: X-linked agammaglobulinemia (XLA), where patients do not develop mature B-cells, low levels of IgG and lack all other immunobglobulins
7
Q
Why do symptoms of B-cell deficiencies typically appear around 7-9 months old?
A
It is around 7-9 months that the antibody pool from the mother decreases, the incapability to synthesize normal levels of antibodies of the infant becomes apparent
8
Q
Increase in susceptibility to infection, especially encapsulated bacteria is the result of what class of deficiencies?
A
B-cell deficiencies
9
Q
X-linked agammaglobulinemia (XLA) is what type of immunodefficiency?
A
B-cell deficiencies
10
Q
Describe X-linked agammaglobulinemia (XLA)
A
- B-cell deficiency
- X-linked and recessive, thus occurs almost exclusively in males
- Patients do not develop mature B-cells
- Low levels of IgG and lack all other immunoglobulins
- Patients are extremely susceptible to bacterial infections, but susceptibility to viral and fungal infections remains unchanged (cell mediated immune responses are normal)
11
Q
Describe T-cell deficiencies
A
- Dyscfunctional T lymphocytes or a decrease in their prevalence
- Decreased cell-mediated immunity (which kills infected or abnormal cells)
- Increased susceptibility to viruses, protozoans, and fungi
- Frequent infections beginning 3-4 months after birth (eg: pneumonia, candidiasis)
Example: DiGeorge Syndrome
12
Q
Describe Secondary immunodeficiencies
A
- Are acquired and result from environmental factors affecting/compromising the immune system
- Causes; chemotherapy, chronic infection (eg: AIDS), developing cancer
- AIDS is the most studied
13
Q
What is the most studied secondary immunodefiency?
A
AIDS
14
Q
Describe Complement deficiencies
A
Genetic deficiencies in complement components
- Prone to frequent severe bacterial infections and complications arising from inability to clear immune complexes
- Patients with C3 deficiencies display the severest symptoms, reflective of the central role played by this component in complement activities
Example: Hereditary Angionedema
15
Q
Describe phagocytic deficiencies
A
remember phagocytes engulf and destroy pathogens
- Phagocytic deficiencies can appear at any steps of phagocytosis
- Bacterial and fungal infections are unusually frequent and severe, often causing deep abscesses
Example: Chronic Granulomatous (CGD)
16
Q
Describe combined T-cells and B-cells deficiencies
A
- Dysfunctional and/or low numbers of lymphocytes
- Both humoral and cell-mediated responses are compromised (adaptive immunity)
- Little or no resistance to infection thus pathogens that cause mild diseases in average person (eg: chicken pox) may be life threatening
- Often suffer fatal infections within the 1st year of life
17
Q
What kind of immunodeficiency is DiGeorge Syndrome?
A
T-cell deficiency
18
Q
Describe DiGeorge Syndrome
A
- Caused by deletion of a small segment of chromosome 22
- Absent or underdeveloped thymus, which results in the absence of mature T-cells
- Also causes abnormalities in the heart, face, and palate + learning disabilities
19
Q
Name a T-cell deficiency
A
DiGeorge Syndrome
20
Q
Name a B-cell deficiency
A
X-linked agammaglobulinemia (XLA)
21
Q
What kind of immunodeficiency is Hereditary Angioedema (HAE)
A
Complement deficiencies
22
Q
Name a Complement deficiency
A
Hereditary Angioedema (HAE)
23
Q
Describe Hereditary Angioedema (HAE)
A
- Dysfunction in the REGULATION of complement pathways
- caused by a lack of regulator of C1
- results in swelling of the face, lips, larynx, or GI tract. Swelling of larynx and GI trac are of particular concern because it can lead to suffocation
24
Q
What kind of immunodeficiency is Chronic Granulomatous (CGD)?
A
Phagocytic deficiency
25
Name a phagocytic deficiency
Chronic Granulomatous (CGD)
26
Describe Chronic Granulomatous (CGD)
- Body's phagocytes do not make the chemicals needed to kill the rest of the body
- Name derived from tendency of patient to form non-malignant granulomas in order to attempt to separate foreign materials from the rest of the body
27
Name a combined T-cell and B-cell deficiency
Severe Combined Inherited Immunodeficiency (SCID)
28
What kind of immunodeficiency is Severe Combined Inherited Immunodeficiency (SCID)
Combined T-cell and B-cell deficiency
29
Describe Severe Combined Inherited Immunodeficiency (SCID)
- Combined T-cell and B-cell deficiency
- David "Bubble Boy" Vetter lived in a bubble for 12 years (germ free). Passed away after a bone marrow transplant (intended to treat his disease) contained an unexpected infectious agent
30
What is the most well-known and studied secondary immunodeficiency?
AIDS
31
What does the acronym AIDS mean?
Acquired - not inherited
ImmunoDeficiency - breakdown of immune system
Syndrome - plethora of rare but ravaging diseases that take advantage of the body's collapsed defences
32
What is the most common mode of transmission of HIV in;
1- North America
2- Africa
3- Eastern Europe/Central Asia
1- Sexual Intercourse
2- Heterosexual sex with a concomitant epidemic in children through vertical transmission (mother-to-child)
3- Non-sterile injecting drug paraphernalia
33
What are the stages of HIV infection? (4)
1- Primary Infection
2- Acute Infection
3- Chronic Infection
4- AIDS
34
Describe the primary infection stage with HIV?
Most people will mount an effective immune response to the virus for the first couple of weeks
This response will prove ineffective over time (through stages)
35
Describe the acute infection stage with HIV
HIV targets and infects cells with CD4 on their surface (including CD4+ Helper Tcells)
- Causes drastic decrease in the level of CD4+ Helper T cells while level of virus in the blood increases
- Within 2-4 weeks of exposure, some people will experience flu-like symptoms including fever, headache, and rash
36
Why do CD4+ Helper T cells level stop crashing after the acute infection?
Some antibodies are formed against the virus allowing the immune system to recover some of the lost cell population
37
Describe the Chronic infection stage with HIV (aka clinical latency)
HIV continues to multiply in the body at a steady state
- patients often do not experience symptoms but transmission is still possible
- anti-HIV antibodies are detectable during this phase, but HIV can begin to evade immune response by changing their antigens through high mutations rate
- duration of this phage is 8-10 years
38
Describe the AIDS stage of HIV
Throughout latency CD4+ Helper T Cells get "exhausted" and depleted by constantly fighting a chronic HIV infection.
AIDS is diagnosed when the CD4+ Helper T cell level are less than 200 cells/mm3
- Viral load drastically increases as the virus acquire mutations that allow it to further avoid immune defenses
- Immune System is severely weakened, patients become extremely susceptible to opportunistic infections
- In absence of treatments patients typically survive about 3 years
39
When was the first antiretroviral approved?
1987
40
How does antiretroviral therapy work?
It prevents the virus from replicating (does not kill it)
Utilizes a panel of antiretroviral drugs in different combinations to prevent drug resistance by the rapidly-mutating virus
- Led to declines of AIDS and AIDS associated deaths
41
What are screening techniques?
Methods or strategies used to identify the possible presence of a disease in individuals who may be pre-symptomatic or have unrecognized symptoms of the disease
- Allow for early intervention and management of the disease to reduce suffering and mortality
42
What are the two major screening methods for primary and secondary immunodeficiency?
- Complete Blood Counts (CBC)
| - Quantitative Serum immunoglobulin
43
What is Complete Blood Count?
- screening method for immunodeficiency
- Shows how many of each cell types are present in a small sample of patients' blood. It is then compared to a reference range values commonly found in healthy people
- Used to highlight severe defect in the blood that could potentially be caused by immunodeficiency
- readily available for doctors
44
What is Quantitative Serum Immunoglobulin test?
- Screening method for primary and secondary immunodeficiency
- Measure the levels of IgG, IgA, IgM in patients' blood serum + compare them to control
- if levels are lower than normal it could be a sign of humoral deficiency
- Further testing (eg: complet blood counts & urine protein electrophoresis) can be used to pinpoint the source of hypogammaglobulinemia
45
Which specific immune cells does HIV preferentially replicated in?
Helper T-cell
46
What is Autoimmunity?
In some circumstances, the immune system initiates a reaction in response to its own cells. (lack of self recognition or overactive immune system)
47
What is an autoimmune disease?
Failure of an organism to distinguish self from non-self causes the immune system to initiate a response against its own cells and tissues
Any disease that results from such an aberrant immune response is termed autoimmune
48
How many kinds of autoimmune diseases are there&
80+
49
What is the prevalence of autoimmune diseases within the general population?
5-7%
50
Which gender is more commonly affected by autoimmune diseases?
Women (about 78%)
51
What is the development of autoimmune disease highly dependent on?
Genetics, but many other factors like infection by bacteria/viruses or chemical exposure can play a role in their development
52
What is the main cause of autoimmune diseases?
genetics
53
What are the 2 main categories of autoimmune diseases?
1- Organ specific
| 2- Systemic
54
Describe organ specific autoimmune diseases (3)
- Immune response directed to an antigen that is unique to a single organ or gland (disease manifestations limited to the specific organ)
- Most commonly affect organs: thyroid gland, Stomach, Adrenal Glands, Pancreas
- Example: Graves' disease (type of hyperthyroidism)
55
What is Graves Disease?
Organ specific autoimmune disease where patients produce autoantibodies that continuously bind to the TSH receptors
- TSH is produced by pituitary gland and stimulates production of thyroid hormones
Results in an unregulated overproduction of thyroid hormones
Causing:
- a goiter (enlargement of the thyroid gland)
- Metabolic dysfunction; weight loss, rapid heart beat, poor regulation of body temp, muscle weakness and irritability
56
Describe systemic autoimmune diseases (2)
- Immune response is directed towards a broad range of antigens that are characteristic of a number of organs and tissues
- Example: Rheumatoid arthritis
57
What is rheumatoid arthritis ?
Systemic autoimmune disease
- most commonly observed in women 40 to 0
- Many patients produce autoantibodies (most commonly IgM) to portions of the Fc receptor of IgG which are referred to as rheumatoid factors
- Rheumatoid factors bind to circulating IgG forming immune complexes that become deposited inside the joints
- These deposits can activate the complement cascade leading to prolonged inflammation and, ultimately, joint tissue damage
58
How is autoimmunity cured and/or treated?
- Not curable
| - Treated by reducing the reactions through immunosuppression, which has unfortunate secondary effects
59
What is immunosuppression?
Through the use of drugs, we can suppress of reduce the strength of the body,s immune response
- Useful in treating autoimmune diseases and organ transplants
60
Name the 4 classes of Immunosuppressive drug, their actions, and a drug name?
```
1- Corticosteroids:
- Anti-inflammatory, Kill T-cells
- Prednisone
2- Cytotoxic Drugs
- Block cell division non specifically
- Cyclophosphamide, methotrexate
3- Immunophilins
- Blocks T-cells
4- Lymphocyte-depleting therapies
```
61
What type of immunosupressant is prednisone and name its effect
- Corticosteroid
| - Relief for inflamed areas of the body
62
Name 2 immunosuppressive drugs that are cytotoxic
Cyclophosphamide, methotrexate
63
What type of immunosupressant is cyclophosphamide and name its effect
- Cytotoxic Drug
| - Treats cancer by slowing or stopping cell growth
64
What type of immunosupressant is Methotrexate and name its effect
- cytotoxic
| - Treats cancer by stopping or slowing cell growth
65
What type of immunosuppressant is anti-inflammatory and kills T-cells?
corticosteroids
66
What type of immunosuppressant blocks cell division nonspecifically
Cytotoxic drugs
67
What type of immunosuppressant blocks T-cell response?
Immunophilins
68
What type of immunosuppressant kills t-cells non-specifically and kills activated T-cells?
Lymphocyte-depleting therapies
69
What type of immunosuppressant provides relief for inflamed areas of the body?
corticosteroids
70
What type of immunosuppressant treats cancer by slowing or stopping cell growth?
cytotoxic drugs
71
What type of immunosuppressant is used to prevent rejection in those receiving a transplant?
Immunophilins
72
What type of immunosuppressant is used to prevent acute rejection in organ transplantation?
lymphocyte-depleting therapies
73
What is the use of corticosteroids?
provides relief for inflamed areas of the body
74
What is the use of cytotoxic drugs?
treats cancer by slowing or stopping cell growth
75
What is the use of immunophilins?
used to prevent rejection in those receiving a transplant
76
What is the use of lymphocyte-depleting therapies?
used to prevent acute rejection in organ transplantation
77
What are potential side effects of Immunophilin?
Nephrotoxicity, hypertension, hirsutism, hypertichosis, gingival hyperplasia
78
What are potential side effects of Cytotoxic drugs?
Nausea, vomiting, loss of appetite, stomach ache, diarrhea, darkening of skin/nails
Hair loss, tiredness, dixxiness, chills, headache, mouth sores, sores in lungs, increased risk of skin infection, sun sensitivity, rash, stuffy or runny nose, sore throat, low blood cell levels
79
What are potential side effects of corticosteroids?
Osteoporosis, hirsutism, hypertrichosis, diabetogenic
80
What are some impacts of immunosuppression on the host? (2)
Latent infections (reactivation of pathogens that are usually associated with latent infections; TB HSV1)
Opportunistic infections
(Reactivation of a pathogen that is already present in the host, but blunted immune response is unable to combat pathogen; bacteria, viruses, parasites or fungi)
81
Name 4 opporutnistic fungal infections
- PCP (pneumonia)
- Cryptococcal disease
- Candidiasis (thrush)
- Aspergillosis
82
Name 2 opportunistic bacterial infections
Tuberculosis
| MAC
83
Name 1 opportunistic parasitic infection
Toxoplasmosis
84
Name 4 opportunistic viral infections
- CMV
- Chicken Pox
- Herpes
- Epstein-barr
85
What kind of infections are - PCP (pneumonia), Cryptococcal disease, Candidiasis (thrush), Aspergillosis
Fungal
86
What kind of infections are Tuberculosis, MAC ?
Bacterial
87
What kind of infections are
- CMV
- Chicken Pox
- Herpes
- Epstein-barr
viral
88
What kind of infection is toxoplasmosis?
parasitic
89
What is the other name of Type I hypersensitivity?
Immediate/anaphylaxis
90
What are the key mediators of Type I hypersensitivity? (4)
Allergens
IgE
Basophils
Mast cells
91
What is the mechanism of reaction of type 1 hypersensivity?
Primary exposure:
Allergen induces humoral immune response whein plasma cells secrete an excessive amount of IgE antibodies which bind to mast cell and Basophils
Secondary exposure:
Membrane-bound IgE cross-link with the allergen which initiates the degranulation of basophils and mast cells releasing vasoactive mediators causing vasodilation and smooth muscle contraction
92
What are clinical manifestations of type 1 hypersensitivity? (4)
Allergic rhinitis
Atopic dermatitis
Asthma
Hives
93
What is the other name of Type II hypersensitivity?
Cytotoxic hypersensitivity
94
What are the key mediators of Type II hypersensitivity? (4)
IgG
IgM
NK cells
Complement system
95
What is the mechanism of reaction of type II hypersensivity?
IgGs or IgMs bind to antigens on the surface of cells
Fc region activate classical complement activation and antibody-dependent cell mediated cytotoxicity (ADCC)
Destruction of the cells leading to excessive inflammatory response
96
What is the other name of Type III hypersensitivity?
Immune complex-mediated
97
What are the key mediators of Type III hypersensitivity? (3)
Immune complexes (antibody + antigens)
Neutrophils
Complement proteins
98
What is the mechanism of reaction of type III hypersensivity?
Antibodies + antigens forming immune complexes which deposit in tissues
Immune complexes activate the complement which leads to neutrophils attraction to the site of deposition
Neutrophils release lytics enzyme to try to phagocytose the immune complexes which weakens surrounding cell membranes ultimately causing tissue damage
99
What are clinical manifestations of type 2 hypersensitivity? (2)
Transfusion reactions
| Drug induced hemolytics anemia
100
What are clinical manifestations of type 3 hypersensitivity? (1)
Serum sickness
101
What is the other name of Type IV hypersensitivity?
Delayed-type
102
What are the key mediators of Type IV hypersensitivity? (3)
CD8 CD4 macrophages
103
What is the mechanism of reaction of type IV hypersensivity?
After exposure to antigens, T-cells become activated and initiate an immune response
Sensitized helper T-cells (Th1) will release cytokines that activate macrophages or cytotoxic T-cells which mediate direct cellular damage
104
What are clinical manifestations of type 4 hypersensitivity? (2)
Inflammatory Bowel disease
| Contact Dermatitis
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