Immune Deficiency And Complement System

Front 1

What cells are involved in the innate vs the adaptive immunity?

Back 1

Innate Immunity = Phagocytes, Eosinophils, Basophils, Mast cells and APCs(antigen presenting cells)

Adaptive immunity =B cells and T cells, Antbodies

Front 2

What are the two processes by which the innate and adaptive immune systems can become defective?

Back 2

Immunodeficiency can occur either as a result of Primary or Secondary Defects.

Primary defects - due to congenital or genetic cause

Secondary defects - diseases, drugs or environment

*secondary immune deficiency is far more common*

Front 3

What is the classic clinical presentation if somebody has primary defect of there phagocytic (umbrella term for neutrophils, monocytes, macrophages ect) innate immunity?

Back 3

Pneumonia, osteomyelitis, skin/mucos membrane infection, liver abscess, suppurating lymph nodes

Due to susceptibility to bacteria and fungus due to lack of neutrophils.

Front 4

If there is a primary deficiency in neutrophils what type of organisms is the body susceptible to?

I.e what organisms are nuetrophils responsible for attacking

Back 4

Neutrophils responsable for attacking bacteria and fungi.

So if low then body is susceptible to Staphylococci, E.coli, salmonella and Candida (fungus)

Front 5

What is the complement system?

Back 5

The complement system is basically all the extra proteins that support and stimulate the cells involved in the innate immune system.

They enhance the ability of phagocytes and antibodies to remove microbes.

They work by triggering and supporting the innate immune system and so without them the immune system is weakened.

Front 6

What are the 4 main functions of the complement system?

Back 6

Chemotaxis (chemical stimulation) of neutrophils and macrophages to the site of inflammation.

Responsible for Oponisation - opsin are any cells which aid phagocytosis by marking an antigen for immune response or dead cells for recycling

Lysis of microorganisms - rupturing membranes of foreign cells

Front 7

If a patient has a deficiency or defect in their complement system then what 4 infections are they most at risk of?

Back 7

Streptococcus

Staphylococcus

Heamophillus inlfuenza

Meningoccocal infection

Front 8

What is the name of the immune deficiency that is an autosomal dominant condition characterised by recurrent attacks of painless, non-pitting, non-pruritic, non-erthymematous swellings in subcutaneous tissues, intestinal wall and larynx/oropharynx?

Due to a deficiency in the C1-compliment inhibitor which is a major control protein in prevention inappropriate activation of classical complement pathway

Back 8

Hereditary Angioedema

Front 9

Primary immunodeficiencies manifest with mainly what?

Back 9

PIDs mainly manifest with infection

Front 10

Where in the body are the complement proteins produced?

Back 10

Complement proteins are produced in the liver

Front 11

There are 30 complement proteins and they all interact with each other in different ways depending on the pathogen they come across. This creates many different complement pathways depending on what proteins are interacting with what.

What are the three main complement pathways?

Back 11

Classical pathway

Alternative Pathway

Lectin Pathway

*all of these pathways come together to stimulate C3 protein - most important complement protein because it is responsible for the cell lysis, opsimation and recruitment of inflammation*

Front 12

What is more common in primary defects of the adaptive immunity - B cell defects or T cell defects?

Back 12

B cell defects are 5 x more common than T cell defects

Front 13

What are the 4 types of defects of the adaptive immunity (T and B cells)?

Back 13

Severe Combined Immunodeficiency (SCID)

Predominantly antibody deficiencies

Predominantly T cell deficiencies

Combination of B and T cell deficiencies

Front 14

What types of immune cells are deficient in Severe Combined Deficiency (SCID)?

And what are the clinical features of SCID?

Back 14

SCID is a disease of the new born where they are deficiency in Pluripotentent stem cells, Lymphoid stem cells and T&B cells.

Clinical features of SCID:

Usually well for first 3 months of life (because they are able to function of IgG passed down from mother)

Persistant superficial candida

Diarrhoea and failure to thrive

Chronic bronchitis

Interstitial Pneumonitis

Overwhelming bacteria sepsis

Front 15

What is a treatment for a newborn presenting with signs of SCID (primary defect in their adaptive immunity)?

Back 15

Intensive therapy required with nutritional support

Prophylactic and therapeutic antibiotics, anti-fungals, antivirals and immunoglobulin replacement therapy.

These are supportive measures only, cure can only be effected by finding a suitable donor for bone marrow transplantation.

Front 16

What is the only curative treatment for Severe combined immune deficiency (SCID)?

Back 16

BMT - bone marrow transplant

*the quicker the transplant given the better, once child starts presenting with bronchopneumonia and interstitial pneumonitis then survival rate drops from 70% to 30%*

Front 17

What type of antibody is most commonly deficient in Primary Antibody deficiencies?

Back 17

IgA antibody is most commonly affected in antibody deficiencies

Front 18

IgA deficiency is due to what type of mutation of the IgA gene?

Back 18

IgA deficiency due to deletion mutation of the IgA gene.

Front 19

Typically IgA deficiency is due to a genetic cause, however sometimes it can be secondary to drug reactions - what drugs can cause IgA deficiency?

Back 19

Phenyotoin, Penicillamine, Gold or Sulphasalzine

Front 20

IgG subclass deficiency is associated with the recurrence of what type of infection?

Back 20

IgG subclass def associated with Recurrent respiratory tract infections

Front 21

Which immunoglobulins are affected and which are unaffected in the genetic disease 'common variable immune deficiency' which has symptom onset in 3rd/4th decades of life?

Back 21

Common variable immune deficiency presents with low IgG and IgA but normal IgM.

Front 22

What is the name of the syndrome which is associated with a Primary adaptive immunity deficiency of T cells?

Back 22

Di George's Syndrome - Associated with T cell deficiency

Front 23

What are the clinical features of Di George syndrome?

(deficiency in T cells)

Back 23

Cardiac abnormalities

Abnormal face

Thymic hypoplasia - producing T cell dysfunction

Cleft Palate

Hypocalceamia which results from abnormal development of the parathyroid glands

Front 24

Why does Di Georges syndrome causes a T cell deficiency?

Back 24

Causes children to be born with a Thymic Hypopalsia - which means T cells cant mature in the thymus and so are dysfunctional.

Front 25

What type of infection are children with Di Georges most susceptible to?

Back 25

Due to the type of T cell deficient in Di George's, children are susceptible to Fungal infection;

So you often see them getting frequent Candidal infections of the skin, nails mouth and vagina

Front 26

The most common type of T&B cell primary deficiency is Wiskott Aldrich syndrome, what is the genetic linkage of this disease and what clinical signs does it classically present with?

Back 26

Wiskott Aldrich is an X-Linked deficiency in T&B cells.

It presents with Eczema and Platelet abnormalities.

Front 27

What are the general signs which present in a child who has a Adaptive immune deficiency?

Back 27

Unexplained failure to thrive

Excessive infections

Abnormal lymphoid tissue

Unexplained enlargement of liver/spleen

Unexplained joint symptoms

Front 28

What are the common complications in a person who has Adaptive immune deficiency?

Back 28

Infection - ranging from standard to severe

Malignant disease

Autoimmune disease

Hypersensitivity disorders

Iatrogenic problems

Front 29

If a patient has a defect in there antibodies, what type of bacteria are they most susceptible to?

Back 29

Defect in antibodies makes patients most vulnerable to bacterial infections:

Stpahylococci

Streptocci

Haemophilus

Expect to see signs of pneumonia and sore throats in patients who have a defect in Antibodies.

Front 30

If a patient has a defect in their T cells then what type of infections are they most susceptible to?

Back 30

T cell defects make them most susceptible to Viruses and Fungi

Expect to see signs of measles, herpes or Candida (thrush) in patients who have a defect of T cells.

Front 31

What are the general principles for a treating a patient who is immunodeficient and prophylaxis precautions?

Back 31

Treatment of underlying diseases/causative organisms (if any)

Appropriate antimicrobial agents for the infections(large doses for long periods)

Avoid blood transfusions

Avoid immunisation with live vaccines

Genetic counselling

Prenatal diagnosis where possible

Front 32

What are the specific therapies used to treat immunodeficiencies?

Back 32

Immunoglobulin replacement

Thymic hormones

Transplantation - bone marrow, fetal liver, fetal thymus (Di Georges)

Gene therapy

Cytokine therapy

Front 33

When should you suspect immunodeficiency in a patient?

Back 33

Immunodeficiency should be suspected in any patient who has serious, resistant, unusual or recurring infections.

*secondary causes are more common than primary disorders*

Front 34

What is the name of the Cell-mediated Adaptive Primary defective immunity?

Back 34

SCID - Severe combined immune deficiency

Front 35

What type of defective immunity condition causes Nephrotic syndrome?

Back 35

Nephrotic syndrome is caused by a Secondary Adaptive deficiency of antibodies

Front 36

What type of defective immunity condition causes SLE?

Back 36

SLE is caused by a Secondary Innate deficiency of Complement system.

*auto immune disease leads to destruction of compliment system*

Front 37

What type of defective immunity condition causes AIDs?

Back 37

AIDs is caused by a Secondary (HIV) Adaptive (CD4 part of adaptive immunity) cell mediated deficiency (lack of T cells and B cells)

Front 38

What is the most common primary defect of the adaptive immunity?

Back 38

Selective IgA deficiency is the most common primary defect of the adaptive immunity.

*although overall secondary defects are more common*

Front 39

What type of infections do primary antibody deficiencies typically present with?

Back 39

Expect patients to have recurrent bacterial infections - e.g stpahyloccoi, streptococcus pneumonia and heamophilus influenza

Front 40

What type of infections would you expect in a patient who has primary cell-mediated deficiency?

(T and B cells)

Back 40

Fungal - candida, aspergillus

Front 41

What type of infections would you expect in a patient who has primary defect in phagocyte function?

Back 41

Phagocytes are mainly responsible for destroying Fungi and Bacteria - so expect rise in fungal and bacterial infections

Front 42

What infections are patients with a Complement deficiency (C3 and co.) susceptible to?

Back 42

Complement deficiency makes patients extremely susceptible to life-threatening bacterial infections.

e.g Pneumonia, septicemia and meningitis.

*strongly associated with Nisserial infections*