Immunodeficiency Disorders - ( Easy way to Remember ) - USMLE

CVID :

B cells normal in numbers ; but decrease in IgG IgM and IgA

• Recurrent sinopulmonary infections in adults 
• Decreased response to Antigen stimulation of B cells .
• NORMAL amount of lymphoid tissues 

Rx : IV immunoglobulins

X-linked (Bruton) Agammaglobulinemia :

• Male Children 
• B cells and Lymphoid tissue are diminished 
• Absence of the tonsils, adenoids , lymph nodes . T cell NORMAL 

Rx : IVIG

SCID :

Combined so Both B and T cells - related to both : B cells : recurrent sinopulmonary infection as early 6 month. T cells : Candida , AIDS , PCP

Rx : BMT

IgA deficiency :

• sinopulmonary infections : Difference it also have Atopic diseases , Anaphylaxis to blood tranfusion when blood is given from a patient who has normal levels of IgA
• Sprue like condition with fat malabsorption 

Rx : infections and use blood from igA-deficient donors or that has been washed.

Hyper IgE: skin infections with staph.

CGD:

lymph nodes with purulent material leaking out . Abnormal NBT testing .

List of Granulomatous diseases

• Bartonella henselae(cat scratch disease)
• Berylliosis
• Churg-Strauss syndrome
• Crohn disease
• Francisella tularensis
• Fungal infections (e.g., histoplasmosis, 
• blastomycosis)
• Granulomatosis with polyangiitis (Wegener)
• Listeria monocytogenes(granulomatosis 
• infantiseptica)
• M. leprae(leprosy; Hansen disease)
• M. tuberculosis
• Treponema pallidum(tertiary syphilis)
• Sarcoidosis 
• Schistosomiasis

Th1cells secrete γ-interferon, activating macrophages. TNF-αfrom macrophages 

induce and maintain granuloma formation. Anti-TNF drugs can, as a side effect, cause 

sequestering granulomas to breakdown, leading to disseminated disease. Always test for 

latent TB before starting anti-TNF therapy.

Pneumococcal polysaccharide vaccine (PPSV) for Adults

Pneumococcal polysaccharide vaccine (PPSV) should be given once to all adults age > 65. it should also be given to all adults age < 65 with chronic diseases:

Chronic lung disease

• Asthma
• COPD
• Emphysema

• Chronic cardiovascular disease
• Diabetes mellitus
• Chronic liver disease
• Alcoholism
• Cochlear implants
• CSF leaks
• Immunocompromising diseases

Functional or anatomic asplenia

• Sickle cell
• Other hemoglobinopathies
• Splenectomy
• Acquired asplenia.

Enzyme-linked immunosorbent assay (ELISA)

Enzyme-linked immunosorbent assay (ELISA)

assays are serological tests that examine for the presence or adsence of antibody in human serum directed against the pathogen being tested. ELISA is the first test done in assessment of a patient with suspected HIV infection and positive ELISA results are confirmed by western blotting.The most frequently used form of ELISA is the indirect form where the test detects antibody in the patient's serum directed against a known antigen. The specific steps of this assay are outlined below.

1.Known antigen,such as antigen from the HIV virus,is fixed to the bottom of a well.

2.Patient serum is then added to these wells containing known antigen. If present, patient antibody specific for the known antigen will bind the antigen and remain fixed to the well.

3.The plate is washed to remove unbond patient antibody. After this wash, only the patient antibody-known antigen complexes(Patient anti-HIV antibody complexed to HIV antigen ) remain attached to the well.

4.Next a second antibody is added to the wells. This antibody is an anti-human IgG antibody, and as such it will bind to the patient immunoglobulin that was bound to the fixed antigen in the previous steps. These second antibodies are coupled to the substrate-modifying enzyme (''enzyme linked'')

5.Wash the wells so that excess unbound enzyme-linked antibodies are removed.

6.Apply a substrate, such as chromogen, which is converted by the enzyme to elicit a chromogenic or fluorescent signal.

Process of Immunity (images)

Outer cortex containing follicles and an inner medulla. B, The location of B cells and T cells (stained red). C, A germinal center.

T cell receptor and its interaction with MHC molecule

Activation of B cells and the immunoglobulin molecule structure

Antigen presenting cells of the skin called dendritic cells

Natural killer cells: body’s innnate immunity and one of the first line of defence

Antigen processing and presentation on the surface of APCs with MHC I complex- causing activation of CD8 killer T cells.

Comparison of RA and Osteoarthritis.

(Click to View)

Roles of HLA / MHC in autoimmune diseases.

1.Ankylosing spondylitis B27

2.Postgonococcal arthritis B27

3.Acute anterior uveitis B27

4.Rheumatoid arthritis DR4

5.Autoimmune hepatitis DR3

6.Primary Sjögren syndrome DR3

7.Type 1 diabetes mellitus DR3/DR4

Some important autoimmune diseases.

1.Hashimoto thyroiditis

2.Systemic lupus erythematosus

3.Autoimmune hemolytic anemia

4.Rheumatoid arthritis

5.Pernicious anemia due to atrophic gastritis

6.Multiple sclerosis

7.Inflammatory myopathies

8.Goodpasture syndrome

9.Systemic sclerosis (scleroderma)

10.Idiopathic thrombocytopenic purpura

11.Polyarteritis nodosa

12.Insulin-dependent diabetes mellitus

13.Myasthenia gravis

14.Graves disease

15.Primary biliary cirrhosis

16.Autoimmune hepatitis

17.Inflammatory bowel disease( ulcerative colitis and Crohn’s disease)

What is left shift?

A left shift is an increase in the number of immmature neutrophils or polymorphonuclear leukocytes (PMN's). These are called band or stab neutrophils, and in more severe cases there may be metamyelocytes or myelocytes present. Mature (normal) neutrophils are referred to as segmented neutrophils or segs. In a normal differential there should be 0-6 bands per 100 WBC's and no metamyelocytes or myelocytes.

These immature cells make it into the bloodstream because chemical signals (cytokines, complement, etc.) released from the site of inflammation stimulate the bone marrow to release them prematurely. They continue to mature after entering the bloodstream, and the left shift will usually disappear within a few days if the cause of the inflammation is addressed.

An increased neutrophil count with a left shift is typically associated with bacterial infection, and may be increased in other inflammatory conditions or post-surgically.

What is LR?

A leukemoid reaction (LR) is a hematological disorder, defined by a leukocyte count greater than 50,000 cells/mcL with reactive causes outside the bone marrow

LR is characterized by a significant increase in mature neutrophils in the peripheral blood and a differential count showing left shift.

The diagnosis of LR is based on the exclusion of chronic myelogenous leukemia (CML) and chronic neutrophilic leukemia (CNL).

Causes of leukocytosis. (a)

Neutrophilic leukocytosis

Acute bacterial infections, especially those caused by pyogenic organisms;

sterile inflammation caused by, for example, tissue necrosis (myocardial infarction, burns)

Eosinophilic leukocytosis(eosinophilia)

Allergic disorders such as asthma, hay fever

allergic skin diseases (e.g., pemphigus, dermatitis herpetiformis)

parasitic infestations;

drug reactions;

certain malignancies (e.g., Hodgkin disease and some non-Hodgkin lymphomas);

collagen vascular disorders and some vasculitides;

Causes of leukocytosis. (b)

Basophilic leukocytosis(basophilia)

Rare, often indicative of a myeloproliferative disease (e.g., chronic myelogenous leukemia)

Monocytosis

Chronic infections (e.g., tuberculosis), bacterial endocarditis, rickettsiosis and malaria;

collagen vascular diseases (e.g., systemic lupus erythematosus)

inflammatory bowel diseases (e.g., ulcerative colitis)

Lymphocytosis

Accompanies monocytosis in many disorders associated with chronic immunologic stimulation (e.g., tuberculosis, brucellosis);

viral infections (e.g.,hepatitis A, cytomegalovirus, Epstein-Barr virus);

Bordetella pertussis infection.

HLA

The human leukocyte antigen system (HLA) is the name of the major histocompatibility complex (MHC) in humans. The superlocus contains a large number of genes related to immune system function in humans. This group of genes reside on chromosome 6, and encode cell-surface antigen-presenting proteins and many other genes. The HLA genes are the human versions of the MHC genes that are found in most vertebrates (and thus are the most studied of the MHC genes). The proteins encoded by certain genes are also known as antigens, as a result of their historic discovery as factors in organ transplantations. The major HLA antigens are essential elements for immune function. Different classes have different functions:
HLA class I antigens (A, B & C) present peptides from inside the cell (including viral peptides if present). These peptides are produced from digested proteins that are broken down in the proteasomes. The peptides are generally small polymers, about 9 amino acids in length. Foreign antigens attract killer T-cells (also called CD8 positive- or cytotoxic T-cells) that destroy cells.
HLA class II antigens (DP,DM, DOA,DOB,DQ, & DR) present antigens from outside of the cell to T-lymphocytes. These particular antigens stimulate T-helper cells to multiply, and these T-helper cells then stimulate antibody-producing B-cells to produce Antibodies to that specific antigen. Self-antigens are suppressed by suppressor T-cells.
HLA class III antigens encode components of the complement system.
HLA have other roles. They are important in disease defense. They may be the cause of organ transplant rejections. They may protect against or fail to protect (if down regulated by an infection) cancers. They may mediate autoimmune disease (examples: type I diabetes, coeliac disease). Also, in reproduction, HLA may be related to the individual smell of people and may be involved in mate selection.
Aside from the genes encoding the 6 major antigens, there are a large number of other genes, many involved in immune function, located on the HLA complex. Diversity of HLA in human population is one aspect of disease defense, and, as a result, the chance of two unrelated individuals having identical HLA molecules on all loci is very low. Historically, HLA genes were identified as a result of the ability to successfully transplant organs between HLA similar individuals.

What is Passive Immunity?

Passive Immunity
Thus far, all the acquired immunity we have discussed
has been active immunity. That is, the person’s own
body develops either antibodies or activated T cells in
response to invasion of the body by a foreign antigen.
However, temporary immunity can be achieved in a
person without injecting any antigen. This is done by
infusing antibodies, activated T cells, or both obtained
from the blood of someone else or from some other
animal that has been actively immunized against the
antigen.
Antibodies last in the body of the recipient for 2 to
3 weeks, and during that time, the person is protected
against the invading disease. Activated T cells last for
a few weeks if transfused from another person but
only for a few hours to a few days if transfused
from an animal. Such transfusion of antibodies or T
lymphocytes to confer immunity is called passive
immunity.

Innate Immunity

The human body has the ability to resist almost all

types of organisms or toxins that tend to damage the

tissues and organs. This capability is called immunity.

Much of immunity is acquired immunity that

does not develop until after the body is first

attacked by a bacterium, virus, or toxin, often

requiring weeks or months to develop the immunity. An additional portion of

immunity results from general processes, rather than from processes directed

at specific disease organisms. This is called innate immunity. It includes the

following:

1. Phagocytosis of bacteria and other invaders by white blood cells and cells

of the tissue macrophage system,

2. Destruction of swallowed organisms by the acid secretions of the stomach

and the digestive enzymes.

3. Resistance of the skin to invasion by organisms.

4. Presence in the blood of certain chemical compounds that attach to

foreign organisms or toxins and destroy them. Some of these compounds

are (1) lysozyme, a mucolytic polysaccharide that attacks bacteria and

causes them to dissolute; (2) basic polypeptides, which react with and

inactivate certain types of gram-positive bacteria; (3) the complement

complex that is described later, a system of about 20 proteins that can be

activated in various ways to destroy bacteria; and (4) natural killer

lymphocytes that can recognize and destroy foreign cells, tumor cells, and

even some infected cells.

This innate immunity makes the human body resistant to such diseases as

some paralytic viral infections of animals, hog cholera, cattle plague, and distemper—

a viral disease that kills a large percentage of dogs that become

afflicted with it. Conversely, many lower animals are resistant or even immune

to many human diseases, such as poliomyelitis, mumps, human cholera, measles,

and syphilis, which are very damaging or even lethal to human beings.

Myasthenia gravis

is a neuromuscular disorder characterized by variable weakness of voluntary muscles, which often improves with rest and worsens with activity. The condition is caused by an abnormal immune response.

Causes
In myasthenia gravis, weakness occurs when the nerve impulse to initiate or sustain movement does not adequately reach the muscle cells. This is caused when immune cells target and attack the body's own cells (an autoimmune response). This immune response produces antibodies that attach to affected areas, preventing muscle cells from receiving chemical messages (neurotransmitters) from the nerve cell.
The cause of autoimmune disorders such as myasthenia gravis is unknown. In some cases, myasthenia gravis may be associated with tumors of the thymus (an organ of the immune system). Patients with myasthenia gravis have a higher risk of having other autoimmune disorders like thyrotoxicosis, rheumatoid arthritis, and systemic lupus erythematosus.
Myasthenia gravis affects about 3 of every 10,000 people and can affect people at any age. It is most common in young women and older men.

Muscle weakness, including:
Swallowing difficulty, frequent gagging, or choking
Paralysis
Muscles that function best after rest
Drooping head
Difficulty climbing stairs
Difficulty lifting objects
Need to use hands to rise from sitting positions
Difficulty talking
Difficulty chewing
Vision problems:
Double vision
Difficulty maintaining steady gaze
Eyelid drooping
Additional symptoms that may be associated with this disease:
Hoarseness or changing voice
Fatigue
Facial paralysis
Drooling
Breathing difficulty