Immunodeficiency Disorders

Immunodeficiency Disorders

• Immunodeficiency disorders increase susceptibility to infections
• They are classified as primary (congenital or hereditary) or secondary (developed due to factors like malnutrition, cancer, HIV)
• Primary immunodeficiency disorders (DIP) are inherited through mutations of the X chromosome, presenting as autosomal recessive

What is the Immune System?

• The immune system consists of organs, tissues, and cells
• It protects the body from foreign substances, microorganisms, toxins, and neoplastic cells
• It participates in inflammation and healing processes
• Inefficiency in the inflammatory and cicatrization processes can lead to immunodeficiency disorders
• Immunodeficiency disorders can be caused by impaired innate or adaptive immune responses

Types of Immunoglobulins

• IgG fights bacteria, viruses, and toxins
• IgA protects mucous surfaces such as respiratory, digestive, and urinary tracts
• IgM responds rapidly to initial infections
• IgE defends against parasites and allergic reactions
• IgD participates in B lymphocyte activation

Components of the Immune System

• Innate Immune System: Rapid response, non-specific, lacks memory, includes physical barriers, phagocytes, and NK cells
• Adaptive Immune System: Slow response (days or weeks), specific to pathogens, possesses memory, includes lymphocytes T and B, and antibodies

States of Immunodeficiency

• Humoral Immunodeficiency (Cell B): Can be primary (e.g., X-linked hypogammaglobulinemia, common variable immunodeficiency, selective deficiency of IgG, IgA, and IgM) or secondary (e.g., increased loss of immunoglobulin in nephrotic syndrome)
• Cellular Immunodeficiency (Cell T): Can be primary (e.g., congenital thymic aplasia/DiGeorge syndrome, hyper-IgM syndrome) or secondary (e.g., malignant disease, transient suppression by viral infection, HIV/AIDS)
• Combined Immunodeficiency (Cells B and T): Can be primary (e.g., severe combined immunodeficiency linked to X chromosome, autosomal recessive conditions, Wiskott-Aldrich syndrome) or secondary (e.g., radiation, immunosuppression, cytotoxic drugs)
• Primary deficiencies can affect the complement system and phagocytosis
• Secondary deficiencies can affect the complement system due to consumption of complement factors
• Secondary deficiencies can affect phagocytosis by induced caused by drugs or diabetes mellitus

Complications of DIP

• Immunodeficiency disorders have debilitating and life-threatening complications, early detection being essential
• Children with DIP often have recurrent respiratory infections and do not respond to antibiotics
• Other signs include growth retardation, oral moniliasis, and mycotic infections

Microorganisms Associated with Immunodeficiency Disorders

• Viruses: Enterovirus (humoral), Herpes virus (T-cell mediated), or any virus (combined)
• Bacteria: Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae, Salmobella tiphy, and any mycobacteria
• Fungi: Candida albicans, Coccidioides immitis, Histoplasma capsulatum, Pneumocystis jirovecii, A. fumigatus, and Nocardia asteroides
• Protozoa: Giardia Lambila and Toxoplasma gondii

Deficiencies in Humoral Immunity (B Cells)

• Relates to B cell dysfunction and decreased Ig synthesis
• B lymphocytes produce antibodies and are essential for defense against bacteria whereas T lymphocytes detect antigens
• T lymphocyte function is typically unaffected, with normal responses to viral infections

Transient Hypogammaglobulinemia of Infancy (HTNL)

• At birth, infants are protected by maternal IgG antibodies
• Maternal antibodies gradually decrease over the first 6 months of life
• Infants with HTNL experience reduced Ig levels, which may lead to recurrent infections
• Treatment involves prophylactic antibiotics and intravenous immunoglobulin (IVIg)
• The majority of HTNL cases resolve spontaneously around 3 years of age

X-linked Agammaglobulinemia

• ALX is a hereditary sex-linked recessive disorder affecting males, results from a defect in early B cell development which leads to decreased mature B lymphocyte formation
• It results in profound decreases in immunoglobulin levels
• Affected males develop dangerous infections as maternal antibodies diminish and they can be diagnosed through low or absent Ig levels
• Treatment includes chronic IVIg administration and prophylactic antibiotics

Common Variable Immunodeficiency

• This is an immune system problem results in the body not producing enough antibodies to defend against infections
• The B cells are present in a normal count, however they do not function properly and they are often heterogenous
• There isn't a singular known genetic root

Common Variable Immunodeficiency Signs and Symptoms

• Low IgG levels
• Potentially low levels of IgA and IgM
• Increased risk of severe infections
• Frequent infections
• Autoimmune problems
• Increased risk of great illnesses such as lymphomas

Common Variable Immunodeficiency Treatments

• IVIg
• Management of infections with prophylactic antibiotics

Selective Immunoglobulin A Deficiency (ISIGA)

• It is the most common primary immunodeficiency disorder and results from a serum and secretory IgA depletion without affecting the IgG and IgM
• ISIGA affects 1 in 200-900 and some functions include:
• It is a primary antibody in digestive, urogenital and respiratory mucosa
• It neutralized toxins and pathogens
• Secretion mediated by cells inside the mucosal epitelium

Selective Immunoglobulin A Deficiency (ISIGA) Pathophysiology

• B lymphocytes create IGA but cannot differentiate to cell plasmatic IGA
• gene TACL mutations
• Monocyte CD40 expression or T regulator cell disfunction is possible
• the IVC is genetically linked

Selective Immunoglobulin A Deficiency (ISIGA) Clinic Manifestations

• Asintomatical (most people affected)
• compensated immune response
• typical IgG and IgM
• at age 14 50% of children grow over the insuficiency
• Sintomatical (most severe cases)
• recurrent lung (pneumonia and sinusitis) and/or intestinal infections
• Increased risk of autoimmune disorders and allergies (lupus, celiac, arthritis)
• AntilgA antibodies caused by anaphilaxis by transfusion in 20%-40% patients

Selective Immunoglobulin A Deficiency (ISIGA) Treatments

• Using antibiotics when relevant
• IgA's short half life recommends against therapy
• IgA transfusions must be avoided
• Use red cells from ISIGA donors or washed red cells

IgG Subclass Deficiency

• The antibody IgG can be divided in the subclass between IGG1-IGG4. A deficiancy can show in one sub class with normal IGG levels
• IGG1 and IGG3 defend from antigentic proteins
• IGG2 responds to the antigen polysacarids.
• IGG1 (70%) and IGG (20%) circulate
• IGG2 deficiancy poses risks such as sinisitus, otitis and pneumonias caused from encapsuled bacterias (N. meningitidis, S. pneumonaiea, H. influezae)
• Treatsments
• Prophyl active antibiotics for mild cases
• Immunoglobulina for more severe cases

Disorders Caused by Secondary Immunodeficiency.

• Excessive loss of immunoglobulins is one mecanism. Examples are nefrotic syndroms, lymphona and leoucemia or an effect that happened from medication
• When having Nefrotic sydrom the IGG gets lost in urine, when IGA und IGM stay or increase due to bigger molecule sign
• The causes come from malnouishment, burns or nefrotitic syndrome, malginant illnesses also certain medicines.
• Treatments revert the ill effects to the treatment
• Another mechnaism is when not enough is syntesized because of leokemia or lymphoa
• A result of secondary effect of medication is when antieptinsives, glucociortioids and anticonvulsives are taken

Deficiencies in Cell Mediated Immunity.

• All kind of illneses are produced because of fault on the immune respons on cellular level.
• The function has lots of diferent from the immunity perspectiva.
• They divided cells c4 (cooperators) y y CD8 (citotoxic, key function
• Key founctions include internal fungus defendion, protozoarios,virus, malign cellular control and immune response

Illnesses from cell immunity by disfunction cells

• Most severe from all disfunction cell is immunity
• viral infection because of early
• disfuncion with T cells sintensis, citocolinas, and activating ceull types.
• trasplante
• medula ose

Syndrome from Digeorge

• Moderate and weak immunit disfuncition because the absence of thyme
• Cardiac anomaly
• face misshapen
• skeletol disfunction
• affect both genders

Ligados Syndrome

• Is a prime disorder that affect men
• Has issues with integration CD40L (CD40L)
• High levesl igM & deficient IGG

Immunodeficiency Signs

• Recurrent issues
• Pneumonia
• More risk disautonomas
• Intestional and neuroendocrinos

Secoandary Insufiency with mediated immuntiy of cells

• Causes infection (Sarampion & citmegalovirus)
• The cells (vih herpexivirus)
• linfomas
• Casos idopaticos
• Anergia is the risk

Combined Cells & Syndromes

• Defect in the cells
• The function
• In the form MCH AND Cytotoxins

Gen Tratamient

• Es una combinacion grave
• Mas de 13 mutaciones
• Genera trastorno grande

Underficiation

• En la enfermedad linfonopeia
• Infeccion oppurtn
• Diarreia y atraganto
• Fallescer al poco

Trato

• Reemplantar una gran cantidad de huesos

Deficency combination

• Not much
• The body is weack
• Risk

Ataxia (AT)

• Gen disorder
• ATM
• Inmunitario
• T lincopemia
• Celles pulmonares

Discot & Syndrome (SWA)

• Es x cromison disease gen mutation

Transtorn del Sistema

• The system with cell memory helps againsr inkection wuth ayuda

Is the sistem the tranmistes

Afecta & Codominenre es un problema

Anemia del Angionauretico hereditare

• La producion afecta
• Hay un gene llamado serping
• En los vasossesangulions
• El liquido causes infalcion

Illness Transtorno de la facocitosis

• Facositus
• Inmunitaria
• Destruie a cuerpos extraños