W8L12-13 - Immune Diseases Flashcards
Inadequate Immune Response
Primary immunodeficiency - present at birth (genetic disorder)
Secondary immunodeficiency - acquired (drug or infection)
Examples of Primary Immune Deficiency
X-linked agammaglobulinemia (Brutons)
IgA deficiency
DiGeorge syndrome
Severe combined immune deficiency (SCID)
X-linked Agammaglobulinemia (Brutons)
Low number of B cells Low immunoglobulin levels No humoral immunity Mutation in B cell tyrosine kinase gene on X chromosome - BKT essential for B cell maturation - males affected mostly
IgA Deficiency
Reduced level of IgA production
Usually asymptomatic
Patients tend to have increased respiratory infections due to reduced sIgA
DiGeorge Syndrome
Failure to form T cells due to hypoplasia of thymus (partial or incomplete)
Infants have cleft palate, facial cleft, low ears, absence of parathyroid gland and heart is malformed
Vulnerable to virus and intracellular bacterial infection
Severe Combined Immune Deficiency (SCID)
Failure to develop T and B cells
Thymus and lymphoid tissue reduced
Early in life child has recurrent infections
Adenosine deaminase deficiency leads to accumulation of toxic waste in lymphocytes
Examples of Secondary Immune Deficiency
Severe malnutrition
Infants first 6 months only maternal Ig
Drug therapy
HIV/AIDS
Whats does HIV and AIDS stand for?
HIV - human immunodeficiency virus
AIDS - acquired immune deficiency syndrome
How does HIV/AIDS work?
Helper T cells destroyed by HIV
- helper T cells help B cells and cytotoxic T cells
Loss of helper T cell leads to severe immunosuppression
Death due to infection or cancer
Why does HIV enter macrophages 10x better than T lymphocytes?
HIV has higher affinity for co receptor CCR5 on macrophages than CXCR4 on T lymphocytes
How can you be immune to HIV?
If you are homozygous for mutant allele of CC-CKR5 gene on chromosome 3
This encodes for cell surface protein CCR5 (co-receptor for HIV)
Mutation is a deletion of 32 bp
The resulting protein shortened and loss function
Therefore HIV cant bind
Type 1 Hypersensitivity
Immediate hypersensitivity
Anaphylactic shock
Th2 response leading to excessive IgE to antigen
Normal response to worm infection however abnormal for some allergens
Type 2 Hypersensitivity
Circulating antibodies binding to antigen on cell surface or tissue inappropriately Causes: - complement activation - phagocytosis - NK cells
Type 3 Hypersensitivity
Soluble antigen reacts with antibody and these complexes deposit into tissues Often in blood vessel walls Causes: - complement activation - mast cell degranulation - attracts neutrophils
Type 4 Hypersensitivity
Delayed type hypersensitivity
Antigen presenting cells leads to Th1 response
Cytokine response activation cytotoxic T cells
Allergies and Asthma
Type 1 reaction (immediate hypersensitivity)
Th2 response
Involves IgE, mast cells and eosinophils
- exposure to allergen leads to activation of Th2 cells producing large amounts of IL-4
- B cells switch to IgE prodcution
- IgE binds to mast cells via Fc receptor
- second exposure to antigen causing crosslinking of IgE on mast cells causing degranulation and attracting eosinophils
What are the 2 types of autoimmune disease?
Organ specific
- response directed to variety of antigens within organ
- antigens usually molecules expressed on sruface of lving cells
- restricted pattern
Non-organ specific
- reponse to self antigens that are widely distributed
- often intracellular molecules
- multi-system disorders
Factors involved in Autoimmune Disease
Sequestered antigen
- antigens normally hidden to immune system
- accidental exposure to antigen
Cross reactivity with microbial antigen
- T cell or antibody directed against a microbe antigen also reacts against self antigen
- aka molecular mimicry
Polyclonal activation
- microbial activation of many clones of T or B cells
- non-specific so auto reactive clone may be activated
Non infectious triggers
- drugs, chemicals, hormones
What is tolerance?
Unresponsiveness to self antigens
Mechanisms of Self Tolerance
Anergy
- non-responsiveness of cells upon contact with antigen
Receptor editing
- genetic rearrangement of the variable region of BCR and TCR
- BCR and TCR no longer specific for antigen
Clonal deletion
- auto reactive T and B cells eliminated by apoptosis during development
Clonal ignorance
- cells that remain inactivated due to low affinity with self antigen
- low concentration of antigen = low signal
T cell suppressors
- Treg cells regulate/suppress T cells
Myasthenia Gravis
Antibodies directed to the acetylcholine receptor at neuromuscular junction
Blocks binding of acetylcholine from nerve to receptor on muscle
Receptors also internalised and broken down so fewer available
Weakness and fatigue of voluntary muscles
Occurs in:
40-50% young women
- high levels of anti-AChR antibodies
15-30% older men
Treatment:
- immunosuppressant drugs
- cholinesterase inhibitors
Systemic Lupus Erythematosus
Erythematosus = reddening of skin
Production of anti nuclear antibodies (ANA)
- positive ANA strongly supports SLE but is not confirmatory
- usually homogenous or speckled pattern
Patients can develop arthritis, skin lesions, kidney disease, pulmonary and neurological damage
SLE 10x more common in women because high oestrogen levels accelerate disease
Pathology of SLE
Mediated by auto-antibody type 2 and 3 hypersensitivity
- immune complex disease
Tissue damage due to deposition of dsDNA-Ab complexes (kidney)
SLE people may have defective mechanism of clearing DNA after apoptosis, so exposing DNA as antigen
UV light triggers flair up of disease
- UV light induces apoptosis of keratinocytes in skin
Rheumatoid Arthritis
Inflammation of synovium in joints
Progressive - invades cartilage and bone
Joint destruction
