Module 2.4 Immune disorders Flashcards
Primary Immune disorders
Congenital or inherited
Why are primary disorders increasing in number over time
increased awareness and diagnosis. NOT increased incidence.
Humoral Immunity
B-cells, antibody immunity
Cell Mediated Immunity
T-Cell
4 Major Categories of Immune system
Humoral
Cell-Mediated
Compliment System
Phagocytosis (bridge between innate and acquired)
B-cell immunodeficiency is associated with
Enteroviruses Streptococcus H. Influenzae Giardia lamblia (protozoa) NO FUNGALS
T-Cell Immunodeficiency is associated with
Herpes
Salmonella
Mycobacteria
Candida Albicans and many other fungal infections
Combined T-cell and B-cell immunodeficiency is associated with
All viruses
Neisseria Meningitis
Toxoplasmosis gondii
Allografts
from other people
Autografts
From self
Transient Hypogammaglobulinemia of infancy
transient deficiency in some infants. Causes recurrent pyrogenic illnesses
B-cell immunodeficiency is usually not associated viruses. Why? What’s the exception?
B-cells don’t engage with intracellular pathogens.
Exception: enteroviruses
What causes x-linked agammaglobulinemia
Pre-B Cells fail to migrate to lymphoid tissue resulting in no immunoglobulin production at all
DiGeorge Syndrome
Primary T-Cell Deficiency
Congenital heart disease
Hypocalcemia
Complete or partial failure of Thymus and parathyroid development.
Most common primary immunodeficiency
Primary Humoral (B-cell) deficiency. (70%)
Secondary Cell Mediated immunodeficiencies are caused by
Acute viral syndromes
some cancers
Severe Combined Immunodeficiency (SCIDs)
X-linked inheritance
Combined T cell and B cell deficiency
Ataxia–telangiectasia
Autosomal Recessive Inheritance
Combined T cell and B cell deficiency
Ataxia–telangiectasia S/S
Occulocutaneous telangiectasis (big red vessels in eyes). Ataxia (kid cant walk when it's time to learn).
Ataxia-telangiectasis immune effects
T-Cell function unchanged but decreased in number
Deficiency in IgA IgE and IgG
Wiskott-Aldrich Syndrome
X- Linked recessive (affects boys primarily)
Combined T cell and B cell deficiency
Wiskott-Aldrich Syndrome S/S
Thrombocytopenia
Recurrent Infections
Eczema
Wiskott-Aldrich Syndrome Prognosis
life expectancy 15 years
Wiskott-Aldrich Syndrome immune effects
Low IgM
High IgA and IgE
Limited T-cell function which improves with time
Wiskott-Aldrich Syndrome treatment
Stem Cell or Bone Marrow transplant
How are most primary compliment system disorders acquired
autosomal recessive
Hereditary angioneurotic edema is associated with
Primary compliment system disorders.
Hereditary angioneurotic edema is caused by
Swollen mucous membranes (airway, lips, deep localized tissue swelling)
What causes Secondary compliment system disorders
Rapid activation -> depletion
or reduced synthesis of compliment components
Dysfunction of the phagocytic system would make one particularly susceptible to:
FUNGAL INFECTIONS!
Candida species
Filamentous fungi
May also result in chronic granulomatous disease (CGD)
Hypersensitivity types and their associated systems
Type I - IgE mediated
Type II - Antibody mediated
Type III - Complement mediated
Type IV - T-Cell Mediated
Type I hypersensitivity
Allergies! Causes release of histamines from MAST cells
Management of Type I
Avoid offending agent
Nasal steroids
Cromolyn Sodium (Mast cell stabilizer)
Desensitization (allergy shots)
What is the basic principle behind desensitization
Increase IgG antibodies to the antigen so that IgG binds rather than IgE which is what causes the reaction.
Primary/initial phase of Type 1 response
IgE stimulates Mast cells, basophils and eosinophils.
Vasodilation
Vascular Leakage (swelling)
Smooth muscle contraction
Secondary/late phase of Type 1 response
More intense infiltration of tissue with eosinophils
Endothelial cell damage
What causes the secondary/late phase response of type 1 hypersensitivities
T-cell recruitment of eosinophils
+
Degranulation of mast cells causing release of membrane phospholipids (arachidonic acid, prostaglandins, leukotriens).
What determines the severity of type 1 reactions
Degree of Sensitization (# of IgE receptors on mast cells or number of mast cells).
NOT the quantity of exposure.
Grades of Type reactions
I: Cutaneous and Muscle Erythema, Urticaria.
II: Multisystem S/S Hypotens. Tachycardia, dyspnea, N/V, Diarrhea
III: Bronchospasm, dysrhythmias
IV. Cardiac Arrest
ABC priority
BAC now
Type II (cytotoxic) reactions are mediated by
IgG and IgM
Most common Type II reaction example
Blood transfusion reactions and Hemolytic disease of the newborn
Which antibody causes hemolytic disease of the newborn
IgG - only one that can cross placenta
SEE PAGE 319 IN BOOK FOR TYPE 2 REACTION TABLE
SEE PAGE 319 IN BOOK FOR TYPE 2 REACTION TABLE
Serum Sickness
Systemic Type 3 (immune complex) reaction
Takes 1-2 weeks to manifest
Arthus Reaction
Localized Type 3 (immune complex) reaction
What causes type 3 reaction
Antibody-Antigen complex forms, binds to cell membrane causing compliment system activation which attracts inflammatory cells
Type IV hypersensitivity
T-cell mediated.
Can be Direct cell-mediated or Delayed Type
Delayed Type IV reaction
CD4 T cells release cell damaging cytokines
Contact dermatitis, farmer’s lung,
Direct Cell Mediated Type IV reaction
CD8 T Cells kill antigen bearing target cells
Latex reactions are what type of reactions
Can be type I or IV
Symptoms determine the type
Transplanted tissue categories and definitions
Allogeneic - Similar HLA types between donor and recipient (may or may not be related)
Syngeneic - Identical twins
Autologous - Same person
Central tolerance
Elimination of self reactive T-cells (in thymus) and B-cells (in bone marrow)
Peripheral tolerance
Deletion of auto-reactive cells that escaped central tolerance elimination
Hyperacute Transplant Rejection
occurs almost immediately.
Type II reaction, arthus reaction.
Acute Transplant Rejection
Occurs in first few months
T-Lymphocytes respond to antigens in graft tissue.
Chronic Host-Versus-Graft Rejection
Occurs over years
Fibrosis of blood vessels in transplanted organ. unknown mechanism
Graft Versus Host Disease
Grafted organ attacks host body. takes 10-14 days
GVHD requirements
must be an organ with functional immune component
Host immune system must be compromised to the point of being unable to destroy the transplanted organ.
GVHD Clinical manifestations
Palm and feet rashes
Systemic Lupus Erythematosus
Autoimmune disease
Butterfly rash
Causes systemic issues with most organs/systems
Autoimmune Hemolytic Anemia
Antibodies attack host blood cells
Pemphigus Vulgaris
Blistering of skin and Epithelial linings.
Hashimoto Thyroid
first ever autoimmune disease discovered
Causes hypothyroid
Diagnostic criteria for autoimmune disorders
Evidence of autoimmune reaction
Determination that it’s not secondary to another condition
Lack of other identified causes
Lab tests
Lab tests to demonstrate autoimmune reactions
Indirect Fluorescent Antibody Assay (IFA)
Particle agglutination assay
Enzyme Linked Immunosorbent assay (ELISA)
