Antigen
- It is a high molecular weight foreign substance, a protein of polysaccharide in nature
- Any foreign molecule that can trigger an immune response
- Any substance capable of inducing a specific immune response and reacting with the products of that response
Antibody
- It is a protein substance produced as a result of antigenic stimulation
- Antibodies types- IgG, IgA, IgM, IgE & IgD
Antigen and antibody reaction
- Antigen (Ag) and antibody (Ab) combine specifically with each other. This interaction between them is called antigen-antibody complex or reaction
- It is written/abbreviated as Ag-Ab reaction
- These reactions (serological reactions) form the basis for detection of infectious disease causing agents and also some non-specific Ag’s like enzymes
Uses of Antigen and antibody reaction
- Blood grouping (ABO and Rh)
- Cross matching before blood transfusion
- Diagnosis of infectious diseases (Enteric fever)
- Identification of microorganisms
- Diagnosis of immune disorders
Types of Antigen and antibody reaction
- Agglutination reaction
- Precipitation reaction
- Complement fixation reaction
- Neutralization reaction
- Immunoelectrophoresis and counterimmunoelectrophoresis
- ELISA
- Immunofluorescence reactions
- Radioimmunoassay (RIA)
Shock
- life threatening clinical syndrome of cardio-vascular collapse
- characterized by hypotension and hypoperfusion
- An acute reduction of effective circulating blood volume (hypotension)
- An inadequate perfusion of cells and tissues (hypoperfusion)
- If uncompensatedàlead to impaired cellular metabolism and death
Shock Definition
- clinical state of circulatory collapse resulting in hypo-perfusion of tissues with subsequent impaired tissue oxygenation
Types of Shock- 5 types
Hypovolemic Shock
- Due to acute reduction in circulating blood volume or inadequate circulatory blood volume
- Causes
- severe hemorrhage (loss of red cell mass and plasma) or
- massive loss of fluid
- dehydration
Pathophysiology of Hypovolemic Shock
- Severity à clinical features
- Severity of clinical features depends upon degree of blood volume
- Less than 1000 ml: Compensated
- 1000-1500 ml: Mild
- 1500-2000 ml: Moderate
- Greater than 2000 ml: Severe
Hypovolemic Shock Clinical Features
- increased heart rate (tachycardia),
- hypotension,
- low urinary output,
- altered mental state (agitated to confused to lethargic)
- Restlessness
- Sweating and cold
- Rapid shallow breasthing
Cardiogenic shock
- No actual reduction of blood volume
- Cause due to Heart disease like severe left ventricular dysfunction such as myocardial damage
- Acute circulatory failure Due to decrease cardiac output
Septic/Toxaemic Shock-septicimia
- Caused by systemic microbial or bacterial infection in a whole system
- Two types of shock
- Endotoxic shock or Gram negative septicemia
- Exotoxic shock or gram positive septicimia
Neurogenic Shock
- Associated with accident or spinal cord injury, severe trauma
- Results from causes of interruption of sympathetic vasomotor supply
- Neurogenic Shock pathophysiology
Anaphylactic Shock
- It is hypersensitivity reactions
- It is initiated by generalized by IgE mediated hypersensitivity reaction leading to systemic vasodilatation and increased vascular permeability
- Pathophysiology of Anaphylytic Shock
- 3 Stages of shock
- Progressive disorder that lead to death if uncorrected
- Compensated Shock/ Non-progressive/ Initial/ Reversible
- If good treatmentà recovery and become normal
- Compensetory mechanism activatedà perfusion of vital organs maintained
- Activation of various neuro-hormonal mechanisms
- widespread vasoconstriction and
- fluid conservation by the kidney
- Purpose is to maintain adequate cerebral and coronary blood supply by redistribution of blood so that the vital organs (brain and heart) are adequately perfused and oxygenated
- Widespread vasoconstriction
- Fluid conservation by the kidney
- To compensate the actual loss of blood volume in hypovolaemic shock, the following factors may assist in restoring the blood volume and improve venous return to the heart
- Release of aldosterone from hypoxic kidney by activation of renin-angiotensin-aldosterone mechanism
- Release of ADH due to decreased effective circulating blood volume
- Shifting of tissue fluids into plasma due to lowered capillary hydrostatic pressure (hypotension)
Stimulation of adrenal medulla
- In response to low cardiac output, adrenal medulla is stimulated to release excess of catecholamines (epinephrine and non-epinephrine)
- This increase heart rate as well as increase cardiac output
Progressive decompensated shock
- When the patient suffers from some other stress or risk factors (e.g pre-existing cardiovascular and lung diseases) besides persistence of the shock so that there is progressive deterioration
- It worsen pulmonary perfusion (pulmonary hypoperfusion) and increase vascular permeability resulting in tachyponea and ARDS
- Impaired tissue perfusion causes switch from aerobic to anaerobic glycolysis resulting in metabolic lactic acidosis
- Lactic acidosis lowers the tissue pH which cause vasomotor response ineffective. This results in vasodilatation and peripheral pooling of blood
- Clinically, patient develops confusion and worsening of renal function
Irreversible decompensated shock
- When the shock is severe that in spite of compensatory mechanisms and despite therapy and control of etiology agent (shock) and no recovery takes place
Immunity
- Types of Immunity
- Natural or innate immunity
Non-specific Immnity
- Considered as the first line of defense without antigenic specificity
Specific immunity or adaptive immunity
- Characterized by antigenic specificity
Immune deficiency disorders
- Deficiencies of host defense systems result in an immunologic imbalance that can lead to a susceptibility to infection, an autoimmune disease, or a predisposition to malignancies
- Characterized by deficient cellular and/or humoral immune functions
- Includes
- Primary immune deficiency disorder
- Secondary immune deficiency disorder
Primary Immune deficiency disorder
- -Causes in immune system component
- a. According of component
- i) Complements
- ii) Phagocytic
- iii) B cells (Humoral)
- iv) T Cells (cellular)
- b. According to the etiology
- i) Congenital (X-linked disease)
- ii) Acquired (AIDS)
- iii) Embryogenesis (Digoerge syndrome)
- iv) Idiopathic
Secondary immune deficiency disorder
- -Non Immunogenic causes
- Prematurity
- Mal nutrition
- Malignancy
- Injury, Burns, Splenectomy
- Drugs
Hypersensitivity reactions
- Defined as the state of exaggerated immune response to an antigen
- Characterized by hyperfunction of the immune system and cover the various mechanisms of immunologic tissue injury
Types of hypersensitivity reactions
Type I hypersensitivity reactions
- Known as Anaphylactic reaction
- Defined as a state of rapidly developing or anaphylactic type of immune response to an antigen to which the individual is previously sensitized
- Reaction occurs within 15-30 minutes of exposure to antigen
- IgE mediated reactions
- Associated with allergens such as bee stings, peanuts
Type II hypersensitivity reactions
- Known as cytotoxic reaction
- Defined as reactions by humoral antibodies that attack cell surface antigens on the specific cells and tissues and cause lysis of target cells
- Reaction occurs within hours to days of exposure to antigen
- IgG or IgM mediated reactions
- Examples- autoimmune haemolytic anaemia, transfusions reaction, myasthenia gravis
Type III hypersensitivity reactions
- Known as Immune Complex Mediated Reaction
- Result from deposition of antigen-antibody complexes on tissues which is followed by activation of the complement system and inflammatory reaction, resulting in cell injury
- Reaction occurs within 1-3 weeks of exposure to antigen
- Immune complex mediated reactions
- Examples- SLE, Immune complex glomerulonephritis
- Type IV Hypersensitivity Reactions
- Known as delayed hypersensitivity reaction
- Defined as a tissue injury by cell mediated immune response without formation of antibodies but a slow and prolonged response of specifically sensitized T lymphocyctes
- Reaction occurs after 24 hours to days and weeks of exposure to antigen
- T cell mediated reactions
- Examples- tuberculin reaction, leprosy (reaction against mycobacterial infection), transplant rejection
Auto immune disorders
- Normally lymphocytes recognize body’s own proteins, so antibodies are not developed against them
- However, sometimes body suffer from antibody or cell mediated attack against its own, causing damage of normal cells and their function leading to autoimmune disease
- example- rheumatic heart disease
- Defined as a state in which the body’s immune system fails to distinguish between ‘self’ and ‘non self’ and reacts by formation of autoantibodies against one’s own tissue antigens
- There is loss of tolerance to one’s own tissues (autoimmunity)
- Caused by immunological factors, genetic factors and microbial factors
Types of autoimmune diseases
Organ specific diseases
- Autoantibodies formed react specifically against an organ or target tissue component and cause its chronic inflammatory destruction
- Example-thyroid, pancreatic islets of langerhans
Organ non-specific (systemic) diseases
- Autoantibodies formed which reacts with antigens in many tissues and thus causes systemic lesions
- Example- Systemic lupus erythematous, Rheumatoid arthritis, Sjogren’s syndrome
Genetic disorders
- Genetic disorder is due to inherited defects in chromosomes
Classification of genetic disorders
- Single gene defect
- Multifactorial disorder
- Cytogenetic (Karyotypic) disorder or chromosomal abnormalities
Single gene disorders
- Know as mendelian disorders
- These disorders are due to defect in a single gene or result of mutation of a single gene
- Example- sickle cell anemia, Beta thalassaemia
Multifactorial genetic/inheritance disorders
- Those disorders which result from the combined effect of genetic composition and environmental influences
- Example- congenital heart disease, diabetes mellitus, cleft palate, congenital heart disease
- Cytogenetic or chromosomal disorders
- This disorder may be due to aberrations in the number of structure of chromosomes
- A chromosomes number which is an exact multiple of the haploid number and exceeds the diploid number is called polypoidy and which is not an exact multiple is called aneuploidy
Examples Down’s syndrome (Trisomy 21), Edward’s syndrome (Trisomy 18)